Mozart's movements and behaviour: a case of Tourette's syndrome?

PubMed

Ashoori, A; Jankovic, J

2008-06-01

In this review, we intend to explore the often asked question: "Did Mozart have Tourette's syndrome?" Although there are numerous reports attributing Mozart's peculiar personality and behaviour to a spectrum of neurobehavioural disorders such as Tourette's syndrome, autistic disorder, Asperger's syndrome, attention deficit hyperactivity disorder, obsessive-compulsive disorder and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, the evidence for any of these disorders is lacking. Whether Mozart's behaviour was nothing more than a reflection of his unique personality or a more complex neurological disorder, aggravated later in life by enormous demands by his father and society, his behaviour has been the subject of many biographies. It will also remain unknown to what extent his accomplishments and failures were shaped by his childhood experiences, pressured lifestyle, and his innate genius and extraordinary talent. Lessons from his life may have important implications for other gifted individuals and savants whose special attributes may lead them to succeed or, on the other hand, suppress their emotional growth and make them more vulnerable to stress and failure.

A link between perianal strep and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS).

PubMed

Toufexis, Megan; Deoleo, Caroline; Elia, Josephine; Murphy, Tanya K

2014-04-01

Perianal streptococcal dermatitis is an infection caused by group A streptococcus (GAS). Children with a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) phenotype may have tics or obsessive compulsive symptoms secondary to a systemic immune activation by GAS infecting perianal areas. In this retrospective case series, the authors describe three children with symptoms consistent with PANDAS and a confirmed perianal streptococcal dermatitis as the likely infectious trigger. Concomitant perianal dermatitis and new-onset obsessive-compulsive symptoms and/or tics are strong indications for perianal culture and rapid antigen detection test in young children.

Annotation: PANDAS--A Model for Human Autoimmune Disease

ERIC Educational Resources Information Center

Swedo, Susan E.; Grant, Paul J.

2005-01-01

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated…

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

PubMed Central

Tan, Jason; Smith, Christine H.; Goldman, Ran D.

2012-01-01

Abstract Question I have heard about children who have tic disorders that seem to be exacerbated by group A β-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Answer Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A β-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy. PMID:22972724

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

PubMed

Tan, Jason; Smith, Christine H; Goldman, Ran D

2012-09-01

I have heard about children who have tic disorders that seem to be exacerbated by group A β-hemolytic streptococcal infection. Should children presenting with this phenomenon receive treatment with antibiotics, receive prophylactic treatment, or use immunomodulators to treat the symptoms? Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) constitute a condition that includes neuropsychiatric symptoms, mainly obsessive-compulsive disorder or tic disorders, temporally associated with an immune-mediated response to streptococcal infections. The actual existence of PANDAS as a unique clinical entity is still up for debate, as a temporal association between group A β-hemolytic streptococcal infections and symptom exacerbations has been difficult to prove thus far. Based on only a few studies, positive results have been found using antibiotic prophylaxis and immunomodulatory therapy in children with PANDAS. At this time, however, evidence does not support a recommendation for long-term antibiotic prophylaxis or immunomodulatory therapy.

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview.

PubMed

Rhee, Hanna; Cameron, Daniel J

2012-01-01

Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed.

Pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS): update.

PubMed

Shulman, Stanford T

2009-02-01

To review recent developments related to the proposed entity Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococci (so-called 'PANDAS'). The relationship between obsessive-compulsive disorder (OCD) or tics/Tourette's syndrome in childhood to antecedent group A streptococci (GAS) is unclear. One recent prospective cohort study found that more than 85% of clinical exacerbations in OCD/tic behavior in patients who met criteria for PANDAS had no relationship to GAS infection. Another study found no correlation between clinical exacerbations and changes in a variety of markers of brain autoimmunity, the proposed pathogenesis of PANDAS. A third recent study concluded that, compared with specialty clinic diagnoses, patients diagnosed with tics or Tourette's by physicians in the community were significantly more likely to be diagnosed with PANDAS without meeting the proposed criteria, most lacked supporting laboratory evidence of GAS infection, and they were more likely to be treated with unjustified short-term to chronic antibiotic and/or immunomodulatory therapy. Despite continued research in the field, the relationship between GAS and specific neuropsychiatric disorders (PANDAS) remains elusive. It is possible that GAS infection may be but one of the many stressors that can exacerbate tic/Tourette's or OCD in a subset of such patients.

Is It PANS, CANS, or PANDAS? Neuropsychiatric Pediatric Disorders That Are Not Black and White--Implications for the School Nurse.

PubMed

Bagian, Kathy; Hartung, Sheila Q

2015-03-01

The terms pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), pediatric acute-onset neuropsychiatric syndrome (PANS), and childhood acute neuropsychiatric symptoms (CANS) have all been used to describe certain acute onset neuropsychiatric pediatric disorders. Additionally, controversy is ongoing concerning the diagnosis and etiology of the disorders. The school nurse, as a member of a multidisciplinary team, benefits from an awareness of these disorders, the resulting impact on school performance, and the recommended treatment. The school nurse assists the team through the development of an Individualized Healthcare Plan to help the student to achieve success in school. © 2014 The Author(s).

Medical conditions with neuropsychiatric manifestations.

PubMed

Isaac, Margaret L; Larson, Eric B

2014-09-01

Medical disease sometimes affects patients through neuropsychiatric manifestations. When neuropsychiatric symptoms are predominant, identifying medical disease early in the illness course is imperative because many of these conditions are reversible with appropriate treatment. A high index of suspicion is required on the part of clinicians, particularly when patients also present with physical signs or unexplained symptoms that might suggest a broader, systemic process. The processes that most commonly cause neuropsychiatric symptoms include infectious, autoimmune, endocrinologic, metabolic, and neoplastic diseases. This article focuses on the most common of these conditions, and conditions for which early diagnosis and treatment are particularly important. Copyright © 2014 Elsevier Inc. All rights reserved.

The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children.

PubMed

Mostafa, Gehan Ahmed; Al-Ayadhi, Laila Yousef

2012-09-01

Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies. This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale. Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001. Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS): an overview

PubMed Central

Rhee, Hanna; Cameron, Daniel J

2012-01-01

Lyme disease (LD) is a complex, multisystemic illness. As the most common vector- borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed. PMID:22393303

Mozart's movements and behaviour: a case of Tourette's syndrome?

PubMed Central

Ashoori, Aidin; Jankovic, Joseph

2007-01-01

In this review, we intend to explore the often asked question: “Did Mozart have Tourette's syndrome?” Although there are numerous reports attributing Mozart's peculiar personality and behaviour to a spectrum of neurobehavioural disorders such as Tourette's syndrome, autistic disorder, Asperger's syndrome, attention deficit hyperactivity disorder, obsessive–compulsive disorder and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, the evidence for any of these disorders is lacking. Whether Mozart's behaviour was nothing more than a reflection of his unique personality or a more complex neurological disorder, aggravated later in life by enormous demands by his father and society, his behaviour has been the subject of many biographies. It will also remain unknown to what extent his accomplishments and failures were shaped by his childhood experiences, pressured lifestyle, and his innate genius and extraordinary talent. Lessons from his life may have important implications for other gifted individuals and savants whose special attributes may lead them to succeed or, on the other hand, suppress their emotional growth and make them more vulnerable to stress and failure. PMID:17940168

The role of tonsillectomy in the treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

PubMed

Demesh, Daniel; Virbalas, Jordan M; Bent, John P

2015-03-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) in children describes neuropsychiatric symptom exacerbations that relate temporally to streptococcal infections. Recent case reports suggest tonsillectomy may effectively reduce these symptoms; however, no consensus treatment guidelines exist. This study examines whether tonsillectomy improves neuropsychiatric symptoms in children with PANDAS who have incomplete response to antibiotic therapy. Ten patients met strict diagnostic criteria for PANDAS. Comparisons were made between parental reports of symptom severity at diagnosis, after antibiotic treatment (in 10 patients), and after tonsillectomy (in 9). From a baseline severity score of 10, antibiotics alone improved symptoms to a median (interquartile range [IQR]) score of 8 (6.5-10.0) (P = .03). Nine children who subsequently underwent tonsillectomy reported symptom improvement in comparison with treatment with antibiotics alone, including those with no response to antibiotics. Symptom severity improved at all periods after tonsillectomy compared with antibiotics alone. The median score [IQR] 3 months postoperatively was 3 (0.0-6.5) (P = .01); 6 months postoperatively, 3 (0.0-5.0) (P = .02); 1 year postoperatively, 3 (0.0-5.0) (P = .02); and 3 years postoperatively, 0.5 (0.0-2.3) (P = .03). Four of the 9 had complete resolution after tonsillectomy. This PANDAS cohort whose neuropsychiatric symptoms did not respond sufficiently to antibiotics may have gained benefit from tonsillectomy.

Severe aplastic anaemia and Grave's disease in a paediatric patient.

PubMed

Kumar, Manjusha; Goldman, Jeffrey

2002-07-01

Severe aplastic anaemia (SAA) is considered to be an autoimmune disorder affecting the haematopoietic cells and most often is idiopathic. An association between SAA and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus and thyroid disorders. We describe the first paediatric patient with chronic relapsing SAA and Grave's disease. We discuss the difficulty in diagnosis of Grave's disease, the possibility of its manifestation due to withdrawal of immunosuppressants, and issues to consider in the treatment of this disease in the setting of bone marrow failure.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces depression-like behavior and cognitive dysfunction in non-autoimmune mice

PubMed Central

Wen, Jing; Chen, Chris; Stock, Ariel; Doerner, Jessica; Gulinello, Maria; Putterman, Chaim

2016-01-01

Fn14, the sole known signaling receptor for the TNF family member TWEAK, is inducibly expressed in the central nervous system (CNS) in endothelial cells, astrocytes, microglia, and neurons. There is increasing recognition of the importance of the TWEAK/Fn14 pathway in autoimmune neurologic conditions, including experimental autoimmune encephalomyelitis and neuropsychiatric lupus. Previously, we had found that Fn14 knockout lupus-prone MRL/lpr mice display significantly attenuated neuropsychiatric manifestations. To investigate whether this improvement in disease is secondary to inhibition of TWEAK/Fn14 signaling within the CNS or the periphery, and determine whether TWEAK-mediated neuropsychiatric effects are strain dependent, we performed intracerebroventricular (ICV) injection of Fc-TWEAK or an isotype matched control protein to C57Bl6/J non-autoimmune mice. We found that Fc-TWEAK injected C57Bl6/J mice developed significant depression-like behavior and cognitive dysfunction. Inflammatory mediators associated with lupus brain disease, including CCL2, C3, and iNOS, were significantly elevated in the brains of Fc-TWEAK treated mice. Furthermore, Fc-TWEAK directly increased blood brain barrier (BBB) permeability, as demonstrated by increased IgG deposition in the brain and reduced aquaporin-4 expression. Finally, Fc-TWEAK increased apoptotic cell death in the cortex and hippocampus. In conclusion, TWEAK can contribute to lupus-associated neurobehavioral deficits including depression and cognitive dysfunction by acting within the CNS to enhance production of inflammatory mediators, promote disruption of the BBB, and induce apoptosis in resident brain cells. Our study provides further support that the TWEAK/Fn14 signaling pathway may be a potential therapeutic target for inflammatory diseases involving the CNS. PMID:26721417

New-Onset Headache in Patients With Autoimmune Encephalitis Is Associated With anti-NMDA-Receptor Antibodies.

PubMed

Schankin, Christoph J; Kästele, Fabian; Gerdes, Lisa Ann; Winkler, Tobias; Csanadi, Endy; Högen, Tobias; Pellkofer, Hannah; Paulus, Walter; Kümpfel, Tania; Straube, Andreas

2016-06-01

We tested the hypotheses (i) that autoimmune encephalitis is associated with new-onset headache, and (ii) that the occurrence of headache is associated with the presence of anti-N-methyl-D-aspartate (NMDA)-receptor antibodies. Autoimmune encephalitis presents with cognitive dysfunction as well as neuro-psychiatric symptoms. Its pathophysiology might involve antibody-mediated dysfunction of the glutamatergic system as indicated by the presence of anti-NMDA-receptor antibodies in some patients. In this cross-sectional study, patients with autoimmune encephalitis were assessed with a standardized interview for previous headache and headache associated with autoimmune encephalitis. Headache was classified according to the International Classification of Headache Disorders, second edition. Clinical and paraclinical findings were correlated with the occurrence of headache. Of 40 patients with autoimmune encephalitis, 19 did not have a history of headache. Of those, nine suffered from encephalitis-associated headache. Seven of these nine had anti-NMDA-receptor antibodies in contrast to only two among the remaining 10 patients without new-onset headache (P = .023, odds ratio: 14, 95% confidence interval: 1.5; 127). In most patients headache occurred in attacks on more than 15 days/month, was severe, and of short duration (less than 4 hours). International Headache Society criteria for migraine were met in three patients. New-onset headache is a relevant symptom in patients with autoimmune encephalitis who have no history of previous headache, especially in the subgroup with anti-NMDA-receptor antibodies. This indicates a thorough investigation for secondary headaches including anti-NMDA-R antibodies for patients with new-onset headache and neuropsychiatric findings. Glutamatergic dysfunction might be important for the generation of head pain but may only occasionally be sufficient to trigger migraine-like attacks in nonmigraineurs. © 2016 American Headache Society.

Post-infectious autoimmune disorders: Sydenham's chorea, PANDAS and beyond.

PubMed

Williams, Kyle A; Swedo, Susan E

2015-08-18

Infections, and the resulting immune response to these infections, have recently received increased recognition as pathogenic mechanisms for neuropsychiatric disorders. Sydenham's chorea (SC), a widely recognized post-streptococcal autoimmune disorder, represents a model for this proposed pathogenesis. In SC, a dysregulated immune response to a streptococcal infection is hypothesized to result in inflammation of neuronal networks, particularly the basal ganglia nuclei. The resulting dysfunction in the basal ganglia nuclei are hypothesized to lead to a constellation of adventitious movements and psychiatric symptoms, which investigations have shown are amenable to immunomodulatory therapies. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections) has been proposed as a variant of SC, and is hypothesized to share a pathogenic mechanism, despite a unique symptom profile of predominantly psychiatric symptoms. In this review, we present the clinical aspects of both disorders, the data for potential shared etiopathogenesis between them, and the evidence for the therapeutic use of immunomodulatory therapies for the symptoms of SC and PANDAS. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Implications for Advanced Practice Nurses When Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS) Is Suspected: A Qualitative Study.

PubMed

McClelland, Molly; Crombez, Mary-Margaret; Crombez, Catherine; Wenz, Catherine; Lisius, Margaret; Mattia, Amanda; Marku, Suzana

2015-01-01

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is a relatively new but controversial diagnosis affecting hundreds of children and their families. It is generally thought to be an autoimmune disorder resulting from a streptococcal infection that causes significant and bizarre behavioral changes in children. Currently no definitive diagnostic or treatment modalities exist, which has led to misdiagnoses, ineffective treatments, and delayed care. A qualitative study was conducted that included 60 families with at least one child diagnosed with PANDAS. The purpose was to explore how families experience the disorder and what nurses can do to provide effective care. Using paradigmatic analysis of transcribed interviews, three themes were identified: fear, frustration, and not being heard. Results from this study suggest that more information is needed to better understand this challenging phenomenon from both medical and nursing perspectives. The study also reaffirms the importance of practicing the art of nursing, especially when the science is not yet established. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

Juvenile systemic lupus erythematosus in Nigeria.

PubMed

Adelowo, O O; Olaosebikan, B H; Animashaun, B A; Akintayo, R O

2017-03-01

Juvenile systemic lupus erythematosus (JSLE) is a complex multisystemic autoimmune disorder of unknown cause. It accounts for about one in five cases of SLE. The tendency for SLE to run a fulminant course when it starts in childhood has made JSLE a potentially more severe disease than adult SLE. Reports of JSLE from sub-Saharan Africa are scanty in spite of the increasing reports of adult SLE. We conducted a 4-year retrospective study of JSLE cases seen at the Lagos State University Teaching Hospital between January 2010 and December 2014. Out of the 12 patients studied, eight were girls and four were boys. All patients had positive antinuclear antibody and extractable nuclear antibody tests. Anti-dsDNA antibody was positive in 10 patients. Eight patients had renal disease while four patients had neuropsychiatric manifestations. Haematological abnormalities and constitutional symptoms were present in all patients. Patients were treated with pulse methylprednisolone, oral prednisolone, hydroxychloroquine and azathioprine. Three patients also received rituximab. In conclusion, JSLE exists in Nigeria and exhibits clinical and immunological characteristics similar to its pattern in other parts of the world. It is, however, diagnosed late and is possibly being underdiagnosed as there is no paediatric rheumatologist in the country.

PANDAS: The Need to Use Definitive Diagnostic Criteria.

PubMed

Singer, Harvey S

2015-01-01

In Response to: Helm CE, Blackwood RA. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS): Experience at a tertiary referral center. Tremor Other Hyperkinet Mov. 2015; 5. doi: 10.7916/D8348JCX.

[NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS].

PubMed

Stryjer, Rafael; Shriki Tal, Liron; Gizunterman, Alex; Amital, Daniela; Amital, Howard; Kotler, Moshe

2017-12-01

This review deals with the neuropsychiatric disorders resulting from systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease that impacts all systems in the human body, including the central nervous system. Neuropsychiatric symptoms in SLE are a common complication of the disease. This complication has significant implications for the severity of the illness. In most cases no thorough psychiatric assessment is performed during initial evaluation of the disease and no protocol or clear guidelines for treating the psychiatric symptoms in SLE are available. Early diagnosis of the psychiatric symptoms in SLE is critical since absence of treatment may result in severe psychiatric complications. Clinical pharmacological studies are needed in order to develop guidelines for treating psychiatric symptoms in SLE.

A new clinical feature associated with familial early-onset of dystonic-guttural tics: An unusual diagnosis of PANDAS.

PubMed

Vitaliti, Giovanna; Trifiletti, Rosario R; Falsaperla, Raffaele; Parano, Enrico; Spalice, Alberto; Pavone, Piero

2014-01-01

Until today there is a large debate about the existence of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) or PANS (pediatric acute onset neuropsychiatric syndrome). These children usually have dramatic, "overnight" onset of symptoms, including motor or vocal tics, obsessions, and/or compulsions. In addition to these symptoms, children may also have comorbid features of associated disorders. Herein, we report a family with an early onset of tics, with exclusively dystonic and guttural tics. All patients had a particularly strong excitement trigger. Two of the patients were shown to have signs suggestive of PANDAS and all family members were Group A beta-hemolytic Streptococcus (GABHS) carriers. The PANDAS spectrum is probably a group of disorders. We have described a PANDAS variant, in which the family seems to share common autoimmune pattern and may be viewed in the large spectrum of PANDAS.

Thyroid autoimmunity and function among Ugandan children and adolescents with type-1 diabetes mellitus.

PubMed

Muhame, Rugambwa Michael; Mworozi, Edison Arwanire; McAssey, Karen; Lubega, Irene

2014-01-01

Up to 30% of type-1 diabetes mellitus (T1DM) patients have co-existent thyroid autoimmunity with up to 50% of them having associated thyroid dysfunction. Routine screening for thyroid autoimmunity and dysfunction is recommended in all T1DM patients. However, this was not currently practiced in Ugandan paediatric diabetes clinics. There was also paucity of data regarding thyroid autoimmunity and dysfunction in African children and adolescents with diabetes mellitus. The objective of this study was to quantify the magnitude of thyroid autoimmunity and dysfunction in Ugandan children with TIDM. This was a cross sectional descriptive study to determine the prevalence of thyroid autoantibodies and describe thyroid function among children and adolescents aged 1-19 years with diabetes mellitus attending the paediatric diabetes clinic at Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we obtained details of clinical history and performed physical examination. Blood (plasma) was assayed to determine levels of antibodies to thyroid peroxidase (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). The prevalence of thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO positive subjects. All study subjects were clinically euthyroid; however, 7.3% (5/69) of the study subjects had subclinical hypothyroidism. These data strengthen the argument for routine screening of all diabetic children and adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by international guidelines. We also recommend evaluation of thyroid function in diabetic children and adolescents to minimize the risk of undiagnosed thyroid dysfunction.

Autoimmune encephalitis update

PubMed Central

Dalmau, Josep; Rosenfeld, Myrna R.

2014-01-01

Cancer-associated immune-mediated disorders of the central nervous system are a heterogeneous group. These disorders include the classic paraneoplastic neurologic disorders and the more recently described autoimmune encephalitis associated with antibodies to neuronal cell-surface or synaptic receptors that occur with and without a cancer association. Autoimmune encephalitis is increasingly recognized as the cause of a variety of neuropsychiatric syndromes that can be severe and prolonged. In contrast to the classic paraneoplastic disorders that are poorly responsive to tumor treatment and immunotherapy, autoimmune encephalitis often responds to these treatments, and patients can have full or marked recoveries. As early treatment speeds recovery, reduces disability, and decreases relapses that can occur in about 20% of cases, it is important that the immune pathogenesis of these disorders is recognized. PMID:24637228

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept

PubMed Central

Macerollo, Antonella; Martino, Davide

2013-01-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham’s chorea (SC)—the prototypical post-streptococcal neuropsychiatric disorder—and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo’s criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo’s criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders. PMID:24106651

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): An Evolving Concept.

PubMed

Macerollo, Antonella; Martino, Davide

2013-01-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders.

CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors

PubMed Central

Cutforth, Tyler; DeMille, Mellissa MC; Agalliu, Ilir; Agalliu, Dritan

2016-01-01

Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS. PMID:27110222

Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference

PubMed Central

Frankovich, Jennifer; Cooperstock, Michael; Cunningham, Madeleine W.; Latimer, M. Elizabeth; Murphy, Tanya K.; Pasternack, Mark; Thienemann, Margo; Williams, Kyle; Walter, Jolan; Swedo, Susan E.

2015-01-01

Abstract On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS. PMID:25325534

Autoimmune paediatric liver disease

PubMed Central

Mieli-Vergani, Giorgina; Vergani, Diego

2008-01-01

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy. PMID:18528933

Autoimmune paediatric liver disease.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy.

Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

PubMed

Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

2014-12-01

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS): Experience at a Tertiary Referral Center.

PubMed

Helm, Caitlin E; Blackwood, R Alexander

2015-01-01

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an autoimmune disorder presenting with obsessive compulsive disorder and/or tics. Like Sydenham's chorea, its presumed pathogenesis consists of autoantibodies cross-reacting with neurons in response to a group A beta-hemolytic streptococcal infection (GASI). There are currently no diagnostic laboratory findings and management ranges from antibiotic prophylaxis to intravenous immunoglobulin to plasmapheresis. The diagnosis remains controversial, resulting in inconsistent referrals and significant patient anxiety. A retrospective study was performed on all patients referred to the Pediatric Infectious Disease Division with a pre-referral diagnosis of PANDAS. Patients were analyzed by demographics, medical history, co-morbidities, symptoms, prior treatment, laboratory tests, management strategies, and treatment outcomes. From 2003 to 2013, there were 21 patients with a pre-referral diagnosis of PANDAS. Only five met the diagnostic criteria. No patient at referral had an objective scale to monitor symptoms. Eight referrals had a major psychiatric disorder, and none fulfilled diagnostic criteria (p<0.01). The majority of the patients referred with a pre-diagnosis of PANDAS do not fulfill diagnostic criteria nor do they have objective criteria for symptom monitoring. Major psychiatric disorders do not seem to be associated with PANDAS, and better physician education may prevent misdiagnoses. Multidisciplinary management is recommended.

Vitamin D Deficiency in Obsessive-Compulsive Disorder Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections: A Case Control Study.

PubMed

Çelik, Gonca; Taş, Didem; Tahiroğlu, Ayşegül; Avci, Ayşe; Yüksel, Bilgin; Çam, Perihan

2016-03-01

Previous studies have indicated that vitamin D deficiency is common in psychiatric patients, particularly in those with neuropsychiatric disorders such as autism and schizophrenia. Vitamin D is an important neurosteroid hormone and immunomodulatory agent that also has bone metabolic effects. There has been an increasing interest in immune-related neuropsychiatric symptoms that are triggered by group A beta-hemolytic streptococcal infections. In this study, we aimed to compare the serum levels of vitamin D between obsessive-compulsive disorder (OCD) patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and control subjects. Thirty-three OCD patients with PANDAS and 20 healthy controls were enrolled in the study. Serum 25-hydroxyvitamin D (25-(OH) D), calcium, phosphorus, alkaline phosphatase, and parathormone levels of the two groups were compared. Serum 25-(OH) D levels of <15 ng/mL were classified as vitamin D deficiency. The children's Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impression (CGI) were used to assess the severity of OCD symptoms. There was no significant difference in serum 25-(OH) D levels between the patient and control groups. However, vitamin D deficiency was significantly more frequent in the patient group than in the control group (48.5% vs. 20.0%; p=0.038). Moreover, OCD patients with vitamin D deficiency had higher rates of comorbid ADHD than those without vitamin D deficiency (87.5% vs. 52.6%; p=0.027). While serum phosphorus levels were negatively correlated with age as well as alkaline phosphatase and ASO levels, they were positively correlated with the YBOCS total score and global severity score. Serum parathormone levels were positively correlated with the YBOCS total score, compulsion score, obsession score, and global severity score. This study supports the hypothesis that an association between vitamin D metabolism and PANDAS-related OCD exists. We suggest that biochemical parameters predicting metabolic bone diseases are more common in PANDAS patients. There is a need for prospective studies to show a clear association between PANDAS and bone metabolic turnover based on autoimmune mechanisms.

Genetic disorders of thyroid metabolism and brain development

PubMed Central

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

PubMed Central

Brimberg, Lior; Benhar, Itai; Mascaro-Blanco, Adita; Alvarez, Kathy; Lotan, Dafna; Winter, Christine; Klein, Julia; Moses, Allon E; Somnier, Finn E; Leckman, James F; Swedo, Susan E; Cunningham, Madeleine W; Joel, Daphna

2012-01-01

Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders. PMID:22534626

Severe dysautonomia as a main feature of anti-GAD encephalitis: Report of a paediatric case and literature review.

PubMed

Ben Achour, Nedia; Ben Younes, Thouraya; Rebai, Ibtihel; Ben Ahmed, Melika; Kraoua, Ichraf; Ben Youssef-Turki, Ilhem

2018-05-01

Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are a rare cause of autoimmune encephalitis. This entity is mainly recognized in adults and very few cases were reported in children. We report on a paediatric case of anti-GAD encephalitis with severe presentation and uncontrollable dysautonomia. A 9-year-old girl was referred to our department for refractory seizures and behavioral disturbances. Brain magnetic resonance imaging (MRI) was normal. Repeat screening for antineuronal antibodies showed negative results for anti-NMDA receptor antibodies but positive results for anti-GAD65 with a low positivity of anti-Ma2 antibodies. Although a transient improvement was noticed after immunomodulatory treatment, the patient developed severe intractable autonomic imbalance including dysrythmia, alternating bradycardia/tachycardia, hypotension/hypertension, hypothermia/hyperthermia and hyperhidrosis. She deceased six months after onset. Our report intends to raise awareness of autoimmune encephalitis with anti-GAD65 antibodies which may involve extralimbic brain regions and manifest with fatal dysautonomia. We highlight the need for prompt diagnosis and aggressive management for this underdiagnosed entity in children. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus, and Related Disorders: A Way Forward

PubMed Central

Kurlan, Roger; Leckman, James

2010-01-01

Abstract Obsessive-compulsive disorder (OCD) and related conditions including Tourette's disorder (TD) are chronic, relapsing disorders of unknown etiology associated with marked impairment and disability. Associated immune dysfunction has been reported and debated in the literature since the late 80s. The immunologic culprit receiving the most interest has been Group A Streptococcus (GAS), which began to receive attention as a potential cause of neuropsychiatric symptoms, following the investigation of the symptoms reported in Sydenham's chorea (SC) and rheumatic fever, such as motor tics, vocal tics, and both obsessive-compulsive and attention deficit/hyperactivity symptoms. Young children have been described as having a sudden onset of these neuropsychiatric symptoms temporally associated with GAS, but without supporting evidence of rheumatic fever. This presentation of OCD and tics has been termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC, OCD, and TD often begin in early childhood and share common anatomic areas—the basal ganglia of the brain and the related cortical and thalamic sites—adding support to the possibility that these disorders might share a common immunologic and/or genetic vulnerability. Relevant manuscripts were identified through searches of the PsycINFO and MedLine databases using the following keywords: OCD, immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus. Articles were also identified through reference lists from research articles and other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010. Considering the overlap of clinical and neuroanatomic findings among these disorders, this review explores evidence regarding the immunobiology as well as the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS. PMID:20807070

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety.

PubMed

Frey, Sarabel G; Chelo, David; Kinkela, Mina N; Djoukoue, Florence; Tietche, Felix; Hatz, Christoph; Weber, Peter

2010-10-21

Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.

Clinical characterization of autoimmune encephalitis and psychosis.

PubMed

Hao, Qinjian; Wang, Dahai; Guo, Lanting; Zhang, Bo

2017-04-01

Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy. Data for patients admitted to the West China Hospital with autoimmune encephalitis diagnoses from 2015 to 2016 were collected and the corresponding clinical features were analyzed. We ultimately included 70 patients with autoimmune encephalitis: 56 (80%) anti-NMDAR encephalitis patients, 8 (11%) LGI1 antibody encephalitis patients, and 6 (9%) GABAbR antibody encephalitis patients. The median age of the 70 patients was 33years, 40% were female, and the initial symptoms in 31 patients (44%) were psychiatric in nature. Psychiatric disturbance appeared in 58 patients (83%) during inpatient treatment, after which 57 patients (81%) recovered. Many patients with autoimmune encephalitis present psychotic symptoms; psychiatric symptoms typically appear before neurological features emerge. Timely diagnosis and treatment may yield favorable prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered cerebral glucose metabolism normalized in a patient with a pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS)-like condition following treatment with plasmapheresis: a case report.

PubMed

Nave, A H; Harmel, P; Buchert, R; Harms, L

2018-05-02

Pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed. We present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized. This is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS): Experience at a Tertiary Referral Center

PubMed Central

Helm, Caitlin E.; Blackwood, R. Alexander

2015-01-01

Background Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an autoimmune disorder presenting with obsessive compulsive disorder and/or tics. Like Sydenham’s chorea, its presumed pathogenesis consists of autoantibodies cross-reacting with neurons in response to a group A beta-hemolytic streptococcal infection (GASI). There are currently no diagnostic laboratory findings and management ranges from antibiotic prophylaxis to intravenous immunoglobulin to plasmapheresis. The diagnosis remains controversial, resulting in inconsistent referrals and significant patient anxiety. Methods A retrospective study was performed on all patients referred to the Pediatric Infectious Disease Division with a pre-referral diagnosis of PANDAS. Patients were analyzed by demographics, medical history, co-morbidities, symptoms, prior treatment, laboratory tests, management strategies, and treatment outcomes. Results From 2003 to 2013, there were 21 patients with a pre-referral diagnosis of PANDAS. Only five met the diagnostic criteria. No patient at referral had an objective scale to monitor symptoms. Eight referrals had a major psychiatric disorder, and none fulfilled diagnostic criteria (p<0.01). Discussion The majority of the patients referred with a pre-diagnosis of PANDAS do not fulfill diagnostic criteria nor do they have objective criteria for symptom monitoring. Major psychiatric disorders do not seem to be associated with PANDAS, and better physician education may prevent misdiagnoses. Multidisciplinary management is recommended. PMID:26196024

Cognitive-Behavioral Therapy for PANDAS-Related Obsessive-Compulsive Disorder: Findings From A Preliminary Waitlist Controlled Open Trial

ERIC Educational Resources Information Center

Storch, Eric A.; Murphy, Tanya K.; Geffken, Gary R.; Mann, Giselle; Adkins, Jennifer; Merlo, Lisa J.; Duke, Danny; Munson, Melissa; Swaine, Zoe; Goodman, Wayne K.

2006-01-01

Objective: To provide preliminary estimates of the effectiveness of cognitive-behavioral therapy (CBT) in treating pediatric obsessive-compulsive disorder (OCD) of the pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) subtype. Method: Seven children with OCD of the PANDAS subtype (range 9-13 years) were treated…

Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

ERIC Educational Resources Information Center

Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

2011-01-01

Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

Evaluation of poststreptococcal illness.

PubMed

Hahn, Ricardo G; Knox, Lynda M; Forman, Todd A

2005-05-15

Group A beta-hemolytic streptococcal pharyngitis, scarlet fever, and rarely asymptomatic carrier states are associated with a number of poststreptococcal suppurative and nonsuppurative complications. As in streptococcal pharyngitis, acute rheumatic fever, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and poststreptococcal glomerulonephritis most often occur in children. The hallmarks of rheumatic fever include arthritis, carditis, cutaneous disease, chorea, and subsequent acquired valvular disease. Pediatric autoimmune neuropsychiatric disorders encompass a subgroup of illnesses involving the basal ganglia in children with obsessive-compulsive disorders, tic disorders, dystonia, chorea encephalitis, and dystonic choreoathetosis. Poststreptococcal glomerulonephritis is most frequently encountered in children between two and six years of age with a recent history of pharyngitis and a rash in the setting of poor personal hygiene during the winter months. The clinical examination of a patient with possible poststreptococcal complications should begin with an evaluation for signs of inflammation (i.e., complete blood count, erythrocyte sedimentation rate, C-reactive protein) and evidence of a preceding streptococcal infection. Antistreptolysin O titers should be obtained to confirm a recent invasive streptococcal infection. Other important antibody markers include antihyaluronidase, antideoxyribonuclease B, and antistreptokinase antibodies.

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

PubMed Central

Li, Yun R.; Zhao, Sihai D.; Li, Jin; Bradfield, Jonathan P.; Mohebnasab, Maede; Steel, Laura; Kobie, Julie; Abrams, Debra J.; Mentch, Frank D.; Glessner, Joseph T.; Guo, Yiran; Wei, Zhi; Connolly, John J.; Cardinale, Christopher J.; Bakay, Marina; Li, Dong; Maggadottir, S. Melkorka; Thomas, Kelly A.; Qui, Haijun; Chiavacci, Rosetta M.; Kim, Cecilia E.; Wang, Fengxiang; Snyder, James; Flatø, Berit; Førre, Øystein; Denson, Lee A.; Thompson, Susan D.; Becker, Mara L.; Guthery, Stephen L.; Latiano, Anna; Perez, Elena; Resnick, Elena; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Silverberg, Mark S.; Lie, Benedicte A.; Punaro, Marilynn; Russell, Richard K.; Wilson, David C.; Dubinsky, Marla C.; Monos, Dimitri S.; Annese, Vito; Munro, Jane E.; Wise, Carol; Chapel, Helen; Cunningham-Rundles, Charlotte; Orange, Jordan S.; Behrens, Edward M.; Sullivan, Kathleen E.; Kugathasan, Subra; Griffiths, Anne M.; Satsangi, Jack; Grant, Struan F. A.; Sleiman, Patrick M. A.; Finkel, Terri H.; Polychronakos, Constantin; Baldassano, Robert N.; Luning Prak, Eline T.; Ellis, Justine A.; Li, Hongzhe; Keating, Brendan J.; Hakonarson, Hakon

2015-01-01

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10% of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, UC, CD, PS, SPA and CVID, attributable to common genomic variations (SNP-h2). SNP-h2 estimates are most significant for T1D (0.863±s.e. 0.07) and JIA (0.727±s.e. 0.037), more modest for UC (0.386±s.e. 0.04) and CD (0.454±0.025), largely consistent with population estimates and are generally greater than that previously reported by adult GWAS. On pairwise analysis, we observed that the diseases UC-CD (0.69±s.e. 0.07) and JIA-CVID (0.343±s.e. 0.13) are the most strongly correlated. Variations across the MHC strongly contribute to SNP-h2 in T1D and JIA, but does not significantly contribute to the pairwise rG. Together, our results partition contributions of shared versus disease-specific genomic variations to pAID heritability, identifying pAIDs with unexpected risk sharing, while recapitulating known associations between autoimmune diseases previously reported in adult cohorts. PMID:26450413

Streptococcal infections of skin and PANDAS.

PubMed

Carelli, Rosanna; Pallanti, Stefano

2014-01-01

Group A streptococcal infections are associated with a variety of infections and a subset of obsessive-compulsive disorder and/or tic disorders. Screening of obsessive-compulsive symptoms and tics in patient with streptococcal infection of skin must be effective in identifying subjects who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). © 2013 Wiley Periodicals, Inc.

[Clinical Phenomenology of Autoimmune Encephalitis].

PubMed

Holle, J F; Jessen, F; Kuhn, J

2016-05-01

Antibody-associated disorders of the central nervous system constitute a heterogeneous group of disorders that can be roughly divided into two categories: Classic paraneoplastic syndromes associated with so-called well-characterized antibodies (paraneoplastic neurological disorders, PND) and autoimmune disorders with antibodies to membrane-bound or synaptic antigens (autoimmune encephalitis, AE). The discovery of autoimmune encephalitis has led to a paradigm shift in diagnosis and therapy as well as a reclassification of some neuropsychiatric syndromes that were previously classified as idiopathic or simply covered with descriptive terms.In this review article, especially clinical aspects of autoimmune encephalitis will be discussed, as there has been a rapid increase in knowledge in this regard within the past decade; increasingly overlap syndromes and associations with other disease entities have been detected. In addition to general aspects, characteristics of anti-NMDAR-, anti-LGI1-, anti-GABAA and GABABR, anti-AMPAR-, anti-CASPR2-, anti-mGluR, anti-GlycinR-, anti-GAD, anti- DPPX- and anti-D2 R encephalitis and the anti-IgLON5 encephalopathy will be presented. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical Factors Associated with PANDAS

PubMed Central

Murphy, Tanya K.; Storch, Eric A.; Lewin, Adam B.; Edge, Paula J.; Goodman, Wayne K.

2011-01-01

Objective To explore associated clinical factors in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS). Study design Children with tics and/or OCD (n = 109) were examined by personal and family history, diagnostic interview, physical examination, medical record review, and measurement of baseline levels of streptococcal antibodies. Results Significant group differences were found on several variables, such that those diagnosed with PANDAS (versus without PANDAS) were more likely to have had dramatic onset; definite remissions; remission of neuropsychiatric symptoms during antibiotic therapy; a history of tonsillectomies/adenoidectomies; evidence of GAS infection, and clumsiness. Conclusion The identification of clinical features associated with PANDAS should assist in delineating risks for this subtype of OCD/tics. PMID:21868033

Tonsillectomy remains a questionable option for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

PubMed

Windfuhr, Jochen P

2016-01-01

Background: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a disease attributed to children with obsessive compulsive disorders (OCD) or tic disorders associated with streptococcal infections. Because otolaryngologists examine a large number of pediatric patients with recurrent streptococcal infections, tonsillectomy (TE) is a common option of therapy. This study was conducted to evaluate the efficacy of TE in patients presenting with verified PANDAS. Material and methods: A PubMed review was performed using search terms "tonsillectomy" and "PANDAS", "OCD", "compulsive" "pediatric autoimmune", "chorea" and "tic" limited by publication date of January 1, 1995, to July 31, 2015. Reviews without patients were not included in the review. Results: Nine papers matched our search criteria, including 6 case reports with 8 patients and 3 case series. Most case reports were in favor of TE, but this was by far not supported by the findings in the case series. The follow-up ranged from 2 to 36 months in case reports and from 24 to 36 in case series. Conclusion: Establishing the diagnosis of PANDAS is complicated because of underlying comorbidities in the field of neurology-psychiatry and the lack of a reliable biomarker. The positive outcome after TE as reported in case studies may be influenced by the postoperative medication and is not supported by the results of large-scale studies. In the light of the considerable postoperative morbidity rate, it appears wise to indicate TE for PANDAS only in supervised clinical studies.

An anti-NMDA receptor encephalitis mimicking an HIV encephalitis.

PubMed

Haneche, Fatiha; Demeret, Sophie; Psimaras, Dimitri; Katlama, Christine; Pourcher, Valérie

2018-05-14

The incidence of HIV associated neurocognitive disorders (HAND) were reduced with the use of antiretroviral therapy. In case of neuropsychiatric symptoms, after elimination of all infections, auto-immune encephalitis could be evocated as a differential diagnosis. We describe a case of anti-N-Methyl-d-Aspartate receptor encephalitis in an HIV-1 infected woman. Copyright © 2018. Published by Elsevier Inc.

Immune-mediated extrapyramidal movement disorders, including Sydenham chorea.

PubMed

Dale, Russell C

2013-01-01

Immune-mediated extrapyramidal movement disorders typically occur in previously healthy children. Immune-mediated movement disorders may occur as a postinfectious, paraneoplastic, or idiopathic process. Sydenham chorea (SC) is the classical poststreptococcal movement and psychiatric disorder, and may be associated with other features of rheumatic fever. The outcome is typically good, although residual chorea, psychiatric disturbance, and relapses are possible. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a syndrome of streptococcal-induced tics and obsessive-compulsive disorder. Although a number of investigators have reported an association between streptococcal infection and neuropsychiatric syndromes, the PANDAS hypothesis is controversial. Encephalitis lethargica is an encephalitic illness with parkinsonism, dyskinesias, and psychiatric disturbance as dominant features. The exact disease mechanism is not understood, although an autoimmune process is suspected. NMDA-R encephalitis is a new entity characterized by encephalitis with dramatic psychiatric disturbance, dyskinesias, cognitive alteration, and seizures. Patients have autoantibodies against the NMDA-R that appear to be pathogenic: immune therapies appear warranted to minimize disability. Movement disorders are also described associated with systemic lupus erythematosus and antiphospholipid syndrome. The differential diagnosis and investigation approach of acute-onset movement disorders are also discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

PubMed Central

Maroz, Natallia; Bernhardt, Nechama; Chow, Robert Dobbin

2012-01-01

We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH=18.6 MIU/ml, T3reverse=0.44nmol/L, T4=0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30) with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids. PMID:23882359

Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Williams, Kyle A; Swedo, Susan E; Farmer, Cristan A; Grantz, Heidi; Grant, Paul J; D'Souza, Precilla; Hommer, Rebecca; Katsovich, Liliya; King, Robert A; Leckman, James F

2016-10-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS. A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I. During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24. IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666. Published by Elsevier Inc.

Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses.

PubMed

Tu, Xiaoning; Li, Shan; Zhao, Lijuan; Xiao, Ran; Wang, Xiuling; Zhu, Fan

2017-08-01

Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases, including autoimmune disorders, and it could activate innate immunity. However, there are no reports investigating whether human leukemia antigen (HLA)-A*0201 + restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases. In the present study, HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy. Five peptides displaying HLA-A*0201-binding motifs were predicted using SYFEPITHI and BIMAS, and synthesized. A CCK-8 assay showed peptides W, Q and T promoted lymphocyte proliferation. Stimulation of peripheral blood mononuclear cells from HLA-A*0201 + donors with each of these peptides induced peptide-specific CD8 + T cells. High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W, Q and T. Besides lysis of HERV-W env-loaded target cells, specific apoptosis was also observed. These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W, Q and T) and, moreover, pose a high killing potential toward HERV-W env-expressing U251 cells. In conclusion, peptides W Q and T, which are HERV-W env antigenic epitopes, have both antigenicity and immunogenicity, and can cause strong T cell immune responses. Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases, such as multiple sclerosis and schizophrenia. These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

Comparison of Clinical Characteristics of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections and Childhood Obsessive-Compulsive Disorder

PubMed Central

Victor, Andrea M.; Pipal, Allison J.; Williams, Kyle A.

2010-01-01

Abstract Objective The objectives of this study were to identify unique clinical characteristics of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) compared with a control group of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to ancillary symptoms, types of obsessions and compulsions, symptom severity, and co-morbid DSM-IV diagnoses. Method Classification of PANDAS was based on review of pediatric and psychiatric records using the criteria developed by Swedo and colleagues. Children aged 6–14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18) were assessed by blind independent evaluators using the PANDAS Questionnaire, Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale, and Anxiety Disorders Interview Schedule for DSM-IV. Results PANDAS children were significantly more likely to present with separation anxiety, urinary urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in school performance during their initial episode of neuropsychiatric illness compared with children with OCD. Total tics and vocal tics were more severe in PANDAS children. Separation anxiety disorder and social phobia were more prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were significantly more likely to include others in their rituals. There were no significant differences between groups on demographics or severity of OCD. Conclusions Distinguishing clinical characteristics in PANDAS, which included urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting, are linked to basal ganglia functions. These clinical characteristics will aid in the differentiation of PANDAS children for research and clinical purposes and ultimately advance our understanding and treatment of this disorder. PMID:20807071

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview.

PubMed

Esposito, S; Bianchini, S; Baggi, E; Fattizzo, M; Rigante, D

2014-12-01

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been used to describe a syndrome characterized by various obsessions, compulsions, tics, hyperactivity, motor stereotypies, and paroxysmal movement disorders that are correlated with prior infection by group A beta-hemolytic Streptococcus pyogenes (GABHS) infections. Five clinical criteria can be used to diagnose PANDAS: (1) the presence of obsessive-compulsive disorder (OCD) and/or any other tic disorders; (2) prepuberal onset (between 3 years of age and the start of puberty); (3) abrupt onset and relapsing-remitting symptom course; (4) a distinct association with GABHS infection; and (5) association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity). The exact pathogenesis of PANDAS remains unclear, and several theories that focus on multiple etiologic or contributive factors have emerged. PANDAS appears to be a neurobiological disorder that potentially complicates GABHS infections in genetically susceptible individuals. The current standard of care for PANDAS patients remains symptomatic, and cognitive behavioral therapy, such as exposure and response prevention, combined with family counseling and psychoeducation, should be the first approach for treating PANDAS. This review examines current theories of PANDAS pathogenesis, identifies possible treatments for managing this complex condition, and highlights areas for future research. Moving forward, developing more standardized diagnostic criteria and identifying specific laboratory markers to facilitate PANDAS diagnoses are crucial.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

PubMed

Januś, D; Wójcik, M; Drabik, G; Wyrobek, Ł; Starzyk, J B

2018-03-01

The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions

PubMed Central

Murphy, Tanya; Leckman, James; Shaw, Richard; Williams, Kyle; Kapphahn, Cynthia; Frankovich, Jennifer; Geller, Daniel; Bernstein, Gail; Chang, Kiki; Elia, Josephine; Swedo, Susan

2017-01-01

Abstract Objective: This article outlines the consensus guidelines for symptomatic treatment for children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Syndrome Associated with Streptococcal Infection (PANDAS). Methods: Extant literature on behavioral, psychotherapeutic, and psychopharmacologic treatments for PANS and PANDAS was reviewed. Members of the PANS Research Consortium pooled their clinical experiences to find agreement on treatment of PANS and PANDAS symptoms. Results: Current guidelines result from consensus among the Consortium members. Conclusion: While underlying infectious and inflammatory processes in PANS and PANDAS patients are treated, psychiatric and behavioral symptoms need simultaneous treatment to decrease suffering and improve adherence to therapeutic intervention. Psychological, behavioral, and psychopharmacologic interventions tailored to each child's presentation can provide symptom improvement and improve functioning during both the acute and chronic stages of illness. In general, typical evidence-based interventions are appropriate for the varied symptoms of PANS and PANDAS. Individual differences in expected response to psychotropic medication may require marked reduction of initial treatment dose. Antimicrobials and immunomodulatory therapies may be indicated, as discussed in Parts 2 and 3 of this guideline series. PMID:28722481

Electroconvulsive therapy for severe neuropsychiatric lupus with psychosis.

PubMed

Tan, Lynnette Pei Lin; Tan, Lynnette Ee Sing

2013-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder that requires long-term management and can have a profound impact on the quality of life of patients. Among patients with SLE, neuropsychiatric manifestations are fairly common, occurring in up to 75% of patients with SLE. Neuropsychiatric symptoms of SLE (NPSLE) presenting with psychosis, however, is less common, with a prevalence of up to 11%. Treatment of psychosis in NPSLE has largely involved antipsychotics and immunosuppressants, with not much in the literature about the use of electroconvulsive therapy (ECT) as a method of treatment. We report 3 cases of patients who presented with psychosis during a lupus relapse, who were treated successfully with ECT after their symptoms did not improve on medical treatment. Although all 3 patients were treated with antipsychotics and immunosuppressants simultaneously with the ECT sessions, the time scale of these 3 case studies suggests that ECT played a role in the resolution of these patients' symptoms. Our 3 cases highlight that ECT can be safely and effectively used in patients with NPSLE with prominent psychotic symptoms.

Development and psychometric properties of the parent version of the Profile of Neuropsychiatric Symptoms (PONS) in children and adolescents.

PubMed

Santosh, Paramala; Gringras, Paul; Baird, Gillian; Fiori, Federico; Sala, Regina

2015-05-19

The use of neuropsychiatric Patient Centred Outcome Measures (PCOMs) in routine child mental health and paediatric services is very time consuming and often requires multiple scales being completed as no single scale covers all areas of psychopathology. The use of a web-based programme can overcome these problems and contribute to improved use of PCOMs in clinical practice. We aim to develop a web-based scale (using HealthTracker™) to screen and identify young people with significant neuropsychiatric symptoms to enable early intervention. Qualitative development of the Profile of Neuropsychiatric Symptoms (PONS) and quantitative evaluation of the psychometric properties of the PONS scale (parent version). Parents of 929 from the general population and 147 with neuropsychiatric disorders (5-18 years old) completed the PONS online. In addition, those children with neuropsychiatric disorders were assessed for the presence of current and lifetime psychiatric disorders using the Development and Well-Being Assessment (DAWBA). The PONS scale (parent version) consists of 30 symptom domains rated on a 7-point scale for both frequency and impairment. We found an intra-class correlation coefficient for single measures was 0.44 (0.42-0.46 95 % CI, F = 22.84, p ≤ 0.0001) and for average measures was 0.96 (0.95-0.96 95 % CI, F = 22.84, p ≤ 0.0001). The factor analysis showed a 4-factor model: Neurodevelopmental Disability; Behavioural and Emotional Dysregulation; Psychoses and Personality Dysfunction; and Anxiety and Depression. The receiver operating characteristic area for the 4-factors was 0.96 (SE = 0.006; 0.95-0.97 95 % CI). The PONS scale (parent version) is a web-based PCOM on the HealthTracker™ system that is a rapid, engaging measure that has excellent reliability and validity. The system allows for automated scoring and immediate feedback of statistical cut-off points and assists clinicians with diagnostic decision-making and optimises use of clinician time.

Postviral autoimmune encephalitis: manifestations in children and adults.

PubMed

Prüss, Harald

2017-06-01

Autoimmune encephalitis is an increasingly recognized neuropsychiatric condition seen in patients of all ages. Herpes virus infections of the brain can antedate the development of pathogenic autoantibodies against N-methyl-D-aspartate receptors and further neuronal surface proteins, leading to neuronal dysfunction and relapsing symptoms. This review will recapitulate the recent scientific progress, clinical manifestations in children and adults, therapeutic options, and etiological concepts on how autoimmunity develops. Postviral autoimmune encephalitis has been established as disease mechanism after herpes simplex virus encephalitis. Relapsing symptoms in the absence of virus occur in up to 20% of cases. The clinical presentation is relatively stereotyped in children, consisting of choreoathetosis and reduced levels of consciousness. Adults commonly present with psychiatric abnormalities and cognitive changes. Virus-induced antibody generation seems to be a widespread mechanism not confined to Herpesviridae and N-methyl-D-aspartate receptor antibodies SUMMARY: The presence of prolonged, atypical, or relapsing symptoms after virus encephalitis must be actively determined, requiring early follow-up visits of patients, and should always prompt the search for underlying autoantibodies. Relapsing symptoms can markedly improve with immunotherapy, thus treatment, including corticosteroids, plasma separation, immunoglobulins, and rituximab is usually recommended, even if no specific antibody was detected.

Autoimmune encephalitis in children: clinical phenomenology, therapeutics, and emerging challenges.

PubMed

Dale, Russell C; Gorman, Mark P; Lim, Ming

2017-06-01

Auto-antibodies that bind to conformational extracellular epitopes of neuronal receptors or synaptic proteins have provided clinicians with essential biomarkers in acute neurology. This review summarizes the current status and challenges in the field. In children, anti-N-methyl-D-aspartate receptor encephalitis remains the most identifiable autoimmune encephalitis, although many patients have a clinical syndrome of brain inflammation in which no antibodies are identified. Anti-myelin oligodendrocyte glycoprotein antibody associated demyelination is now recognized as a major cause of monophasic and relapsing demyelination, often presenting with encephalopathy. We discuss the importance of auto-antibody detection methodology and the possible influence of intrathecal antibody synthesis on the speed of recovery and response to immune therapy. The current, often pragmatic rather than evidence-based therapeutic pathway will be discussed, highlighting key challenges such as the timing of second-line therapy, monitoring of disease activity, and identifying the patient who is responding poorly to treatment. Although there have been significant developments, future priorities include the need for paediatric-specific consensus definitions for seronegative suspected autoimmune encephalitis, novel tools for monitoring patients with autoimmune encephalitis, consensus treatment recommendations, and neuroprotective strategies.

Autoimmune liver disease in children.

PubMed

Mieli-Vergani, G; Vergani, D

2003-03-01

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Disordered eating and food restrictions in children with PANDAS/PANS.

PubMed

Toufexis, Megan D; Hommer, Rebecca; Gerardi, Diana M; Grant, Paul; Rothschild, Leah; D'Souza, Precilla; Williams, Kyle; Leckman, James; Swedo, Susan E; Murphy, Tanya K

2015-02-01

Sudden onset clinically significant eating restrictions are a defining feature of the clinical presentation of some of the cases of pediatric acute-onset neuropsychiatric syndrome (PANS). Restrictions in food intake are typically fueled by contamination fears; fears of choking, vomiting, or swallowing; and/or sensory issues, such as texture, taste, or olfactory concerns. However, body image distortions may also be present. We investigate the clinical presentation of PANS disordered eating and compare it with that of other eating disorders. We describe 29 patients who met diagnostic criteria for PANS. Most also exhibited evidence that the symptoms might be sequelae of infections with Group A streptococcal bacteria (the pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections [PANDAS] subgroup of PANS). The clinical presentations are remarkable for a male predominance (2:1 M:F), young age of the affected children (mean=9 years; range 5-12 years), acuity of symptom onset, and comorbid neuropsychiatric symptoms. The food refusal associated with PANS is compared with symptoms listed for the new Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) diagnosis of avoidant/restrictive food intake disorder (ARFID). Treatment implications are discussed, as well as directions for further research.

The relationship between group A beta hemolytic streptococcal infection and psychiatric symptoms: a pilot study.

PubMed

Cengel-Kültür, S Ebru; Cöp, Esra; Kara, Ateş; Cengiz, Ali Bülent; Uludağ, Ali Kerem; Unal, Fatih

2009-01-01

The aim of this study was to test if children with group A beta hemolytic streptococcal infection (GABHS) are more likely to develop neuropsychiatric symptoms or the syndrome of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) compared to children with GABHS-negative throat cultures. Children aged 8 to 12 years (n = 81) with upper respiratory tract infection were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version, Children's Yale Brown Obsession Compulsion Scale, Yale Global Tic Severity Scale, Child Behavior Checklist for Ages 4-18, Conners Parent Rating Scale, and State-Trait Anxiety Inventory for Children at baseline and six weeks later. One case of PANDAS was diagnosed and no other differences were observed between groups and time points. It was suggested that GABHS infection may be a triggering factor for PANDAS in some genetically prone individuals.

Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings.

PubMed

Swedo, Susan E; Seidlitz, Jakob; Kovacevic, Miro; Latimer, M Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

2015-02-01

The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described >15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). RESULTS were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86-92%), school issues (75-81%), sleep disruptions (71%), tics (60-65%), urinary symptoms (42-81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS).

A case report: anti-NMDA receptor encephalitis

PubMed Central

Bhat, Pavan; Ahmed, Ameer; Jolepalem, Preetam; Sittambalam, Charmian

2018-01-01

ABSTRACT N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis is a potentially fatal autoimmune syndrome in which there is antibody production against the NMDAR causing profound dysregulation of neurotransmission. The syndrome is frequently associated with ovarian teratomas and women are disproportionately affected. Patients most often present with a constellation of neuropsychiatric signs and symptoms, including memory loss, hallucinations, and decreased level of consciousness. This condition is lethal if left untreated. Immunotherapy and surgical resection of the culprit malignancy often results in the rapid resolution of symptoms. PMID:29915659

Treatment of PANDAS and PANS: a systematic review.

PubMed

Sigra, Sofia; Hesselmark, Eva; Bejerot, Susanne

2018-03-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD) thought to be caused by an autoimmune response to group A streptococcal infection. Based on this proposed pathophysiology, alternative treatments for acute-onset OCD have been introduced, including antibiotics and immunomodulatory interventions. However, the literature on treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking. We conducted a systematic review of articles in PubMed, Cochrane Library, and Scopus that addressed treatment for PANDAS and related disorders. Twelve research studies involving the following treatments met inclusion criteria: penicillin, azithromycin, intravenous immunoglobulin, plasma exchange, tonsillectomy, cognitive behavior therapy, NSAID and corticosteroids. In addition, 65 case reports in which patients received immunomodulatory treatments, antibiotics, and/or psychotropics were identified. We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter . In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

PubMed Central

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R.; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies. PMID:29686658

[Anti-basal ganglia antibody].

PubMed

Hayashi, Masaharu

2013-04-01

Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS.

Autoimmune encephalitis in psychiatric institutions: current perspectives

PubMed Central

Bost, Chloe; Pascual, Olivier; Honnorat, Jérôme

2016-01-01

Autoimmune encephalitis is a rare and newly described group of diseases involving autoantibodies directed against synaptic and neuronal cell surface antigens. It comprises a wide range of neuropsychiatric symptoms. Sensitive and specific diagnostic tests such as cell-based assay are primordial for the detection of neuronal cell surface antibodies in patients’ cerebrospinal fluid or serum and determine the treatment and follow-up of the patients. As neurological symptoms are fairly well described in the literature, this review focuses on the nature of psychiatric symptoms occurring at the onset or during the course of the diseases. In order to help the diagnosis, the main neurological symptoms of the most representative synaptic and neuronal cell surface autoantibodies were detailed. Finally, the exploration of these autoantibodies for almost a decade allowed us to present an overview of autoimmune encephalitis incidence in psychiatric disease and the general guidelines for the management of psychiatric manifestations. For the majority of autoimmune encephalitis, the prognosis depends on the rapidity of the detection, identification, and the management of the disease. Because the presence of pronounced psychiatric symptoms drives patients to psychiatric institutions and can hinder the diagnosis, the aim of this work is to provide clues to help earlier detection by physicians and thus provide better medical care to patients. PMID:27822050

[Evaluation of a Neuropsychiatric Disorder: From PANDAS to PANS and CANS].

PubMed

Baytunca, Muharrem Burak; Donuk, Tuğba; Erermiş, Serpil

2016-01-01

PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) syndrome is a disorder seen before adolescence that possesses an abrupt onset of obsessive-compulsive disorder symptoms and/or tics. Swedo and colleagues defined this disorder in 1998 as a syndrome related to Group A streptoccoccus (GAS) infection with neurological issues, such as motor hyperactivation and choreiform movements. The progress of the disorder may be described as wax-and-waning, apart from abrupt onset, and this relapse and remission course is associated with exacerbating infections, according to the creators of PANDAS syndrome. Ruling out of Rheumatoid Fever and Sydenham's Chorea was a necessity for making a proper diagnosis. Since the recognition of this syndrome, clinicians encountered many children who could not fulfill all 5 criteria, which must be met for PANDAS diagnosis. In addition, due to literature showing failure and lack of strong evidence of a major role of GAS, the newly-defined categories PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) and CANS (Childhood Acute Neuropsychiatric Syndrome) were created to encompass those of "almost met" non-PANDAS cases. PANS and CANS include concurrent significant psychiatric symptoms with abrupt onset of OCD symptoms and/or tics but do not require identification of any infection agent, immune dysfunction, or enviromental precipitants. In this paper, we aimed to discuss PANS/ CANS, alterations of PANDAS, and diagnoses in which "almost met" PANDAS patients should be classified on the basis of a case who developed an abrupt onset of anxiety, obsessions, and vocal tics.

On the connection between autoimmunity, tic disorders and obsessive-compulsive disorders: a meta-analysis on anti-streptolysin O titres.

PubMed

Pozzi, Marco; Pellegrino, Paolo; Carnovale, Carla; Perrone, Valentina; Antoniazzi, Stefania; Perrotta, Cristiana; Radice, Sonia; Clementi, Emilio

2014-12-01

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95% C.I. 1.51-6.88) as compared to healthy controls and 16.14 (95% C.I. 8.11-32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95% C.I. 25.21-115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders.

Clinical significance of autoantibodies in autoimmune hepatitis.

PubMed

Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

2013-10-01

The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vaccination in paediatric patients with auto-immune rheumatic diseases: a systemic literature review for the European League against Rheumatism evidence-based recommendations.

PubMed

Heijstek, M W; Ott de Bruin, L M; Borrow, R; van der Klis, F; Koné-Paut, I; Fasth, A; Minden, K; Ravelli, A; Abinun, M; Pileggi, G; Borte, M; Bijl, M; Wulffraat, N M

2011-12-01

To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients. A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18 years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria. 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events. Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders.

PubMed

Evrensel, Alper; Ceylan, Mehmet Emin

2016-08-31

Fecal microbiota transplantation has a 1700-year history. This forgotten treatment method has been put into use again during the last 50 years. The interest in microbiota-gut-brain axis and fecal microbiota transplantation is rapidly increasing. New evidence is obtained in the etiopathogenesis of neuropsychiatric disorders. There is a large number of experimental and clinical researches in the field of gut-brain axis. There is limited information on fecal microbiota transplantation. Despite this, initial results are promising. It is commonly used in the treatment of gastrointestinal diseases such as Clostridium difficile infection, Crohn's disease, ulcerative colitis. It is also experimentally used in the treatment of metabolic and autoimmune diseases. There are case reports that it is effective in the treatment of autism, Parkinson's disease, multiple sclerosis, chronic fatigue syndrome and irritable bowel syndrome. Its implementation is easy, and it is a cheap and reliable treatment method. However, the long-term risks are unknown. Additionally, standard application protocols have not yet been established. There are a lot of questions to be answered. A university in Turkey has got official permission this year, and started to apply fecal microbiota transplantation. In this review, neuropsychiatric areas of use of fecal microbiota transplantation have been discussed in the light of the current information.

N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children.

PubMed

Wright, Sukhvir; Hacohen, Yael; Jacobson, Leslie; Agrawal, Shakti; Gupta, Rajat; Philip, Sunny; Smith, Martin; Lim, Ming; Wassmer, Evangeline; Vincent, Angela

2015-06-01

N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK. A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians. Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy. Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Tonsillectomy remains a questionable option for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)

PubMed Central

Windfuhr, Jochen P.

2016-01-01

Background: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a disease attributed to children with obsessive compulsive disorders (OCD) or tic disorders associated with streptococcal infections. Because otolaryngologists examine a large number of pediatric patients with recurrent streptococcal infections, tonsillectomy (TE) is a common option of therapy. This study was conducted to evaluate the efficacy of TE in patients presenting with verified PANDAS. Material and methods: A PubMed review was performed using search terms “tonsillectomy” and “PANDAS”, “OCD”, “compulsive” “pediatric autoimmune”, “chorea” and “tic” limited by publication date of January 1, 1995, to July 31, 2015. Reviews without patients were not included in the review. Results: Nine papers matched our search criteria, including 6 case reports with 8 patients and 3 case series. Most case reports were in favor of TE, but this was by far not supported by the findings in the case series. The follow-up ranged from 2 to 36 months in case reports and from 24 to 36 in case series. Conclusion: Establishing the diagnosis of PANDAS is complicated because of underlying comorbidities in the field of neurology-psychiatry and the lack of a reliable biomarker. The positive outcome after TE as reported in case studies may be influenced by the postoperative medication and is not supported by the results of large-scale studies. In the light of the considerable postoperative morbidity rate, it appears wise to indicate TE for PANDAS only in supervised clinical studies. PMID:28025607

Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS).

PubMed

Leon, Jill; Hommer, Rebecca; Grant, Paul; Farmer, Cristan; D'Souza, Precilla; Kessler, Riley; Williams, Kyle; Leckman, James F; Swedo, Susan

2018-05-01

Little is known about the natural history of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). This study prospectively followed 33 children with PANDAS for up to 4.8 years (mean 3.3 ± 0.7 years) after enrollment in a 24-week randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin (IVIG) (N = 35). Fourteen of eighteen children randomized to placebo received open label IVIG 6 weeks after the blinded infusion, so follow-up results reported below largely reflect outcomes in a population of children who received at least one dose of IVIG. Telephone interviews with the parents of participants found that at the time of phone follow-up, 29 (88%) were not experiencing clinically significant obsessive-compulsive symptoms. During the interim period (6-57 months after entering the clinical trial), 24 (72%) had experienced at least one exacerbation of PANDAS symptoms, with a median of one exacerbation per child (range 1-12; interquartile range 0-3). A variety of treatment modalities, including antibiotics, IVIG, psychiatric medications, cognitive behavioral therapy, and others, were used to treat these exacerbations, and were often used in combination. The outcomes of this cohort are better than those previously reported for childhood-onset OCD, which may support conceptualization of PANDAS as a subacute illness similar to Sydenham chorea. However, some children developed a chronic course of illness, highlighting the need for research that identifies specific symptoms or biomarkers that can be used to predict the longitudinal course of symptoms in PANDAS.

Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections in Research and Community Settings

PubMed Central

Seidlitz, Jakob; Kovacevic, Miro; Latimer, M. Elizabeth; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul

2015-01-01

Abstract Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described>15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS. Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48). Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by ∼ 2:1, and symptoms began in early childhood (7.3±2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86–92%), school issues (75–81%), sleep disruptions (71%), tics (60–65%), urinary symptoms (42–81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections. Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS). PMID:25695941

Genetics of hereditary neurological disorders in children.

PubMed

Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study.

PubMed

Hegvik, Tor-Arne; Instanes, Johanne Telnes; Haavik, Jan; Klungsøyr, Kari; Engeland, Anders

2018-05-01

Several studies have demonstrated associations between neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), and the immune system, including autoimmune diseases. Since ADHD and many autoimmune diseases show sex-specific properties, such associations may also differ by sex. Using Norwegian national registries, we performed a cross-sectional study based on a cohort of 2,500,118 individuals to investigate whether ADHD is associated with common autoimmune diseases. Associations between ADHD and autoimmune diseases in females and males were investigated with logistic regression and effect modification by sex was evaluated. Several subanalyses were performed. The strongest association was found between ADHD and psoriasis in females, adjusted odds ratio (adjOR) = 1.57 (95% confidence interval: 1.46-1.68) and males, adjOR = 1.31 (1.23-1.40); p value for interaction < 0.0001. Furthermore, among females, ADHD was associated with Crohn's disease, adjOR = 1.44 (1.16-1.79) and ulcerative colitis, adjOR = 1.28 (1.06-1.54). In contrast, males with ADHD had lower odds of Crohn's disease, adjOR = 0.71 (0.54-0.92), in addition to a trend for lower odds of ulcerative colitis, adjOR = 0.86 (0.71-1.03); p values for interaction < 0.0001 and 0.0023, respectively. In a group of females where information on smoking and body mass index was available, adjustment for these potential mediators did not substantially alter the associations. Our findings support previously reported associations between ADHD and diseases of the immune system. The associations differ by sex, suggesting that sex-specific immune-mediated neurodevelopmental processes may be involved in the etiology of ADHD.

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

PubMed Central

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-01-01

Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease.

PubMed

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-11-01

Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. © 2013 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Complete neurologic and cognitive recovery after plasmapheresis in a patient with chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation.

PubMed

Vogl, Ursula; Leitner, Gerda; Dal-Bianco, Assunta; Bojic, Marija; Mitterbauer, Margit; Rabitsch, Werner; Kalhs, Peter; Schulenburg, Axel

2016-05-01

Neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT) are rare but poorly understood. We present a case report of a 57-year-old-male patient who was diagnosed in 2009 with acute myeloid leukemia (AML). He received two standard induction chemotherapies, as well as a following consolidation. Six months later, an allogeneic HSCT was performed. Shortly after HSCT the patient developed progressive polyneuropathy of the lower legs and hypoesthesia. Five months later a severe dementia followed. All images of the brain and spine showed no specific pathologies. High dose corticosteroids and immunoglobulins did not improve the neurologic symptoms. Due to severe worsening of the neuropsychiatric status and the clinical presentation, chronic inflammatory demyelinating polyneuropathy (CIDP) was suspected. Therefore, the patient received ten cycles of plasmapheresis. The patient showed a significant improvement of the neuropsychiatric symptoms and cognitive status. Immune mediated neuropathies after allogeneic HSCT, such as CIDP, have great variability in symptoms and presentation and are challenging to diagnose and treat. Plasmapheresis is a safe and efficient treatment for patients with unclear persisting autoimmune neuropathy after HSCT.

Paroxysmal cold haemoglobinuria in an adult with chicken pox.

PubMed

Papalia, M A; Schwarer, A P

2000-05-01

Paroxysmal cold haemoglobinuria (PCH) is an autoimmune disorder characterized by intravascular haemolysis causing haemoglobinuria. It is due to a biphasic haemolysin known as the Donath-Landsteiner antibody, which binds specifically to the P antigen of red blood cells at low temperatures, leading to complement activation and red cell lysis at 37 degrees C. PCH is a rare disease which predominantly affects the paediatric population, occurring mostly during viral infections. We report on what is possibly the first case of PCH in an adult to be precipitated by chicken pox infection.

Tic Disorders and PANDAS.

PubMed

Blackburn, Joanna S

2018-04-01

Tics are the most common movement disorder in childhood and are a frequent reason for referral to child neurology clinics. The purpose of this review is to examine the phenomenology of tics, discuss what is known regarding their genetic and pathophysiological causes and to evaluate current treatment options. The evidence for the evaluation and treatment of the controversial diagnosis of pediatric autoimmune neuropsychiatric disorders associated with group A streptococci (PANDAS) will also be reviewed. With improved understanding of tic disorders, their etiology and response to current treatment options, we may be able to more effectively diagnose them and identify novel treatment strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Treatment of VGKC complex antibody-associated limbic encephalitis: a systematic review.

PubMed

Radja, Guirindhra Koumar; Cavanna, Andrea Eugenio

2013-01-01

Limbic encephalitis is an autoimmune neuropsychiatric condition characterized by subacute cognitive symptoms, seizures, and affective changes. Although limbic encephalitis is usually caused by an immune reaction secondary to neoplasms, different types of potentially treatable non-paraneoplastic limbic encephalitis (nPLE) have recently been described. In particular, published studies have reported variable responses to immunosuppressive therapy in Voltage-Gated Potassium Channel (VGKC) complex antibody-associated nPLE. This systematic literature review found that the most significant improvements were reported by patients presenting with affective symptoms and consistent neuroradiological changes. In these patients, improved clinical outcomes correlated with the largest decreases in antibody titers.

What has happened in the last 50 years in immunology.

PubMed

Wong, Melanie

2015-02-01

Fifty years ago, in 1964, our understanding of the immune system was very rudimentary. Gell and Coombs had just described classes of hypersensitivity reactions, and Bruton had described and commenced immunoglobulin replacement in agammaglobulinaemia. The distinction between T and B cells was not identified and characterised until the 1960s and 1970s. This was followed by increasing recognition of T and B cell collaboration in immune responses and identification of significant immunodeficiencies. CD4 and CD8 T cells were only recognised in the 1970s and 1980s. We now know of five CD4 subsets; dysfunction of each is associated with different disorders. By 2014, advances in technology have enabled identification of the genetic basis of over 240 primary immunodeficiencies. Research into the gut microbiome and vitamin D holds promise for the understanding, treatment and prevention of autoimmune and allergic diseases. Immunoglobulin preparations for the treatment of antibody deficiencies improved with the development of preparations for intravenous then subcutaneous administration, giving patients choice and the ability for home-based treatment, especially if experiencing infusion associated adverse effects. Newborn screening for severe combined immunodeficiency is a reality. Improvements in haemopoietic stem cell transplantation and now gene therapy, albeit still only available in the research setting, are improving long-term survival in primary immunodeficiencies. Biologic therapeutic agents are improving the control of autoimmune disease but potentially leading to secondary immunodeficiency, increasing the risk of opportunistic infection and malignancy. It is an exciting time. © 2015 The Author. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice

PubMed Central

Sidor, Michelle M.; Sakic, Boris; Malinowski, Paul M.; Ballok, David A.; Oleschuk, Curtis J.; Macri, Joseph

2006-01-01

The systemic autoimmune disease lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric manifestations and brain lesions of unknown etiology. The MRL-lpr mice show behavioral dysfunction concurrent with progression of a lupus-like disease, thus providing a valuable model in understanding the pathogenesis of autoimmunity-induced CNS damage. Profound neurodegeneration in the limbic system of MRL-lpr mice is associated with cytotoxicity of their cerebrospinal fluid (CSF) to mature and immature neurons. We have recently shown that IgG-rich CSF fraction largely accounts for this effect. The present study examines IgG levels in serum and CSF, as well as the permeability of the blood–brain barrier in mice that differ in immune status, age, and brain morphology. In comparison to young MRL-lpr mice and age-matched congenic controls, a significant elevation of IgG and albumin levels were detected in the CSF of aged autoimmune MRL-lpr mice. Two-dimensional gel electrophoresis and MALDI-TOF MS confirmed elevation in IgG heavy and Ig light chain isoforms in the CSF. Increased permeability of the blood–brain barrier correlated with neurodegeneration (as revealed by Fluoro Jade B staining) in periventricular areas. Although the source and specificity of neuropathogenic antibodies remain to be determined, these results support the hypothesis that a breached blood–brain barrier and IgG molecules are involved in the etiology of CNS damage during SLE-like disease. PMID:15972238

Electroconvulsive Therapy in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Case Report and Review of the Literature.

PubMed

Coffey, M Justin; Cooper, Joseph J

2016-12-01

There is a growing scientific literature describing the neuropsychiatric symptoms of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, including the use of electroconvulsive therapy (ECT) to treat those symptoms. We sought to consolidate this literature into a review that highlights its relevance to ECT practitioners. We performed a PubMed search using the terms electroconvulsive therapy and encephalitis, autoimmune encephalitis, or anti-NMDA receptor encephalitis. We reviewed all relevant studies in detail, cross-referenced all bibliographies, and collected key clinical information related to the practice of ECT. We identified 6 studies offering patient-level descriptions of the use of ECT in patients with anti-NMDA receptor encephalitis. In all cases ECT was used to target symptoms of catatonia. Electroconvulsive therapy was delivered safely and effectively irrespective of the timing of diagnosis, tumor removal, or immunotherapy. There are no controlled data on the use of ECT in anti-NMDA receptor encephalitis. Further investigation is needed to determine whether ECT has a disease-modifying effect on this form of autoimmune encephalitis.

A case of seropositive Neuromyelitis Optica in a paediatric patient with co-existing acute nephrotic syndrome.

PubMed

Volkman, Thomas; Hemingway, Cheryl

2017-11-01

Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system constituting less than 1% of demyelinating diseases (Jeffery and Buncic, 1996). It preferentially affects the optic nerves and spinal cord, with the brain parenchyma generally spared. Demyelinating lesions are characterised by longitudinally extensive transverse myelitis (LETM) and often longitudinally extensive optic neuritis. Following the discovery of a novel pathogenic antibody, Aquaporin 4 in 2004 (Lennon et al., 2004) this disease has been seen as a separate entity from Multiple Sclerosis (MS). We report the case of a severe AQP4 IgG case of NMO in a 10 year old child. This case unusually had a coexisting diagnosis of acute nephrotic syndrome which has only been reported once previously in the literature 2 . This article will examine some of the treatment challenges and the spectrum of co-existing autoimmune disease in NMOSD. Copyright © 2017. Published by Elsevier B.V.

Complications of Cushing's syndrome: state of the art.

PubMed

Pivonello, Rosario; Isidori, Andrea M; De Martino, Maria Cristina; Newell-Price, John; Biller, Beverly M K; Colao, Annamaria

2016-07-01

Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action.

PubMed

Burchi, Elisabetta; Pallanti, Stefano

2018-05-03

Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome, respectively). This review examines the best-quality evidence supporting the practice-based use of antibiotics in these psychiatric conditions. PubMed was searched for English-language articles published between January 1994 and July 2017 using the search terms [PANDAS OR PANS OR new-onset pediatric OCD] AND [antibiotics OR macrolides OR beta-lactams]. Randomized clinical trials, observational studies, and case reports concerning antibiotic use in PANDAS/PANS were reviewed. Four publications were included in the quantitative synthesis. The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. Although the single studies conveyed no statistically significant results, there is some evidence for efficacy of antibiotic therapy in reducing neuropsychiatric symptoms in the PANDAS/PANS population. Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. Studies that compare antibiotics with other therapies, as well as studies that assess safety and efficacy of long-term use of antibiotic therapy in PANDAS/PANS, are still lacking. However, the available research supports evidence of a subgroup in the pediatric OCD population that is sensitive to antibiotic treatment and immunomodulatory therapy, independent of ongoing infectious conditions. Thus, more studies are warranted in the overall OCD spectrum. © Copyright 2018 Physicians Postgraduate Press, Inc.

[Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism].

PubMed

Creten, C; van der Zwaan, S; Blankespoor, R J; Maatkamp, A; Klinkenberg, S; van Kranen-Mastenbroek, V H J M; Nicolai, J; Dhossche, D M; van Os, J; Schieveld, J N M

2012-01-01

Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA.

Is disomic homozygosity at the APECED locus the cause of increased autoimmunity in Down's syndrome?

PubMed Central

Shield, J.; Wadsworth, E.; Hassold, T.; Judis, L. A.; Jacobs, P.

1999-01-01

AIMS—To examine the age of onset of insulin dependent diabetes mellitus (IDDM) in children with Down's syndrome compared with non-trisomic individuals, and to assess whether differences might be related to disomic homozygosity at the autoimmune polyglandular disease type 1 (APECED) gene locus.
METHODS—Children with Down's syndrome and IDDM were identified through the Down's syndrome association newsletter and from paediatricians. DNA was extracted from mouthbrush preparations provided by the parents and patients using standard techniques. Mapping techniques were then used to identify areas of reduction to homozygosity, including a marker that overlaps the locus for APECED. The frequency of disomic homozygosity for all markers (n = 18) was compared with a control group of 99 patients with Down's syndrome and their parents. The families also answered a questionnaire concerning diabetes and related autoimmune conditions in the family. Details were compared with the British Paediatric Surveillance Group 1988diabetes study.
RESULTS—Children with Down's syndrome and IDDM were diagnosed significantly earlier than the general population (6.7 v 8.0 years) with a far higher proportion diagnosed in the first 2 years of life (22% v 7%). There was no evidence of increased disomic homozygosity in the region of the APECED locus in Down's syndrome patients with IDDM compared with simple Down's syndrome.
CONCLUSIONS—The natural history of IDDM in Down's syndrome is different from that of the general population. Although children with Down's syndrome have features similar to cases of APECED, disomic homozygosity in this region does not explain the predilection for autoimmune disease.

 PMID:10490523

[Autoimmunity in children with chronic hepatitis C treated with interferon alpha and ribavirin].

PubMed

Gora-Gebka, Magdalena; Liberek, Anna; Bako, Wanda; Raczkowska-Kozak, Janina; Sikorska-Wisniewska, Grazyna; Korzon, Maria

2004-01-01

The role of interferon alpha or the virus itself in the pathogenesis and the risk of autoimmunological disorders in patients infected with HCV, still remain unknown, especially in children. The aim of the study was to evaluate the incidence of autoantibodies and the risk of autoimmunological disorders in children with chronic hepatitis C, treated with interferon alpha and ribavirin in the Department of Paediatrics, Paediatric Gastroenterology and Oncology in Gdansk. In the studied group of 12 patients, in 4 cases autoantibodies were present in low titers prior to the treatment and they had no prognostic value for the response to the therapy or the risk of autoimmunological disorders. Positive response for the treatment was achieved in 4 cases; in 3 cases indications for discontinuation of the therapy were established. During the therapy with interferon alpha and ribavirin, in 2 children elevation of serum titers of antibodies to liver-kidney microsome type 1 (anti-LKM1) (> 1:640) with normal gammaglobulin levels was noted. In none of the children autoimmunological disorders were observed.

Vitamin D and Chronic Diseases

PubMed Central

Wang, Hanmin; Chen, Weiwen; Li, Dongqing; Yin, Xiaoe; Zhang, Xiaode; Olsen, Nancy; Zheng, Song Guo

2017-01-01

Vitamin D is one of the essential nutrients to sustain the human health. As a member of the steroid hormone family, it has a classic role in regulating metabolism of calcium and a non-classic role in affecting cell proliferation and differentiation. Epidemiological studies have shown that 25OHD deficiency is closely associated with common chronic diseases such as bone metabolic disorders, tumors, cardiovascular diseases, and diabetes. 25OHD deficiency is also a risk factor for neuropsychiatric disorders and autoimmune diseases. 25OHD deficiency is highly prevalent in the world. It is therefore necessary to know the adverse health effects of 25OHD deficiency, and to design interventions and early treatments for those who are likely to have low levels of 25OHD. PMID:28580189

Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection.

PubMed

Saeed, Muhammad; Dabbagh, Omar; Al-Muhaizae, Muhammad; Dhalaan, Hesham; Chedrawi, Aziza

2014-11-01

Epstein-Barr Virus (EBV) causes a broad spectrum of disease in humans with several clinical syndromes and is ubiquitous, infecting more than 95% of the world's population. Central Nervous System (CNS) disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. Systemic viral illness in children and complications are rare, but may occur. In few cases, it is associated with a variety of CNS and hematological complications like acute disseminated encephalomyelitis, transverse myelitis, neuropsychiatric syndrome, GBS, autoimmune thrombocytopenia and hemolytic anemia and they usually respond to immunotherapy. We report previously healthy boy, who presented with left sided weakness, headache and thrombocytopenia following EBV infection. The thrombocytopenia was resistant to intravenous immunoglobulin and methylprednisolone but responded well to Rituximab.

The link between autoimmune diseases and obsessive-compulsive and tic disorders: A systematic review.

PubMed

Pérez-Vigil, Ana; Fernández de la Cruz, Lorena; Brander, Gustaf; Isomura, Kayoko; Gromark, Caroline; Mataix-Cols, David

2016-12-01

Immunological factors are increasingly recognized as being important in a range of neuropsychiatric disorders. We aimed to summarize the disperse and often conflicting literature on the potential association between autoimmune diseases (ADs) and obsessive-compulsive disorder (OCD) and tic disorders. We searched PubMed, EMBASE, and PsycINFO for original studies evaluating the relationship between ADs and OCD/tic disorders until July, 13th 2016. Seventy-four studies met inclusion criteria. Overall, the studies were of limited methodological quality. Rates of OCD were higher in rheumatic fever patients who were also affected by its neurological manifestation, Sydenham's chorea. The literature on other ADs was scarce and the findings inconclusive. Few studies examined the association between ADs and tic disorders. A handful of family studies reported elevated rates of ADs in first-degree relatives of individuals with OCD/tic disorders, and vice versa, potentially suggesting shared genetic and/or environmental mechanisms. In conclusion, at present, there is modest evidence for a possible association and familial co-aggregation between ADs and OCD/tic disorders. We offer some suggestions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

PANDAS and anorexia nervosa--a spotters' guide: suggestions for medical assessment.

PubMed

Vincenzi, Brenda; O'Toole, Julie; Lask, Bryan

2010-03-01

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) should be considered in sudden onset, prepubertal Anorexia Nervosa (AN), arising shortly after an apparent streptococcal infection. However, the absence of a specific biological marker of PANDAS renders the diagnosis difficult. This paper critically reviews available tests for PANDAS and recommends a standardized approach to its investigation. Medline database review between 1990 and 2008. Existing tests may be categorized as: (i) Non-specific markers of inflammation or immune response (Erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; Neopterin), (ii) specific markers of streptococcal infection (throat swab and anti-streptococcal antibodies, Anti-streptolysin, ASO; Antideoxyribonuclease B, antiDNaseB), (iii) non-specific markers of auto-immune reaction (Antineuronal antibodies, AnAb; D8/17). No one test reliably identifies PANDAS. The lack of specificity and methodological problems may lead to errors of diagnosis. When PANDAS-Anorexia Nervosa (PANDAS-AN) is suspected clinically we recommend conducting all the above investigations. The more positive results there are the more likely is the diagnosis, but particular weighting should be given to AnAb and D8/17. Copyright (c) 2010 John Wiley & Sons, Ltd., and Eating Disorders Association.

[Neuropsychiatric manifestations ushering pernicious anemia].

PubMed

Mrabet, S; Ellouze, F; Ellini, S; Mrad, M F

2015-12-01

Biermer disease or pernicious anemia is an autoimmune atrophic gastritis characterized by the lack of secretion of gastric intrinsic factor. This leads to an insufficient absorption of vitamin B12 in the ileum. Clinical manifestations are mainly hematologic. Neuropsychiatric manifestations are known but are less frequent especially early in the disease. Inaugural neuropsychiatric arrays are rare and various thus making diagnosis difficult. In this article, we report through two clinical cases different neuropsychiatric manifestations revealing pernicious anemia. Mrs. C.O., aged 56, presented after surgery for gallstones, an acute psychiatric array associated with gait disorders. She had no history of neurological or psychiatric problems. The psychiatric interview revealed delirious syndrome, depressive symptoms and anxiety. Neurological examination noted a flaccid paraplegia with peripheral neuropathic syndrome and myoclonus in the upper limbs. At the full blood count, a macrocytosis (VGM: 112.2fl) without anemia was found. The level of vitamin B12 in the blood was low. Cerebro-spinal MRI was suggestive of a neuro-Biermer and showed hyper signal in the cervical cord on T2-weighted sagittal section. In axial section, hyper signal appears at the posterior columns in the form of V. There were no brain abnormalities. A sensorimotor axonal polyneuropathy was diagnosed. The patient received vitamin B12 intramuscularly for ten days associated with neuroleptic treatment. Mrs. R.M., aged 40, was brought to the psychiatry consultation for acute behavioral disorders progressively worsening over a month. An anxiety syndrome, depressive syndrome and delirious syndrome were identified. Neurological examination showed a posterior cordonal syndrome with quadripyramidal syndrome. Full blood count showed a macrocytic anemia. Serum B12 level was collapsed. Cerebro-spinal MRI was normal. She received vitamin B12 with clinical and biological improvement. Features of pernicious anemia vary according to studies and age range. Digestive and hematological manifestations are well known. Neurological and psychiatric manifestations of pernicious anemia were also described in the early literature. They can be the initial symptoms or the only ones. However, inaugural neuropsychiatric features are often unrecognized. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. Neurological involvement includes mainly combined spinal sclerosis, peripheral neuropathy and dementia. Cerebellar ataxia and movement disorders are reported less often. Severity of neuropsychiatric features and therapeutic efficacy depends on the duration of signs and level of B12 deficiency. Macrocytic anemia may lack. Neuropsychiatric manifestations could be isolated or be the first manifestation of vitamin deficiency and occur without any hematological or gastrointestinal context. Pernicious anemia and serum B12 assay should be discussed in all patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. Nevertheless, B12 level could be normal in genuine pernicious anemia diseases and macrocytic anemia may lack. Substitutive vitaminotherapy is required when diagnosis is strongly suspected and etiologic assessment is negative. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses.

PubMed

Xu, Man; Tan, Xiangliang; Zhang, Xinyuan; Guo, Yihao; Mei, Yingjie; Feng, Qianjin; Xu, Yikai; Feng, Yanqiu

2017-01-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory female-predominant autoimmune disease that can affect the central nervous system and exhibit neuropsychiatric symptoms. In SLE patients without neuropsychiatric symptoms (non-NPSLE), recent diffusion tensor imaging studies showed white matter abnormalities in their brains. The present study investigated the entire brain white matter structural connectivity in non-NPSLE patients by using probabilistic tractography and connectivity-based analyses. Whole-brain structural networks of 29 non-NPSLE patients and 29 healthy controls (HCs) were examined. The structural networks were constructed with interregional probabilistic connectivity. Graph theory analysis was performed to investigate the topological properties, and network-based statistic was employed to assess the alterations of the interregional connections among non-NPSLE patients and controls. Compared with HCs, non-NPSLE patients demonstrated significantly decreased global and local network efficiencies and showed increased characteristic path length. This finding suggests that the global integration and local specialization were impaired. Moreover, the regional properties (nodal efficiency and degree) in the frontal, occipital, and cingulum regions of the non-NPSLE patients were significantly changed and negatively correlated with the disease activity index. The distribution pattern of the hubs measured by nodal degree was altered in the patient group. Finally, the non-NPSLE group exhibited decreased structural connectivity in the left median cingulate-centered component and increased connectivity in the left precuneus-centered component and right middle temporal lobe-centered component. This study reveals an altered topological organization of white matter networks in non-NPSLE patients. Furthermore, this research provides new insights into the structural disruptions underlying the functional and neurocognitive deficits in non-NPSLE patients.

[Anti-NMDA receptor encephalitis: two paediatric cases].

PubMed

González-Toro, M Cristina; Jadraque-Rodríguez, Rocío; Sempere-Pérez, Ángela; Martínez-Pastor, Pedro; Jover-Cerdá, Jenaro; Gómez-Gosálvez, Francisco

2013-12-01

Encephalitis associated to anti-N-methyl D-aspartate (NMDA) receptor antibodies is an autoimmune neurological pathology that has been reported increasingly more frequently in the paediatric population in recent years. We report two cases from our own experience with similar clinical pictures. Case 1: a 5-year-old girl who began with clinical signs and symptoms of convulsions and altered consciousness, associated to movement disorders and regression of previously acquired abilities that developed into autism. Case 2: a 13-year-old girl who presented left-side hemiparesis, abnormal movements, conduct disorder and dysautonomia. In both cases positive anti-NMDA receptor antibodies were obtained in cerebrospinal fluid and they were diagnosed with anti-NMDA receptor encephalitis. In the first case, treatment was established with intravenous perfusion of corticoids and immunoglobulins, and rituximab also had to be associated. In the second case, treatment consisted in corticoids and immunoglobulins. Progress was favourable in both cases, with a slight language disorder as a sequela in the first case and a relapse in the second case, with full resolution. Anti-NMDA receptor encephalitis is a treatable disorder and early diagnosis and treatment are crucial, since this improves the prognosis and diminishes the chances of relapses.

Myelitis and Lupus: Clinical Manifestations, Diagnosis and Treatment. Review.

PubMed

Chiganer, Edson Hernán; Hryb, Javier Pablo; Carnero Contentti, Edgar

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Myelopathy is one of 19 neuropsychiatric syndromes related to SLE defined by the American College of Rheumatology. Although infrequent, it is a severe manifestation, leading to motor and sensory deficits, and sphincter dysfunction. The pathogenesis is not clearly known, but may be related to arterial thrombosis and vasculitis. Diagnosis is based on clinical findings, laboratory tests and the use of gadolinium-enhanced magnetic resonance imaging. The standard therapy is the combination of intravenous cyclophosphamide and glucocorticoids. In refractory disease, other treatments such as plasmapheresis or rituximab have been used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Wernicke-Korsakoff syndrome in the course of thyrotoxicosis - a case report.

PubMed

Wierzbicka-Chmiel, Joanna; Wierzbicki, Krzysztof; Kajdaniuk, Dariusz; Sędziak, Ryszard; Marek, Bogdan

2011-01-01

Wernicke-Korsakoff syndrome (also called Wernicke's encephalopathy) is a potentially fatal, neuropsychiatric syndrome caused most frequently by thiamine deficiency. The three classic symptoms found together are confusion, ataxia and eyeball manifestations. Memory disturbances can also be symptoms. Wernicke's encephalopathy mainly results from alcohol abuse, but also from malnutrition, cancer, chronic dialysis, thyrotoxicosis and, in well-founded cases, encephalopathy associated with autoimmune thyroid disease (EAATD). The coexistence of many factors makes a proper diagnosis difficult, delays appropriate treatment and consequently reduces the chance of complete recovery. We present the case of a 53 year-old female with Wernicke's encephalopathy caused by chronic malnutrition, surgical operation, as well as thyrotoxicosis. She received treatment with intravenous thiamine administration and also anti-thyroid treatment which caused satisfactory regression of her neurological symptoms.

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

PubMed Central

Karageorgas, Theophanis P.; Tseronis, Dimitrios D.; Mavragani, Clio P.

2011-01-01

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target. PMID:22162633

Coexistence of antiphospholipid antibodies and cephalalgia.

PubMed

Islam, Md Asiful; Alam, Fahmida; Gan, Siew Hua; Cavestro, Cinzia; Wong, Kah Keng

2018-03-01

Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals. Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence. Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p < 0.0001) in individuals without any underlying diseases. Our analysis of shortlisted case reports (n = 17) showed that a higher frequency of anticardiolipin antibodies were present in subjects with different autoimmune disorders (70.6%). Corticosteroids were highly effective in resolving headache in aPLs-positive individuals. Conclusion Higher frequency of comorbidity between aPLs and headache was observed in healthy individuals and patient cases. Therefore, experimental studies are warranted to evaluate the aPLs-induced pathogenic mechanism of headache.

Cross-Sectional Evaluation of Plasma Vitamin D Levels in a Large Cohort of Italian Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.

PubMed

Stagi, Stefano; Lepri, Gemma; Rigante, Donato; Matucci Cerinic, Marco; Falcini, Fernanda

2018-03-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are immune-mediated diseases characterized by obsessive-compulsive symptoms and/or tics triggered by group A Streptococcus infections. Despite the well-known action of 25-hydroxyvitamin D [25(OH)D] on different conditions driven by systemic inflammation, there are no data about the 25(OH)D status in patients with PANDAS. To evaluate plasma 25(OH)D levels in a large cohort of children and adolescents with PANDAS and comparing the results with healthy controls. We have evaluated plasma 25(OH)D levels in 179 Italian patients with PANDAS (49 females, 130 males, mean age at diagnosis: 101.4 ± 30.1 months) and in an age-, gender-, and body mass index-matched control group of 224 healthy subjects. Patients with PANDAS have shown more frequently reduced 25(OH)D levels (<30 ng/mL) in comparison with controls (94.6% vs. 82.5%, p = 0.0007). Patients with PANDAS had also lower levels of 25(OH)D than controls (20.4 ± 6.9 ng/mL vs. 24.8 ± 7.3 ng/mL, p < 0.0001). This difference was observed during both winter (13.7 ± 3.25 ng/mL vs. 21.4 ± 5.9 ng/mL, p < 0.0001) and summer (21.8 ± 6.5 ng/mL vs. 32.5 ± 8.7 ng/mL, p < 0.0001). Notably, serum 25(OH)D levels correlated with both number of streptococcal (strep) infections before diagnosis of PANDAS (p < 0.005) and with infection recurrence (p < 0.005). PANDAS patients have reduced 25(OH)D levels, which appear related to streptococcal infections and the probability of recurrence. Further long-term studies with higher number of patients are needed to investigate and confirm this relationship.

No Cases of PANDAS on Follow-Up of Patients Referred to a Pediatric Movement Disorders Clinic.

PubMed

Kilbertus, Sarah; Brannan, Renee; Sell, Erick; Doja, Asif

2014-01-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) remains a controversial diagnosis and it is unclear how frequently it is encountered in clinical practice. Our study aimed to determine how many children with acute-onset tics and/or Obsessive-Compulsive Disorder (OCD) met criteria for PANDAS. A retrospective review was performed on 39 children who presented to a movement disorders clinic with acute-onset tics or OCD from 2005 to 2012. Out of 284 patients seen over the course of 7 years, only 39 had acute-onset tics and/or OCD symptoms. None of the 39 children who presented to us acutely met full criteria for PANDAS. Thirty-eight percent had no association between their symptoms and group A beta-hemolytic streptococcal infection, while 54% had prior inconclusive laboratory testing done and no exacerbations during the course of the study. Only 8% of patients had an acute exacerbation after their initial visit; however, testing for GAHBS in these patients was negative Discussion: Our results support the notion that PANDAS, if it exists, is an exceedingly rare diagnosis encountered in a pediatric movement disorder clinic. While none of our patients met criteria for PANDAS, two with acute-onset OCD would have met criteria for pediatric acute-onset neuropsychiatric syndrome (PANS) indicating that PANS may be a more appropriate diagnosis.

[Unexplicated neuropsychiatric disorders: Do not ignore dysimmune encephalitis. A case report of a dysimmune encephalitis with anti-leucine rich glioma inactivated 1 (LGI-1) antibodies].

PubMed

Le Dault, E; Lagarde, S; Guedj, E; Dufournet, B; Rey, C; Kaphan, E; Tanguy, G; Bregigeon, M; Sagui, E; Brosset, C

2016-02-01

Anti-leucine rich glioma inactivated 1 encephalitis is a common and a treatable etiology of autoimmune encephalitis. Its diagnosis is a challenge because the initial diagnostic work-up is often normal. A 48-year-old man experienced cognitive and behavioral troubles, facio-brachial dystonic seizures and a syndrome of inappropriate antidiuretic hormone secretion. First line tests excluded infectious, neoplastic, systemic inflammatory, endrocrine or toxic etiologies. Cerebral (18)Fluoro-desoxy-glucose (FDG) position emission tomography and research of specific antibodies in cerebro-spinal fluid and serum led to diagnose an anti-leucine rich glioma inactivated 1 encephalitis. Intravenous immunoglobulins and corticosteroids were partially effective. Cyclophosphamid permitted a good recovery. In the presence of acute neuropsychiatric disorders with a negative etiologic research, physician should think about dysimmune encephalitis. Facio-brachial dystonic seizures and syndrome of inappropriate antidiuretic hormone secretion are highly evocative of anti-leucine rich glioma inactivated 1 encephalitis. The diagnosis needs specific diagnostic tests (cerebral (18)FDG position emission tomography and antibodies research in cerebro-spinal fluid and in serum), after the exclusion of alternative diagnoses. Extensive and repeated diagnostic work-up for neoplasia is required. Immunosupressive therapies are effective in most cases. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

The role of microbiome in central nervous system disorders

PubMed Central

Wang, Yan; Kasper, Lloyd H.

2014-01-01

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.

PubMed

Anand, Shweta; Tong, Henry; Besag, Frank M C; Chan, Esther W; Cortese, Samuele; Wong, Ian C K

2017-06-01

A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients.

PubMed

Honorat, Josephe A; Komorowski, Lars; Josephs, Keith A; Fechner, Kai; St Louis, Erik K; Hinson, Shannon R; Lederer, Sabine; Kumar, Neeraj; Gadoth, Avi; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew

2017-09-01

To describe the phenotypes, treatment response, and outcome of IgLON5 autoimmunity. Archived serum and CSF specimens from 367 patients known to harbor unclassified antibodies which stained neural synapses diffusely (mimicking amphiphysin-IgG) were reevaluated by indirect immunofluorescence assay (IFA) using a composite of mouse tissues and recombinant IgLON5-transfected cell-based assay (CBA, Euroimmun). Available specimens (serum, 25; CSF, 9) from 26/367 patients (7%) had identical IFA appearance and robust IgLON5 CBA positivity. Clinical information was available for 20/26 patients; 13 were women. Median disease-onset age was 62 years (range, 46-75 years). Most patients had insidious onset and progression of neurological symptoms affecting movement and sleep predominantly. Sleep disorders were sleep-disordered breathing (11) and parasomnias (3). Brainstem disorders were gait instability (14), dysphagia (10), abnormal eye movements (7), respiratory dysfunction (6), ataxia (5), craniocervical dystonia (3), and dysarthria (3). Findings compatible with hyperexcitability included myoclonus (3), cramps (3), fasciculations (2), and exaggerated startle (2). Neuropsychiatric disorders included cognitive dysfunction (6), psychiatric symptoms (5), and seizures (1). Dysautonomia, in 9, affected bladder function (7), gastrointestinal motility (3), thermoregulation (3), and orthostatic tolerance (1). Just 2 patients had coexisting autoimmune disease. Brain MRI findings were nonspecific and CSF was noninflammatory in all tested. Seven of 9 immunotherapy-treated patients improved: 6 of those 7 were stable at last follow-up. Three untreated patients died. Each IgLON5-IgG subclass (1-4) was readily detectable in ≥80% of specimens using CBA. IgLON5-IgG is diagnostic of a potentially treatable neurological disorder, where autoimmune clues are otherwise lacking.

Pediatric Autoimmune Disorders Associated with Streptococcal Infections and Tourette's Syndrome in Preclinical Studies

PubMed Central

Spinello, Chiara; Laviola, Giovanni; Macrì, Simone

2016-01-01

Accumulating evidence suggests that Tourette's Syndrome (TS) – a multifactorial pediatric disorder characterized by the recurrent exhibition of motor tics and/or vocal utterances – can partly depend on immune dysregulation provoked by early repeated streptococcal infections. The natural and adaptive antibody-mediated reaction to streptococcus has been proposed to potentially turn into a pathological autoimmune response in vulnerable individuals. Specifically, in conditions of increased permeability of the blood brain barrier (BBB), streptococcus-induced antibodies have been proposed to: (i) reach neuronal targets located in brain areas responsible for motion control; and (ii) contribute to the exhibition of symptoms. This theoretical framework is supported by indirect evidence indicating that a subset of TS patients exhibit elevated streptococcal antibody titers upon tic relapses. A systematic evaluation of this hypothesis entails preclinical studies providing a proof of concept of the aforementioned pathological sequelae. These studies shall rest upon individuals characterized by a vulnerable immune system, repeatedly exposed to streptococcus, and carefully screened for phenotypes isomorphic to the pathological signs of TS observed in patients. Preclinical animal models may thus constitute an informative, useful tool upon which conducting targeted, hypothesis-driven experiments. In the present review we discuss the available evidence in preclinical models in support of the link between TS and pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS), and the existing gaps that future research shall bridge. Specifically, we report recent preclinical evidence indicating that the immune responses to repeated streptococcal immunizations relate to the occurrence of behavioral and neurological phenotypes reminiscent of TS. By the same token, we discuss the limitations of these studies: limited evidence of behavioral phenotypes isomorphic to tics and scarce knowledge about the immunological phenomena favoring the transition from natural adaptive immunity to pathological outcomes. PMID:27445678

Recurrent hypoglycaemia in type-1 diabetes mellitus may unravel the association with Addison's disease: a case report.

PubMed

Passanisi, Stefano; Timpanaro, Tiziana; Lo Presti, Donatella; Caruso-Nicoletti, Manuela

2014-09-12

Primary adrenocortical insufficiency or Addison's disease is caused by a progressive destruction of the adrenal cortex, resulting into a reduction of glucocorticoids, mineralocorticoids, and androgens. Autoimmune Addison's disease is the most common etiological form, accounting for about 80% of all cases. We describe the case of a 16-year-old Caucasian boy affected by type-1 diabetes mellitus and autoimmune thyroiditis, who experienced recurrent hypoglycaemia as presenting symptom of Addison's disease. Hypoglycaemia is not a common presenting feature of Addison's disease, both in patients with type-1 diabetes mellitus and in non-diabetic patients. However, hypoglycaemia may occur in association with primary and secondary glucocorticoid deficiency as a result of an enhanced insulin sensitivity. Hypoglycaemia is the most common acute complication of insulin therapy in patients with type-1 diabetes mellitus. Addison's disease has been described in approximately 0.5% of patients with type-1 diabetes mellitus, being more frequent in females and occurring in middle-aged patients. An association among type-1 diabetes mellitus, autoimmune thyroiditis, and Addison's disease is found in the "Schmidt's syndrome", a rare disorder that may occur in the paediatric age. Our case suggests that the presence of Addison's disease should be taken into consideration in patients with type-1 diabetes mellitus and frequent episodes of hypoglycaemia. We wish to highlight that there are no specific indications to screen for the association between Addison's disease and type-1 diabetes mellitus, although an early diagnosis of Addison's disease in diabetic patients would prevent the morbidity and potential mortality of this association.

[Tonsillectomy for PANDAS?].

PubMed

Windfuhr, J P

2016-04-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a disease attributed to children with obsessive compulsive or tic disorders associated with streptococcal infections. Because otolaryngologists evaluate a large number of pediatric patients with recurrent streptococcal infections, tonsillectomy (TE) is a common option of therapy. This study was undertaken to evaluate the efficacy of tonsillectomy in patients presenting with a verified PANDAS. A PubMed research was performed using search terms "tonsillectomy" and "PANDAS", "OCD", "compulsive", "pediatric autoimmune", "Chorea" and "Tic" limited by publication date January 1, 1995 to July 31, 2015. Reviews without patients were not included in the review. Nine papers matched our search terms, including 6 case reports with 8 patients and 3 case series. Most case reports were in favor for TE, but this was by far not supported by the findings in the case series. The follow-up ranged form 2-36 months (case reports) and 24-36 months (case series). establishing the diagnosis of PANDAS is complicated by underlying co-morbidities in the field of neurology-psychiatry and the lack of a reliable biomarker. The positive outcome after TE as reported in case studies may be influenced by the postoperative medication and is not supported by the results of large-scale studies. In the light of the considerable postoperative morbidity and unavoidable mortality rate it appears wise to indicate TE only in clinical studies with standardized inclusion criteria. © Georg Thieme Verlag KG Stuttgart · New York.

Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells.

PubMed

Dileepan, Thamotharampillai; Smith, Erica D; Knowland, Daniel; Hsu, Martin; Platt, Maryann; Bittner-Eddy, Peter; Cohen, Brenda; Southern, Peter; Latimer, Elizabeth; Harley, Earl; Agalliu, Dritan; Cleary, P Patrick

2016-01-01

Group A streptococcal (GAS) infection induces the production of Abs that cross-react with host neuronal proteins, and these anti-GAS mimetic Abs are associated with autoimmune diseases of the CNS. However, the mechanisms that allow these Abs to cross the blood-brain barrier (BBB) and induce neuropathology remain unresolved. We have previously shown that GAS infection in mouse models induces a robust Th17 response in nasal-associated lymphoid tissue (NALT). Here, we identified GAS-specific Th17 cells in tonsils of humans naturally exposed to GAS, prompting us to explore whether GAS-specific CD4+ T cells home to mouse brains following i.n. infection. Intranasal challenge of repeatedly GAS-inoculated mice promoted migration of GAS-specific Th17 cells from NALT into the brain, BBB breakdown, serum IgG deposition, microglial activation, and loss of excitatory synaptic proteins under conditions in which no viable bacteria were detected in CNS tissue. CD4+ T cells were predominantly located in the olfactory bulb (OB) and in other brain regions that receive direct input from the OB. Together, these findings provide insight into the immunopathology of neuropsychiatric complications that are associated with GAS infections and suggest that crosstalk between the CNS and cellular immunity may be a general mechanism by which infectious agents exacerbate symptoms associated with other CNS autoimmune disorders.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Catatonia Update.

PubMed

Brar, Kanwarjeet; Kaushik, Sachin S; Lippmann, Steven

2017-10-26

Catatonia is a neuropsychiatric condition characterized by physical presentations ranging from profound immobility to excessive motor activity. Emotional aspects of catatonia vary clinically between psychomotor retardation and extreme excitability. In the past, catatonia was considered to be a variant of schizophrenia. However, the disorder actually occurs as a clinical expression of many different psychiatric, neurologic, or medical diagnoses. A prompt diagnostic evaluation should identify any underlying diseases with consideration of somatic pathologies, especially those affecting central nervous system function. The workup focuses on a range of metabolic, traumatic, infectious, degenerative, autoimmune, drug-related, or other possible conditions, including psychiatric etiologies. Appropriate interventions should be instituted as quickly as possible to avoid complications like dehydration or deep vein thromboses. Symptomatic treatment commonly includes various pharmaceuticals or electroconvulsive therapy. Benzodiazepine drugs are, and have long been, the most preferred pharmacotherapy. These medications are usually fast acting and effective, are safe, and remain the catatonia treatment of choice. © Copyright 2017 Physicians Postgraduate Press, Inc.

Psychoneuroimmunology of mental disorders.

PubMed

Soria, Virginia; Uribe, Javiera; Salvat-Pujol, Neus; Palao, Diego; Menchón, José Manuel; Labad, Javier

The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

A preliminary examination of self-concept in older adolescents and young adults with Gilles de la Tourette syndrome.

PubMed

Silvestri, Paola R; Chiarotti, Flavia; Baglioni, Valentina; Neri, Valeria; Cardona, Francesco; Cavanna, Andrea E

2017-05-01

Gilles de la Tourette syndrome (GTS) is a childhood-onset neuropsychiatric disorder characterised by multiple tics and often associated with behavioural problems. Although there is evidence of significantly reduced self-esteem in children and adolescents with GTS, little is known about perceived self-concept and its clinical determinants at the transition age between adolescence and adulthood. We therefore set out to investigate self-concept in a clinical sample of young patients with GTS at this crucial age for personal development. In addition to standard demographic and clinical data, we collected self-ratings using a standardised battery of psychometric instruments, as well as the Multidimensional Self Concept Scale, a comprehensive questionnaire developed to assess self-concept in subjects aged 9- to 19 years, tapping into the social, competence, affect, academic, family, and physical domains. We found that patients diagnosed with at least one co-morbid psychiatric disorder ("GTS-plus" phenotype) reported significantly lower self-concept than patients with "pure GTS", whereas tic-related variables had no impact on self-concept. Anxiety symptoms were the main determinants of self-concept, especially trait anxiety with regard to social and affective domains. Affective symptoms could also have a negative impact on the physical, affective, competence, and social domains of self-concept. Routine screening for anxiety and affective symptoms should be recommended in all patients with GTS seen at transition clinics from paediatric to adult care, in order to implement effective treatment interventions whenever possible. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Therapeutic Plasma Apheresis as a Treatment for 35 Severely Ill Children and Adolescents with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections

PubMed Central

Latimer, M. Elizabeth; L'Etoile, Nathan; Seidlitz, Jakob

2015-01-01

Abstract Background: Because of its reported similarities to Sydenham chorea, therapeutic plasma apheresis (TPA) has been proposed as a potential treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). To date, support for the use of TPA has been limited to a few anecdotal reports and a small placebo-controlled trial demonstrating dramatic symptom improvements at 1 month and 1 year follow-up. To evaluate the safety and efficacy of TPA further, we undertook a retrospective review of all PANDAS patients treated with TPA at Georgetown University Hospital between August 2009 and October 2013. Methods: Forty patients were identified, and sufficient information was available from medical records and telephone interview for 35 cases (88%). All 35 (23 boys; 12 girls) met diagnostic criteria for PANDAS (Swedo et al. 1998) and had severe symptoms. The TPA procedures were performed at Georgetown University Hospital using a protocol that processes a total of 4.5 blood volumes over 3–5 days (three treatments of 1.5 volumes each). Overall symptom improvements at 6 months post-TPA and long-term follow-up were estimated by parents, who also rated changes in individual symptoms to provide information about patterns of improvement. Results: All patients were reported to have received at least some benefit from TPA, with average improvement of 65% at 6 months post-TPA and 78% at longer-term follow-up. A decrease in the number of reported symptoms also occurred, with particular improvements in obsessive-compulsive disorder (OCD), anxiety, tics, and somatic symptoms, including dysgraphia, sleep difficulties, and urinary urgency or frequency. Contrary to expectations, preceding duration of illness was not correlated with degree of improvement following TPA, suggesting that acuity of illness is not a factor affecting response. Only two adverse events were reported: both involved reopening of the site where the central line had been placed and resolved immediately following application of pressure and re-dressing of the puncture site. Conclusions: Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option. PMID:25658452

Therapeutic plasma apheresis as a treatment for 35 severely ill children and adolescents with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

PubMed

Latimer, M Elizabeth; L'Etoile, Nathan; Seidlitz, Jakob; Swedo, Susan E

2015-02-01

Because of its reported similarities to Sydenham chorea, therapeutic plasma apheresis (TPA) has been proposed as a potential treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). To date, support for the use of TPA has been limited to a few anecdotal reports and a small placebo-controlled trial demonstrating dramatic symptom improvements at 1 month and 1 year follow-up. To evaluate the safety and efficacy of TPA further, we undertook a retrospective review of all PANDAS patients treated with TPA at Georgetown University Hospital between August 2009 and October 2013. Forty patients were identified, and sufficient information was available from medical records and telephone interview for 35 cases (88%). All 35 (23 boys; 12 girls) met diagnostic criteria for PANDAS (Swedo et al. 1998 ) and had severe symptoms. The TPA procedures were performed at Georgetown University Hospital using a protocol that processes a total of 4.5 blood volumes over 3-5 days (three treatments of 1.5 volumes each). Overall symptom improvements at 6 months post-TPA and long-term follow-up were estimated by parents, who also rated changes in individual symptoms to provide information about patterns of improvement. All patients were reported to have received at least some benefit from TPA, with average improvement of 65% at 6 months post-TPA and 78% at longer-term follow-up. A decrease in the number of reported symptoms also occurred, with particular improvements in obsessive-compulsive disorder (OCD), anxiety, tics, and somatic symptoms, including dysgraphia, sleep difficulties, and urinary urgency or frequency. Contrary to expectations, preceding duration of illness was not correlated with degree of improvement following TPA, suggesting that acuity of illness is not a factor affecting response. Only two adverse events were reported: both involved reopening of the site where the central line had been placed and resolved immediately following application of pressure and re-dressing of the puncture site. Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option.

Pseudotumor cerebri syndrome in a patient with narcolepsy type 1.

PubMed

Rossor, Thomas; Lim, Ming; VanDenEshof, Kirandeep; Gringras, Paul

2018-01-01

Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep. NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO 2 levels overnight. Many of these are predisposing factors for pseudotumor cerebri syndrome (PTCS). We present a case of a young girl with both NT1 and PTCS that responded well to treatment with acetazolamide after early identification, with improvement of headache and resolution of hypoventilation. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes.

PubMed

Gandhi, K; Tosur, M; Schaub, R; Haymond, M W; Redondo, M J

2017-10-01

To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes. We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3-18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and 14.8% African-American children, and 7.4% were of other, mixed or unknown race. The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P<0.001) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P<0.001), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number. At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention. © 2017 Diabetes UK.

Differential binding of antibodies in PANDAS patients to cholinergic interneurons in the striatum.

PubMed

Frick, Luciana R; Rapanelli, Maximiliano; Jindachomthong, Kantiya; Grant, Paul; Leckman, James F; Swedo, Susan; Williams, Kyle; Pittenger, Christopher

2018-03-01

Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus, or PANDAS, is a syndrome of acute childhood onset of obsessive-compulsive disorder and other neuropsychiatric symptoms in the aftermath of an infection with Group A beta-hemolytic Streptococcus (GABHS). Its pathophysiology remains unclear. PANDAS has been proposed to result from cross-reactivity of antibodies raised against GABHS with brain antigens, but the targets of these antibodies are unclear and may be heterogeneous. We developed an in vivo assay in mice to characterize the cellular targets of antibodies in serum from individuals with PANDAS. We focus on striatal interneurons, which have been implicated in the pathogenesis of tic disorders. Sera from children with well-characterized PANDAS (n = 5) from a previously described clinical trial (NCT01281969), and matched controls, were infused into the striatum of mice; antibody binding to interneurons was characterized using immunofluorescence and confocal microscopy. Antibodies from children with PANDAS bound to ∼80% of cholinergic interneurons, significantly higher than the <50% binding seen with matched healthy controls. There was no elevated binding to two different populations of GABAergic interneurons (PV and nNOS-positive), confirming the specificity of this phenomenon. Elevated binding to cholinergic interneurons resolved in parallel with symptom improvement after treatment with intravenous immunoglobulin. Antibody-mediated dysregulation of striatal cholinergic interneurons may be a locus of pathology in PANDAS. Future clarification of the functional consequences of this specific binding may identify new opportunities for intervention in children with this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

PubMed

Magro-Checa, C; Beaart-van de Voorde, L J J; Middelkoop, H A M; Dane, M L; van der Wee, N J; van Buchem, M A; Huizinga, T W J; Steup-Beekman, G M

2017-04-01

Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the only important predictor. The change in SF-36 MCS was also independently associated with neuropsychiatric systemic lupus erythematosus ( B = 5.783; p < 0.05) and inflammatory neuropsychiatric systemic lupus erythematosus ( B = 11.133; p < 0.001). Disease duration and change in disease activity were the only predictors in both cases. The change in SF-36 PCS was only negatively associated with age. Conclusion Inflammatory neuropsychiatric systemic lupus erythematosus events have better clinical outcome and meaningful improvement in SF-36 MCS than ischaemic neuropsychiatric systemic lupus erythematosus or non-neuropsychiatric systemic lupus erythematosus.

Persistent Changes in Circulating and Intestinal γδ T Cell Subsets, Invariant Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Children and Adults with Coeliac Disease

PubMed Central

Dunne, Margaret R.; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G.; Feighery, Conleth F.

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity. PMID:24124528

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

PubMed

Dunne, Margaret R; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G; Feighery, Conleth F

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long-term outcome.

PubMed

Nosadini, Margherita; Mohammad, Shekeeb S; Suppiej, Agnese; Sartori, Stefano; Dale, Russell C

2016-11-01

Intravenous immunoglobulin (IVIG) is an expensive therapy used in immunodeficiency and autoimmune disorders. Increasing demands and consequent shortages result in a need for usage to conform to guidelines. We retrospectively evaluated IVIG use for neuroimmunological indications and adherence to existing guidelines in a major Australian paediatric hospital between 2000 and 2014. One-hundred and ninety-six children (96 male, 100 female; mean age at disease onset 6y 5mo [range 3mo-15y 10mo], mean age at first IVIG dose 7y 2mo [range 3mo-16y 5mo]) received IVIG for neuroimmunological indications during the study period (28.1% had Guillain-Barré syndrome), representing 15.5% of all hospital indications. In total, 1669 IVIG courses were administered (total 57 221g, median 78g/patient, range 12-5748g). The highest median numbers of courses were in chronic inflammatory demyelinating polyneuropathies, opsoclonus-myoclonus ataxia syndrome, suspected immune-mediated epilepsies, and Rasmussen's encephalitis. Adverse reactions occurred in 25.5% of patients, but these were mostly minor. Outcome at follow-up was best in anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, Guillain-Barré syndrome, and myasthenia gravis, and worst in Rasmussen's encephalitis and epilepsies. The total cost of IVIG was US$2 595 907 (median $3538/patient, range $544-260 766). Of patients receiving IVIG, 45.4% to 57.1% were given the therapy for 'weak' indications or indications 'not listed' in international guidelines. Some entities commonly treated with IVIG in current practice, such as anti-NMDAR encephalitis and transverse myelitis, are not listed in most guidelines. Our study demonstrates that IVIG is generally well tolerated but expensive, and discloses discrepancies between guidelines and clinical practice in paediatric neurology, suggesting both the need for greater adherence to current recommendations, and for recommendations to be updated to accommodate emerging indications. © 2016 Mac Keith Press.

Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology.

PubMed

Dubey, Divyanshu; Alqallaf, Abdulradha; Hays, Ryan; Freeman, Matthew; Chen, Kevin; Ding, Kan; Agostini, Mark; Vernino, Steven

2017-04-01

Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016. Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom. Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an autoimmune cause of epilepsy were seen in 23 patients (20.5%). Certain clinical features, such as autonomic dysfunction, neuropsychiatric changes, viral prodrome, faciobrachial dystonic spells or facial dyskinesias, and mesial temporal sclerosis abnormality on magnetic resonance imaging, correlated with seropositivity. The APE score was a useful tool in predicting positive serologic findings. Patients who were Ab positive were more likely to have good seizure outcome than were patients with epilepsy of unknown etiology (15 of 23 [65.2%] vs 24 of 89 [27.0%]; odds ratio, 4.8; 95% CI, 1.8-12.9; P = .002). In patients who were seropositive, reduction in seizure frequency was associated with use of immunomodulatory therapy. Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs suggesting an autoimmune etiology. Certain clinical features (encoded in the APE score) could be used to identify patients with the highest probability of harboring neurological Abs.

Anti-Ma2-encephalitis in a 2 year-old child: A newly diagnosed case and literature review.

PubMed

Mrabet, Saloua; Ben Achour, Nedia; Kraoua, Ichraf; Benrhouma, Hanène; Klaa, Hedia; Rouissi, Aida; Ben Ahmed, Malika; Ben Youssef Turki, Ilhem

2015-11-01

Anti-Ma2-associated encephalitis is a rare paraneoplastic neurological syndrome characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. It is rarely reported in children. We describe the clinical data of a 2-year-old girl referred to our department for refractory focal seizures associated with fever, followed by behavioural changes, speech disturbances and confusional episodes. Brain magnetic resonance imaging (MRI) showed left temporoparietal brain involvement. Haematological, biochemical and infectious evaluations were unremarkable. Autoimmune encephalitis was suspected. Paraneoplastic antibodies tests showed positive results for anti-Ma2 antibodies. Screening for underlying tumour was negative. Immunomodulatory treatment was administrated. The patient showed improvement of vigilance and behaviour. However, she kept refractory epilepsy. Although poor response to immunotherapy, early diagnosis and appropriate treatment of this disorder may prevent irreversible sequelae. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS

PubMed Central

2016-01-01

There is accumulating evidence that immune dysregulation contributes to the pathophysiology of obsessive-compulsive disorder (OCD), Tourette syndrome, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The mechanistic details of this pathophysiology, however, remain unclear. Here we focus on one particular component of the immune system: microglia, the brain's resident immune cells. The role of microglia in neurodegenerative diseases has been understood in terms of classic, inflammatory activation, which may be both a consequence and a cause of neuronal damage. In OCD and Tourette syndrome, which are not characterized by frank neural degeneration, the potential role of microglial dysregulation is much less clear. Here we review the evidence for a neuroinflammatory etiology and microglial dysregulation in OCD, Tourette syndrome, and PANDAS. We also explore new hypotheses as to the potential contributions of microglial abnormalities to pathophysiology, beyond neuroinflammation, including failures in neuroprotection, lack of support for neuronal survival, and abnormalities in synaptic pruning. Recent advances in neuroimaging and animal model work are creating new opportunities to elucidate these issues. PMID:28053994

Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS.

PubMed

Frick, Luciana; Pittenger, Christopher

2016-01-01

There is accumulating evidence that immune dysregulation contributes to the pathophysiology of obsessive-compulsive disorder (OCD), Tourette syndrome, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The mechanistic details of this pathophysiology, however, remain unclear. Here we focus on one particular component of the immune system: microglia, the brain's resident immune cells. The role of microglia in neurodegenerative diseases has been understood in terms of classic, inflammatory activation, which may be both a consequence and a cause of neuronal damage. In OCD and Tourette syndrome, which are not characterized by frank neural degeneration, the potential role of microglial dysregulation is much less clear. Here we review the evidence for a neuroinflammatory etiology and microglial dysregulation in OCD, Tourette syndrome, and PANDAS. We also explore new hypotheses as to the potential contributions of microglial abnormalities to pathophysiology, beyond neuroinflammation, including failures in neuroprotection, lack of support for neuronal survival, and abnormalities in synaptic pruning. Recent advances in neuroimaging and animal model work are creating new opportunities to elucidate these issues.

Localized scleroderma en coup de sabre in the Neurology Clinic.

PubMed

Pinho, João; Rocha, João; Sousa, Filipa; Macedo, Cristiana; Soares-Fernandes, João; Cerqueira, João; Maré, Ricardo; Lourenço, Esmeralda; Pereira, João

2016-07-01

Localized scleroderma en coup de sabre (LScs) is a form of localized scleroderma thought to be an autoimmune disorder. Central nervous system involvement is not rare and neurological manifestations include seizures, focal neurological deficits, headache and neuropsychiatric changes. Patients attending the Neurology Clinic with the final diagnosis of LScs with neurological manifestations were identified and clinical and imagiological records reviewed. Five patients (0.024%) had LScs with neurological involvement, presenting with transient focal neurologic deficits, seizures, headache or migraine with aura. Neuroimaging studies confirmed localized skin depression and showed bone thinning, white matter lesions, brain calcifications, sulcal effacement and meningeal enhancement. Three patients experienced clinical improvement after immunosuppressive therapy, and in two of these patients neuroimaging findings also improved. Recognizing typical dermatologic changes is keystone for the diagnosis of LScs with neurological involvement. It is a diagnosis of exclusion and extensive etiological diagnostic evaluation should be performed. Treatment options, including conservative follow-up or immunosuppressive therapy, should be carefully considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis.

PubMed

Espinola-Nadurille, Mariana; Bautista-Gomez, Paola; Flores, Jose; Rivas-Alonso, Veronica; Perez-Esparza, Rodrigo; Solís-Vivanco, Rodolfo; Vargas-Cañas, Steven

2018-01-01

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

Current and emerging treatment options in the management of lupus

PubMed Central

Jordan, Natasha; D’Cruz, David

2016-01-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058

Prevalence of anti-basal ganglia antibodies in adult obsessive-compulsive disorder: cross-sectional study.

PubMed

Nicholson, Timothy R J; Ferdinando, Sumudu; Krishnaiah, Ravikumar B; Anhoury, Sophie; Lennox, Belinda R; Mataix-Cols, David; Cleare, Anthony; Veale, David M; Drummond, Lynne M; Fineberg, Naomi A; Church, Andrew J; Giovannoni, Gavin; Heyman, Isobel

2012-05-01

Symptoms of obsessive-compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis. To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults. Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n = 33) and schizophrenia (n = 17). Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact test P = 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls. These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.

Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

PubMed

Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

2015-01-01

Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder.

PubMed

Cox, Carol J; Zuccolo, Amir J; Edwards, Erica V; Mascaro-Blanco, Adita; Alvarez, Kathy; Stoner, Julie; Chang, Kiki; Cunningham, Madeleine W

2015-02-01

Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD. Study participants (n=311; ages 4-27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5-14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted >1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum. Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p<0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p<0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p<0.033 for each). Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.

Antineuronal Antibodies in a Heterogeneous Group of Youth and Young Adults with Tics and Obsessive-Compulsive Disorder

PubMed Central

Cox, Carol J.; Zuccolo, Amir J.; Edwards, Erica V.; Mascaro-Blanco, Adita; Alvarez, Kathy; Stoner, Julie; Chang, Kiki

2015-01-01

Abstract Background and objective: Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD. Methods: Study participants (n=311; ages 4–27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5–14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted >1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum. Results: Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p<0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p<0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p<0.033 for each). Conclusion: Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology. PMID:25658702

Gestational outcomes in patients with neuropsychiatric systemic lupus erythematosus.

PubMed

de Jesus, G R; Rodrigues, B C; Lacerda, M I; Dos Santos, F C; de Jesus, N R; Klumb, E M; Levy, R A

2017-04-01

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Psychiatric and cognitive manifestations of hypothyroidism

PubMed Central

Samuels, Mary H

2014-01-01

Purpose of review Overt hypothyroidism has major effects on neuropsychiatric function, but patients with mild hypothyroidism may attribute unrelated neuropsychiatric symptoms to their thyroid condition. This review will summarize data on neuropsychiatric effects of hypothyroidism, and provide guidelines regarding the relationship between hypothyroidism and neuropsychiatric issues, and treatment indications. Recent findings Clinical investigations and functional imaging studies confirm that overt hypothyroidism is associated with affective and cognitive decrements, largely reversible with treatment. In contrast, subclinical hypothyroidism is not associated with major neuropsychiatric deficits, although studies utilizing sensitive measures show small deficits in memory and executive function. Neuropsychiatric complaints are more common when patients are aware of their thyroid disease, regardless of their thyroid function at the time of testing. Summary Neuropsychiatric dysfunction is common in overt hypothyroidism, and will improve (although perhaps not completely resolve) with therapy. On the other hand, deficits related to thyroid dysfunction are usually mild in subclinical hypothyroidism, and realistic expectations need to be set regarding symptom reversibility with treatment. Patients with mild hypothyroidism and significant distress related to neuropsychiatric symptoms most likely have independent diagnoses that should be evaluated separately. PMID:25122491

Risk factors for neuropsychiatric manifestations in children with systemic lupus erythematosus: case-control study.

PubMed

Zuniga Zambrano, Yenny Carolina; Guevara Ramos, Juan David; Penagos Vargas, Nathalia Elena; Benitez Ramirez, Diana Carol; Ramirez Rodriguez, Sandra Milena; Vargas Niño, Adriana Carolina; Izquierdo Bello, Alvaro Hernando

2014-09-01

Neuropsychiatric symptoms in children with systemic lupus erythematosus cause high morbidity and disability. This study analyzed risk factors associated with neuropsychiatric presentation in patients with systemic lupus erythematosus aged <18 years. A case-control study was performed. Medical record information of patients with a diagnosis of systemic lupus erythematosus who were hospitalized with or without neuropsychiatric symptoms was collected between March 2007 and January 2012. Clinical variables, laboratory examinations, neuroimages, and disease activity (Systemic Erythematosus Lupus Disease Activity Index) and damage (Systemic Lupus International Collaborating Clinics) indices were analyzed. A total of 90 patients were selected, 30 with neuropsychiatric symptoms. The patients' average age was 12.2 years. The most common neuropsychiatric symptoms were seizures, migraine, and depression. The average Systemic Erythematosus Lupus Disease Activity Index was 19.86 (S.D. 10.83) and the average Systemic Lupus International Collaborating Clinics index was 2.02 (S.D. 2.43), with higher values in patients with neuropsychiatric symptoms (P = 0.001). The levels of complement C3 and C4 were significantly higher in patients with a neuropsychiatric disorder (P = 0.003). Lupus anticoagulant was found in 51.5% of patients with neuropsychiatric symptoms (odds ratio, 3.7; 95% confidence interval, 1.3-10.0). Immunosuppression with azathioprine, rituximab, or cyclophosphamide delayed the time to neuropsychiatric systemic lupus erythematosus development by 18.5 months (95% confidence interval, 10.6-26.5) compared to patients who did not receive these agents. The presence of lupus anticoagulant was a risk factor in our patients. The use of immunosuppressants, such as cyclophosphamide, rituximab, and azathioprine, delayed the presentation of neuropsychiatric manifestations of lupus. Copyright © 2014 Elsevier Inc. All rights reserved.

NMDA Receptor Autoantibodies in Autoimmune Encephalitis Cause a Subunit-Specific Nanoscale Redistribution of NMDA Receptors.

PubMed

Ladépêche, Laurent; Planagumà, Jesús; Thakur, Shreyasi; Suárez, Irina; Hara, Makoto; Borbely, Joseph Steven; Sandoval, Angel; Laparra-Cuervo, Lara; Dalmau, Josep; Lakadamyali, Melike

2018-06-26

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder mediated by autoantibodies against the GluN1 subunit of the NMDAR. Patients' antibodies cause cross-linking and internalization of NMDAR, but the synaptic events leading to depletion of NMDAR are poorly understood. Using super-resolution microscopy, we studied the effects of the autoantibodies on the nanoscale distribution of NMDAR in cultured neurons. Our findings show that, under control conditions, NMDARs form nanosized objects and patients' antibodies increase the clustering of synaptic and extrasynaptic receptors inside the nano-objects. This clustering is subunit specific and predominantly affects GluN2B-NMDARs. Following internalization, the remaining surface NMDARs return to control clustering levels but are preferentially retained at the synapse. Monte Carlo simulations using a model in which antibodies induce NMDAR cross-linking and disruption of interactions with other proteins recapitulated these results. Finally, activation of EphB2 receptor partially antagonized the antibody-mediated disorganization of the nanoscale surface distribution of NMDARs. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists

PubMed Central

Thomas, Sunil; Izard, Jacques; Walsh, Emily; Batich, Kristen; Chongsathidkiet, Pakawat; Clarke, Gerard; Sela, David A.; Muller, Alexander J.; Mullin, James M.; Albert, Korin; Gilligan, John P.; DiGuilio, Katherine; Dilbarova, Rima; Alexander, Walker; Prendergast, George C.

2017-01-01

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well-being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active immune system necessary to prevent disease later in life. Exposure to microorganisms educates the immune system, induces adaptive immunity and initiates memory B and T cells that are essential to combat various pathogens. The correct microbial-based education of immune cells may be critical in preventing the development of autoimmune diseases and cancer. This review provides a broad overview of the importance of the host microbiome and accumulating knowledge of how it regulates and maintains a healthy human system. PMID:28292977

Hashimoto's Encephalopathy Presenting with Unusual Behavioural Disturbances in an Adolescent Girl

PubMed Central

Subashini, Viswanath; Balakrishnan, Ramasamy

2017-01-01

Hashimoto's encephalopathy (HE) is a rare autoimmune disorder with neurological and neuropsychiatric manifestations and elevated titres of anti-thyroid antibodies. Here we are reporting a case of HE in a 19-year-old girl who presented with seizure-like episodes, confusion, and behavioural disturbances with catatonic symptoms such as posturing, echopraxia, echolalia, and ambivalence. Patient did not respond to antipsychotics and anticonvulsants. On further investigation, patient was found to have high serum anti-TPO antibodies of about 1261 U/mL with euthyroid status, which supported a suspicion of HE. Our consultant neurologist confirmed the diagnosis and she was started on injection of methylprednisolone 750 mg OD. Since patient started showing clinical improvement, her antipsychotic medications were tapered off. On follow-up, patient has recovered and is functioning well. Since HE is a diagnosis of exclusion, very high anti-TPO antibodies and good response to steroids supported the diagnosis of HE in this patient after excluding other etiological possibilities. This case has been reported because the clinical presentation was predominantly neurobehavioural manifestations which is uncommon with HE. PMID:28607558

Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients.

PubMed

Bergallo, Massimiliano; Montanari, Paola; Mareschi, Katia; Merlino, Chiara; Berger, Massimo; Bini, Ilaria; Daprà, Valentina; Galliano, Ilaria; Fagioli, Franca

2017-12-01

The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression. Our findings show that HERV-K expression was significantly higher in leukaemia patients when compared to healthy donors of a similar median age. We observed a significantly high expression of HERV-K in acute lymphoblastic leukemia (ALL) patients. In this study, we also found a relative overexpression of the endogenous retrovirus HERV-K in BM cells from the majority of leukemia samples analyzed, in particular in ALL. This overexpression might be related to lymphatic leukemogenesis and it warrants further investigations.

Uncoupling the widespread occurrence of anti-NMDAR1 autoantibodies from neuropsychiatric disease in a novel autoimmune model.

PubMed

Pan, Hong; Oliveira, Bárbara; Saher, Gesine; Dere, Ekrem; Tapken, Daniel; Mitjans, Marina; Seidel, Jan; Wesolowski, Janina; Wakhloo, Debia; Klein-Schmidt, Christina; Ronnenberg, Anja; Schwabe, Kerstin; Trippe, Ralf; Mätz-Rensing, Kerstin; Berghoff, Stefan; Al-Krinawe, Yazeed; Martens, Henrik; Begemann, Martin; Stöcker, Winfried; Kaup, Franz-Josef; Mischke, Reinhard; Boretius, Susann; Nave, Klaus-Armin; Krauss, Joachim K; Hollmann, Michael; Lühder, Fred; Ehrenreich, Hannelore

2018-02-09

Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons. The age dependence of seroprevalence is lost in nonhuman primates in captivity and in human migrants, raising the intriguing possibility that chronic life stress may be related to NMDAR1-AB formation, predominantly of the IgA class. Active immunization of ApoE -/- and ApoE +/+ mice against four peptides of the extracellular NMDAR1 domain or ovalbumin (control) leads to high circulating levels of specific AB. After 4 weeks, the endogenously formed NMDAR1-AB (IgG) induce psychosis-like symptoms upon MK-801 challenge in ApoE -/- mice, characterized by an open blood-brain barrier, but not in their ApoE +/+ littermates, which are indistinguishable from ovalbumin controls. Importantly, NMDAR1-AB do not induce any sign of inflammation in the brain. Immunohistochemical staining for microglial activation markers and T lymphocytes in the hippocampus yields comparable results in ApoE -/- and ApoE +/+ mice, irrespective of immunization against NMDAR1 or ovalbumin. These data suggest that NMDAR1-AB of the IgG class shape behavioral phenotypes upon access to the brain but do not cause brain inflammation on their own.

Schizophrenia or Atypical Lupus Erythematosus with Predominant Psychiatric Manifestations over 25 Years: Case Analysis and Review

PubMed Central

Mack, Axel; Pfeiffer, Christiane; Schneider, E. Marion; Bechter, Karl

2017-01-01

We observed a case over 25 years of relapsing–remitting schizophrenic spectrum disorder, varying regarding the main symptomatology between more depressive or more schizoaffective or rather typical schizophrenic syndrome. Diseased phases were repeatedly accompanied by minor skin lesions, which were initially classified as mixed tissue disorder. Psychotic phases were waxing–waning over years. During one later relapse, skin involvement was severe, classified to likely represent an allergic reaction to psychopharmaca; this generalized exanthema remitted rapidly with cortisone treatment and azathioprine. Under continued azathioprine and low dose neuroleptics, the patient remitted completely, appearing psychiatrically healthy for 16 years. When azathioprine was set off due to pregnancy, an extraordinary severe relapse of schizophrenia like psychosis accompanied by most severe skin lesions developed within a few weeks, then requiring 2 years of psychiatric inpatient treatment. Finally, a diagnosis of systemic lupus erythematodes plus neuropsychiatric lupus was made. A single CSF sample in 2013 showed suspicious biomarkers, matching with CSF cytokine profiling in schizophrenic and affective spectrum disorder patients and indicated mild neuroinflammation. Complex immune suppressive treatment was reinitiated short after relapse, but was only partially successful. However, surprisingly the psychosis and skin lesions remitted (in parallel) when belimumab was given (add-on). The very details of this complicated, long-term disease course are discussed also with regard to general ideas, in particular with respect to the question if this case of seemingly comorbid schizophrenia with minor autoimmunity signs represented a case of one emerging autoimmune disorder with variant manifestations systemically and within the CNS, though atypically with predominant appearance as a schizophrenia spectrum disorder. PMID:28798699

High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults.

PubMed

Clark, Uraina S; Sweet, Lawrence H; Morgello, Susan; Philip, Noah S; Cohen, Ronald A

2017-06-01

Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); HIV+ High-ELS (N = 13); HC Low-ELS (N = 16); and HC High-ELS (N = 9). Participants completed a battery of neuropsychiatric measures. BOLD fMRI assessed amygdala reactivity during explicit observation of fearful/angry faces. High-ELS participants demonstrated reduced levels of amygdala reactivity relative to Low-ELS participants. HIV+ High-ELS participants reported higher levels of neuropsychiatric symptoms than all other groups. In the HIV+ group, lower amygdala responses were associated with higher neuropsychiatric symptoms, particularly depression, anxiety, and alexithymia. Collectively, these results suggest that high ELS exposure is a significant risk factor for neuropsychiatric symptoms in HIV+ adults. Furthermore, our results implicate ELS-related abnormalities in amygdala activity in the etiology of neuropsychiatric symptoms in HIV+ adults.

Prevalence of neuropsychiatric symptoms in Alzheimer's disease: a cross-sectional descriptive study in Thailand.

PubMed

Charernboon, Thammanard; Phanasathit, Muthita

2014-05-01

To estimate the prevalence of neuropsychiatric symptoms in Thai patients with Alzheimer's disease. The present study is a cross-sectional descriptive design. The participants comprised 62 patients from the Memory Clinic at Thammasat University Hospital, Thailand. Subjects were diagnosed as having Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria and received global Clinical Dementia Rating scale (CDR) score of at least stage 1. All participants were assessed using the Neuropsychiatric Inventory Questionnaire (NPI) and the Thai Mental State Examination (TMSE). The subjects were female 62.9% and male 37.1%, the mean age was 76 +/- 6.7 years. The majority of them (62.9%) were in the mild stage (CDR = 1). The result showed that the prevalence of neuropsychiatric symptoms (> or = 1 symptom) reported was 100%. The most common symptoms were apathy (71%), aberrant motor behavior (61.3%), sleep problems (56.5%), eating problems (51.6%) and agitation/aggression (45.2%), whereas the least was euphoria (6.5%). The number of neuropsychiatric symptoms increased with severity of the disease. The result also showed that 61.3% of the participants presented with the chief complaint of neuropsychiatric symptoms, whereas memory complaints were only 38.7%. Neuropsychiatric symptoms are very common in Thai Alzheimer's disease patients. Therefore, management of Alzheimer's patients should include an assessment of neuropsychiatric symptoms and also concentrate on reducing these symptoms. The number of neuropsychiatric symptoms increases with disease progression. Moreover, neuropsychiatric symptoms were the most common presenting problem rather than memory problem in Thai patients with Alzheimer's disease.

Assessment of the neuropsychiatric comorbidities in Chinese children with epilepsy using the MINI-KID tool.

PubMed

Li, Taoli; Zhou, Hao; Li, Yijie; Li, Chunpei; Zhang, Yunjian; Zhou, Yuanfeng; Wang, Yi

2018-02-01

This study aimed to assess neuropsychiatric comorbidities and analyze risk factors in Chinese children with epilepsy. Children with epilepsy aged between 6 and 16 years from the Children's Hospital of Fudan University were included. Children with asthma and typically developing children were matched for age and gender, and served as control groups. Neuropsychiatric disorders were assessed by interviewing the parents or guardians using the Mini International Neuropsychiatric Interview for children (MINI-KID) (parent version). Basic information and clinical data were also collected using an author designed questionnaire. Multiple logistic regression analysis was done to identify the risk factors associated with neuropsychiatric comorbidities. In this study, 140 children with epilepsy, 70 children with asthma and 70 typically developing children were recruited. Neuropsychiatric disorders were significantly more common in children with epilepsy (41.4%) as compared with the asthma group (15.7%) and the control group (10.0%). Of the 58 children with epilepsy who had neuropsychiatric comorbidities, only 29.3% had been diagnosed before our study. Multivariate analysis revealed that a younger age at seizure onset (OR=0.877, 95%CI: 0.773∼0.996), seizures occurring more than once monthly during the past year (OR=3.526, 95%CI: 1.177∼10.562), polytherapy (OR=2.632, 95%Cl: 1.066∼6.501) were all significantly associated with neuropsychiatric comorbidities in children with epilepsy. In conclusion, children with epilepsy are more likely to have neuropsychiatric comorbidities, and up to 70% of them were undiagnosed. Early screening, diagnosis and treatment of neuropsychiatric comorbidities in children with epilepsy may improve the long-term prognosis. Copyright © 2017. Published by Elsevier B.V.

Canadian Paediatric Neurology Workforce Survey and Consensus Statement.

PubMed

Doja, Asif; Orr, Serena L; McMillan, Hugh J; Kirton, Adam; Brna, Paula; Esser, Michael; Tang-Wai, Richard; Major, Philippe; Poulin, Chantal; Prasad, Narayan; Selby, Kathryn; Weiss, Shelly K; Yeh, E Ann; Callen, David Ja

2016-05-01

Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.

Neuropsychiatry of fragile X-premutation carriers with and without fragile X-associated tremor-ataxia syndrome: implications for neuropsychology.

PubMed

Bourgeois, James A

2016-08-01

Clinical neuropsychologists benefit from clinical currency in recently ascertained neuropsychiatric illness, such as fragile X premutation (FXPM) disorders. The author reviewed the clinical literature through 2016 for neuropsychiatric phenotypes in FXPM disorders, including patients with fragile X-associated tremor/ataxia syndrome (FXTAS). A PubMed search using the search terms 'Fragile X,' 'Premutation,' 'Carriers,' 'Psychiatric,' 'Dementia,' 'Mood,' and 'Anxiety' for citations in the clinical literature through 2016 was reviewed for studies specifically examining the neuropsychiatric phenotype in FXPM patients. The relevant articles were classified according to specific neuropsychiatric syndromes, including child onset, adult onset with and without FXTAS, as well as common systemic comorbidities in FXPM patients. Eighty-six articles were reviewed for the neuropsychiatric and other phenotypes in FXPM patients. The neuropsychiatric phenotype in FXPM patients is distinct from that of full mutation (Fragile X Syndrome) patients. FXTAS is associated with a specific cortical-subcortical major or mild neurocognitive disorder (NCD). FXPM patients are at risk for neuropsychiatric illness. In addition, FXPM patients are at risk for other systemic conditions that should raise suspicion for FXPM-associated illnesses. Clinicians should consider a diagnosis of FXPM-associated neuropsychiatric illness when patients with specific clinical scenarios are encountered; especially in patient pedigrees consistent with a typical (often multigenerational) presentation of fragile X-associated conditions, confirmatory genetic testing should be considered. Clinical management should take into account the psychological challenges of a multigenerational genetic neuropsychiatric illness with a variable CNS and systemic clinical phenotype.

Morbidity among Israeli paediatric travellers.

PubMed

Rabinowicz, Shira; Schwartz, Eli

2017-09-01

International travel, particularly to developing countries, is becoming increasingly common among the Israeli population, including an increase in the number of travelling children. Since children are a distinct travellers' population, data about their post-travel morbidity are needed. A retrospective study which examined all children (0-19 years old) who presented to our centre after international travel from 1999 to 2015. About 314 children were seen. The mean age was 10 years (SD ± 5.8). Most of the patients (80.6%) were tourists, and the rest were expatriates. The main destinations visited were South-Asia (46.5%), Sub-Saharan Africa (33.4%), Latin-America (7%) and Europe (6.4%). Overall, the most common diagnoses were gastrointestinal (GI) (mainly chronic) disorders (30.6%), followed by febrile diseases (26.4%), among which 18.1% of patients were diagnosed with dengue fever and 12% with malaria. Dermatologic conditions accounted for 25.2%. Additional diagnoses were schistosomiasis (6.4%) and neuropsychiatric symptoms (2.2%). A substantial part, 10.8%, had eosinophilia, either symptomatic or asymptomatic. Travellers to Asia, compared to travellers to Africa, presented more commonly with GI illness (OR 2.02, 95% confidence interval 1.13-3.61), and dermatologic conditions (OR 1.94, 95% confidence interval 1.05-3.61). Morbidity was associated with a variety of transmission modes, such as food-borne illnesses (30.9%), bite and sting wounds (10.2%), mosquito-borne infections (8%), freshwater contact (6.7%) and tick-borne infections (2.2%). The main conditions seen in paediatric returning travellers were GI, febrile and dermatologic illnesses, some may be rare in their country of origin. Targeting care for the suspected pathogens based on updated knowledge of epidemiology and thorough travel history is essential. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Citation context and impact of ‘sleeping beauties’ in paediatric research

PubMed Central

Završnik, Jernej; del Torso, Stefano; Blažun Vošner, Helena

2016-01-01

Objectives ‘Sleeping beauties’, i.e. publications that are not cited for a long while, present interesting findings in science. This study analysed the citation trends of sleeping beauties in paediatric research. Methods The study used bibliometric software to analyse the papers citing sleeping beauties in paediatric research, to understand the context in which paediatric sleeping beauties were finally cited and the impact of these sleeping beauties on paediatric research. Results Two paediatric sleeping beauties, addressing medical homes and the transition from paediatric to adult health care, respectively, awakened in response to organizational needs. Both presented novel concepts of paediatric service organization that became important because of an increased need for optimization of services. Conclusion All sleeping beauties bring new knowledge that becomes important only after several years. Paediatric sleeping beauties exhibited unique characteristics; however, their presence in paediatric research shows that knowledge acquisition in paediatrics resembles that in other disciplines. PMID:27834306

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India.

PubMed

Pradhan, Vandana; Patwardhan, Manisha; Rajadhyaksha, Anjali; Dhawale, Nivedita; Ghosh, Kanjaksha

2015-03-01

Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients.

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the National Alzheimer's Coordinating Center.

PubMed

Hanfelt, John J; Wuu, Joanne; Sollinger, Ann B; Greenaway, Melanie C; Lah, James J; Levey, Allan I; Goldstein, Felicia C

2011-11-01

To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups. Latent class analysis using 1,655 patients with MCI. Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers. Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater. UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit. Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD. Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

PubMed

Spalletta, Gianfranco; Musicco, Massimo; Padovani, Alesandro; Rozzini, Luca; Perri, Roberta; Fadda, Lucia; Canonico, Vincenzo; Trequattrini, Alberto; Pettenati, Carla; Caltagirone, Carlo; Palmer, Katie

2010-11-01

Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.

Attenuation of neuropsychiatric symptoms and caregiver burden in Alzheimer's disease by motor intervention: a controlled trial.

PubMed

Stella, Florindo; Canonici, Ana Paula; Gobbi, Sebastião; Galduroz, Ruth Ferreira Santos; Cação, João de Castilho; Gobbi, Lílian Teresa Bucken

2011-01-01

To analyze the effects of motor intervention on the neuropsychiatric symptoms of Alzheimer's disease and on the caregivers' burden. This is a controlled trial evaluating the effects of a motor intervention program on the neuropsychiatric symptoms. The intervention was performed on community patients from two university centers specializing in physical exercise for the elderly. Patients with Alzheimer's disease were divided into two groups: sixteen received the motor intervention and sixteen controls (five controls were excluded because of clinical intercurrences). Aerobic exercises (flexibility, strength, and agility) and functional balance exercises were conducted over six months for 60 minutes three times per week. Psychopathological features of patients were evaluated with the Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Caregivers were evaluated using the Neuropsychiatric Inventory-Distress and Burden Interview. A two-way analysis of variance (ANOVA) was applied to observe interactions (pre- vs. post-intervention; participants vs. controls). Patients from the intervention presented a significant reduction in neuropsychiatric conditions when compared to controls (Neuropsychiatric Inventory: F: 11.12; p = 0.01; Cornell Depression scale: F: 11.97; p = 0.01). The burden and stress of caregivers responsible for patients who participated in the intervention significantly decreased when compared to caregivers responsible for controls (Neuropsychiatric Inventory-Distress: F: 9.37; p = 0.01; Burden Interview: F: 11.28; p = 0.01). Aerobic exercise was associated with a reduction in the neuropsychiatric symptoms and contributed to attenuate the caregivers' burden. However, the researchers were not blinded to the patient's intervention status, which constitutes an important limitation of this study.

[Promotion of breast feeding in paediatric outpatient settings].

PubMed

Böse-O'Reilly, S; Wermuth, I; Hellmann, J; Siebert, U; Lob-Corzilius, T

2008-03-01

With some data and examples it can be shown that the competence and the knowledge of paediatric doctor's assistants and paediatric nurses can and should be improved. The training courses to become a "prevention assistant" have been very positively accepted by doctor's assistants and paediatric nurses, and it seems an appropriate method to reach these aims. Prevention and especially promotion of breast feeding is possible in paediatric outpatient settings. The immediate contact between infants, parents, paediatric doctor's assistants, paediatric nurses, and doctors offers a unique opportunity to promote the health of children, mainly due to the high acceptance of regular check-ups. So why not introduce the promotion of breast feeding in paediatric outpatient settings with specially trained doctor's assistants and paediatric nurses?

[Kikuchi-Fujimoto disease prior to childhood-systemic lupus erythematosus diagnosis].

PubMed

Martins, Sofia S; Buscatti, Izabel M; Freire, Pricilla S; Cavalcante, Erica G; Sallum, Adriana M; Campos, Lucia M A; Silva, Clovis A

2014-01-01

Kikuchi-Fujimoto disease (KFD) is a self-limiting histiocytic necrotizing lymphadenitis of unknown origin. Of note, KFD was infrequently reported in adult systemic lupus erythematosus (SLE), with rare occurrence in childhood-SLE (C-SLE) patients. To our knowledge, the prevalence of KFD in the paediatric lupus population was not studied. Therefore, in a period of 29 consecutive years, 5,682 patients were followed at our institution and 289 (5%) met the American College of Rheumatology classification criteria for SLE, one had isolated KFD (0.03) and only one had KFD associated to C-SLE diagnoses, which case was reported herein. A 12 year-old female patient had high fever, fatigue and cervical and axillary lymphadenopathy. The antinuclear antibodies (ANA) were negative, with positive IgM and IgG herpes simplex virus type 1 and type 2 serologies. Fluorine-18-fluoro-deoxy-glucose positron emission tomography/computed tomography (PET/CT) imaging demonstrated diffuse lymphadenopathy. The axillary lymph node biopsy showed necrotizing lymphadenitis with histiocytes, without lymphoproliferative disease, compatible with KFD. After 30 days, she presented spontaneous regression and no therapy was required. Nine months later, she developed malar rash, photosensitivity, oral ulcers, lymphopenia and ANA 1:320 (homogeneous nuclear pattern). At that moment the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 and she was treated with prednisone (1.0mg/kg/day) and hidroxychloroquine showing progressive improvement of hers signs and symptoms. In conclusion, KFD is a benign and rare disease in our paediatric lupus population. We also would like to reinforce the relevance of autoimmune diseases diagnosis during the follow-up of patients with KFD. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

6-Mercaptopurine modifies cerebrospinal fluid T cell abnormalities in paediatric opsoclonus-myoclonus as steroid sparer.

PubMed

Pranzatelli, M R; Tate, E D; Allison, T J

2017-11-01

The purpose of this study was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus-myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion) using a comprehensive panel of cell surface adhesion, activation and maturation markers by flow cytometry, and referenced to 18 paediatric controls. Drug metabolites, lymphocyte counts and liver function tests were used clinically to monitoring therapeutic range and toxicity. In CSF, adjunctive oral 6-MP was associated with a 21% increase in the low percentage of CD4 + T cells in OMS, restoring the CD4/CD8 ratio. The percentage of CD4 + T cells that were interferon (IFN)-γ + was reduced by 66%, shifting the cytokine balance away from T helper type 1 (Th1) (proinflammatory) predominance. The percentage of natural killer (NK) cells decreased significantly in CSF (-32%) and blood (-67 to -82%). Low blood absolute lymphocyte count was more predictive of improvement in CSF lymphocyte proportions (correlated with % CD4 + T cells) than the 6-thioguanine level (no correlation). 6-MP was difficult to titrate: 50% achieved the target absolute lymphocyte count (< 1·5 K/mm); 20%, the 'therapeutic' 6-thioguanine level; and 40% the non-toxic 6-methylmercaptopurine level. Side effects and transaminase elevation were mild and reversible. Clinical steroid-sparing properties and lowered relapse frequency were demonstrated. 6-MP displayed unique pharmacodynamic properties that may be useful in OMS and other autoimmune disorders. Its steroid sparer capacity is limited to children in whom the therapeutic window can be reached without limiting pharmacokinetic factors or side effects. © 2017 British Society for Immunology.

Demographic, clinical and therapeutic findings in a monocentric cohort of adult patients with suspected PFAPA syndrome.

PubMed

Vitale, Antonio; Orlando, Ida; Lopalco, Giuseppe; Emmi, Giacomo; Cattalini, Marco; Frediani, Bruno; Galeazzi, Mauro; Iannone, Florenzo; Rigante, Donato; Cantarini, Luca

2016-01-01

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a non-Mendelian autoinflammatory disorder until now considered to be specifically limited to paediatric age. Recently, an increasing number of reports seems to suggest that PFAPA syndrome, diagnosed by the Marshall criteria revised by Thomas et al., can also affect adults. The Marshall/Thomas criteria have been applied to 989 adult patients presenting for recurrent fever episodes: all patients enrolled were reviewed for demographic, clinical, and therapeutic data. Infectious, neoplastic, autoimmune and other autoinflammatory diseases were ruled out. We identified 30 adult patients (19 males, 11 females) with a suspected PFAPA syndrome: their mean age at disease onset was 33.75±14.01 years, mean age at diagnosis 39.1±14.39 years, and mean body temperature peak 39.5±0.7°C. In addition, the mean frequency of febrile episodes was 11.58±8.97 per year. More precisely, patients complained of pharyngitis (77%), cervical adenitis (73%), asthenia (63%), arthralgia (67%), oral aphthosis (50%), myalgia (54%), cephalalgia (43%), abdominal pain (27%), nausea/vomiting (17%), periorbital pain (17%), and arthritis (10%). Six out of 30 (20%) patients had suffered from PFAPA syndrome also during childhood, and the disease had reappeared in adulthood. We provide the largest monocentric cohort of patients diagnosed with a suspected PFAPA syndrome in adulthood confirming that this syndrome can occur also during adulthood; moreover, due to the medical history of our patients and based on our experience, PFAPA syndrome might relapse during adulthood after a temporary remission reached in the course of paediatric age.

Major cluster of chilblain cases in a cold dry Western Australian winter.

PubMed

Larkins, Nicholas; Murray, Kevin J

2013-02-01

Primary chilblains are an idiopathic cold-induced vasculopathy affecting the soft tissues of the hands and feet. Secondary chilblains occur in different forms of vasculitis and chronic autoimmune connective tissue disorders. Idiopathic chilblains are rarely reported in children and may generate significant anxiety to doctors and patients. We describe a cluster of idiopathic chilblains encountered over the winter of 2010 in Perth, Western Australia. This is a retrospective review of patients identified from a prospectively compiled database of all new cases seen in our department. Data on history, examination, investigations, prescribed treatments and outcomes were collected. Thirty-two patients with isolated idiopathic chilblains were included, including 20 females and 12 males with a median age at onset of 13.5 years. Lesions were papular with signs of peripheral vasoconstriction causing acrocyanosis, and uncomfortable due to pain and/or pruritis in most. Thickening of the small joints was common where lesions involved these areas. Ulceration of lesions also occurred in some. One patient required hospitalisation for secondary bacterial infection. Most received some form of treatment including non-steroidal anti-inflammatory drugs, prednisolone or nifedipine. Most patients improved spontaneously with warmer weather or responded to cold protection advice. All had resolved completely by late spring (November). Our cluster of chilblains was associated with an unusually cold winter in Perth 2010. It is the largest series reported in the literature, suggesting that chilblains may be more common than previously thought. Chilblains are almost always benign in nature and patients are systemically well and usually need no further investigation and only symptomatic treatment. Prompt recognition can avoid excessive investigation and anxiety, allowing appropriate simple advice and treatment. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Consultant paediatric outreach clinics--a practical step in integration.

PubMed

Spencer, N J

1993-04-01

Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest.

Consultant paediatric outreach clinics--a practical step in integration.

PubMed Central

Spencer, N J

1993-01-01

Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest. PMID:8503675

In the beginning, there was general paediatrics ….

PubMed

Gunasekera, Hasantha; Kilham, Henry

2015-01-01

In this article, we address how general paediatrics has evolved and adapted to change over the past 50 years and speculate on its future directions. We compare the state of general paediatrics with that of general adult medicine. We argue that general paediatrics must continue to have a strong role both in paediatric teaching hospitals and the community. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Attenuation of neuropsychiatric symptoms and caregiver burden in Alzheimer's disease by motor intervention: a controlled trial

PubMed Central

Stella, Florindo; Canonici, Ana Paula; Gobbi, Sebastião; Santos-Galduroz, Ruth Ferreira; de Castilho Cação, João; Gobbi, Lílian Teresa Bucken

2011-01-01

OBJECTIVE: To analyze the effects of motor intervention on the neuropsychiatric symptoms of Alzheimer's disease and on the caregivers' burden. DESIGN: This is a controlled trial evaluating the effects of a motor intervention program on the neuropsychiatric symptoms. SETTING: The intervention was performed on community patients from two university centers specializing in physical exercise for the elderly. SUBJECTS: Patients with Alzheimer's disease were divided into two groups: sixteen received the motor intervention and sixteen controls (five controls were excluded because of clinical intercurrences). INTERVENTIONS: Aerobic exercises (flexibility, strength, and agility) and functional balance exercises were conducted over six months for 60 minutes three times per week. MAIN MEASURES: Psychopathological features of patients were evaluated with the Neuropsychiatric Inventory and Cornell Scale for Depression in Dementia. Caregivers were evaluated using the Neuropsychiatric Inventory-Distress and Burden Interview. A two-way analysis of variance (ANOVA) was applied to observe interactions (pre- vs. post-intervention; participants vs. controls). RESULTS: Patients from the intervention presented a significant reduction in neuropsychiatric conditions when compared to controls (Neuropsychiatric Inventory: F∶11.12; p = 0.01; Cornell Depression scale: F∶11.97; p = 0.01). The burden and stress of caregivers responsible for patients who participated in the intervention significantly decreased when compared to caregivers responsible for controls (Neuropsychiatric Inventory-Distress: F: 9.37; p = 0.01; Burden Interview: F: 11.28; p = 0.01). CONCLUSIONS: Aerobic exercise was associated with a reduction in the neuropsychiatric symptoms and contributed to attenuate the caregivers' burden. However, the researchers were not blinded to the patient's intervention status, which constitutes an important limitation of this study. PMID:21915483

Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.

PubMed

Levite, Mia

2014-08-01

Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity--detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in the serum and CSF of subpopulations of patients with a kaleidoscope of human neurological diseases, can undoubtedly do so too, by inducing several very potent pathological effects in the CNS. Collectively, the family of anti-glutamate receptor autoimmune antibodies seem to be the most widespread, potent, dangerous and interesting anti-brain autoimmune antibodies discovered up to now. This impression stems from taking together the presence of various types of anti-glutamate receptor antibodies in a kaleidoscope of human neurological and autoimmune diseases, their high levels in the CNS due to intrathecal production, their multiple pathological effects in the brain, and the unique and diverse mechanisms of action by which they can affect glutamate receptors, signaling and effects, and subsequently impair neuronal signaling and induce brain damage. The two main families of autoimmune anti-glutamate receptor antibodies that were already found in patients with neurological and/or autoimmune diseases, and that were already shown to be detrimental to the CNS, include the antibodies directed against ionotorpic glutamate receptors: the anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies and anti-NMDA-NR2 antibodies, and the antibodies directed against Metabotropic glutamate receptors: the anti-mGluR1 antibodies and the anti-mGluR5 antibodies. Each type of these anti-glutamate receptor antibodies is discussed separately in this very comprehensive review, with regards to: the human diseases in which these anti-glutamate receptor antibodies were found thus far, their presence and production in the nervous system, their association with various psychiatric/behavioral/cognitive/motor impairments, their possible association with certain infectious organisms, their detrimental effects in vitro as well as in vivo in animal models in mice, rats or rabbits, and their diverse and unique mechanisms of action. The review also covers the very encouraging positive responses to immunotherapy of some patients that have either of the above-mentioned anti-glutamate receptor antibodies, and that suffer from various neurological diseases/problems. All the above are also summarized in the review's five schematic and useful figures, for each type of anti-glutamate receptor antibodies separately. The review ends with a summary of all the main findings, and with recommended guidelines for diagnosis, therapy, drug design and future investigations. In the nut shell, the human studies, the in vitro studies, as well as the in vivo studies in animal models in mice, rats and rabbit revealed the following findings regarding the five different types of anti-glutamate receptor antibodies: (1) Anti-AMPA-GluR3B antibodies are present in ~25-30% of patients with different types of Epilepsy. When these anti-glutamate receptor antibodies (or other types of autoimmune antibodies) are found in Epilepsy patients, and when these autoimmune antibodies are suspected to induce or aggravate the seizures and/or the cognitive/psychiatric/behavioral impairments that sometimes accompany the seizures, the Epilepsy is called 'Autoimmune Epilepsy'. In some patients with 'Autoimmune Epilepsy' the anti-AMPA-GluR3B antibodies associate significantly with psychiatric/cognitive/behavior abnormalities. In vitro and/or in animal models, the anti-AMPA-GluR3B antibodies by themselves induce many pathological effects: they activate glutamate/AMPA receptors, kill neurons by 'Excitotoxicity', and/or by complement activation modulated by complement regulatory proteins, cause multiple brain damage, aggravate chemoconvulsant-induced seizures, and also induce behavioral/motor impairments. Some patients with 'Autoimmune Epilepsy' that have anti-AMPA-GluR3B antibodies respond well (although sometimes transiently) to immunotherapy, and thanks to that have reduced seizures and overall improved neurological functions. (2) Anti-NMDA-NR1 antibodies are present in patients with autoimmune 'Anti-NMDA-receptor Encephalitis'. In humans, in animal models and in vitro the anti-NMDA-NR1 antibodies can be very pathogenic since they can cause a pronounced decrease of surface NMDA receptors expressed in hippocampal neurons, and also decrease the cluster density and synaptic localization of the NMDA receptors. The anti-NMDA-NR1 antibodies induce these effects by crosslinking and internalization of the NMDA receptors. Such changes can impair glutamate signaling via the NMDA receptors and lead to various neuronal/behavior/cognitive/psychiatric abnormalities. Anti-NMDA-NR1 antibodies are frequently present in high levels in the CSF of the patients with 'Anti-NMDA-receptor encephalitis' due to their intrathecal production. Many patients with 'Anti-NMDA receptor Encephalitis' respond well to several modes of immunotherapy. (3) Anti-NMDA-NR2A/B antibodies are present in a substantial number of patients with Systemic Lupus Erythematosus (SLE) with or without neuropsychiatric problems. The exact percentage of SLE patients having anti-NMDA-NR2A/B antibodies varies in different studies from 14 to 35%, and in one study such antibodies were found in 81% of patients with diffuse 'Neuropshychiatric SLE', and in 44% of patients with focal 'Neuropshychiatric SLE'. Anti-NMDA-NR2A/B antibodies are also present in subpopulations of patients with Epilepsy of several types, Encephalitis of several types (e.g., chronic progressive limbic Encephalitis, Paraneoplastic Encephalitis or Herpes Simplex Virus Encephalitis), Schizophrenia, Mania, Stroke, or Sjorgen syndrome. In some patients, the anti-NMDA-NR2A/B antibodies are present in both the serum and the CSF. Some of the anti-NMDA-NR2A/B antibodies cross-react with dsDNA, while others do not. Some of the anti-NMDA-NR2A/B antibodies associate with neuropsychiatric/cognitive/behavior/mood impairments in SLE patients, while others do not. The anti-NMDA-NR2A/B antibodies can undoubtedly be very pathogenic, since they can kill neurons by activating NMDA receptors and inducing 'Excitotoxicity', damage the brain, cause dramatic decrease of membranal NMDA receptors expressed in hippocampal neurons, and also induce behavioral cognitive impairments in animal models. Yet, the concentration of the anti-NMDA-NR2A/B antibodies seems to determine if they have positive or negative effects on the activity of glutamate receptors and on the survival of neurons. Thus, at low concentration, the anti-NMDA-NR2A/B antibodies were found to be positive modulators of receptor function and increase the size of NMDA receptor-mediated excitatory postsynaptic potentials, whereas at high concentration they are pathogenic as they promote 'Excitotoxcity' through enhanced mitochondrial permeability transition. (4) Anti-mGluR1 antibodies were found thus far in very few patients with Paraneoplastic Cerebellar Ataxia, and in these patients they are produced intrathecally and therefore present in much higher levels in the CSF than in the serum. The anti-mGluR1 antibodies can be very pathogenic in the brain since they can reduce the basal neuronal activity, block the induction of long-term depression of Purkinje cells, and altogether cause cerebellar motor coordination deficits by a combination of rapid effects on both the acute and the plastic responses of Purkinje cells, and by chronic degenerative effects. Strikingly, within 30 min after injection of anti-mGluR1 antibodies into the brain of mice, the mice became ataxic. Anti-mGluR1 antibodies derived from patients with Ataxia also caused disturbance of eye movements in animal models. Immunotherapy can be very effective for some Cerebellar Ataxia patients that have anti-mGluR1 antibodies. (5) Anti-mGluR5 antibodies were found thus far in the serum and CSF of very few patients with Hodgkin lymphoma and Limbic Encephalopathy (Ophelia syndrome). The sera of these patients that contained anti-GluR5 antibodies reacted with the neuropil of the hippocampus and cell surface of live rat hippocampal neurons, and immunoprecipitation from cultured neurons and mass spectrometry demonstrated that the antigen was indeed mGluR5. Taken together, all these evidences show that anti-glutamate receptor antibodies are much more frequent among various neurological diseases than ever realized before, and that they are very detrimental to the nervous system. As such, they call for diagnosis, therapeutic removal or silencing and future studies. What we have learned by now about the broad family of anti-glutamate receptor antibodies is so exciting, novel, unique and important, that it makes all future efforts worthy and essential.

Training in paediatric clinical pharmacology in the UK

PubMed Central

Choonara, Imti; Dewit, Odile; Harrop, Emily; Howarth, Sheila; Helms, Peter; Kanabar, Dipak; Lenney, Warren; Rylance, George; Vallance, Patrick

2004-01-01

Aims To produce a training programme in paediatric clinical pharmacology. Methods A working group, consisting of clinical pharmacologists (paediatric and adult), general paediatricians and the pharmaceutical industry was established to produce the training programme. Results Following a two year training programme in general paediatrics, a three year training programme in clinical pharmacology has been established. This includes one year of research in clinical pharmacology (paediatric or adult). The other two years involve training in different aspects of paediatric clinical pharmacology and general paediatrics. Conclusion The existence of a formal training programme should result in a significant increase in the number of paediatric clinical pharmacologists. PMID:15255806

Observed and projected trends in paediatric health resources and services in China between 2003 and 2030: a time-series study

PubMed Central

Zhang, Xin-yu; Gao, Ying; Li, Chang-ping; Zheng, Rong-xiu; Chen, Jie-li; Zhao, Lin; Wang, You-fa; Wang, Yao-gang

2017-01-01

Objectives The two-child policy took effect in China on 1 January 2016, thus officially ending the one-child policy. The resultant growth in the population will create a considerable demand for public services such as paediatric healthcare, even while there are limited paediatric resources. We estimated the relationship between paediatric health resources and services and child mortality to determine the degree of the deficiency of such resources in China. Projecting the quantity of paediatric health resource allocation and service supply through 2030 will help provide data reference for future policy decision making. Design Time-series study. Setting The People’s Republic of China. Participants Paediatric patients whose data were recorded between 2003 and 2012 from the National Health and Family Planning Commission of the People’s Republic of China. Primary and secondary outcome measures Child mortality and paediatric health resources and services data were entered into a cubic polynomial regression model to project paediatric health resources and services to 2030. Results Child mortality decreased throughout the past decade. Furthermore, the number of paediatric beds, paediatricians and nurses increased between 2003 and 2012, although the proportions increased rather slowly. Both the number and proportion of paediatric outpatients and inpatients increased rapidly. The observed and model-predicted values matched well (adjusted R2=93.8% for paediatric beds; adjusted R2=96.6% for paediatric outpatient visits). Overall, the projection indicated that paediatric beds, paediatricians and nurses will reach 460 148, 233 884 and 184 059 by 2030, respectively. Regarding paediatric services, the number of paediatric outpatient visits and inpatients is expected to reach upwards of 449.95 million and 21.83 million by 2030, respectively. Conclusions Despite implementation of the two-child policy, resource allocation in paediatrics has many deficiencies. Proper measures should be taken to actively respond to the demand for paediatric health services. PMID:28647724

Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children?

PubMed

Perrin, Eliana Miller; Murphy, Marie Lynd; Casey, Janet R; Pichichero, Michael E; Runyan, Desmond K; Miller, William C; Snider, Lisa A; Swedo, Susan E

2004-09-01

To determine whether group A beta-hemolytic streptococcal infections increase the risk of developing symptoms characteristic of the diagnosis pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Prospective cohort study. Children (N = 814) aged 4 to 11 years seen for sore throat or well-child care in a large pediatric practice in Rochester, NY, were enrolled from October 2001 to June 2002 (group A beta-hemolytic streptococcal [GAS] infected, n = 411; GAS uninfected, n = 403, of whom 207 had a sore throat of presumed viral etiology and 196 were well children). Symptomatic children with GAS infection (n = 399) were treated with antibiotics. At baseline and 2 and 12 weeks following baseline, all parents completed a 20-item questionnaire about the presence/absence of recent PANDAS symptoms in their children, and capable children answered 10 items about worries, obsessions, and compulsions. The relative risk of developing a "mild PANDAS variant" (> or = 2 new PANDAS symptoms) by illness type (GAS positive, presumed viral, or well child) and by parent and child report was determined and adjusted for potential covariates. By parent report, ill children more frequently manifested several PANDAS symptoms at baseline than well children. However, neither new symptoms nor the risk of developing a mild PANDAS variant developed during the subsequent 12 weeks more commonly in children with GAS infection than in those with presumed viral illness or in well children by parent or child report. Ill children with GAS infection, treated for their GAS infection, were not at increased risk for developing PANDAS symptoms or a mild PANDAS variant compared with children with presumed viral illness or well children. The role of antibiotics in the prevention or treatment of PANDAS as well as the investigation of PANDAS in the asymptomatic, infectious host deserves future research.

A multimodal MRI approach to identify and characterize microstructural brain changes in neuropsychiatric systemic lupus erythematosus.

PubMed

Ercan, Ece; Ingo, Carson; Tritanon, Oranan; Magro-Checa, Cesar; Smith, Alex; Smith, Seth; Huizinga, Tom; van Buchem, Mark A; Ronen, Itamar

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.

Paediatric cardiopulmonary resuscitation training program in Latin-America: the RIBEPCI experience.

PubMed

López-Herce, Jesús; Matamoros, Martha M; Moya, Luis; Almonte, Enma; Coronel, Diana; Urbano, Javier; Carrillo, Ángel; Del Castillo, Jimena; Mencía, Santiago; Moral, Ramón; Ordoñez, Flora; Sánchez, Carlos; Lagos, Lina; Johnson, María; Mendoza, Ovidio; Rodriguez, Sandra

2017-09-12

To describe the design and to present the results of a paediatric and neonatal cardiopulmonary resuscitation (CPR) training program adapted to Latin-America. A paediatric CPR coordinated training project was set up in several Latin-American countries with the instructional and scientific support of the Spanish Group for Paediatric and Neonatal CPR. The program was divided into four phases: CPR training and preparation of instructors; training for instructors; supervised teaching; and independent teaching. Instructors from each country participated in the development of the next group in the following country. Paediatric Basic Life Support (BLS), Paediatric Intermediate (ILS) and Paediatric Advanced (ALS) courses were organized in each country adapted to local characteristics. Five Paediatric Resuscitation groups were created sequentially in Honduras (2), Guatemala, Dominican Republican and Mexico. During 5 years, 6 instructors courses (94 students), 64 Paediatric BLS Courses (1409 students), 29 Paediatrics ILS courses (626 students) and 89 Paediatric ALS courses (1804 students) were given. At the end of the program all five groups are autonomous and organize their own instructor courses. Training of autonomous Paediatric CPR groups with the collaboration and scientific assessment of an expert group is a good model program to develop Paediatric CPR training in low- and middle income countries. Participation of groups of different countries in the educational activities is an important method to establish a cooperation network.

Neuropsychiatric Disorders of Childhood. Matrix No. 11B.

ERIC Educational Resources Information Center

Cohen, Donald J.; And Others

The general nature of neuropsychiatric disorders of childhood, and the areas in which gains in understanding such disorders have been made are discussed in the first portion of this paper. Thereafter, discussion focuses on the contemporary approach to neuropsychiatric disorders of childhood as exemplified by three serious disturbances: attention…

Paediatric cardiac intensive care unit: current setting and organization in 2010.

PubMed

Fraisse, Alain; Le Bel, Stéphane; Mas, Bertrand; Macrae, Duncan

2010-10-01

Over recent decades, specialized paediatric cardiac intensive care has emerged as a central component in the management of critically ill, neonatal, paediatric and adult patients with congenital and acquired heart disease. The majority of high-volume centres (dealing with over 300 surgical cases per year) have dedicated paediatric cardiac intensive care units, with the smallest programmes more likely to care for paediatric cardiac patients in mixed paediatric or adult intensive care units. Specialized nursing staff are also a crucial presence at the patient's bedside for quality of care. A paediatric cardiac intensive care programme should have patients (preoperative and postoperative) grouped together geographically, and should provide proximity to the operating theatre, catheterization laboratory and radiology department, as well as to the regular ward. Age-appropriate medical equipment must be provided. An optimal strategy for running a paediatric cardiac intensive care programme should include: multidisciplinary collaboration and involvement with paediatric cardiology, anaesthesia, cardiac surgery and many other subspecialties; a risk-stratification strategy for quantifying perioperative risk; a personalized patient approach; and anticipatory care. Finally, progressive withdrawal from heavy paediatric cardiac intensive care management should be institutionalized. Although the countries of the European Union do not share any common legislation on the structure and organization of paediatric intensive care or paediatric cardiac intensive care, any paediatric cardiac surgery programme in France that is agreed by the French Health Ministry must perform at least '150 major procedures per year in children' and must provide a 'specialized paediatric intensive care unit'. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Observed and projected trends in paediatric health resources and services in China between 2003 and 2030: a time-series study.

PubMed

Zhang, Xin-Yu; Gao, Ying; Li, Chang-Ping; Zheng, Rong-Xiu; Chen, Jie-Li; Zhao, Lin; Wang, You-Fa; Wang, Yao-Gang

2017-06-24

The two-child policy took effect in China on 1 January 2016, thus officially ending the one-child policy. The resultant growth in the population will create a considerable demand for public services such as paediatric healthcare, even while there are limited paediatric resources. We estimated the relationship between paediatric health resources and services and child mortality to determine the degree of the deficiency of such resources in China. Projecting the quantity of paediatric health resource allocation and service supply through 2030 will help provide data reference for future policy decision making. Time-series study. The People's Republic of China. Paediatric patients whose data were recorded between 2003 and 2012 from the National Health and Family Planning Commission of the People's Republic of China. Child mortality and paediatric health resources and services data were entered into a cubic polynomial regression model to project paediatric health resources and services to 2030. Child mortality decreased throughout the past decade. Furthermore, the number of paediatric beds, paediatricians and nurses increased between 2003 and 2012, although the proportions increased rather slowly. Both the number and proportion of paediatric outpatients and inpatients increased rapidly. The observed and model-predicted values matched well (adjusted R 2 =93.8% for paediatric beds; adjusted R 2 =96.6% for paediatric outpatient visits). Overall, the projection indicated that paediatric beds, paediatricians and nurses will reach 460 148, 233 884 and 184 059 by 2030, respectively. Regarding paediatric services, the number of paediatric outpatient visits and inpatients is expected to reach upwards of 449.95 million and 21.83 million by 2030, respectively. Despite implementation of the two-child policy, resource allocation in paediatrics has many deficiencies. Proper measures should be taken to actively respond to the demand for paediatric health services. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The neuropsychiatric phenotype in Darier disease.

PubMed

Gordon-Smith, K; Jones, L A; Burge, S M; Munro, C S; Tavadia, S; Craddock, N

2010-09-01

Darier disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. It is caused by mutations in a single gene, ATP2A2, which is expressed in the skin and brain. To conduct the first systematic investigation of the neuropsychiatric phenotype in DD. One hundred unrelated individuals with DD were assessed using a battery of standardized neuropsychiatric measures. Data were also obtained on a number of clinical features of DD. Individuals with DD were found to have high lifetime rates of mood disorders (50%), specifically major depression (30%) and bipolar disorder (4%), and suicide attempts (13%) and suicidal thoughts (31%). These were more common in DD when compared with general population data. The prevalence of epilepsy (3%) in the sample was also higher than the prevalence in the general population. There was no consistent association of specific dermatological features of DD and presence of psychiatric features. These findings highlight the need for clinicians to assess and recognize neuropsychiatric symptoms in DD. The results do not suggest that neuropsychiatric symptoms are simply a psychological reaction to having a skin disease, but are consistent with the pleiotropy hypothesis that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features. Further research is needed to investigate genotype-phenotype correlations between the types and/or locations of pathogenic mutations within ATP2A2 and the expressed neuropsychiatric phenotypes. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Psychosocial difficulties from the perspective of persons with neuropsychiatric disorders.

PubMed

Coenen, Michaela; Cabello, Maria; Umlauf, Silvia; Ayuso-Mateos, José Luis; Anczewska, Marta; Tourunen, Jouni; Leonardi, Matilde; Cieza, Alarcos

2016-01-01

The objective of this study is to determine whether persons with neuropsychiatric disorders experience a common set of psychosocial difficulties using qualitative data from focus groups and individual interviews. The study was performed in five European countries (Finland, Italy, Germany, Poland and Spain) using the focus groups and individual interviews with persons with nine neuropsychiatric disorders (dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinson's disease, schizophrenia, stroke and substance dependence). Digitally recorded sessions were analysed using a step-by-step qualitative and quantitative methodology resulting in the compilation of a common set of psychosocial difficulties using the International Classification of Functioning, Disability and Health (ICF) as a framework. Sixty-seven persons participated in the study. Most persons with neuropsychiatric disorders experience difficulties in emotional functions, sleeping, carrying out daily routine, working and interpersonal relationships in common. Sixteen out of 33 psychosocial difficulties made up the common set. This set includes mental functions, pain and issues addressing activities and participation and provides first evidence for the hypothesis of horizontal epidemiology of psychosocial difficulties in neuropsychiatric disorders. This study provides information about psychosocial difficulties that should be covered in the treatment and rehabilitation of persons with neuropsychiatric disorders regardless of clinical diagnoses. Emotional problems, work and sleep problems should be addressed in all the treatments of neuropsychiatric disorders regardless of their specific diagnosis, etiology and severity. Personality issues should be targeted in the treatment for neurological disorders, whereas communication skill training may also be useful for mental disorders. The effects of medication and social environment on patient's daily life should be considered in all the neuropsychiatric conditions.

Three years of paediatric regulation in the European Union.

PubMed

Olski, Thorsten M; Lampus, Simona F; Gherarducci, Giulia; Saint Raymond, Agnes

2011-03-01

To investigate whether the Paediatric Regulation has already succeeded in addressing the needs of the paediatric population both quantitatively with respect to paediatric development plans and trials, and qualitatively with respect to the content of the plans. The Paediatric Regulation No 1901/2006 entered into force in Europe on 26 January 2007, with the aim to improve the development of medicinal products, to address the lack of age-appropriate formulations and to provide information on efficacy, safety and dosing for the paediatric population. The Regulation requires applications for marketing authorisations to be accompanied by either a product-specific waiver or a paediatric investigation plan, to be agreed by the Paediatric Committee (PDCO) of the European Medicines Agency (EMA). A retrospective analysis of the applications for Paediatric Investigation Plans (PIPs) and Waivers submitted to the EMA, from 2007 until end of 2009, was performed. The content of scientific opinions adopted by the Paediatric Committee was compared to the proposals submitted by industry, and the paediatric clinical trials registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database were examined. An increasing paediatric medicine development can be expected following the adoption of this legal framework. The highest number of PIPs was in the fields of endocrinology (13.4%), oncology (11%) and infectious (10.8%) and cardiovascular diseases (7.1%), but most therapeutic areas now benefit from paediatric development. A large number of PIPs include measures for the development of age-appropriate formulations (23%), and most include studies on dosing, efficacy and safety to cover the respective paediatric subsets, including the mostly neglected neonates (26%). In many proposals (38%), however, the PDCO had to request major modifications to the proposed PIPs to ensure that the results will meet the needs, in particular by requesting better methodology. The proportion of paediatric trials as a percentage of all clinical trials has moderately increased (from 8.2 to 9.4% of all trials), and this may reflect the fact that paediatric trials are generally deferred (82%) until after adult development. This is the first analysis of the general impact of the Paediatric Regulation on the development of medicinal products in Europe. Three years after the implementation of the Paediatric Regulation, we were able to identify that the PIPs address the main gaps in knowledge on paediatric medicines. The key objective of the Paediatric Regulation, namely, the availability of medicines with age-appropriate information, is going to be achieved. It is clear also that modifications of the initial proposals as requested by the PDCO are necessary to ensure the quality of paediatric developments. The impact on the number of clinical trials performed remains modest at this point in time, and it will be of high interest to monitor this performance indicator, which will also inform us whether paediatric medicine research takes place in Europe or elsewhere.

A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease.

PubMed

Nascimento, Carla M C; Teixeira, Camila V L; Gobbi, Lilian T B; Gobbi, Sebastião; Stella, Florindo

2012-06-01

To analyze the influence of a six-month exercise program on neuropsychiatric disorders and on the performance of instrumental activities in elderly patients with Alzheimer's disease (AD). The study included 20 patients with AD in the mild to moderate stages of the Clinical Dementia Rating (CDR) divided into two groups: the experimental group, composed of 10 women who participated in the six-month exercise program, and the control group, composed of the 10 remaining AD patients who did not take part in an exercise program during the same period. All participants were evaluated using the Mini-Mental State Exam for global cognitive function, the Neuropsychiatric Inventory Questionnaire for neuropsychiatric disorders, and the Pfeffer Functional Activities Questionnaire for the degree of functional impairment. The control group showed functional and neuropsychiatric deterioration in the comparisons between pre- and post-intervention times and between groups. The experimental group showed a propensity for less deterioration in neuropsychiatric disorders and performance of instrumental activities compared to the sedentary group.

Interventional Radiology in Paediatrics.

PubMed

Chippington, Samantha J; Goodwin, Susie J

2015-01-01

As in adult practice, there is a growing role for paediatric interventional radiology expertise in the management of paediatric pathologies. This review is targeted for clinicians who may refer their patients to paediatric interventional radiology services, or who are responsible for patients who are undergoing paediatric interventional radiology procedures. The article includes a brief overview of the indications for intervention, techniques involved and the commonest complications. Although some of the procedures described are most commonly performed in a tertiary paediatric centre, many are performed in most Children's hospitals.

Clinical neuropsychiatric symptoms in perpetrators of severe crimes against persons.

PubMed

Söderström Anckarsäter, Henrik

2005-01-01

The objective of the study was to explore the possibility of common signs and symptoms of childhood-onset neuropsychiatric disorders and personality disorders, especially psychopathy, in a cohort of violent offenders. A structured neuropsychiatric status comprising features recorded in childhood-onset neuropsychiatric disorders and adult personality disorders was assessed in 89 perpetrators of severe crimes against other persons, analysed for factor structure, and compared to clinical diagnostics of neuropsychiatric disorders and independent assessments of psychopathy rated by the Psychopathy Checklist Revised (PCL-R). One or several childhood-onset neuropsychiatric disorders [autism, attention-deficit/hyperactivity disorder (AD/HD), tics and learning disability] affected the majority of adult offenders. A factor analysis yielded four higher-order problem constellations: Executive Dysfunction, Compulsivity, Social Interaction Problems and Superficiality. All four constellations were positively correlated with life histories of aggression, stressing the clinical importance of these problems in adult forensic psychiatry. Compulsivity and Social Interaction Problems were associated with autistic traits and tics, Executive Dysfunction with AD/HD, conduct disorder and psychopathic as well as autistic traits. Superficiality was a distinct aspect of AD/HD and psychopathic traits, especially the PCL-R factor reflecting interpersonal callousness. Neuropsychiatric disorders and personality disorders such as psychopathy share common symptoms. The various facets of psychopathy are associated with executive dysfunction and empathy deficits with superficial understanding of self, others and the rules of communication.

Anti-P ribosomal antibodies induce defect in smell capability in a model of CNS -SLE (depression).

PubMed

Katzav, Aviva; Ben-Ziv, Tal; Chapman, Joab; Blank, Miri; Reichlin, Morris; Shoenfeld, Yehuda

2008-12-01

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with more than 100 different autoantibodies, some of which may be associated with specific neuropsychiatric (NPSLE) manifestations. Injection of anti-P ribosomal antibodies (anti-P) directly to the brain ventricles of mice induces depression manifested by increased immobility time in the forced swim test (FST). Mice were injected intracerebroventricularily (ICV) with affinity-purified human anti-P antibodies or normal commercial IgG as control. Mice were examined for depression by the forced swimming test (FST) and for olfactory function by the smell threshold test. Treatments included the antidepressant drug fluoxetine or aroma therapy by exposure to lemon or cinnamon odor. Mice injected with anti-P developed depression-like behavior, which improved significantly upon treatment with fluoxetine. Depressed mice had a significant deficit in olfactory function which was not reversed by fluoxetine. Exposure of anti-P-injected mice to lemon odor was associated with some improvement of the immobility time, a measure of depression. ICV injection of anti-P induces both depression-like behavior and impaired olfactory function in mice. Fluoxetine and possibly lemon odor exposure improve depressive behavior in these mice.

An altered gut microbiota in HIV infection: future prospective of FMT therapy.

PubMed

Kang, Yongbo; Cai, Yue

2018-06-07

Human immunodeficiency virus (HIV) infection progressively destroys CD4+ mononuclear cells leading to profound cellular immune deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). Gut microbiota play key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contribute to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidences have has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation (FMT) may be a more straightforward and better therapy for HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and large amount of scientific research work need to be done in the near further.

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants

PubMed Central

Bagley, Steven C.; Sirota, Marina; Chen, Richard; Butte, Atul J.; Altman, Russ B.

2016-01-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups. PMID:27115429

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

PubMed

Bagley, Steven C; Sirota, Marina; Chen, Richard; Butte, Atul J; Altman, Russ B

2016-04-01

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

Neuronal Surface Autoantibodies in Neuropsychiatric Disorders: Are There Implications for Depression?

PubMed Central

Zong, Shenghua; Hoffmann, Carolin; Mané-Damas, Marina; Molenaar, Peter; Losen, Mario; Martinez-Martinez, Pilar

2017-01-01

Autoimmune diseases are affecting around 7.6–9.4% of the general population. A number of central nervous system disorders, including encephalitis and severe psychiatric disorders, have been demonstrated to associate with specific neuronal surface autoantibodies (NSAbs). It has become clear that specific autoantibodies targeting neuronal surface antigens and ion channels could cause severe mental disturbances. A number of studies have focused or are currently investigating the presence of autoantibodies in specific mental conditions such as schizophrenia and bipolar disorders. However, less is known about other conditions such as depression. Depression is a psychiatric disorder with complex etiology and pathogenesis. The diagnosis criteria of depression are largely based on symptoms but not on the origin of the disease. The question which arises is whether in a subgroup of patients with depression, the symptoms might be caused by autoantibodies targeting membrane-associated antigens. Here, we describe how autoantibodies targeting membrane proteins and ion channels cause pathological effects. We discuss the physiology of these antigens and their role in relation to depression. Finally, we summarize a number of studies detecting NSAbs with a special focus on cohorts that include depression diagnosis and/or show depressive symptoms. PMID:28725222

Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review

PubMed Central

Batchelor, Hannah K.

2015-01-01

The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food–drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food–drug interactions within paediatric populations. PMID:27417362

[Naples: the historic capital of Italian paediatrics].

PubMed

Farnetani, I; Farnetani, F

2008-06-01

No other Italian city has contributed to the birth and development of paediatrics more than Naples. This is why it can be considered the historic capital of Italian paediatrics. Here are the main reasons: Luigi Somma was the first professor of Italian paediatrics whereas Francesco Fede was the first president of the Italian Paediatrics Association. Neapolitan paediatricians have been the most numerous amongst the founder members. The first three Italian journals of paediatrics were founded in Naples as well as the journal ''La Pediatria'' which was the most distributed and long-lasting journal in this field. Moreover, Neapolitans have been the most numerous presidents of the Italian Paediatrics Association, while Rocco Jemma was the one who remained the longest in charge. ''Rocco Jemma's school'' taught not only to most professors in paediatrics who afterwards taught in most Italian universities, but also four out of five paediatricians who took charge of the position as president. The first regional department of the Italian Paediatrics Association was founded in Naples as well as the Association of Nipiology.

Neuropsychiatric Symptoms in Latino Elders with Dementia or Cognitive Impairment without Dementia and Factors that Modify Their Association with Caregiver Depression

ERIC Educational Resources Information Center

Hinton, Ladson; Haan, Mary; Geller, Sue; Mungas, Dan

2003-01-01

Purpose: The purpose of this study was to determine neuropsychiatric symptom frequency and intensity in demented and cognitively impaired but not demented Latino elderly persons, evaluate whether overall neuropsychiatric symptom intensity is associated with higher levels of caregiver depression, and identify factors that modify the relationship…

Secular trends in new childhood epidemics: insights from evolutionary medicine.

PubMed

Brüne, Martin; Hochberg, Ze'ev

2013-10-21

In the last few decades, pediatric medicine has observed a dramatic increase in the prevalence of hitherto rare illnesses, among which obesity, diabetes, allergies and other autoimmune diseases stand out. In addition, secular trends towards earlier onset of puberty and sexual activity contribute to the psychological problems of youth and adolescents. All this has occurred in spite of the improved health care provision for children, yet traditional concepts of medicine have failed to explain these new "epidemics". A recent conference and science school of the European Society of Paediatric Endocrinology (ESPE) in Acre, Israel, has taken up this challenge. Experts across disciplines including medicine, anthropology and developmental psychology discussed potential causes of childhood ill-health from an evolutionary point-of-view. Seen from an evolutionary vantage point, the "epidemics" of childhood obesity, diabetes and psychological dysfunction appear, in part, to be related to a mismatch between ancestral adaptations and novel environmental contingencies. These include changing exposures to pathogens, which impact on the function of the immune system, as well as changing patterns of parenting, which influence the timing of puberty and the risk for developing psychopathology.

Management of myasthenic crisis in a child.

PubMed

Rybojad, Beata; Lesiuk, Witold; Fijałkowska, Anna; Rybojad, Paweł; Sawicki, Marek; Lesiuk, Leszek

2013-01-01

Myasthenia gravis is an autoimmune disorder of peripheral nervous system, leading to fluctuating muscle weakness. It is caused by circulating antibodies that block acetylcholine nicotinic postsynaptic receptors at the postsynaptic neuromuscular junction. Myasthenic crisis is a life-threatening complication, which is defined as weakness from acquired myasthenia gravis. In this paper we described a 15-year-old boy who was admitted to the Paediatric Intensive Care Unit due to myasthenic crisis. He had suffered not only from myasthenia gravis but also hypothyroidism, cerebral palsy and epilepsy. The patient required mechanical ventilation and was successfully treated with both plasmapheresis and intravenous immunoglobulins. He recovered from the crisis and then thymectomy was performed. Perioperative period and anaesthesia passed uncomplicated. Discharged home from the hospital after 2.5 month-treatment, for the last 4 years, he has only come on scheduled outpatient medical appointments. This case reveals that myasthenic crisis, albeit rare, may occur in male adolescents. In such cases multidisciplinary care followed by surgery becomes a procedure of choice. Concomitant medical problems, if well controlled, do not affect the results of outcome of the underlying disease.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

PubMed

Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

2010-03-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

Transitioning of special needs paediatric patients to adult special needs dental services.

PubMed

Borromeo, G L; Bramante, G; Betar, D; Bhikha, C; Cai, Y Y; Cajili, C

2014-09-01

Special needs dentistry is in its infancy compared to other dental specialties. Continuity of care through transition from paediatric to adult dental care providers is unknown. This study seeks to determine the nature of transition practices adopted by paediatric and special needs (SN) specialists practising throughout Australia. A survey was sent to all paediatric and SN specialist dentists in Australia to determine the nature of current transition practices for paediatric SN patients in Australia. Two subsequent mail-outs were sent to non-responders. Forty-nine specialist dentists registered across Australia completed the survey, of which 35 (71%) were paediatric dentists and 14 (29%) were SN dentists. Both paediatric and SN dentists treated patients over the age of 18. Of the total paediatric dentists who had transition discussions with their paediatric patients and their families, the majority (over 80%) discussed treatment options available as part of future oral care management. Paediatric dentists identified level of independence and financial situations as the most significant barrier for transition. Key factors exist that should be discussed with SN patients and their parents and/or guardians in order to enhance the prospect of sustained dental care into adulthood. © 2014 Australian Dental Association.

Pharmaceutical research in paediatric populations and the new EU Paediatric Legislation: an industry perspective

PubMed Central

Auby, Philippe

2008-01-01

A large proportion of medicines used in children are prescribed off-label, and children have often been denied access to new or innovative medications. Because such situation is unethical, the need to obtain paediatric information for medicines used in children seems nowadays a matter of consensus on a global basis. Based on this, it was clear in EU, like what has happened in the US, that there was a need for a legal obligation for Pharmaceutical Companies to perform studies. This new European Paediatric Regulation that entered into force in 2007 opens a new era of European drug regulatory history and will offer a major opportunity to improve children's health through advancements in research by providing a new framework for evaluating the efficacy and safety of medicines for children. But, paediatric development remains challenging and the hurdles of conducting research in paediatric population are numerous. The article presents the new European Paediatric Regulation, illustrates its rationale through paediatric psychopharmacology, and discusses some of its consequences on paediatric research from an industry perspective. Recommendations for further international collaboration are also suggested to make global paediatric development plans. PMID:19063723

Key paediatric messages from Amsterdam

PubMed Central

Barben, Jürg; Bohlin, Kajsa; Everard, Mark L.; Hall, Graham; Pijnenburg, Mariëlle; Priftis, Kostas N.; Rusconi, Franca; Midulla, Fabio

2016-01-01

The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early origins of respiratory diseases; a meet the expert session on paediatric lung function test reference values; and the annual paediatric grand round. In this report the Chairs of the Paediatric Assembly's Groups highlight the key messages from the abstracts presented at the Congress. PMID:27730186

Impact of the European paediatric legislation in paediatric rheumatology: past, present and future.

PubMed

Ruperto, Nicolino; Vesely, Richard; Saint-Raymond, Agnes; Martini, Alberto

2013-12-01

Conducting clinical trials in paediatric rheumatology has been difficult mainly because of the lack of funding for academic studies and the lack of interest by pharmaceutical companies in the small and non-rewarding paediatric market. The situation changed dramatically a few years ago with the introduction of the Best Pharmaceuticals for Children Act in the USA and of specific legislation for the development of paediatric medicines (Paediatric Regulation) in the European Union (EU). The EU Paediatric Regulation had a positive impact in paediatric rheumatology-in particular, on the development of new treatments for children with juvenile idiopathic arthritis (JIA). Some problems remain, however, such as greater harmonisation of the regulatory aspects of medicines, how to handle me-too agents, how to conduct adequate pharmacokinetic studies and develop age-appropriate formulations, ethical problems in study review and implementation, and a change in the current JIA classification. The introduction of specific legislation, coupled with the existence of large international networks such as the Pediatric Rheumatology Collaborative Study Group (PRCSG at http://www.prcsg.org), covering North America, and the Paediatric Rheumatology International Trials Organisation (PRINTO at http://www.printo.it), covering more than 50 countries, has led to great advances in paediatric rheumatology. Future changes might increase the possibility of conducting trials with similar approaches in other paediatric rheumatological conditions and provide evidence-based treatments for children affected by rheumatic diseases.

Current educational status of paediatric rheumatology in Europe: the results of PReS survey.

PubMed

Demirkaya, E; Ozen, S; Türker, T; Kuis, W; Saurenmann, R K

2009-01-01

To understand the status of education and problems in paediatric rheumatology practice in Europe, through a survey. A 26-item questionnaire was conducted during the 14th Congress of the Paediatric Rheumatology European Society in Istanbul, 2007. Physicians who were practicing or studying within the field of paediatric rheumatology for at least one year were included in the survey. One hundred and twenty eight physicians, 79 paediatric rheumatologists (including 5 paediatric immunologists and 10 paediatric nephrologists), 34 paediatric rheumatology fellows and 15 adult rheumatologists completed the survey. The physicians were from: Europe 95 (81.9%), South America 12 (10.4%), Middle East 5 (4.3%), Asia 2 (1.7%), Africa 2 (1.7%). The duration of training for paediatric rheumatology ranged between 1-5 years (mean: 3.12+/-1.11). Sixty physicians scored their education as unsatisfactory and among those, 48 physicians were from Europe. Physicians reported good skills in the following items; intraarticular injections (83.3%); soft tissue injections (47.6%); evaluation of radiographs (67.5%); whereas competence in the evaluation of computed tomography/magnetic resonance imaging (30.5%); and musculoskeletal sonography (16.7%) was much lower. A need for improved basic science and rotations among relevant fields were specifically expressed. Being a relatively new speciality in the realm of paediatrics, paediatric rheumatology education at the European level needs to be further discussed, revised and uniformed.

Assessment of neuropsychiatric symptoms in dementia: toward improving accuracy

PubMed Central

Stella, Florindo

2013-01-01

The issue of this article concerned the discussion about tools frequently used tools for assessing neuropsychiatric symptoms of patients with dementia, particularly Alzheimer's disease. The aims were to discuss the main tools for evaluating behavioral disturbances, and particularly the accuracy of the Neuropsychiatric Inventory – Clinician Rating Scale (NPI-C). The clinical approach to and diagnosis of neuropsychiatric syndromes in dementia require suitable accuracy. Advances in the recognition and early accurate diagnosis of psychopathological symptoms help guide appropriate pharmacological and non-pharmacological interventions. In addition, recommended standardized and validated measurements contribute to both scientific research and clinical practice. Emotional distress, caregiver burden, and cognitive impairment often experienced by elderly caregivers, may affect the quality of caregiver reports. The clinician rating approach helps attenuate these misinterpretations. In this scenario, the NPI-C is a promising and versatile tool for assessing neuropsychiatric syndromes in dementia, offering good accuracy and high reliability, mainly based on the diagnostic impression of the clinician. This tool can provide both strategies: a comprehensive assessment of neuropsychiatric symptoms in dementia or the investigation of specific psychopathological syndromes such as agitation, depression, anxiety, apathy, sleep disorders, and aberrant motor disorders, among others. PMID:29213846

Epidural analgesia in children. A survey of current opinions and practices amongst UK paediatric anaesthetists.

PubMed

Williams, D G; Howard, R F

2003-11-01

Despite the widespread use of epidural analgesia in children its place in paediatric pain management has not been clearly established. In order to investigate the current practice of paediatric epidural analgesia in the UK paediatric anaesthetists and paediatric pain management teams were surveyed. Questionnaires were sent to the members of the Association of Paediatric Anaesthetists (APA) working within the UK and to lead clinicians and clinical nurse specialists for acute pain in the 26 designated major paediatric centres. The response rate was 72%. There was little consensus regarding drugs and drug combinations used for epidural analgesia. A total of 36% of paediatric centres did not audit their epidural practice, and of those that did the reported incidences of side-effects showed wide variation. Important differences in practice were also identified in the areas of patient selection, informed consent, the use of epidural test doses, drug delivery systems, monitoring and the management of side-effects. Twelve per cent of specialist paediatric hospitals did not have an acute pain team and elsewhere the provision was often limited to staff with few or no specialist skills. There is wide variation in the practice of paediatric epidural analgesia in the UK. Inconsistencies are likely to be related to the poor evidence base available to guide clinical decision making and the lack of a specialized paediatric acute pain service in some centres. More research is required to determine the optimal management of epidural analgesia, and suitable clinical support for paediatric pain control should be more widely available.

Neurodevelopmental and behavioural paediatrics.

PubMed

McDowell, Michael

2015-01-01

One of the notable shifts in Paediatrics across the last 50 years has been towards disorders that are chronic and qualitative in nature. In addition to physical health, these impact on childhood development, behaviour and wellbeing. Understanding and management of these problems extends the traditional biological toolkit of paediatrics into the complexities of uncertainties of psychological and social context. In Australasia, the profession has responded with the development of Community Paediatrics as a recognised sub-specialty, of which Neurodevelopmental and Behavioural Paediatrics is an important component. These developments are reviewed along with consideration of future challenges for this field of health care. © 2015 The Author. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Paediatric fever management: continuing education for clinical nurses.

PubMed

Walsh, Anne M; Edwards, Helen E; Courtney, Mary D; Wilson, Jenny E; Monaghan, Sarah J

2006-01-01

This study examined the influence of level of practice, additional paediatric education and length of paediatric and current experience on nurses' knowledge of and beliefs about fever and fever management. Fifty-one nurses from medical wards in an Australian metropolitan paediatric hospital completed a self-report descriptive survey. Knowledge of fever management was mediocre (Mean 12.4, SD 2.18 on 20 items). Nurses practicing at a higher level and those with between one and four years paediatric or current experience were more knowledgeable than novices or more experienced nurses. Negative beliefs that would impact nursing practice were identified. Interestingly, beliefs about fever, antipyretic use in fever management and febrile seizures were similar; they were not influenced by nurses' knowledge, experience, education or level of practice. Paediatric nurses are not expert fever managers. Knowledge deficits and negative attitudes influence their practice irrespective of additional paediatric education, paediatric or current experience or level of practice. Continuing education is therefore needed for all paediatric nurses to ensure the latest clear evidence available in the literature for best practice in fever management is applied.

Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of life.

PubMed

Monahan, R C; Beaart-van de Voorde, L J J; Steup-Beekman, G M; Magro-Checa, C; Huizinga, T W J; Hoekman, J; Kaptein, A A

2017-10-01

Objective Assess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE). Methods Quality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases. Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role ( p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health ( p = 0.014) and mental component score ( p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE. Conclusion Quality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.

Behavioral and psychological subsyndromes in Alzheimer's disease using the Neuropsychiatric Inventory.

PubMed

Canevelli, Marco; Adali, Nawal; Voisin, Thierry; Soto, Maria Eugenia; Bruno, Giuseppe; Cesari, Matteo; Vellas, Bruno

2013-08-01

Behavioral and psychological symptoms of dementia represent common clinical features of dementias, contributing to the heterogeneous phenotypic expression of Alzheimer's disease (AD). During the last two decades, several studies explored the possible presence of neuropsychiatric subsyndromes in dementia by examining the internal structure of the Neuropsychiatric Inventory (NPI). The aim of the present review is to present available evidence coming from studies adopting factor analysis to explore the NPI and describe neuropsychiatric clusters of symptoms in AD. A systematic review of literature was performed concerning available studies describing neuropsychiatric subsyndromes in AD by adopting the NPI. Overall, our analysis showed a relatively low concordance among available evidence for what concerns the definition and composition of NPI clusters, possibly due (at least in part) to the heterogeneity of the sample populations recruited in the studies. However, we also observed some consistent associations of specific symptoms across studies, defining potential subsyndromes in AD. More consistent results were obtained by studies evaluating the 10-item version of the NPI rather than the more recent 12-item one. This review represents the first attempt to systematically evaluate evidence coming from factor analyses exploring the internal structure of the NPI in order to facilitate the identification of neuropsychiatric syndromes in AD patients. The NPI may support the definition of behavioral subsyndromes in AD. The evaluation of neuropsychiatric subsyndromes should always take into account the main potential confounders, such as age, severity of disease, and concomitant pharmacological treatment. Copyright © 2012 John Wiley & Sons, Ltd.

Voxel-based morphometry findings in Alzheimer's disease: neuropsychiatric symptoms and disability correlations - preliminary results.

PubMed

Vasconcelos, Luciano de Gois; Jackowski, Andrea Parolin; Oliveira, Maira Okada de; Flor, Yoná Mayara Ribeiro; Bueno, Orlando Francisco Amodeo; Brucki, Sonia Maria Dozzi

2011-01-01

The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.

Paediatric cardiovascular clinical trials: an analysis of ClinicalTrials.gov and the Food and Drug Administration Pediatric Drug Labeling Database.

PubMed

Hill, Kevin D; Henderson, Heather T; Hornik, Christoph P; Li, Jennifer S

2015-08-01

Recent regulatory initiatives in the United States of America and Europe have transformed the paediatric clinical trials landscape by significantly increasing capital investment and paediatric trial volume. The purpose of this manuscript was to review the impact of these initiatives on the paediatric cardiovascular trials landscape when compared with other paediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major paediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field.

Choosing a career in paediatrics: do trainees' views change over the first year of specialty training?

PubMed

Goodyear, Helen M; Lakshminarayana, Indumathy; Wall, David; Bindal, Taruna

2014-09-01

To look at why a regional cohort of UK doctors chose a paediatric career and to ascertain views on their career near the end of training year one. A 20-item questionnaire was sent to all new regional paediatric specialty trainees. Three focus groups were held with trainees near the end of year one to elicit key themes. West Midlands Deanery, UK. Twenty-nine new regional paediatric specialty trainees in year one completed the questionnaire. A total of 15 trainees participated in the focus groups near the end of year one training. Reasons for choosing a paediatric career and factors which further influence career choice for trainees during their first specialty training year. Key influencing factors for choosing paediatrics were enjoying working with children and positive undergraduate experience of the specialty. All trainees had paediatrics as their first choice specialty and undertook a paediatric Foundation post. Near the end of year one, doubts were cast on career aspirations due to seeing middle grade colleagues struggling with work-life balance and a growing feeling that family came first. Senior trainees need to be aware that they act as powerful role models for their more junior colleagues and therefore have an influential role on how juniors perceive a paediatric career. Family friendly flexible working patterns in paediatrics are vital to retain junior trainees. All paediatric staff are role models and need to be enthusiastic, keen to teach and to promote a positive working environment.

The EU paediatric regulation: still a large discrepancy between therapeutic needs and approved paediatric investigation plans.

PubMed

Wimmer, Stefan; Rascher, Wolfgang; McCarthy, Suzanne; Neubert, Antje

2014-10-01

Prior to the implementation of the EU Paediatric Regulation, the European Medicines Agency (EMA) defined unmet paediatric needs for active substances already available on the market. Seven years after the Paediatric Regulation came into force, we investigated the extent to which previously identified needs have led to programmes for generating evidence necessary for the regulatory approval of medicines for managing childhood conditions. The websites of the EMA and the European Commission Community Research and Development Information Service (CORDIS) were systematically screened to identify active substances from the assessment of paediatric needs, off-patent priority list, agreed Paediatric Investigation Plans (PIP) and 7th Framework Programme (FP7) projects related to paediatric medicines. A total of 357 active substances with paediatric needs were identified by June 2013. 511 PIPs were agreed by the Paediatric Committee at the EMA (PDCO), including 51 (14.3 %) PIPs for a previously identified need. Amongst those, 21 were off-patent at the time of the PIP approval, 15 of which received funding from the European Commission's FP7. According to the assessment of paediatric needs, evidence is particularly needed for active substances treating cardiovascular diseases (n = 61), cancer (n = 40) and in the field of anaesthesiology (n = 38). Whereas oncology drugs (n = 66) were frequently represented in PIPs, drugs for cardiovascular diseases (n = 39) and anaesthesiology (n = 3) rarely were. Most PIPs are attributable to marketing authorisations of new active substances, whereas off-patent drugs which are commonly used off-label remain unstudied to a large extent. More effort including ongoing research funding is essential to further regularise and standardise paediatric pharmacotherapy.

Paediatric manpower: towards the 21st century.

PubMed Central

Appleyard, W J; Jackson, A D

1988-01-01

The British Paediatric Association (BPA) has carried out a national survey of paediatric medical manpower in the hospital and community child health services. The results of the survey relating to England and Wales are presented and compared with Department of Health and Social Security (DHSS) manpower statistics. On the basis of the survey findings and current trends in the pattern of paediatric care paediatric manpower requirements over the next 10 years are estimated. PMID:3178274

Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis

PubMed Central

Kothur, Kavitha; Wienholt, Louise; Mohammad, Shekeeb S.; Tantsis, Esther M.; Pillai, Sekhar; Britton, Philip N.; Jones, Cheryl A.; Angiti, Rajeshwar R.; Barnes, Elizabeth H.; Schlub, Timothy; Bandodkar, Sushil; Brilot, Fabienne; Dale, Russell C.

2016-01-01

Background Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications. Aim To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis. Methods We measured and compared 32 cytokine/chemokines using multiplex immunoassay and APRIL and BAFF using ELISA in CSF collected prior to commencing treatment from paediatric patients with confirmed acute disseminated encephalomyelitis (ADEM, n = 16), anti-NMDAR encephalitis (anti-NMDAR E, n = 11), and enteroviral encephalitis (EVE, n = 16). We generated normative data using CSF from 20 non-inflammatory neurological controls. The sensitivity of CSF cytokine/chemokines to diagnose encephalitis cases was calculated using 95th centile of control values as cut off. We correlated CSF cytokine/chemokines with disease severity and follow up outcome based on modified Rankin scale. One-way hierarchical correlational cluster analysis of molecules was performed in different encephalitis and outcome groups. Results In descending order, CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 had the best sensitivity (>79.1%) when all encephalitis patients were included. The combination of IL-6 and IFN-α was most predictive of inflammation on multiple logistic regression with area under the ROC curve 0.99 (CI 0.97–1.00). There were no differences in CSF cytokine concentrations between EVE and anti-NMDAR E, whereas ADEM showed more pronounced elevation of Th17 related (IL-17, IL-21) and Th2 (IL-4, CCL17) related cytokine/chemokines. Unlike EVE, heat map analysis showed similar clustering of cytokine/chemokine molecules in immune mediated encephalitis (ADEM and anti-NMDAR E). Th1 and B cell (CXCL13 and CXCL10) molecules clustered together in patients with severe encephalopathy at admission and worse disability at follow up in all encephalitis. There was no correlation between CSF neopterin and IFN-γ or IFN-α. Conclusion A combination panel of cytokine/chemokines consisting of CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 measured using multiplex immunoassay may be used to diagnose and monitor intrathecal inflammation in the brain. Given their association with worse outcome, certain key chemokines (CXCL13, CXCL10) could represent potential therapeutic targets in encephalitis. PMID:27575749

Role of Brain Perfusion SPECT with 99mTc HMPAO in the Assessment of Response to Drug Therapy in Patients with Autoimmune Vasculitis: A Prospective Study

PubMed Central

Mauro, Liberatore; Manuela, Morreale; Valentina, Megna; Sara, Collorone; Chondrogiannis, Sotirios; Maria, Drudi Francesco; Christos, Anagnostou; Liana, Civitelli; Ada, Francia; Maffione, Anna Margherita; Marzola, Maria Cristina; Rubello, Domenico

2015-01-01

Background: The diagnosis of vasculitis in the brain remains a quite difficult achievement. To the best of our knowledge, there is no imaging method reported in literature which is capable of reaching to a diagnosis of vasculitis with very high sensitivity. Aim: The aim of this study was to determine whether perfusion brain single photon emission computed tomography (SPECT) can be usefully employed in monitoring the treatment of vasculitis, allowing treating only potentially responder patients and avoiding the side effects on patients who do not respond. Materials and Methods: Twenty patients (two males and 18 females) suffering from systemic lupus erythematosus (SLE; n = 5), Behcet's disease (BD; n = 5), undifferentiated vasculitis (UV; n = 5), and Sjogren's syndrome (SS; n = 5) were included in the study. All patients underwent a wide neurological anamnestic investigation, a complete objective neurological examination and SPECT of the brain with 99mTc-hexamethyl-propylene-aminoxime (HMPAO). The brain SPECT was then repeated after appropriate medical treatment. The neurological and neuropsychiatric follow-up was performed at 6 months after the start of the treatment. Results: Overall, the differences between the scintigraphic results obtained after and before the medical treatment indicated a statistically significant increase of the cerebral perfusion (CP). In 19 out of 200 regions of interest (ROI) studied, the difference between pre- and post treatment percentages had negative sign, indicating a worsening of CP. This latter event has occurred six times (five in the same patients) in the UV, 10 times (eight in the same patients) in the SLE, never in BD, and three times (two in the same patient) in the SS. Conclusion: The reported results seem to indicate the possibility of identifying, by the means of a brain SPECT, responder and nonresponder (unchanged or worsened CP) patients, affected by autoimmune vasculitis, to the therapy. PMID:25973400

Peer teaching in paediatrics - medical students as learners and teachers on a paediatric course.

PubMed

Schauseil-Zipf, Ulrike; Karay, Yassin; Ehrlich, Roland; Knoop, Kai; Michalk, Dietrich

2010-01-01

Peer assisted learning is known as an effective educational strategy in medical teaching. We established a peer assisted teaching program by student tutors with a focus on clinical competencies for students during their practical training on paediatric wards. It was the purpose of this study to investigate the effects of a clinical skills training by tutors, residents and consultants on students evaluations of the teaching quality and the effects of a peer teaching program on self assessed clinical competencies by the students. Medical student peers in their 6(th) year were trained by an intensive instruction program for teaching clinical skills by paediatric consultants, doctors and psychologists. 109 students in their 5(th) year (study group) participated in a peer assisted teaching program for training clinical skills in paediatrics. The skills training by student peer teachers were supervised by paediatric doctors. 45 students (control group) participated in a conventional paediatric skills training by paediatric doctors and consultants. Students from both groups, which were consecutively investigated, completed a questionnaire with an evaluation of the satisfaction with their practical training and a self assessment of their practical competencies. The paediatric skills training with student peer teachers received significantly better ratings than the conventional skills training by paediatric doctors concerning both the quality of the practical training and the support by the teaching medical staff. Self assessed learning success in practical skills was higher rated in the peer teaching program than in the conventional training. The peer assisted teaching program of paediatric skills training was rated higher by the students regarding their satisfaction with the teaching quality and their self assessment of the acquired skills. Clinical skills training by student peer teachers have to be supervised by paediatric doctors. Paediatric doctors seem to be more motivated for their own teaching tasks if they are assisted by student peer teachers. More research is needed to investigate the influence of peer teaching on the motivation of paediatric doctors to teach medical students und the academic performance of the student peers.

Implementation of mechanism of action biology-driven early drug development for children with cancer.

PubMed

Pearson, Andrew D J; Herold, Ralf; Rousseau, Raphaël; Copland, Chris; Bradley-Garelik, Brigid; Binner, Debbie; Capdeville, Renaud; Caron, Hubert; Carleer, Jacqueline; Chesler, Louis; Geoerger, Birgit; Kearns, Pamela; Marshall, Lynley V; Pfister, Stefan M; Schleiermacher, Gudrun; Skolnik, Jeffrey; Spadoni, Cesare; Sterba, Jaroslav; van den Berg, Hendrick; Uttenreuther-Fischer, Martina; Witt, Olaf; Norga, Koen; Vassal, Gilles

2016-07-01

An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Admission, discharge and triage guidelines for paediatric intensive care units in Spain].

PubMed

de la Oliva, Pedro; Cambra-Lasaosa, Francisco José; Quintana-Díaz, Manuel; Rey-Galán, Corsino; Sánchez-Díaz, Juan Ignacio; Martín-Delgado, María Cruz; de Carlos-Vicente, Juan Carlos; Hernández-Rastrollo, Ramón; Holanda-Peña, María Soledad; Pilar-Orive, Francisco Javier; Ocete-Hita, Esther; Rodríguez-Núñez, Antonio; Serrano-González, Ana; Blanch, Luis

2018-05-01

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Admission, discharge and triage guidelines for paediatric intensive care units in Spain.

PubMed

de la Oliva, Pedro; Cambra-Lasaosa, Francisco José; Quintana-Díaz, Manuel; Rey-Galán, Corsino; Sánchez-Díaz, Juan Ignacio; Martín-Delgado, María Cruz; de Carlos-Vicente, Juan Carlos; Hernández-Rastrollo, Ramón; Holanda-Peña, María Soledad; Pilar-Orive, Francisco Javier; Ocete-Hita, Esther; Rodríguez-Núñez, Antonio; Serrano-González, Ana; Blanch, Luis

2018-05-01

A paediatric intensive care unit (PICU) is a separate physical facility or unit specifically designed for the treatment of paediatric patients who, because of the severity of illness or other life-threatening conditions, require comprehensive and continuous inten-sive care by a medical team with special skills in paediatric intensive care medicine. Timely and personal intervention in intensive care reduces mortality, reduces length of stay, and decreases cost of care. With the aim of defending the right of the child to receive the highest attainable standard of health and the facilities for the treatment of illness and rehabilitation, as well as ensuring the quality of care and the safety of critically ill paediatric patients, the Spanish Association of Paediatrics (AEP), Spanish Society of Paediatric Intensive Care (SECIP) and Spanish Society of Critical Care (SEMICYUC) have approved the guidelines for the admission, discharge and triage for Spanish PICUs. By using these guidelines, the performance of Spanish paediatric intensive care units can be optimised and paediatric patients can receive the appropriate level of care for their clinical condition. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Light Treatment for Neuropsychiatric Behaviors in Alzheimer’s Disease

PubMed Central

Dowling, Glenna A.; Graf, Carla; Hubbard, Erin M.; Luxenberg, Jay S.

2008-01-01

Neuropsychiatric behaviors are common in people with Alzheimer’s disease (AD) and make both professional and lay caregiving difficult. Light therapy has been somewhat successful in ameliorating disruptive behaviors. This randomized trial tested the effects of morning or afternoon bright light exposure compared with usual indoor light on the presence, frequency, severity, and occupational disruptiveness of neuropsychiatric behaviors in nursing home residents with AD. Light was administered for 1 hr daily (Monday–Friday) for 10 weeks. The Neuropsychiatric Inventory–Nursing Home was used to assess behavior at baseline and end of the intervention. Analyses revealed statistically significant differences between groups on agitation/aggression, depression/dysphoria, aberrant motor behavior, and appetite/eating disorders. The magnitude of change was small and may not represent clinically significant findings. Agitation/aggression and nighttime behaviors commonly occurred and were highly correlated with occupational disruptiveness. Interventions that decrease the presence and/or severity of neuropsychiatric behaviors have the potential to significantly decrease caregiver burden. PMID:17596638

Cross-Ethnic Differences in the Severity of Neuropsychiatric Symptoms in Persons With Mild Cognitive Impairment and Alzheimer's Disease.

PubMed

Salazar, Ricardo; Dwivedi, Alok Kumar; Royall, Donald R

2017-01-01

In this cross-sectional study, we examined the neuropsychiatric profile of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Data were available on 875 controls, 339 MCI cases, and 975 AD participants. Surprisingly, differences in neuropsychiatric symptom (NPS) severity by ethnicity in subjects with AD, but not with MCI, were found. More so, in Hispanics with AD, a higher frequency in most of the individual NPI-Q symptom items of the scale was observed, except for apathy. After adjustment for clinical features, some individual NPI-Q symptoms also showed an association with Hispanic ethnicity in the control group that nearly reached statistical significance. There may be cross-ethnic differences in the neuropsychiatric presentation of AD in Hispanics versus non-Hispanic whites. Future studies are needed to clarify the etiology of these differences, and to assess the need for ethnicity-specific treatment and care-giving interventions.

The European Paediatric Mycology Network (EPMyN): Towards a Better Understanding and Management of Fungal Infections in Children.

PubMed

Warris, Adilia

The European Paediatric Mycology Network (EPMyN) was launched in 2014 to create a European platform for research and education in the field of paediatric mycology. The EPMyN aims to address the lack of paediatric specific evidence and knowledge needed to (1) improve the management and outcome of invasive fungal infections in children and neonates and to (2) enhance and develop paediatric antifungal stewardship programmes.

Impact of the new european paediatric regulatory framework on ethics committees: overview and perspectives.

PubMed

Altavilla, A; Manfredi, C; Baiardi, P; Dehlinger-Kremer, M; Galletti, P; Pozuelo, A Alemany; Chaplin, J; Ceci, A

2012-01-01

To evaluate the impact of the new European paediatric regulatory framework on the activities of Ethics Committees operating in Europe and to assess their involvement and interest in paediatric research. Task-force in Europe for Drug Development for the Young Network of Excellence and Relating Expectations and Needs to the Participation and Empowerment of Children in Clinical Trials project set up an inventory of Ethics Committees existing in Europe and conducted a survey on their approach to paediatric trials. Ethics Committees operating in 22 European Countries participated in this survey. Results showed a high lack of knowledge, understanding and awareness of the current European paediatric regulatory framework and a lack of involvement of Ethics Committees in paediatric research, especially in terms of training and education, demonstrated also by the decreasing number of Ethics Committees answering exhaustively to the whole questionnaire. The majority of participating Ethics Committees expressed interest in future initiatives related to paediatric research. Despite a limited knowledge and understanding of the current paediatric regulatory framework, a significant number of Ethics Committees operating in Europe show interest in initiatives related to paediatric research. Networking may be an essential tool to be used to enhance Ethics Committees role in supporting paediatric research. Any initiative should be undertaken at European level in collaboration with European Union Institutions. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Neuropsychiatric aspects of dementia.

PubMed

Ford, Andrew H

2014-10-01

Dementia affects approximately 6.5% of people over the age of 65. Whilst cognitive impairment is central to the dementia concept, neuropsychiatric symptoms are invariably present at some stage of the illness. Neuropsychiatric symptoms result in a number of negative outcomes for the individual and their caregivers and are associated with higher rates of institutionalization and mortality. A number of factors have been associated with neuropsychiatric symptoms including neurobiological changes, dementia type, and illness severity and duration. Specific patient, caregiver and environmental factors are also important. Neuropsychiatric symptoms can be broadly divided into four clusters: psychotic symptoms, mood/affective symptoms, apathy, and agitation/aggression. Neuropsychiatric symptoms tend to persist over time although differing symptom profiles exist at various stages of the illness. Assessment should take into account the presenting symptoms together with an appreciation of the myriad of likely underlying causes for the symptoms. A structured assessment/rating tool can be helpful. Management should focus on non-pharmacological measures initially with pharmacological approaches reserved for more troubling symptoms. Pharmacological approaches should target specific symptoms although the evidence-base for pharmacological management is quite modest. Any medication trial should include an adequate appreciation of the risk-benefit profile in individual patients and discussion of these with both the individual and their caregiver. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neural markers of errors as endophenotypes in neuropsychiatric disorders

PubMed Central

Manoach, Dara S.; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201

Extreme sexual behavior in dementia as a specific manifestation of disinhibition.

PubMed

Bartelet, Marjukka; Waterink, Wim; van Hooren, Susan

2014-01-01

In nursing homes, extreme sexual behavior is one of the most challenging behaviors in dementia. Despite this, however, there is no conformity in the literature regarding how to label and define this type of behavior. Examples of labels used include inappropriate sexual behavior, improper sexual behavior, sexually disinhibited behavior, or hyper sexuality. According to recent theoretical perspectives, extreme sexual behavior may be regarded as a part of disinhibited behavior or could be considered as an independent neuropsychiatric symptom. In this multicenter study, it was investigated whether there is a relationship between extreme sexual behavior and the typical neuropsychiatric symptoms seen in dementia. In 179 residents diagnosed with dementia, extreme sexual behavior was measured using an observation scale. Twelve neuropsychiatric symptoms were measured by the Neuropsychiatric Inventory. Multivariate analysis of covariance with gender showed that residents with observed extreme sexual behavior (n = 43) only showed a higher score on neuropsychiatric symptom 'disinhibition', as compared to residents with non-observed sexual behavior (n = 136). In addition, the effect size was large. These findings indicate that among residents with dementia, extreme sexual behaviors should not be considered as an independent neuropsychiatric symptom. Instead, disinhibition may be an important underlying mechanism for extreme sexual behavior and thus validates the label 'sexually disinhibited behavior'.

Neural markers of errors as endophenotypes in neuropsychiatric disorders.

PubMed

Manoach, Dara S; Agam, Yigal

2013-01-01

Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

Structured physical exercise improves neuropsychiatric symptoms in acute dementia care: a hospital-based RCT.

PubMed

Fleiner, Tim; Dauth, Hannah; Gersie, Marleen; Zijlstra, Wiebren; Haussermann, Peter

2017-08-29

The primary objective of this trial is to investigate the effects of a short-term exercise program on neuropsychiatric signs and symptoms in acute hospital dementia care. Within a hospital-based randomized controlled trial, the intervention group conducted a 2-week exercise program with four 20-min exercise sessions on 3 days per week. The control group conducted a social stimulation program. Effects on neuropsychiatric signs and symptoms were measured via the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, the Neuropsychiatric Inventory, and the Cohen-Mansfield Agitation Inventory. The antipsychotic and sedative dosage was quantified by olanzapine and diazepam equivalents. Eighty-five patients were randomized via minimization to an intervention group (IG) and a control group (CG). Seventy patients (82%) (mean age 80 years, 33 females, mean Mini Mental State Examination score 18.3 points) completed the trial. As compared to the CG (n = 35), the IG (n = 35) showed significantly reduced neuropsychiatric signs and symptoms. Especially, agitated behavior and lability improved. There were no between-group differences concerning antipsychotic and benzodiazepine medication. This exercise program is easily applicable in hospital dementia care and significantly reduces neuropsychiatric signs and symptoms in patients suffering from predominantly moderate stages of dementia. German Clinical Trial Register DRKS00006740 . Registered 28 October 2014.

The Internet and the paediatric surgeon.

PubMed

Srinivas, M; Inumpudi, A; Mitra, D K

1998-12-01

The Internet, which has truly united the world, is an extensive network of inter-linked computers storing immense bytes of information that can be accessed by anyone, transcending all barriers. The paediatric surgery Internet consists of exponentially growing material that deals with information specifically for paediatric surgeons and patients of the paediatric age group. We reviewed the methods available to take advantage of this network to enable busy paediatric surgeons to accrue the benefits easily and efficiently rather than be lost in the information ocean by surfing individually. By getting connected to the Internet, the paediatric surgeon gains enormous information that can be useful for patient care. The Internet has revolutionised scientific publications by virtue of its fast and accurate transmission of manuscripts. Paediatric surgeons can send manuscripts by this channel and also access journals, obviating the inherent lag period of communication by post.

Stressors of newly graduated nurses in Shanghai paediatric hospital: a qualitative study.

PubMed

Hu, Yun; Zhang, Yaqing; Shen, Nanping; Wu, Juemin; Wu, Jia; Malmedal, Wenche K

2017-04-01

To identify stressors of newly graduated paediatric nurses at a children's hospital in Shanghai, China. Stress is an international phenomenon in nursing generally, but little is known about its effect on new paediatric nurses at the Shanghai paediatric hospital. Participants in this research were 25 newly graduated paediatric nurses. Their behaviours and perceptions were explored by field observations and interviews. Findings indicated that participants experienced numerous stressors: low work status, insufficient professional competence, heavy workload, inadequate supportive systems and uncertainty of career development. The results of the present study provide useful information for administrators to develop and improve postgraduate programmes to support novice paediatric nurses. Our research highlights the importance of identifying the stressors of new paediatric nurses in the light of a serious nurse shortage and an increasing birth rate. © 2016 John Wiley & Sons Ltd.

Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes

PubMed Central

Rood, M; Keijsers, V; van der Linden, M W; Tong, T; Borggreve, S; Verweij, C; Breedveld, F; Huizinga, T

1999-01-01

OBJECTIVE—To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythematosus (SLE).
METHODS—IL10 haplotypes of 11 healthy volunteers were cloned to confirm that in the Dutch population, only the three common haplotypes (-1082/-819/-592) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patients and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement.
RESULTS—All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suffered from neuropsychiatric manifestations (NP-SLE). In NP-SLE patients, the frequency of the ATA haplotype is 30% versus 18% in the controls and 17% in the non-NP-SLE group (odds ratios 1.9, p=0.02, and 2.1, p=0.04, respectively), whereas the GCC haplotype frequency is lower in the NP-SLE group compared with controls and non-NP-SLE patients (40% versus 55% and 61%, odds ratios 0.6, p=0.02 and 0.4 p=0.006). The odds ratio for the presence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients.
CONCLUSIONS—The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE.

 Keywords: systemic lupus erythematosus; neuropsychiatric manifestations; genetics; interleukin 10 promoter haplotypes PMID:10343522

Prevalence of Vitamin B12 and folic acid deficiency in HIV-positive patients and its association with neuropsychiatric symptoms and immunological response.

PubMed

Adhikari, Prabha M R; Chowta, Mukta N; Ramapuram, John T; Rao, Satish; Udupa, Karthik; Acharya, Sahana Devdas

2016-01-01

Deficiency of micronutrients is prevalent even before the development of symptoms of HIV disease and is associated with accelerated HIV disease progression. This study evaluates the prevalence of folate and Vitamin B 12 deficiency in HIV-positive patients with or without tuberculosis (TB) and its association with neuropsychiatric symptoms and immunological response. Cross-sectional, observational study in an outpatient setting. Four groups of HIV-positive patients with TB (Group I), HIV-positive patients with neuropsychiatric symptoms (Group II), HIV-positive patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative controls with neuropsychiatric symptoms (Group IV). Vitamin B 12 and folate estimation was done using carbonyl metallo-immunoassay method. ANOVA, Kruskal-Wallis and Mann-Whitney, Pearson's correlation. The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9% in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The prevalence of Vitamin B 12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8% in Group III, and 16.7% in Group IV. The patients with folate deficiency had more severe depression and anxiety. Nearly, 30% of the HIV patients had a folic acid deficiency, and about 10% of the HIV patients had Vitamin B 12 deficiency. The folate deficiency was highest among neuropsychiatric patients with or without HIV infection and Vitamin B 12 deficiency was higher among HIV patients with TB.

Biomarkers of vascular risk, systemic inflammation, and microvascular pathology and neuropsychiatric symptoms in Alzheimer's disease.

PubMed

Hall, James R; Wiechmann, April R; Johnson, Leigh A; Edwards, Melissa; Barber, Robert C; Winter, A Scott; Singh, Meharvan; O'Bryant, Sid E

2013-01-01

Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimer's disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.

Substance Use is a Risk Factor for Neurocognitive Deficits and Neuropsychiatric Distress in Acute and Early HIV Infection

PubMed Central

Weber, Erica; Morgan, Erin E.; Iudicello, Jennifer E.; Blackstone, Kaitlin; Grant, Igor; Ellis, Ronald J.; Letendre, Scott L.; Little, Susan; Morris, Sheldon; Smith, Davey M.; Moore, David J.; Woods, Steven Paul

2012-01-01

The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naïve adults with median duration of infection of 75 days, relative to sample a of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States (POMS), a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly five-fold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use. PMID:23250704

Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not?

PubMed

Van Den Bossche, Maarten J; Johnstone, Mandy; Strazisar, Mojca; Pickard, Benjamin S; Goossens, Dirk; Lenaerts, An-Sofie; De Zutter, Sonia; Nordin, Annelie; Norrback, Karl-Fredrik; Mendlewicz, Julien; Souery, Daniel; De Rijk, Peter; Sabbe, Bernard G; Adolfsson, Rolf; Blackwood, Douglas; Del-Favero, Jurgen

2012-10-01

From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (1-2%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders. 2012 Wiley Periodicals, Inc

Balancing research interests and patient interests: a qualitative study into the intertwinement of care and research in paediatric oncology.

PubMed

Dekking, Sara A S; van der Graaf, Rieke; Kars, Marijke C; Beishuizen, Auke; de Vries, Martine C; van Delden, Johannes J M

2015-05-01

Traditionally, in ethical guidelines and in research ethics literature, care and research are clearly separated based on their different objectives. In contrast, in paediatric oncology, research and care are closely combined. Currently, it is unknown how relevant actors in paediatric oncology perceive this combination of research and care. We conducted a qualitative study into the experiences of those involved in Dutch paediatric oncology with the intertwinement of research and care and the dual role of paediatric oncologists as researchers and treating physicians. A qualitative study approach, using two focus groups and 19 semi-structured, in-depth interviews with paediatric oncologists, research coordinators, parents of children with cancer, and adolescents with cancer. Four themes characterize how actors experience the intertwinement of research and care in paediatric oncology. First, research is considered of major importance, and paediatric oncology professionals convey this message to patients and their parents. Second, there is ambiguity about categorization of studies into cancer therapy as either research or treatment. Third, role conflicts appear within the work of the paediatric oncologists. Finally, the various benefits of combining treatment with research are emphasized. Research is regarded as a fundamental and indispensable characteristic of paediatric oncology practice. Paediatric oncology professionals, parents, and patients have a very positive outlook on combining research and care, but they may not be sufficiently critical with respect to potential conflicts. Increased reflection on how to optimally combine research and care could serve as an important protection of the interests of children with cancer and their parents. © 2015 Wiley Periodicals, Inc.

Choosing a career in paediatrics: do trainees’ views change over the first year of specialty training?

PubMed Central

Lakshminarayana, Indumathy; Wall, David; Bindal, Taruna

2014-01-01

Summary Objectives To look at why a regional cohort of UK doctors chose a paediatric career and to ascertain views on their career near the end of training year one. Design A 20-item questionnaire was sent to all new regional paediatric specialty trainees. Three focus groups were held with trainees near the end of year one to elicit key themes. Setting West Midlands Deanery, UK Participants Twenty-nine new regional paediatric specialty trainees in year one completed the questionnaire. A total of 15 trainees participated in the focus groups near the end of year one training. Main outcome measures Reasons for choosing a paediatric career and factors which further influence career choice for trainees during their first specialty training year. Results Key influencing factors for choosing paediatrics were enjoying working with children and positive undergraduate experience of the specialty. All trainees had paediatrics as their first choice specialty and undertook a paediatric Foundation post. Near the end of year one, doubts were cast on career aspirations due to seeing middle grade colleagues struggling with work–life balance and a growing feeling that family came first. Conclusions Senior trainees need to be aware that they act as powerful role models for their more junior colleagues and therefore have an influential role on how juniors perceive a paediatric career. Family friendly flexible working patterns in paediatrics are vital to retain junior trainees. All paediatric staff are role models and need to be enthusiastic, keen to teach and to promote a positive working environment. PMID:25352989

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

PubMed

Ruggieri, L; Giannuzzi, V; Baiardi, P; Bonifazi, F; Davies, E H; Giaquinto, C; Bonifazi, D; Felisi, M; Chiron, C; Pressler, R; Rabe, H; Whitaker, M J; Neubert, A; Jacqz-Aigrain, E; Eichler, I; Turner, M A; Ceci, A

2015-04-01

The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

N-acetylcysteine for neuropsychiatric symptoms in a woman with Williams syndrome.

PubMed

Pineiro, Mildred Lopez; Roberts, Antoinette M; Waxler, Jessica L; Mullett, Jennifer E; Pober, Barbara R; McDougle, Christopher J

2014-11-01

Williams syndrome is a relatively rare genetic disorder caused by the hemizygous microdeletion of a region in chromosome 7q11.23. Individuals with Williams syndrome typically present with a highly social, overfriendly, and empathic personality. Comorbid medical and neuropsychiatric disorders are common. Reports of effective pharmacological treatment of associated neuropsychiatric disorders are limited. The authors describe the successful treatment of interfering anger, aggression, and hair-pulling with N-acetylcysteine in a 19-year-old woman with Williams syndrome. The neuropsychiatric symptoms emerged 1 week following an upper gastrointestinal endoscopy, for which fentanyl, midazolam, and propofol were used as anesthetics. The patient's treatment course and hypothesized mechanisms underlying the clinical presentation and symptom resolution are described. © The Author(s) 2014.

Application of in vitro biopharmaceutical methods in development of immediate release oral dosage forms intended for paediatric patients.

PubMed

Batchelor, Hannah K; Kendall, Richard; Desset-Brethes, Sabine; Alex, Rainer; Ernest, Terry B

2013-11-01

Biopharmaceutics is routinely used in the design and development of medicines to generate science based evidence to predict in vivo performance; the application of this knowledge specifically to paediatric medicines development is yet to be explored. The aim of this review is to present the current status of available biopharmaceutical tools and tests including solubility, permeability and dissolution that may be appropriate for use in the development of immediate release oral paediatric medicines. The existing tools used in adults are discussed together with any limitations for their use within paediatric populations. The results of this review highlight several knowledge gaps in current methodologies in paediatric biopharmaceutics. The authors provide recommendations based on existing knowledge to adapt tests to better represent paediatric patient populations and also provide suggestions for future research that may lead to better tools to evaluate paediatric medicines. Copyright © 2013 Elsevier B.V. All rights reserved.

Paediatric expert witness.

PubMed

Johnson, Sandra L J

2013-08-01

Paediatricians may be asked to provide expert opinion in paediatric cases that come under legal consideration. This article provides suggestions to assist paediatricians in this role and emphasises their duty to the court when giving expert opinion. © 2013 The Author. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Medical students' views on selecting paediatrics as a career choice.

PubMed

Bindal, Taruna; Wall, David; Goodyear, Helen M

2011-09-01

Despite increasing numbers of UK medical students, the number of trainees selecting paediatrics as their specialty choice has decreased. Previous studies show that most students will choose their ultimate career during undergraduate training. We therefore explored the views of students in the final year at Birmingham University about a career in paediatrics. Students completed a 27-item questionnaire during the penultimate week of their paediatric clerkship (PC) and 97% responded (127/131). Prior to the PC, 29% (37/127) of students had considered a career in paediatrics, rising to 50% (63/127) after the PC (p < 0.001). Students felt that paediatricians were enthusiastic and keen on teaching, and the ward working atmosphere was good. However, students perceived paediatrics as a difficult specialty with high competition for training posts. Students felt their paediatric experience was too limited and advice was needed on paediatric careers early in undergraduate training. This study confirmed that focusing on improving the PC is not sufficient if we are to inspire medical students to consider a career in paediatrics. Exposure to the specialty is needed from year 1 of undergraduate training along with career advice to dispel current myths about specialty training. Students would then be able to make more informed career decisions.

Advanced practice physiotherapy in paediatric orthopaedics: innovation and collaboration to improve service delivery.

PubMed

Ó Mír, M; O'Sullivan, C

2018-02-01

One in eight paediatric primary care presentations is for a musculoskeletal (MSK) disorder. These patients are frequently referred to paediatric orthopaedic surgeons; however, up to 50% of referrals are for normal variants. This results in excessive wait-times and impedes access for urgent surgical cases. Adult MSK medicine has successfully utilised advanced practice physiotherapists (APP) managing non-surgical candidates, with documented benefits both to patients and services. There is a gap in the literature with regard to APP in paediatric orthopaedics. In this review, we investigate demands on paediatric orthopaedic services, examine the literature regarding APP in paediatric orthopaedics and explore the value the role has to offer current outpatient services. Paediatric orthopaedic services are under-resourced with concurrent long wait times. Approximately 50% of referrals are for normal variants, which do not require specialist intervention. Poor musculoskeletal examination skills and low diagnostic confidence amongst primary care physicians have been identified as a cause of inappropriate referrals. APP clinics for normal variants have reported independent management rate and discharge rates of 95% and marked reduction in patient wait times. There is limited evidence to support the APP in paediatric orthopaedics. Further studies are needed investigating diagnostic agreement, patient/stakeholder satisfaction, patient outcomes and economic evaluation. Paediatric orthopaedics is in crisis as to how to effectively manage the overwhelming volume of referrals. Innovative multidisciplinary solutions are required so that the onus is not solely on physicians to provide all services. The APP in paediatric orthopaedics may be part of the solution.

A paediatric cardiopulmonary resuscitation training project in Honduras.

PubMed

Urbano, Javier; Matamoros, Martha M; López-Herce, Jesús; Carrillo, Angel P; Ordóñez, Flora; Moral, Ramón; Mencía, Santiago

2010-04-01

It is possible that the exportation of North American and European models has hindered the creation of a structured cardiopulmonary resuscitation (CPR) training programme in developing countries. The objective of this paper is to describe the design and present the results of a European paediatric and neonatal CPR training programme adapted to Honduras. A paediatric CPR training project was set up in Honduras with the instructional and scientific support of the Spanish Group for Paediatric and Neonatal CPR. The programme was divided into four phases: CPR training and preparation of instructors; training for instructors; supervised teaching; and independent teaching. During the first phase, 24 Honduran doctors from paediatric intensive care, paediatric emergency and anaesthesiology departments attended the paediatric CPR course and 16 of them the course for preparation as instructors. The Honduran Paediatric and Neonatal CPR Group was formed. In the second phase, workshops were given by Honduran instructors and four of them attended a CPR course in Spain as trainee instructors. In the third phase, a CPR course was given in Honduras by the Honduran instructors, supervised by the Spanish team. In the final phase of independent teaching, eight courses were given, providing 177 students with training in CPR. The training of independent paediatric CPR groups with the collaboration and scientific assessment of an expert group could be a suitable model on which to base paediatric CPR training in Latin American developing countries. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Inequality of Paediatric Workforce Distribution in China.

PubMed

Song, Peige; Ren, Zhenghong; Chang, Xinlei; Liu, Xuebei; An, Lin

2016-07-12

Child health has been addressed as a priority at both global and national levels for many decades. In China, difficulty of accessing paediatricians has been of debate for a long time, however, there is limited evidence to assess the population- and geography-related inequality of paediatric workforce distribution. This study aimed to analyse the inequality of the distributions of the paediatric workforce (including paediatricians and paediatric nurses) in China by using Lorenz curve, Gini coefficient, and Theil L index, data were obtained from the national maternal and child health human resource sampling survey conducted in 2010. In this study, we found that the paediatric workforce was the most inequitable regarding the distribution of children <7 years, the geographic distribution of the paediatric workforce highlighted very severe inequality across the nation, except the Central region. For different professional types, we found that, except the Central region, the level of inequality of paediatric nurses was higher than that of the paediatricians regarding both the demographic and geographic distributions. The inner-regional inequalities were the main sources of the paediatric workforce distribution inequality. To conclude, this study revealed the inadequate distribution of the paediatric workforce in China for the first time, substantial inequality of paediatric workforce distribution still existed across the nation in 2010, more research is still needed to explore the in-depth sources of inequality, especially the urban-rural variance and the inner- and inter-provincial differences, and to guide national and local health policy-making and resource allocation.

Inequality of Paediatric Workforce Distribution in China

PubMed Central

Song, Peige; Ren, Zhenghong; Chang, Xinlei; Liu, Xuebei; An, Lin

2016-01-01

Child health has been addressed as a priority at both global and national levels for many decades. In China, difficulty of accessing paediatricians has been of debate for a long time, however, there is limited evidence to assess the population- and geography-related inequality of paediatric workforce distribution. This study aimed to analyse the inequality of the distributions of the paediatric workforce (including paediatricians and paediatric nurses) in China by using Lorenz curve, Gini coefficient, and Theil L index, data were obtained from the national maternal and child health human resource sampling survey conducted in 2010. In this study, we found that the paediatric workforce was the most inequitable regarding the distribution of children <7 years, the geographic distribution of the paediatric workforce highlighted very severe inequality across the nation, except the Central region. For different professional types, we found that, except the Central region, the level of inequality of paediatric nurses was higher than that of the paediatricians regarding both the demographic and geographic distributions. The inner-regional inequalities were the main sources of the paediatric workforce distribution inequality. To conclude, this study revealed the inadequate distribution of the paediatric workforce in China for the first time, substantial inequality of paediatric workforce distribution still existed across the nation in 2010, more research is still needed to explore the in-depth sources of inequality, especially the urban-rural variance and the inner- and inter-provincial differences, and to guide national and local health policy-making and resource allocation. PMID:27420083

[Current situation of the organisation, resources and activity in paediatric cardiology in Spain].

PubMed

Sánchez Ferrer, Francisco; Castro García, Francisco José; Pérez-Lescure Picarzo, Javier; Roses Noguer, Ferrán; Centeno Malfaz, Fernándo; Grima Murcia, María Dolores; Brotons, Dimpna Albert

2018-04-26

The results are presented on the «current situation of the organisation, resources and activity in paediatric cardiology in Spain». It was promoted by the Spanish Society of Paediatric Cardiology and Congenital Heart disease. An analysis was carried out on the results obtained from a specifically designed questionnaire, prepared by the Spanish Society of Paediatric Cardiology and Congenital Heart disease, that was sent to all hospitals around the country that offer the speciality of paediatric cardiology. A total of 86 questionnaires were obtained, including 14 hospitals that perform cardiac surgery on children. A total of 190 paediatric cardiology consultants, 40 cardiac surgeons, and 27 middle grade doctors performing their paediatric residency (MIR program) were identified. All hospitals had adequate equipment to perform an optimal initial evaluation of any child with a possible cardiac abnormality, but only tertiary centres could perform complex diagnostic procedures, interventional cardiology, and cardiac surgery. In almost all units around the country, paediatric cardiology consultants were responsible for outpatient clinics and hospital admissions, whereas foetal cardiology units were still mainly managed by obstetricians. The number of diagnostic and therapeutic procedures was similar to those reported in the first survey, except for a slight decrease in the total number of closed cardiac surgery procedures, and a proportional increase in the number of therapeutic catheterisations. Paediatric Cardiology in Spain is performed by paediatric cardiology consultants that were trained initially as general paediatricians, and then completed a paediatric cardiology training period. Almost all units have adequate means for diagnosis and treatment. Efforts should be directed to create a national registry that would not only allow a prospective quantification of diagnostic and therapeutic procedures, but also focus on their clinical outcomes. Copyright © 2018. Publicado por Elsevier España, S.L.U.

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

PubMed Central

2014-01-01

Background Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Methods Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Results Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). Conclusions The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear. PMID:25091201

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children.

PubMed

Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J

2014-08-05

Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear.

A systematic review of neuropsychiatric comorbidities in patients with both epilepsy and intellectual disability.

PubMed

van Ool, Jans S; Snoeijen-Schouwenaars, Francesca M; Schelhaas, Helenius J; Tan, In Y; Aldenkamp, Albert P; Hendriksen, Jos G M

2016-07-01

Epilepsy is a neurological condition that is particularly common in people with intellectual disability (ID). The care for people with both epilepsy and ID is often complicated by the presence of neuropsychiatric disorders, defined as psychiatric symptoms, psychiatric disorders, and behavioral problems. The aim of this study was to investigate associations between epilepsy or epilepsy-related factors and neuropsychiatric comorbidities in patients with ID and between ID and neuropsychiatric comorbidities in patients with epilepsy. We performed a systematic review of the literature, published between January 1995 and January 2015 and retrieved from PubMed/Medline, PsycINFO, and ERIC and assessed the risk of bias using the SIGN-50 methodology. Forty-two studies were identified, fifteen of which were assessed as having a low or acceptable risk-of-bias evaluation. Neuropsychiatric comorbidities were examined in relation to epilepsy in nine studies; in relation to epilepsy-related factors, such as seizure activity, seizure type, and medication in four studies; and in relation to the presence and degree of ID in five studies. We conclude that the presence of epilepsy only was not a clear determinant of neuropsychiatric comorbidity in patients with ID, although a tendency towards negative mood symptoms was identified. Epilepsy-related factors indicating a more severe form of epilepsy were associated with neuropsychiatric comorbidity as was the presence of ID as compared to those without ID in patients with epilepsy, although this should be validated in future research. A large proportion of the studies in this area is associated with a substantial risk of bias. There is a need for high quality studies using standardized methods to enable clear conclusions to be drawn that might assist in improving the quality of care for this population. Copyright © 2016 Elsevier Inc. All rights reserved.

Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children.

PubMed

Mina, T H; Lahti, M; Drake, A J; Räikkönen, K; Minnis, H; Denison, F C; Norman, J E; Reynolds, R M

2017-01-01

Prenatal maternal obesity has been linked to adverse childhood neuropsychiatric outcomes, including increased symptoms of attention deficit hyperactivity disorder (ADHD), internalizing and externalizing problems, affective disorders and neurodevelopmental problems but few studies have studied neuropsychiatric outcomes among offspring born to very severely obese women or assessed potential familial confounding by maternal psychological distress. We evaluated neuropsychiatric symptoms in 112 children aged 3-5 years whose mothers had participated in a longitudinal study of obesity in pregnancy (50 very severe obesity, BMI ⩾40 kg/m2, obese class III and 62 lean, BMI 18.5-25 kg/m2). The mothers completed the Conners' Hyperactivity Scale, Early Symptomatic Syndrome Eliciting Neurodevelopmental Clinical Examination Questionnaire (ESSENCE-Q), Child's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), and Child Behavior Checklist (CBCL) to assess child neuropsychiatric symptoms. Covariates included child's sex, age, birthweight, gestational age, socioeconomic deprivation levels, maternal age, parity, smoking status during pregnancy, gestational diabetes and maternal concurrent symptoms of anxiety and depression assessed using State Anxiety of Spielberger State-Trait Anxiety Index (STAI) and General Health Questionnaire (GHQ), respectively. Children exposed to prenatal maternal very severe obesity had significantly higher scores in the Conners' Hyperactivity Scale; ESSENCE-Q; total sleep problems in CSHQ; hyperactivity, conduct problems and total difficulties scales of the SDQ; higher externalizing and total problems, anxious/depressed, aggressive behaviour and other problem syndrome scores and higher DSM-oriented affective, anxiety and ADHD problems in CBCL. Prenatal maternal very severe obesity remained a significant predictor of child neuropsychiatric problems across multiple scales independent of demographic factors, prenatal factors and maternal concurrent symptoms of anxiety and depression. Prenatal maternal very severe obesity is a strong predictor of increased neuropsychiatric problems in early childhood.

Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects.

PubMed

Marco, Eva M; García-Gutiérrez, María S; Bermúdez-Silva, Francisco-Javier; Moreira, Fabricio A; Guimarães, Francisco; Manzanares, Jorge; Viveros, María-Paz

2011-01-01

Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric disorders, i.e., anxiety disorders, depression, and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB) system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R) in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD), the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation.

Endocannabinoid System and Psychiatry: In Search of a Neurobiological Basis for Detrimental and Potential Therapeutic Effects

PubMed Central

Marco, Eva M.; García-Gutiérrez, María S.; Bermúdez-Silva, Francisco-Javier; Moreira, Fabricio A.; Guimarães, Francisco; Manzanares, Jorge; Viveros, María-Paz

2011-01-01

Public concern on mental health has noticeably increased given the high prevalence of neuropsychiatric disorders. Cognition and emotionality are the most affected functions in neuropsychiatric disorders, i.e., anxiety disorders, depression, and schizophrenia. In this review, most relevant literature on the role of the endocannabinoid (eCB) system in neuropsychiatric disorders will be presented. Evidence from clinical and animal studies is provided for the participation of CB1 and CB2 receptors (CB1R and CB2R) in the above mentioned neuropsychiatric disorders. CBRs are crucial in some of the emotional and cognitive impairments reported, although more research is required to understand the specific role of the eCB system in neuropsychiatric disorders. Cannabidiol (CBD), the main non-psychotropic component of the Cannabis sativa plant, has shown therapeutic potential in several neuropsychiatric disorders. Although further studies are needed, recent studies indicate that CBD therapeutic effects may partially depend on facilitation of eCB-mediated neurotransmission. Last but not least, this review includes recent findings on the role of the eCB system in eating disorders. A deregulation of the eCB system has been proposed to be in the bases of several neuropsychiatric disorders, including eating disorders. Cannabis consumption has been related to the appearance of psychotic symptoms and schizophrenia. In contrast, the pharmacological manipulation of this eCB system has been proposed as a potential strategy for the treatment of anxiety disorders, depression, and anorexia nervosa. In conclusion, the eCB system plays a critical role in psychiatry; however, detrimental consequences of manipulating this endogenous system cannot be underestimated over the potential and promising perspectives of its therapeutic manipulation. PMID:22007164

Clinical Profile of Children and Adolescents Attending the Behavioural Paediatrics Unit OPD in a Tertiary Care Set up

ERIC Educational Resources Information Center

Jayaprakash, R.

2012-01-01

Background: There are limited studies on the clinical profile of children attending child guidance clinic under Paediatric background. Aims: To study clinical profile of Children & adolescents attending the Behavioural Paediatrics Unit (BPU) OPD under department of Paediatrics in a tertiary care set up. Methods: Monthly average turnover in the…

Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice.

PubMed

Van der Jeugd, Ann; Parra-Damas, Arnaldo; Baeta-Corral, Raquel; Soto-Faguás, Carlos M; Ahmed, Tariq; LaFerla, Frank M; Giménez-Llort, Lydia; D'Hooge, Rudi; Saura, Carlos A

2018-04-24

Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer's disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12-14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.

The Spanish Burden of Disease 2010: Neurological, mental and substance use disorders.

PubMed

Lara, Elvira; Garin, Noé; Ferrari, Alize J; Tyrovolas, Stefanos; Olaya, Beatriz; Sànchez-Riera, Lidia; Whiteford, Harvey A; Haro, Josep Maria

2015-01-01

We used data from the Global Burden of Disease, Injuries, and Risk Factors Study 2010 to report on the burden of neuropsychiatric disorders in Spain. The summary measure of burden used in the study was the disability-adjusted life-year (DALY), which sums of the years of life lost due to premature mortality (YLLs) and the years lived with disability (YLDs). DALYs were adjusted for comorbidity and estimated with 95% uncertainty intervals. The burden of neuropsychiatric disorders accounted for 18.4% of total all-cause DALYs generated in Spain for 2010. Within this group, the top five leading causes of DALYs were: depressive disorders, Alzheimer's disease, migraine, substance-use disorders, and anxiety disorder, which accounted for 70.9% of all DALYs due to neuropsychiatric disorders. Neurological disorders represented 5.03% of total all cause YLLs, whereas mental and substance-use disorders accounted for 0.8%. Mental and substance-use disorders accounted for 22.4% of total YLDs, with depression being the most disabling disorder. Neurological disorders represented 8.3% of total YLDs. Neuropsychiatric disorders were one of the leading causes of disability in 2010. This finding contributes to our understanding of the burden of neuropsychiatric disorders in the Spanish population and highlights the importance of prioritising neuropsychiatric disorders in the Spanish public health system. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

Cognitive and Functional Correlates of NPI-Q Scores and Symptom Clusters in Mildly Demented Alzheimer Patients.

PubMed

Travis Seidl, Jennifer N; Massman, Paul J

2016-01-01

Previous research has demonstrated an association between the emotional and behavioral symptoms of dementia, known as neuropsychiatric symptoms, and cognitive and functional decline among patients with Alzheimer disease (AD). The present study aimed to identify associations between neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q) and cognitive and functional performance. Participants were 256 AD patients enrolled in the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine. An exploratory factor analysis of the NPI-Q indicated a 2-factor structure consisting of Negative/Oppositional and Anxiety/Restlessness factors. Regression analyses revealed significant associations between greater total severity of neuropsychiatric symptoms and poorer performance on basic and Instrumental Activities of Daily Living. Greater severity of Anxiety/Restlessness symptoms was associated with poor performance on measures of visuospatial functioning and basic and instrumental activities of daily living. The Negative/Oppositional factor was not related to cognition or functioning. In summary, neuropsychiatric symptoms (particularly Anxiety/Restlessness symptoms) were related to cognition and everyday functioning. Proper assessment and treatment of these symptoms is essential for improving cognition and functioning in AD patients.

Differences in clinical reasoning among nurses working in highly specialised paediatric care.

PubMed

Andersson, Nina; Klang, Birgitta; Petersson, Gunilla

2012-03-01

The aim of the study was to examine differences in clinical reasoning among novice, experienced and specialist paediatric nurses. Highly specialised paediatric care requires specific knowledge and ongoing skill performance of the nurses employed. There is a lack of research in how paediatric nurses manage the daily care problems they encounter and how they acquire the skills required to give patients the best possible care. More knowledge is needed about how paediatric nurses with different experience and education reason and communicate about paediatric patient situations. The study was based on six recorded group discussions of a fictitious, but realistic paediatric case. Three categories of nurses: novices (n = 7), experienced (n = 7) and specialists (n = 7) from a paediatric hospital participated. A qualitative content analysis approach was chosen to examine differences in clinical reasoning. Several themes were uncovered: child's social situation, child abuse and the child's illness, qualitative differences emerged in how the nurses discussed the case. Three approaches were identified: a task-oriented approach (novices and experienced), an action-oriented approach (novices and experienced) and hypothesis-oriented approach (specialists) while discussing the case. When comparing nurses in three competence groups, it was established that the groups with extensive experience and specialist education reasoned differently than the other groups. Between the novice and experienced groups, no obvious differences were found. Thus, the importance of experience alone for the development of competence is still an open question. Experience combined with further education appears important for developing professional competence in paediatric care. Nurses' reasoning in clinical paediatric care is related to experience and training. © 2012 Blackwell Publishing Ltd.

Compliance with dental treatment recommendations by rural paediatric patients after a live-video teledentistry consultation: A preliminary report.

PubMed

McLaren, Sean W; Kopycka-Kedzierawski, Dorota T

2016-04-01

The purpose of this research was to assess the compliance rate with recommended dental treatment by rural paediatric dental patients after a live-video teledentistry consultation. A retrospective dental chart review was completed for 251 rural paediatric patients from the Finger Lakes region of New York State who had an initial teledentistry appointment with a paediatric dentist located remotely at the Eastman Institute for Oral Health in Rochester, NY. The recommended treatment modalities were tabulated and comprehensive dental treatment completion rates were obtained. The recommended treatment modality options of: treatment in the paediatric dental clinic; treatment using nitrous oxide anxiolysis; treatment with oral sedation; treatment in the operating room with general anaesthesia; or teleconsultation were identified for the 251 patients. Compliance rates for completed dental treatment based on initial teleconsultation recommendations were: 100% for treatment in the paediatric dental clinic; 56% for nitrous oxide patients; 87% for oral sedation; 93% for operating room; and 90% for teleconsultations. The differences in the compliance rates for all treatment modalities were not statistically significant (Fisher's exact test, p > 0.05). Compliance rates for completed comprehensive dental treatment for this rural population of paediatric dental patients were quite high, ranging from 56% to 100%, and tended to be higher when treatment was completed in fewer visits. Live-video teledentistry consultations conducted among rural paediatric patients and a paediatric dentist in the specialty clinic were feasible options for increasing dental treatment compliance rates when treating complex paediatric dental cases. © The Author(s) 2015.

Paediatric clinical research from the perspective of hospital pharmacists from France and Canada.

PubMed

Guérin, Aurélie; Tanguay, Cynthia; Lebel, Denis; Prot-Labarthe, Sonia; Bourdon, Olivier; Bussières, Jean-François

2014-12-01

To compare pharmacy support for paediatric research services in France and Canada and to describe the perception of pharmacists and rank the paediatric clinical research issues. This was a cross-sectional descriptive study. All paediatric hospitals from Canada and the main hospitals from France were contacted. A survey was conducted from May-September 2012. Descriptive statistics were performed. Results from 11 paediatric hospitals in Canada (11/12, 92%) and 11 (11/18, 61%) in France were obtained. There was a similar number of ongoing paediatric clinical trials per hospital in France versus Canada (38 (10-81) versus 20 (4-178)). A lower number of pharmacists per hospital was observed in France (17 (11.5-35) versus 45 (18.9-76.8)), but a similar number of pharmacists were assigned to clinical trials (1.5 (1-3) versus 1.9 (0.2-17.4)). Institutional protocols represented the majority of paediatric clinical trials in France (61% (14-100) versus 25% (0-100)). Similar pharmacy support services were offered, but the majority of French respondents also offered help for institutional protocol development (91 versus 50% P = 0.063). The main issues associated with paediatric clinical research were absence of financial interest from the pharmaceutical industry, prohibitive cost versus profit ratio, small patient cohorts and the non-availability of the appropriate drug formulations. Difficulties related to pharmaceutical compounding were identified as the main hindrance to paediatric clinical research; particular attention should be paid to these details when setting up a paediatric trial. © 2014 Royal Pharmaceutical Society.

Advance care planning for adolescent patients with life-threatening neurological conditions: a survey of Japanese paediatric neurologists.

PubMed

Yotani, Nobuyuki; Kizawa, Yoshiyuki; Shintaku, Haruo

2017-01-01

To evaluate current attitudes and barriers to advance care planning for adolescent patients with life-threatening conditions among paediatric neurologists. Cross-sectional study. A self-reported questionnaire was administered to assess the practice of advance care planning, advance directives and barriers to advance care planning for adolescent patients with life-threatening conditions. All board-certified paediatric neurologists in Japan were surveyed and those who had experience in taking care of adolescent patients with decision-making capacity were analysed. We compared the results with those of paediatric haematologists reported previously. In total, 186 paediatric neurologists were analysed. If the patient's prognosis was <3 months, only about 30% of paediatric neurologists reported having discussions with patients, such as 'do not attempt resuscitation' orders (28%) and ventilator use (32%), whereas more than 70% did discuss these topics with patients' families. About half of the paediatric neurologists did not discuss advance directives at the end of life with their patients, whereas over 75% did discuss advance directives with patients' families. Compared with paediatric haematologists, paediatric neurologists had more end-of-life discussions with patients, such as where treatment and care will take place, do not attempt resuscitation orders, and the use of a ventilator, if the patient's prognosis was >1 year. About half or less of the paediatric neurologists discussed advance care planning and advance directives with their adolescent patients who had life-threatening conditions, even if the patient's prognosis was <3 months. They tended to discuss advance care planning and advance directives more with families than with patients themselves.

The proposal of Paediatric Virology and its perspectives: An interview with Professor of Paediatrics Maria Theodoridou

PubMed Central

Mammas, Ioannis N.; Spandidos, Demetrios A.

2017-01-01

Professor Maria Theodoridou, Emeritus Professor of Paediatrics at the University of Athens, is one of the few paediatricians in Greece, who have experienced almost all the infectious diseases of the second half of the 20th century and their severe consequences, prior to the widespread adoption of immunisations. A milestone during her career was the establishment of a specialised National Reference Unit for the care of paediatric patients with acquired immune deficiency syndrome (AIDS) at the ‘Aghia Sophia’ Children's Hospital in Athens, Greece. According to Professor Theodoridou, training on the prevention, management and treatment of neonatal and paediatric viral infections represents a new educational challenge for both community as well as hospital-based paediatric health professionals. The debate of the potential strategically principal role of Paediatric Virology subspecialists in the primary, secondary and tertiary clinical practice is definitely necessary and needs further discussion and evaluation, she adds. She describes the difficulties that Greece, a country under a long-standing financial crisis, faces for the hospital-based management of paediatric viral infections and refers to the future advances, which are expected in the field of diagnosis and treatment of viral infections in neonates and children. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens on October 7th, 2017, Professor Theodoridou will focus on the immigration crisis and vaccination policy. PMID:29042916

The proposal of Paediatric Virology and its perspectives: An interview with Professor of Paediatrics Maria Theodoridou.

PubMed

Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

Professor Maria Theodoridou, Emeritus Professor of Paediatrics at the University of Athens, is one of the few paediatricians in Greece, who have experienced almost all the infectious diseases of the second half of the 20th century and their severe consequences, prior to the widespread adoption of immunisations. A milestone during her career was the establishment of a specialised National Reference Unit for the care of paediatric patients with acquired immune deficiency syndrome (AIDS) at the 'Aghia Sophia' Children's Hospital in Athens, Greece. According to Professor Theodoridou, training on the prevention, management and treatment of neonatal and paediatric viral infections represents a new educational challenge for both community as well as hospital-based paediatric health professionals. The debate of the potential strategically principal role of Paediatric Virology subspecialists in the primary, secondary and tertiary clinical practice is definitely necessary and needs further discussion and evaluation, she adds. She describes the difficulties that Greece, a country under a long-standing financial crisis, faces for the hospital-based management of paediatric viral infections and refers to the future advances, which are expected in the field of diagnosis and treatment of viral infections in neonates and children. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens on October 7th, 2017, Professor Theodoridou will focus on the immigration crisis and vaccination policy.

Future career intentions of higher specialist trainees in general Paediatrics.

PubMed

Butler, Grainne; Breatnach, Colm; Harty, Sinead; Gavin, Patrick; O'Donnell, Colm; O'Grady, Michael J

2018-03-27

A survey of paediatric higher specialist trainees was carried out in 2002 assessing career intentions and perception of training. Fourteen years later, with increased numbers of trainees and a national model of care and a tertiary paediatric hospital on the horizon, we re-evaluated the career intentions of the current trainee workforce. To assess the career intentions of the current paediatric higher specialist trainees. A 28-item questionnaire was developed based on a previously validated instrument and distributed online using the Royal College of Physicians of Ireland trainee database. We distributed the questionnaire to 118 eligible trainees and received responses from 92 (78%). Seventy-nine (86%) respondents desire a consultant post in Ireland. Seventy-five (82%) indicated that their preferred consultant post location was in a tertiary paediatric centre. Sixty-two trainees (67%) intend to become subspecialists with 25 (27%) planning a career in general paediatrics. This contrasts with the 2002 survey when 76% wished to work in urban centres and 61% of trainees planned a career in general paediatrics. There appears to be a mismatch between the career goals of the future paediatric consultant workforce and the requirements for staffing paediatric units nationally. This has the potential to complicate the proposed expansion of general paediatricians in regional centres and result in a significant proportion of current trainees failing to secure a post in their desired location.

Knowledge and training in paediatric medical traumatic stress and trauma-informed care among emergency medical professionals in low- and middle-income countries

PubMed Central

2018-01-01

ABSTRACT Background: Provision of psychosocial care, in particular trauma-informed care, in the immediate aftermath of paediatric injury is a recommended strategy to minimize the risk of paediatric medical traumatic stress. Objective: To examine the knowledge of paediatric medical traumatic stress and perspectives on providing trauma-informed care among emergency staff working in low- and middle-income countries (LMICs). Method: Training status, knowledge of paediatric medical traumatic stress, attitudes towards incorporating psychosocial care and barriers experienced were assessed using an online self-report questionnaire. Respondents included 320 emergency staff from 58 LMICs. Data analyses included descriptive statistics, t-tests and multiple regression. Results: Participating emergency staff working in LMICs had a low level of knowledge of paediatric medical traumatic stress. Ninety-one percent of respondents had not received any training or education in paediatric medical traumatic stress, or trauma-informed care for injured children, while 94% of respondents indicated they wanted training in this area. Conclusions: There appears to be a need for training and education of emergency staff in LMICs regarding paediatric medical traumatic stress and trauma-informed care, in particular among staff working in comparatively lower income countries. PMID:29760867

Knowledge and training in paediatric medical traumatic stress and trauma-informed care among emergency medical professionals in low- and middle-income countries.

PubMed

Hoysted, Claire; Babl, Franz E; Kassam-Adams, Nancy; Landolt, Markus A; Jobson, Laura; Van Der Westhuizen, Claire; Curtis, Sarah; Kharbanda, Anupam B; Lyttle, Mark D; Parri, Niccolò; Stanley, Rachel; Alisic, Eva

2018-01-01

Background : Provision of psychosocial care, in particular trauma-informed care, in the immediate aftermath of paediatric injury is a recommended strategy to minimize the risk of paediatric medical traumatic stress. Objective : To examine the knowledge of paediatric medical traumatic stress and perspectives on providing trauma-informed care among emergency staff working in low- and middle-income countries (LMICs). Method : Training status, knowledge of paediatric medical traumatic stress, attitudes towards incorporating psychosocial care and barriers experienced were assessed using an online self-report questionnaire. Respondents included 320 emergency staff from 58 LMICs. Data analyses included descriptive statistics, t -tests and multiple regression. Results : Participating emergency staff working in LMICs had a low level of knowledge of paediatric medical traumatic stress. Ninety-one percent of respondents had not received any training or education in paediatric medical traumatic stress, or trauma-informed care for injured children, while 94% of respondents indicated they wanted training in this area. Conclusions : There appears to be a need for training and education of emergency staff in LMICs regarding paediatric medical traumatic stress and trauma-informed care, in particular among staff working in comparatively lower income countries.

Validation of the Australian diagnostic reference levels for paediatric multi detector computed tomography: a comparison of RANZCR QUDI data and subsequent NDRLS data from 2012 to 2015.

PubMed

Anna, Hayton; Wallace, Anthony; Thomas, Peter

2017-03-01

The national diagnostic reference level service (NDRLS), was launched in 2011, however no paediatric data were submitted during the first calendar year of operation. As such, Australian national diagnostic reference levels (DRLs), for paediatric multi detector computed tomography (MDCT), were established using data obtained from a Royal Australian and New Zealand College of Radiologists (RANZCR), Quality Use of Diagnostic Imaging (QUDI), study. Paediatric data were submitted to the NDRLS in 2012 through 2015. An analysis has been made of the NDRLS paediatric data using the same method as was used to analyse the QUDI data to establish the Australian national paediatric DRLs for MDCT. An analysis of the paediatric NDRLS data has also been made using the method used to calculate the Australian national adult DRLs for MDCT. A comparison between the QUDI data and subsequent NDRLS data shows the NDRLS data to be lower on average for the Head and AbdoPelvis protocol and similar for the chest protocol. Using an average of NDRLS data submitted between 2012 and 2015 implications for updated paediatric DRLS are considered.

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

PubMed

Lopes, S R M; Gormezano, N W S; Gomes, R C; Aikawa, N E; Pereira, R M R; Terreri, M T; Magalhães, C S; Ferreira, J C; Okuda, E M; Sakamoto, A P; Sallum, A M E; Appenzeller, S; Ferriani, V P L; Barbosa, C M; Lotufo, S; Jesus, A A; Andrade, L E C; Campos, L M A; Bonfá, E; Silva, C A

2017-08-01

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Paediatrics: the etymology of a name.

PubMed

Pearn, John

2011-08-01

Within the history of paediatrics is the history of the name used to describe it. The etymology of the word 'paediatrics' dates from its first written use, recorded as 'pädiatrik' in the German literature and as 'paediatric', later 'pediatric' in the USA, both first in 1850. Professor Robley Dunglison (1788-1869), the British and American medical lexicographer, first defined 'paediatria' as 'the treatment of the diseases of children' in 1855. 'Pediatric medicine' was promoted as a specialty in the USA in 1880. The oldest monumental inscription defining the specialty of 'paediatrics' in the UK is to be found on a plaque added (in 1950) to the memorial to Dr George Armstrong (1719-1789), a founder of the specialty of paediatrics, in Castleton Cemetery, Scottish Borders, Roxburghshire. 'Paediatrics' and 'child health', with subtle semantic distinctions, had become well established in the English-speaking world by the middle of the 20th century. This paper presents an interpretative chronology of the etymology of the descriptors of the specialty that enjoins all who care for children.

How small is small enough? Role of robotics in paediatric urology

PubMed Central

Ganpule, Arvind P.; Sripathi, Venkat

2015-01-01

The well-known advantages of robotic surgery include improved dexterity, three-dimensional operating view and an improved degree of freedom. Robotic surgery is performed for a wide range of surgeries in urology, which include radical prostatectomy, radical cystectomy, and ureteric reimplantation. Robotic paediatric urology is evolving. The major hindrance in the development of paediatric robotics is, first, the differences in practice patterns in paediatric urology compared with adult urology thereby making development of expertise difficult and secondly it is challenging to conduct proper studies in the paediatric population because of the paucity of cases. The difficulties in conducting these studies include difficulty in designing a proper randomised study, difficulties with blinding, and finally, the ethical issues involved, finally the instruments although in the phase of evolution require a lot of improvement. In this article, we review the relevant articles for paediatric robotic surgery. We emphasise on the technical aspects and results in contemporary paediatric robotic case series. PMID:25598599

How small is small enough? Role of robotics in paediatric urology.

PubMed

Ganpule, Arvind P; Sripathi, Venkat

2015-01-01

The well-known advantages of robotic surgery include improved dexterity, three-dimensional operating view and an improved degree of freedom. Robotic surgery is performed for a wide range of surgeries in urology, which include radical prostatectomy, radical cystectomy, and ureteric reimplantation. Robotic paediatric urology is evolving. The major hindrance in the development of paediatric robotics is, first, the differences in practice patterns in paediatric urology compared with adult urology thereby making development of expertise difficult and secondly it is challenging to conduct proper studies in the paediatric population because of the paucity of cases. The difficulties in conducting these studies include difficulty in designing a proper randomised study, difficulties with blinding, and finally, the ethical issues involved, finally the instruments although in the phase of evolution require a lot of improvement. In this article, we review the relevant articles for paediatric robotic surgery. We emphasise on the technical aspects and results in contemporary paediatric robotic case series.

Overview of paediatric obesity for the paediatric mental health provider.

PubMed

Scheimann, Ann O

2012-06-01

Childhood obesity represents a significant challenge for paediatric healthcare delivery. As obesity rates increase, obese children and adolescents are at significant risk for the development of a myriad of medical and surgical problems as well as mental health problems. Moreover, children with mental health problems are increasingly presenting to their psychiatrists with obesity. Treatment of paediatric obesity requires a multidisciplinary approach with incorporation of the family into the treatment plan although still typically only offering suboptimal results. Paediatric providers from all disciplines should focus efforts primarily on obesity prevention and encouragement of healthy lifestyles, while incorporating treatment for obesity when such efforts fail. The goals of this article are to provide an overview of the epidemiology, pathophysiology, genetics, clinical features and treatment strategies for paediatric obesity.

A Review of Applied Aspects of Dealing with Gut Microbiota Impact on Rodent Models.

PubMed

Hansen, Axel Kornerup; Krych, Łukasz; Nielsen, Dennis Sandris; Hansen, Camilla Hartmann Friis

2015-01-01

The gut microbiota (GM) affects numerous human diseases, as well as rodent models for these. We will review this impact and summarize ways to handle this challenge in animal research. The GM is complex, with the largest fractions being the gram-positive phylum Firmicutes and the gram-negative phylum Bacteroidetes. Other important phyla are the gram-negative phyla Proteobacteria and Verrucomicrobia, and the gram-positive phylum Actinobacteria. GM members influence models for diseases, such as inflammatory bowel diseases, allergies, autoimmunity, cancer, and neuropsychiatric diseases. GM characterization of all individual animals and incorporation of their GM composition in data evaluation may therefore be considered in future protocols. Germfree isolator-housed rodents or rodents made virtually germ free by antibiotic cocktails can be used to study diverse microbial influences on disease expression. Through subsequent inoculation with selected strains or cocktails of microbes, new "defined flora" models can yield valuable knowledge on the impact of the GM, and of specific GM members and their interactions, on important disease phenotypes and mechanisms. Rodent husbandry and microbial quality assurance practices will be important to ensure and confirm appropriate and research relevant GM. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Glial Biomarkers in Human Central Nervous System Disease

PubMed Central

Garden, Gwenn A.; Campbell, Brian M.

2017-01-01

There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. PMID:27228454

Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management.

PubMed

Lam, Nguyet-Cam Vu; Ghetu, Maria V; Bieniek, Marzena L

2016-08-15

Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services.

Neuroactive Steroids: Receptor Interactions and Responses

PubMed Central

Tuem, Kald Beshir; Atey, Tesfay Mehari

2017-01-01

Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors. Among these, NSs (especially allopregnanolone) have high potency and extensive GABA-A receptors and hence demonstrate anticonvulsant, anesthetic, central cytoprotectant, and baroreflex inhibitory effects. NSs are also involved in mood and learning via serotonin and anti-nociceptive activity via T-type voltage-gated Ca2+ channels. Moreover, they are modulators of mitochondrial function, synaptic plasticity, or regulators of apoptosis, which have a role in neuroprotective via voltage-dependent anion channels receptors. For proper functioning, NASs need to be in their normal level, whereas excess and deficiency may lead to abnormalities. When they are below the normal, NSs could have a part in development of depression, neuro-inflammation, multiple sclerosis, experimental autoimmune encephalitis, epilepsy, and schizophrenia. On the other hand, stress and attention deficit disorder could occur during excessive level. Overall, NASs are very important molecules with major neuropsychiatric activity. PMID:28894435

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

PubMed

Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia

2015-12-01

Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment. Neuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.

A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer's disease (MAIN-AD).

PubMed

Ballard, Clive; Thomas, Alan; Gerry, Stephen; Yu, Ly-Mee; Aarsland, Dag; Merritt, Claire; Corbett, Anne; Davison, Christopher; Sharma, Narenda; Khan, Zunera; Creese, Byron; Loughlin, Paul; Bannister, Carol; Burns, Alistair; Win, Soe Nyunt; Walker, Zuzana

2015-04-01

Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI -1.80-2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI -0.35-8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI -1.68-11.70; P = .05) and 3.63 (95% CI -1.40-8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Paediatrics in Barcelona.

PubMed

Midulla, Fabio; Lombardi, Enrico; Rottier, Bart; Lindblad, Anders; Grigg, Jonathan; Bohlin, Kajsa; Rusconi, Franca; Pohunek, Petr; Eber, Ernst

2014-08-01

This update will describe the paediatric highlights from the 2013 European Respiratory Society (ERS) annual congress in Barcelona, Spain. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) have been chosen by group officers and are presented in the context of current literature. ©ERS 2014.

Prevention of central venous catheter infections: a survey of paediatric ICU nurses' knowledge and practice.

PubMed

Ullman, Amanda J; Long, Debbie A; Rickard, Claire M

2014-02-01

Central venous catheters are important in the management of paediatric intensive care unit patients, but can have serious complications which worsen the patients' health, prolong hospital stays and increase the cost of care. Evidence-based recommendations for preventing catheter-related bloodstream infections are available, but it is unknown how widely these are known or practiced in the paediatric intensive care environment. To assess nursing knowledge of evidence based guidelines to prevent catheter-related bloodstream infections; the extent to which Australia and New Zealand paediatric intensive cares have adopted prevention practices; and to identify the factors that encouraged their adoption and improve nursing knowledge. Cross-sectional surveys using convenience sampling. Tertiary level paediatric intensive care units in Australia and New Zealand. Paediatric intensive care nursing staff and nurse managers. Between 2010 and 2011, the 'Paediatric Intensive Care Nurses' Knowledge of Evidence-Based Catheter-Related Bloodstream Infection Prevention Questionnaire' was distributed to paediatric intensive care nursing staff and the 'Catheter-Related Bloodstream Infection Prevention Practices Survey' was distributed to nurse managers to measure knowledge, practices and culture. The questionnaires were completed by 253 paediatric intensive care nurses (response rate: 34%). The mean total knowledge score was 5.5 (SD=1.4) out of a possible ten, with significant variation of total scores between paediatric intensive care sites (p=0.01). Other demographic characteristics were not significantly associated with variation in total knowledge scores. All nursing managers from Australian and New Zealand paediatric intensive care units participated in the survey (n=8; response rate: 100%). Wide practice variation was reported, with inconsistent adherence to recommendations. Safety culture was not significantly associated with mean knowledge scores per site. This study has identified that there is variation in the infection prevention approach and nurses' knowledge about catheter-related bloodstream infection prevention. The presence of an improved safety culture, years of paediatric intensive care experience and higher qualifications did not influence the nurses' uptake of recommendations, therefore further factors need to be explored in order to improve understanding and implementation of best practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

Paediatric traumatic cardiac arrest: a Delphi study to establish consensus on definition and management.

PubMed

Rickard, Annette C; Vassallo, James; Nutbeam, Tim; Lyttle, Mark D; Maconochie, Ian K; Enki, Doyo G; Smith, Jason E

2018-04-28

Paediatric traumatic cardiac arrest (TCA) is associated with low survival and poor outcomes. The mechanisms that underlie TCA are different from medical cardiac arrest; the approach to treatment of TCA may therefore also need to differ to optimise outcomes. The aim of this study was to explore the opinion of subject matter experts regarding the diagnosis and treatment of paediatric TCA, and to reach consensus on how best to manage this group of patients. An online Delphi study was conducted over three rounds, with the aim of achieving consensus (defined as 70% agreement) on statements related to the diagnosis and management of paediatric TCA. Participants were invited from paediatric and adult emergency medicine, paediatric anaesthetics, paediatric ICU and paediatric surgery, as well as Paediatric Major Trauma Centre leads and representatives from the Resuscitation Council UK. Statements were informed by literature reviews and were based on elements of APLS resuscitation algorithms as well as some concepts used in the management of adult TCA; they ranged from confirmation of cardiac arrest to the indications for thoracotomy. 73 experts completed all three rounds between June and November 2016. Consensus was reached on 14 statements regarding the diagnosis and management of paediatric TCA; oxygenation and ventilatory support, along with rapid volume replacement with warmed blood, improve survival. The duration of cardiac arrest and the lack of a response to intervention, along with cardiac standstill on ultrasound, help to guide the decision to terminate resuscitation. This study has given a consensus-based framework to guide protocol development in the management of paediatric TCA, though further work is required in other key areas including its acceptability to clinicians. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of paediatric radiology services in hospitals in the UK.

PubMed

Halliday, K; Drinkwater, K; Howlett, D C

2016-12-01

To compare paediatric radiology provision across the UK with national standards published by the Department of Health and the Royal College of Radiologists (RCR). Audit standards and indicators for paediatric imaging were derived from "Delivering quality imaging services for children", 1 "Standards for imaging in cases of suspected non-accidental injury" 2 and "Improving paediatric interventional radiology services" 3 and agreed jointly by the Clinical Radiology Audit Committee and the British Society of Paediatric Radiology. A questionnaire was sent to all hospitals and NHS trusts imaging children aged 16 or younger in the UK in October 2013. The target for all indicators was 100%. Eighty-seven of 196 (44%) eligible institutions submitted data, the size distribution of the institutions was representative when compared to data from "Facing the future: a review of paediatric services" 4 published by the Royal College of Paediatrics and Child health. Only 65% of paediatric images were obtained by staff who had had specific training and only 60% were reported by radiographers or radiologists with appropriate training. Sixty-two percent of centres did not have access to a paediatric opinion 24 hours a day, 7 days a week all year; only 34% of radiographers who regularly imaged children had had any access to continuing professional development (CPD) in the 12 months of the audit. Although all hospitals had facilities for image transfer, only 57% had any formal funding arrangements in place for external reporting of images. The standards set for a network approach to paediatric radiology provision in "Delivering quality imaging services for children" are largely unmet. This failure to make the most of the workforce and resources puts vulnerable children at risk. The authors urge NHS England to work with the RCR to organise and administer a national network for paediatric imaging. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Confidence and authority through new knowledge: An evaluation of the national educational programme in paediatric oncology nursing in Sweden.

PubMed

Pergert, Pernilla; Af Sandeberg, Margareta; Andersson, Nina; Márky, Ildikó; Enskär, Karin

2016-03-01

There is a lack of nurse specialists in many paediatric hospitals in Sweden. This lack of competence is devastating for childhood cancer care because it is a highly specialised area that demands specialist knowledge. Continuing education of nurses is important to develop nursing practice and also to retain them. The aim of this study was to evaluate a Swedish national educational programme in paediatric oncology nursing. The nurses who participated came from all of the six paediatric oncology centres as well as from general paediatric wards. At the time of the evaluation, three groups of registered nurses (n=66) had completed this 2year, part-time educational programme. A study specific questionnaire, including closed and open-ended questions was sent to the 66 nurses and 54 questionnaires were returned. Answers were analysed using descriptive statistics and qualitative content analysis. The results show that almost all the nurses (93%) stayed in paediatric care after the programme. Furthermore, 31% had a position in management or as a consultant nurse after the programme. The vast majority of the nurses (98%) stated that the programme had made them more secure in their work. The nurses were equipped, through education, for paediatric oncology care which included: knowledge generating new knowledge; confidence and authority; national networks and resources. They felt increased confidence in their roles as paediatric oncology nurses as well as authority in their encounters with families and in discussions with co-workers. New networks and resources were appreciated and used in their daily work in paediatric oncology. The programme was of importance to the career of the individual nurse and also to the quality of care given to families in paediatric oncology. The national educational programme for nurses in Paediatric Oncology Care meets the needs of the highly specialised care. Copyright © 2015 Elsevier Ltd. All rights reserved.

Migrant-friendly hospitals: a paediatric perspective - improving hospital care for migrant children

PubMed Central

2013-01-01

Background The European Union (EU) Migrant-Friendly Hospital (MFH) Initiative, introduced in 2002, promotes the adoption of care approaches adapted to meet the service needs of migrants. However, for paediatric hospitals, no specific recommendations have been offered for MFH care for children. Using the Swiss MFH project as a case study, this paper aims to identify hospital-based care needs of paediatric migrants (PMs) and good service approaches. Methods Semi-structured interviews were conducted with principal project leaders of five paediatric hospitals participating in the Swiss MFH project. A review of the international literature on non-clinical hospital service needs and service responses of paediatric MFHs was conducted. Results Paediatric care can be complex, usually involving both the patient and the patient’s family. Key challenges include differing levels of acculturation between parents and children; language barriers; cultural differences between patient and provider; and time constraints. Current service and infrastructural responses include interpretation services for PMs and parents, translated information material, and special adaptations to ensure privacy, e.g., during breastfeeding. Clear standards for paediatric migrant-friendly hospitals (P-MFH) are lacking. Conclusions International research on hospital care for migrant children is scarce. The needs of paediatric migrants and their families may differ from guidance for adults. Paediatric migrant needs should be systematically identified and used to inform paediatric hospital care approaches. Hospital processes from admission to discharge should be revised to ensure implementation of migrant-sensitive approaches suitable for children. Staff should receive adequate support, such as training, easily available interpreters and sufficient consultation time, to be able to provide migrant-friendly paediatric services. The involvement of migrant groups may be helpful. Improving the quality of care for PMs at both policy and service levels is an investment in the future that will benefit native and migrant families. PMID:24093461

Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

PubMed

Chan, D W S; Thomas, T; Lim, M; Ling, S; Woodhall, M; Vincent, A

2017-03-01

Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABA B receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis

PubMed Central

Peschl, Patrick; Ramberger, Melanie; Höftberger, Romana; Jöhrer, Karin; Baumann, Matthias; Rostásy, Kevin; Reindl, Markus

2017-01-01

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers. PMID:28327523

Understanding the Influence of Socioeconomic Environment on Paediatric Antiretroviral Treatment Coverage: Towards Closing Treatment Gaps in Sub-Saharan Africa.

PubMed

Adeyinka, Daniel A; Evans, Meirion R; Ozigbu, Chamberline E; van Woerden, Hugo; Adeyinka, Esther F; Oladimeji, Olanrewaju; Aimakhu, Chris; Odoh, Deborah; Chamla, Dick

2017-03-01

Many sub-Saharan African countries have massively scaled-up their antiretroviral treatment (ART) programmes, but many national programmes still show large gaps in paediatric ART coverage making it challenging to reduce AIDS-related deaths among HIV-infected children. We sought to identify enablers of paediatric ART coverage in Africa by examining the relationship between paediatric ART coverage and socioeconomic parameters measured at the population level so as to accelerate reaching the 90-90-90 targets. Ecological analyses of paediatric ART coverage and socioeconomic indicators were performed. The data were obtained from the United Nations agencies and Forum for a new World Governance reports for the 21 Global Plan priority countries in Africa with highest burden of mother-to-child HIV transmission. Spearman's correlation and median regression were utilized to explore possible enablers of paediatric ART coverage. Factors associated with paediatric ART coverage included adult literacy (r=0.6, p=0.004), effective governance (r=0.6, p=0.003), virology testing by 2 months of age (r=0.9, p=0.001), density of healthcare workers per 10,000 population (r=0.6, p=0.007), and government expenditure on health (r=0.5, p=0.046). The paediatric ART coverage had a significant inverse relationship with the national mother-to-child transmission (MTCT) rate (r=-0.9, p<0.001) and gender inequality index (r=-0.6, p=0.006). Paediatric ART coverage had no relationship with poverty and HIV stigma indices. Low paediatric ART coverage continues to hamper progress towards eliminating AIDS-related deaths in HIV-infected children. Achieving this requires full commitment to a broad range of socioeconomic development goals. Copyright© by the National Institute of Public Health, Prague 2017

Understanding case mix across three paediatric services: could integration of primary and secondary general paediatrics alter walk-in emergency attendances?

PubMed

Steele, Lloyd; Coote, Nicky; Klaber, Robert; Watson, Mando; Coren, Michael

2018-05-04

To understand the case mix of three different paediatric services, reasons for using an acute paediatric service in a region of developing integrated care and where acute attendances could alternatively have been managed. Mixed methods service evaluation, including retrospective review of referrals to general paediatric outpatients (n=534) and a virtual integrated service (email advice line) (n=474), as well as a prospective survey of paediatric ambulatory unit (PAU) attendees (n=95) and review by a paediatric consultant/registrar to decide where these cases could alternatively have been managed. The case mix of outpatient referrals and the email advice line was similar, but the case mix for PAU was more acute.The most common parental reasons for attending PAU were referral by a community health professional (27.2%), not being able to get a general practitioner (GP) appointment when desired (21.7%), wanting to avoid accident and emergency (17.4%) and wanting specialist paediatric input (14.1%). More than half of PAU presentations were deemed most appropriate for community management by a GP or midwife. The proportion of cases suitable for community management varied by the reason for attendance, with it highestl for parents reporting not being able to get a GP appointment (85%), and lowest for those referred by community health professionals (29%). One in two attendances to acute paediatric services could have been managed in the community. Integration of paediatric services could help address parental reasons for attending acute services, as well as facilitating the community management of chronic conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ethical dimensions of paediatric nursing: A rapid evidence assessment.

PubMed

Bagnasco, Annamaria; Cadorin, Lucia; Barisone, Michela; Bressan, Valentina; Iemmi, Marina; Prandi, Marzia; Timmins, Fiona; Watson, Roger; Sasso, Loredana

2018-02-01

Paediatric nurses often face complex situations requiring decisions that sometimes clash with their own values and beliefs, or with the needs of the children they care for and their families. Paediatric nurses often use new technology that changes the way they provide care, but also reduces their direct interaction with the child. This may generate ethical issues, which nurses should be able to address in the full respect of the child. Research question and objectives: The purpose of this review is to describe the main ethical dimensions of paediatric nursing. Our research question was, 'What are the most common ethical dimensions and competences related to paediatric nursing?' A rapid evidence assessment. According to the principles of the rapid evidence assessment, we searched the PubMed, SCOPUS and CINAHL databases for papers published between January 2001 and March 2015. These papers were then independently read by two researchers and analysed according to the inclusion criteria. Ethical considerations: Since this was a rapid evidence assessment, no approval from the ethics committee was required. Ten papers met our inclusion criteria. Ethical issues in paediatric nursing were grouped into three areas: (a) ethical issues in paediatric care, (b) social responsibility and (c) decision-making process. Few studies investigate the ethical dimensions and aspects of paediatric nursing, and they are mainly qualitative studies conducted in critical care settings based on nurses' perceptions and experiences. Paediatric nurses require specific educational interventions to help them resolve ethical issues, contribute to the decision-making process and fulfil their role as advocates of a vulnerable population (i.e. sick children and their families). Further research is needed to investigate how paediatric nurses can improve the involvement of children and their families in decision-making processes related to their care plan.

Tertiary paediatric emergency department use in children and young people with cerebral palsy.

PubMed

Meehan, Elaine; Reid, Susan M; Williams, Katrina; Freed, Gary L; Babl, Franz E; Sewell, Jillian R; Rawicki, Barry; Reddihough, Dinah S

2015-10-01

The aim of this study was to describe the pattern of tertiary paediatric emergency department (ED) use in children and young people with cerebral palsy (CP). A retrospective analysis of ED data routinely collected at the two tertiary paediatric hospitals in Victoria, Australia, cross-matched with the Victorian Cerebral Palsy Register. Data pertaining to the ED presentations of 2183 registered individuals born 1993-2008 were obtained. Between 2008 and 2012, 37% (n = 814) of the CP cohort had 3631 tertiary paediatric ED presentations. Overall, 40% (n = 332) of presenters were residing in inner metropolitan Melbourne; 44% (n = 356) in outer Melbourne; and 13% (n = 108) in regional Victoria. Presenters were more likely than non-presenters to be younger, non-ambulant and have epilepsy. In total, 71% of presentations were triaged as Australasian Triage Scale 1-3 (urgent), and 44% resulted in a hospital admission. Disorders of the respiratory, neurological and gastrointestinal systems, and medical device problems were responsible for 72% of presentations. Many of the tertiary paediatric ED presentations in this group were appropriate based on the high admission rate and the large proportion triaged as urgent. However, there is evidence that some families are bypassing local services and travelling long distances to attend the tertiary paediatric ED, even for less urgent complaints that do not require hospital admission. Alternative pathways of care delivery, and strategies to promote the management of common problems experienced by children and young people with CP in non-paediatric EDs or primary care settings, may go some way towards reducing unnecessary tertiary paediatric ED use in this group. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Neuropsychiatric features associated with nutritional and metabolic status in a gastric bypass patient.

PubMed

Waserman, Jessica E; Hategan, Ana; Bourgeois, James A

2015-01-01

Bariatric patients may present for psychiatric evaluation due to exacerbation of preexisting psychiatric disorders, new onset psychiatric disorders and/or neuropsychiatric complications associated with abnormal nutritional and metabolic states following the surgical procedure. These neuropsychiatric complications can be insidious, and clinical manifestations may vary, possibly due to the individual central nervous system (CNS) vulnerability to nutritional decline. Lack of awareness of these complications and their symptoms can result in delays in diagnosis and treatment. Identifying and correcting underlying pathophysiologic processes that lead to such neuropsychiatric syndromes can be challenging. We report a case of a patient who developed a protracted course of mood and cognitive disorder after gastric bypass surgery, which illustrates some of the complexities encountered in diagnosing and managing these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuropsychiatric and cognitive profile of early Richardson's syndrome, Progressive Supranuclear Palsy-parkinsonism and Parkinson's disease.

PubMed

Pellicano, Clelia; Assogna, Francesca; Cellupica, Nystya; Piras, Federica; Pierantozzi, Mariangela; Stefani, Alessandro; Cerroni, Rocco; Mercuri, Bruno; Caltagirone, Carlo; Pontieri, Francesco E; Spalletta, Gianfranco

2017-12-01

The two main variants of Progressive Supranuclear Palsy (PSP), Richardson's syndrome (PSP-RS) and PSP-parkinsonism (PSP-P), share motor and non-motor features with Parkinson's disease (PD) particularly in the early stages. This makes the precocious diagnosis more challenging. We aimed at defining qualitative and quantitative differences of neuropsychiatric and neuropsychological profiles between PSP-P, PSP-RS and PD patients recruited within 24 months after the onset of symptoms, in order to clarify if the identification of peculiar cognitive and psychiatric symptoms is of help for early PSP diagnosis. PD (n = 155), PSP-P (n = 11) and PSP-RS (n = 14) patients were identified. All patients were submitted to clinical, neurological, neuropsychiatric diagnostic evaluation and to a comprehensive neuropsychiatric and neuropsychological battery. Predictors of PSP-P and PSP-RS diagnosis were identified by multivariate logistic regressions including neuropsychiatric and neuropsychological features that differed significantly among groups. The three groups differed significantly at the Apathy Rating Scale score and at several neuropsychological domains. The multivariate logistic regressions indicated that the diagnosis of PSP-RS was predicted by phonological verbal fluency deficit whereas the presence of apathy significantly predicted the PSP-P diagnosis. Peculiar neuropsychiatric and neuropsychological symptoms are identifiable very precociously in PSP-P, PSP-RS and PD patients. Early phonological verbal fluency deficit identifies patients with PSP-RS whereas apathy supports the diagnosis of PSP-P. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropsychiatric phenomena in the medieval text Cantigas de Santa Maria.

PubMed

Gondim, Francisco De Assis Aquino; Griesbach, Sarah H; Thomas, Florian P

2015-05-12

To discuss the neuropsychiatric phenomena described in Cantigas de Santa Maria (Canticles of St. Mary [CSM]). CSM is a collection of 427 canticles composed in Galician-Portuguese between 1252 and 1284 at the Court of King Alfonso X the Wise of Spain (1221-1284). The canticles (of which 9 are repeated) include devotional and liturgical poems and 353 narrative stories consisting mainly of depictions of Marian miracles. Most are set to music and many are illustrated. We reviewed the canticles for description of miracles and other neuropsychiatric phenomena. Two neurologists reached a consensus about the descriptions. Of the 353 miracles, 279 medically relevant facts (from 187 canticles) and 25 instances of resurrection were reported. Possible neuropsychiatric conditions were described in 98 canticles. Physicians were mentioned in 16 narratives. The most common neurologic conditions detailed were blindness (n = 17), dystonia, weakness, and deformities (n = 20). Other common conditions included psychosis (n = 15), speech disorder/deaf-mutism (n = 12), infections (n = 15), sexual dysfunction/infertility/obstetrical-gynecologic issues (n = 18), head trauma (n = 5), ergotism/St. Anthony's fire (n = 7), and others. There were 9 instances of prodromic mystical experiences/hallucinations heralding death. While limited by retrospection and interpretation of neuropsychiatric phenomena in the medieval context, these short accounts are among the first descriptions of neuropsychiatric conditions in early Portuguese/Galician. They reflect how medieval societies used rational and irrational approaches to understand occurrences in their lives. © 2015 American Academy of Neurology.

[Materials for the paediatric resuscitation trolley or backpack: Expert recommendations].

PubMed

López-Herce Cid, Jesús; Rodríguez Núñez, Antonio; Carrillo Álvarez, Ángel; Zeballos Sarrato, Gonzalo; Martínez Fernández-Llamazares, Cecilia; Calvo Macías, Custodio

2018-03-01

Cardio-respiratory arrest (CPA) is infrequent in children, but it can occur in any place and at any time. This fact means that every health care facility must always have the staff and material ready to resuscitate a child. These recommendations are the consensus of experts of the Spanish Paediatric and Neonatal Resuscitation Group on the material and medication for paediatric and neonatal resuscitation and their distribution and use. CPR trolleys and backpacks must include the essential material to quickly and efficiently perform a paediatric CPR. At least one CPR trolley must be available in every Primary Care facility, Paediatric Intensive Care Unit, Emergency Department, and Pre-hospital Emergency Areas, as well as in paediatric wards, paediatric ambulatory areas, and radiology suites. This trolley must be easily accessible and exclusively include the essential items to perform a CPR and to assist children (from newborns to adolescents) who present with a life-threatening event. Such material must be familiar to all healthcare staff and also include the needed spare parts, as well as enough drug doses. It must also be re-checked periodically. The standardisation and unification of the material and medication of paediatric CPR carts, trolleys, and backpacks, as well as the training of the personnel in their use are an essential part of the paediatric CPR. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Patient disclosure of medical errors in paediatrics: A systematic literature review

PubMed Central

Koller, Donna; Rummens, Anneke; Le Pouesard, Morgane; Espin, Sherry; Friedman, Jeremy; Coffey, Maitreya; Kenneally, Noah

2016-01-01

Medical errors are common within paediatrics; however, little research has examined the process of disclosing medical errors in paediatric settings. The present systematic review of current research and policy initiatives examined evidence regarding the disclosure of medical errors involving paediatric patients. Peer-reviewed research from a range of scientific journals from the past 10 years is presented, and an overview of Canadian and international policies regarding disclosure in paediatric settings are provided. The purpose of the present review was to scope the existing literature and policy, and to synthesize findings into an integrated and accessible report. Future research priorities and policy implications are then identified. PMID:27429578

How well are general practice trainees prepared for paediatric prescribing?

PubMed

Isa, N M; Taylor, Michael W; Helms, Peter J; McLay, James S

2009-03-01

We invited 232 General Practice Trainees to complete an on-line questionnaire to assess how they rated their training for the task of paediatric prescribing and therapeutics in the community. Of the 166 (71%) respondents who completed the questionnaire, 26.5% recalled specific teaching about paediatric prescribing and 59.6% covering one or more relevant topic during their undergraduate years. Undertaking a paediatric post during vocational training was associated with greater prescribing confidence (P < 0.001); however, 35% of respondents were not intending to undertake such a post. This study suggests that many GP trainees perceive their paediatric prescribing training as inadequate.

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Medicinal Plants Used for Neuropsychiatric Disorders Treatment in the Hauts Bassins Region of Burkina Faso

PubMed Central

Kinda, Prosper T.; Zerbo, Patrice; Guenné, Samson; Compaoré, Moussa; Ciobica, Alin; Kiendrebeogo, Martin

2017-01-01

Background: In Burkina Faso, phytotherapy is the main medical alternative used by populations to manage various diseases that affect the nervous system. The aim of the present study was to report medicinal plants with psychoactive properties used to treat neuropsychiatric disorders in the Hauts Bassins region, in the western zone of Burkina Faso. Methods: Through an ethnobotanical survey using structured questionnaire, 53 traditional healers (TH) were interviewed about neuropsychiatric disorders, medicinal plants and medical practices used to treat them. The survey was carried out over a period of three months. Results: The results report 66 plant species used to treat neuropsychiatric pathologies. Roots (36.2%) and leaves (29%) were the main plant parts used. Alone or associated, these parts were used to prepare drugs using mainly the decoction and the trituration methods. Remedies were administered via drink, fumigation and external applications. Conclusions: It appears from this study a real knowledge of neuropsychiatric disorders in the traditional medicine of Hauts Bassins area. The therapeutic remedies suggested in this work are a real interest in the fight against psychiatric and neurological diseases. In the future, identified plants could be used for searching antipsychotic or neuroprotective compounds. PMID:28930246

Addressing neuropsychiatric disturbances during rehabilitation after traumatic brain injury: current and future methods

PubMed Central

Arciniegas, David B.

2011-01-01

Cognitive, emotional, behavioral, and sensorimotor disturbances are the principal clinical manifestations of traumatic brain injury (TBI) throughout the early postinjury period. These post-traumatic neuropsychiatric disturbances present substantial challenges to patients, their families, and clinicians providing their rehabilitative care, the optimal approaches to which remain incompletely developed. In this article, a neuropsychiairically informed, neurobiologically anchored approach to understanding and meeting challenges is described. The foundation for thai approach is laid, with a review of clinical case definitions of TBI and clarification of their intended referents. The differential diagnosis of event-related neuropsychiatric disturbances is considered next, after which the clinical and neurobiological heterogeneity within the diagnostic category of TBI are discussed. The clinical manifestations of biomechanical force-induced brain dysfunction are described as a state of post-traumatic encephalopathy (PTE) comprising several phenomenologically distinct stages, PTE is then used as a framework for understanding and clinically evaluating the neuropsychiatric sequelae of TBI encountered commonly during the early post-injury rehabilitation period, and for considering the types and timings of neurorehabilitative interventions. Finally, directions for future research that may address productively the challenges to TBI rehabilitation presented by neuropsychiatric disturbances are considered. PMID:22034400

Biochemical correlates of neuropsychiatric illness in maple syrup urine disease.

PubMed

Muelly, Emilie R; Moore, Gregory J; Bunce, Scott C; Mack, Julie; Bigler, Don C; Morton, D Holmes; Strauss, Kevin A

2013-04-01

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. Dietary management enables survival and reduces risk of acute crises. Liver transplantation has emerged as an effective way to eliminate acute decompensation risk. Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. We report the prevalence and characteristics of neuropsychiatric problems among 37 classical MSUD patients (ages 5-35 years, 26 on dietary therapy, 11 after liver transplantation) and explore their underlying mechanisms. Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. Using quantitative proton magnetic resonance spectroscopy, we found lower brain glutamate, N-acetylaspartate (NAA), and creatine concentrations in MSUD patients, which correlated with specific neuropsychiatric outcomes. Asymptomatic neonatal course and stringent longitudinal biochemical control proved fundamental to optimizing long-term mental health. Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. These findings may provide insight into general mechanisms of psychiatric illness.

The educational challenge of Paediatric Virology: An interview with Professor of Neonatology Anne Greenough.

PubMed

Mammas, Ioannis N; Spandidos, Demetrios A

2017-10-01

According to Professor Anne Greenough, Professor of Neonatology and Clinical Respiratory Physiology at the King's College London (London, UK), Paediatric Virology is indeed a rapidly increasing educational challenge. Professor Greenough, who in 1992 wrote her book on congenital, perinatal and neonatal infections, believes that during the past 3 decades, paediatric health professionals are becoming increasingly involved in specialised care and follow-up of paediatric patients with viral diseases, who require advanced medical care and innovative technological services. Moreover, she highlights the expected role of new vaccines and antiviral agents that are currently under investigation, as well as the impact of emerging viral diseases that require novel prevention strategies and therapeutic protocols. However, she notes that the number of Paediatric Virologists in any one country is likely to be small; hence, a separate paediatric subspecialty needs to be considered carefully. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor Greenough will give her plenary lecture on the impact of viral infections on the long term outcomes of prematurely born infants.

Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: a new or a complementary diagnostic score?

PubMed

Gatselis, Nikolaos K; Zachou, Kalliopi; Papamichalis, Panagiotis; Koukoulis, George K; Gabeta, Stella; Dalekos, George N; Rigopoulou, Eirini I

2010-11-01

The International Autoimmune Hepatitis Group developed a simplified score for autoimmune hepatitis. We assessed this "new scoring system" and compared it with the International Autoimmune Hepatitis Group original revised score. 502 patients were evaluated namely, 428 had liver diseases of various etiology [hepatitis B (n=109), hepatitis C (n=100), hepatitis D (n=4), alcoholic liver disease (n=28), non-alcoholic fatty liver disease (n=55), autoimmune cholestatic diseases (n=77), liver disorders of undefined origin (n=32) and miscellaneous hepatic disorders (n=23)], 13 had autoimmune hepatitis/overlap syndromes, 18 had autoimmune hepatitis/concurrent with other liver diseases and 43 had autoimmune hepatitis. The specificity of the simplified score was similar to that of the revised score (97% vs. 97.9%). The sensitivity in unmasking autoimmune hepatitis in autoimmune hepatitis/overlap syndromes was also similar in both systems (53.8% and 61.5%). However, the sensitivity for autoimmune hepatitis diagnosis in autoimmune hepatitis patients with concurrent liver disorders was lower by the new score (p=0.001). Liver biopsy proved to be the only independent factor for unmasking autoimmune hepatitis component among patients (p=0.003). The simplified score is a reliable and simple tool for excluding autoimmune hepatitis. However, both systems cannot unmask autoimmune hepatitis component efficiently in autoimmune hepatitis patients with concurrent autoimmune or non-autoimmune liver diseases. This study also strongly reiterates the importance of liver biopsy in the work-up of patients. Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

PubMed

Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

2011-01-01

Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

Neuropsychiatric conditions associated with anesthesia exposure.

PubMed

Gross, Anne F; Stern, Theodore A

2014-01-01

Although anesthetics have been used for more than a century, their mechanisms of action remain poorly understood. Given that a number of intraoperative and postoperative neuropsychiatric syndromes have been linked to the use of anesthetics, practitioners should familiarize themselves with these conditions. Basic concepts about anesthesia are reviewed and neuropsychiatric syndromes associated with anesthesia exposure described. Emergence delirium, postoperative delirium, postoperative cognitive dysfunction, and intraoperative awareness can develop in association with use of inhalation anesthetics and intravenously administered anesthetics. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

PubMed Central

Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

2014-01-01

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

Cognitive and neuropsychiatric impairments in Alzheimer's disease: current treatment strategies.

PubMed

Borisovskaya, Anna; Pascualy, Marcella; Borson, Soo

2014-09-01

This update on Alzheimer's disease (AD) discusses treatment strategies for cognitive and neuropsychiatric symptoms (such as agitation, psychosis, anxiety, and depression) common in this illness, emphasizing in particular nonpharmacologic strategies such as cognitive interventions, physical exercise, and psychotherapy. We provide an overview of cognitive enhancers and their combination strategies and medications commonly used for treatment of neuropsychiatric symptoms in AD. Finally, we give recommendations for providing support to caregivers and suggest how to identify caregiver/patient pairs most in need of intensive dementia care services.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial

PubMed Central

Iro, M A; Sadarangani, M; Absoud, M; Chong, W K; Clark, C A; Easton, A; Gray, V; Kneen, R; Lim, M; Pike, M; Solomon, T; Vincent, A; Willis, L; Pollard, A J

2016-01-01

Introduction Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. Methods and analysis 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is ‘good recovery’ (score of 2 or lower on the Glasgow Outcome Score Extended—paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4–6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. Ethics and dissemination This trial has been approved by the UK National Research Ethics committee (South Central—Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. Trial registration numbers NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results. PMID:27810972

The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype

PubMed Central

Reinauer, Christina; Rosenbauer, Joachim; Bächle, Christina; Herder, Christian; Roden, Michael; Ellard, Sian; De Franco, Elisa; Karges, Beate; Holl, Reinhard W.; Enczmann, Jürgen; Meissner, Thomas

2017-01-01

Introduction: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) DR and DQ haplotypes in a cohort with early-onset (age < 5 years), long term type 1 diabetes (T1D) and explored their influence on clinical and laboratory parameters. Methods: Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years) and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. Results: Genetic variability was low, 44.6% (104/233) of early-onset T1D patients carried the highest-risk genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05), and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n = 83), moderate (n = 106) and low risk (n = 6) genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years), metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (each p > 0.05). Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. Conclusion: In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation. PMID:28534863

Neuropsychiatric Predictors of Post-Injury Headache After Mild-Moderate Traumatic Brain Injury in Veterans.

PubMed

Bomyea, Jessica; Lang, Ariel J; Delano-Wood, Lisa; Jak, Amy; Hanson, Karen L; Sorg, Scott; Clark, Alexandra L; Schiehser, Dawn M

2016-04-01

To determine differences in neuropsychiatric complaints between Veterans with mild to moderate traumatic brain injury (TBI), with and without headache, compared with Veteran controls, and to identify neuropsychiatric predictors of headache severity. Mild to moderate TBI is a common occurrence in Veterans, and is frequently associated with complaints of headache. Neuropsychiatric complaints are also common among individuals who have sustained head injury, although the relationship between these factors and headache after injury is unclear. Research is needed to comprehensively determine differences between individuals with mild to moderate traumatic brain injury who differ with respect to headache, and which injury, psychological, or sleep and fatigue factors predict headache severity. A cross-sectional study compared 85 Veterans in three groups (positive for TBI and headache, positive for TBI without significant headache, and a control group) on a set of injury characteristics and neuropsychiatric variables. Correlates of headache severity were examined, and a regression model was used to identify significant independent predictors of headache severity. Individuals with mild to moderate TBI and headache endorsed significantly greater neuropsychiatric symptoms than participants in the other groups (η(p)2  = .23-.36) Neuropsychiatric complaints, as well as presence of posttraumatic amnesia, were correlated with headache in the subsample with TBI (rs = .44-.57). When entering all predictors into a regression model, only fatigue represented a significant independent predictor of headache severity (β = .59, R2 = .35). Rather than being a global risk factor, mild to moderate TBI was associated with poorer mental health outcomes, particularly for those who endorse headache. Findings underscore the possibility that Veterans with history of TBI who present with complaints of headache may represent a particularly vulnerable subgroup. Additionally, our findings suggest that clinical outcomes may be improved in those with neurotrauma by incorporating a focus on fatigue in treatment. © 2016 American Headache Society.

Anatomical brain images alone can accurately diagnose chronic neuropsychiatric illnesses.

PubMed

Bansal, Ravi; Staib, Lawrence H; Laine, Andrew F; Hao, Xuejun; Xu, Dongrong; Liu, Jun; Weissman, Myrna; Peterson, Bradley S

2012-01-01

Diagnoses using imaging-based measures alone offer the hope of improving the accuracy of clinical diagnosis, thereby reducing the costs associated with incorrect treatments. Previous attempts to use brain imaging for diagnosis, however, have had only limited success in diagnosing patients who are independent of the samples used to derive the diagnostic algorithms. We aimed to develop a classification algorithm that can accurately diagnose chronic, well-characterized neuropsychiatric illness in single individuals, given the availability of sufficiently precise delineations of brain regions across several neural systems in anatomical MR images of the brain. We have developed an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. The method employs a semi-supervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions. We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings. In MRI datasets from persons with Attention-Deficit/Hyperactivity Disorder, Schizophrenia, Tourette Syndrome, Bipolar Disorder, or persons at high or low familial risk for Major Depressive Disorder, our method discriminated with high specificity and nearly perfect sensitivity the brains of persons who had one specific neuropsychiatric disorder from the brains of healthy participants and the brains of persons who had a different neuropsychiatric disorder. Although the classification algorithm presupposes the availability of precisely delineated brain regions, our findings suggest that patterns of morphological variation across brain surfaces, extracted from MRI scans alone, can successfully diagnose the presence of chronic neuropsychiatric disorders. Extensions of these methods are likely to provide biomarkers that will aid in identifying biological subtypes of those disorders, predicting disease course, and individualizing treatments for a wide range of neuropsychiatric illnesses.

Exploring the prevalence and variance of cognitive impairment, pain, neuropsychiatric symptoms and ADL dependency among persons living in nursing homes; a cross-sectional study.

PubMed

Björk, Sabine; Juthberg, Christina; Lindkvist, Marie; Wimo, Anders; Sandman, Per-Olof; Winblad, Bengt; Edvardsson, David

2016-08-22

Earlier studies in nursing homes show a high prevalence of cognitive impairment, dependency in activities of daily living (ADL), pain, and neuropsychiatric symptoms among residents. The aim of this study was to explore the prevalence of the above among residents in a nationally representative sample of Swedish nursing homes, and to investigate whether pain and neuropsychiatric symptoms differ in relation to gender, cognitive function, ADL-capacity, type of nursing-home unit and length of stay. Cross-sectional data from 188 randomly selected nursing homes were collected. A total of 4831 residents were assessed for cognitive and ADL function, pain and neuropsychiatric symptoms. Data were analysed using descriptive statistics and the chi-square test. The results show the following: the prevalence of cognitive impairment was 67 %, 56 % of residents were ADL-dependent, 48 % exhibited pain and 92 % exhibited neuropsychiatric symptoms. The prevalence of pain did not differ significantly between male and female residents, but pain was more prevalent among cognitively impaired and ADL-dependent residents. Pain prevalence was not significantly different between residents in special care units for people with dementia (SCU) and general units, or between shorter-and longer-stay residents. Furthermore, the prevalence of neuropsychiatric symptoms did not differ significantly between male and female residents, between ADL capacities or in relation to length of stay. However, residents with cognitive impairment and residents in SCUs had a significantly higher prevalence of neuropsychiatric symptoms than residents without cognitive impairment and residents in general units. The prevalence rates ascertained in this study could contribute to a greater understanding of the needs of nursing-home residents, and may provide nursing home staff and managers with trustworthy assessment scales and benchmark values for further quality assessment purposes, clinical development work and initiating future nursing assessments.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

PubMed

Porta, Gilda; Carvalho, Elisa de; Santos, Jorge L; Gama, Jorge; Borges, Cristian V; Seixas, Renata B P M; Ferreira, Alexandre R; Miura, Irene K; Silveira, Themis R; Silva, Luciana R; Fagundes, Eleonora D T; Bellomo-Brandao, Maria A; Sawamura, Regina; Vieira, Sandra M; Melere, Melina U; Marques, Cibele D F; Pugliese, Renata P; Danesi, Vera L; Porta, Adriana; Marsillac, Marise E; Valladares, Marcia A; Menezes, Daniela G; Kieling, Carlos; Paula, Mariana N de; Vasconcelos, Juliana R; Ferreira, Cristina T; Perin, Nilza; Resende, Leonardo R; Maia, Jussara; Tommaso, Adriana M A De; Hessel, Gabriel

2018-05-30

This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death. Copyright © 2018. Published by Elsevier Editora Ltda.

Enabling Development of Paediatric Medicines in Europe: 10 Years of the EU Paediatric Regulation.

PubMed

Tomasi, Paolo A; Egger, Gunter F; Pallidis, Chrissi; Saint-Raymond, Agnes

2017-12-01

The year 2017 marks the tenth anniversary of entry into force of the Paediatric Regulation in the European Union (EU). This law aimed to stimulate the development of paediatric medicines and provide more information on their use, as a response to the lack of evidence and approval of medicines for children. The European Medicines Agency (EMA) has had a central role in the implementation of the Regulation. Pharmaceutical companies need to submit a paediatric investigation plan (PIP) to the EMA's Paediatric Committee (PDCO) for every new medicine, unless an exemption (waiver) is granted. The plans, which describe the development of drugs for children, must be agreed well in advance of the request for marketing authorization of the medicine. Deferrals of studies can be granted to allow approval in adults before the completion of paediatric studies. Between January 2007 and December 2016, a total of 273 new medicines and 43 additional pharmaceutical forms appropriate for use in children were authorized in the EU, and 950 PIPs were agreed by the EMA. In addition, 486 waivers of the development of a medicine in one or more medical conditions were agreed. The Paediatric Regulation has had a very positive impact on paediatric drug development, as exemplified by a comparison of two periods of 3 years before and after entry into force of the Regulation. We conclude that the Regulation has resulted in more medicines for children and more information on the pediatric use of medicines in the EU being available to clinicians.

[Investigation of childhood neuropsychiatric disorders in adults often desirable. Functional disabilities can result in social maladjustment].

PubMed

Nylander, Lena; Holmqvist, Maria; Zettervall, Kerstin

2002-04-11

So-called child neuropsychiatric disorders (ADHD/DAMP, autism spectrum disorders, Tourette's syndrome) are being recognized with increasing frequency in child and adolescent psychiatry. Through follow-up studies, case reports and autobiographical accounts it has become evident that these disorders often persist into adulthood, and the need for diagnostic evaluation of adults is increasing. The Neuropsychiatric Diagnostic Team for Adults in Lund, Sweden, was established in 1998 to meet this need. 228 adults, mostly 18-30 years old, have completed the diagnostic process, resulting in one of the above-mentioned diagnoses in 64%. 80 patients had ADHD/DAMP, 59 had autism spectrum disorders and 7 had Tourette's syndrome. The diagnostic process involves clinical interviews and observation, neuropsychological evaluation and, if possible, a parent interview. So far, the impact on quality of life of a child neuropsychiatric diagnosis received in adulthood is not known. Follow-up studies are needed.

Concurrent Use of Cannabis and Alcohol: Neuropsychiatric Effect Consequences.

PubMed

Romaguera, Anna; Torrens, Marta; Papaseit, Esther; Arellano, Ana Lucia; Farré, Magi

2017-01-01

Concurrent use of cannabis and alcohol is frequent. According different studies, the prevalence is among 20-34% depending on different samples studied. In contrast with the wide evidence available about neuropsychiatric effects associated to the use of cannabis or alcohol separately, there are few studies of the neuropsychiatric effects of their combination. Our aim was to review the literature regarding this topic. We performed a search in MEDLINE and from 114 potentially eligible studies, 27 were selected. Most of them studied the relation between cannabis and alcohol, and with them combined to other substances of abuse, but only a few considered their concurrent effect among mental disorders (ADHD, bipolar disorder) and neuropsychological performance. More research in the neuropsychiatric effects of the concomitant use of cannabis and alcohol is needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Physical activity and neuropsychiatric symptoms of Parkinson disease.

PubMed

Abrantes, Ana M; Friedman, Joseph H; Brown, Richard A; Strong, David R; Desaulniers, Julie; Ing, Eileen; Saritelli, Jennifer; Riebe, Deborah

2012-09-01

Neuropsychiatric symptoms of Parkinson disease (PD) such as fatigue, depression, and apathy are common and detract from quality of life. There is little published on the impact of physical activity on the neuropsychiatric symptoms of PD. A convenience sample of 45 patients with PD (mean age = 66.1 years; 33% female) completed questionnaires on physical activity, neuropsychiatric symptoms, and specific exercise preferences. Covarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect. Exercise preferences included moderate intensity (73%), at home (56%), in the morning (73%), scheduled (69%), options for varied activities (73%), and preference for both structured/supervised (50%), and unsupervised/self-paced (50%) programs. Preferred activities included the use of aerobic exercise equipment, resistance training, and yoga. Developing and tailoring exercise programs that incorporate specific preferences may result in more effective interventions for patients with PD.

Sirolimus for Autoimmune Disease of Blood Cells

ClinicalTrials.gov

2017-11-02

Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

Ocular medicines in children: the regulatory situation related to clinical research

PubMed Central

2012-01-01

Background Many ocular medications are prescribed for paediatric patients, but the evidence for their rational use is very scant. This study was planned to compare the availability and the licensing status of ocular medications marketed in Italy, the United Kingdom (UK), and the United States of America (USA) related to the amount of published and un-published RCTs testing these drugs in the paediatric population. Methods A quantitative analysis was performed to evaluate the number of ocular medications with a paediatric license in Italy, the UK, and the USA. A literature search was also performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on ophthalmic pharmacological therapy in children aged < 18 years, published up to December 2010. A search in the international clinical trial registries, the list of paediatric investigation plans (PIPs) approved by European Medicines Agency (EMA), and the table of medicines with new paediatric information approved by Food and Drug Administration (FDA) was also performed. Results In all, of 197 drugs identified, 68 (35%) single drugs are licensed for paediatric use at least in one considered country, while 23 (12%) were marketed in all three countries. More specifically, in Italy 43 single drugs (48% of those marketed) had a paediatric license, while 39 (64%) did in the UK and 22 (54%) did in the USA. Only 13 drugs were marketed with a paediatric license in all countries. The percentage of drugs licensed for paediatric use and for which at least one RCT had been performed ranged between 51% in Italy and 55% in the USA. No published RCTs were found for 11 (48%) drugs licensed for paediatric use in all three countries. In all, 74 (35%) of the retrieved RCTs involved mydriatic/cycloplegic medications. A total of 62 RCTs (56% completed) on 46 drugs were found in the international clinical trial registries. Cyclosporin and bevacizumab were being studied in many ongoing trials. Twenty-six drugs had new paediatric information approved by FDA based on new paediatric clinical trials, while only 4 PIPs were approved by EMA. Conclusions There is a pressing need for further research and clinical development in the pediatric ophthalmic area, where effective up-to-date treatments, and additional research and education on use in children, remain priorities. PMID:22264311

Job satisfaction and burnout among paediatric nurses.

PubMed

Akman, Ozlem; Ozturk, Candan; Bektas, Murat; Ayar, Dijle; Armstrong, Merry A

2016-10-01

This study aims to determine factors of job satisfaction and burnout levels of paediatric nurses. A total of 165 nurses working in paediatric clinics completed the Minnesota job satisfaction scale and the Maslach burnout scale. Average scores of the emotional exhaustion and depersonalisation score were low, while personal accomplishment scores were high. A high level of job satisfaction, being married, increased age and a decreased number of assigned patients were significantly associated with a low level of burnout. Paediatric nurses experience burnout at significant levels. The most important variable that affected job satisfaction was income. The results of the study could guide development of strategies that might prevent or alleviate burnout of paediatric nurses. © 2016 John Wiley & Sons Ltd.

Clinical competence in developmental-behavioural paediatrics: raising the bar.

PubMed

O'Keeffe, Mick

2014-01-01

For our specialist paediatric workforce to be suitably equipped to deal with current childhood morbidity, a high level of competence in developmental-behavioural paediatrics (DBP) is necessary. New models of training and assessment are required to meet this challenge. An evolution of training in DBP, built around the centrepiece of competency-based medical education, is proposed. Summative assessment based upon entrustable professional activities, and a menu of formative workplace-based assessments specific to the DBP context are key components. A pilot project to develop and implement these changes is recommended. © 2013 The Author. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Prospective Incidence of Paediatric Inflammatory Bowel Disease in New Zealand in 2015: Results From the Paediatric Inflammatory Bowel Disease in New Zealand (PINZ) Study.

PubMed

Lopez, Robert N; Evans, Helen M; Appleton, Laura; Bishop, Jonathan; Chin, Simon; Mouat, Stephen; Gearry, Richard B; Day, Andrew S

2018-05-01

The global incidence of paediatric inflammatory bowel disease (IBD) is increasing. Much of the evidence attesting to this has arisen from North America and Europe. There is a relative paucity of information on the epidemiology of paediatric IBD in the Southern Hemisphere. The present study aimed to document the prospectively collected incidence of paediatric IBD in New Zealand in 2015. All patients younger than 16 years of age and diagnosed with IBD in New Zealand between 1 January 2015 and 31 December 2015 were identified. Demographic and disease phenotypic details were collected and entered into a secure database. Age-specific population data for New Zealand were obtained and national incidence rates for IBD and its subtypes were calculated. The prospectively calculated incidence of paediatric IBD, Crohn disease, ulcerative colitis (UC), and IBD unclassified in New Zealand in 2015 were 5.2 (95% confidence interval 3.9-6.8), 3.5 (2.4-4.8), 1.0 (0.5-1.8), and 0.7 (0.3-1.4) per 100,000 children, respectively. Incidence rates of paediatric IBD in New Zealand are comparable to the highest rates published in the literature from Western Europe and North America. Ongoing prospective ascertainment of the incidence of paediatric IBD is required to better understand the environmental factors, which are accounting for this increase in disease burden.

Paediatric emergency department utilisation: is it necessary an educational intervention?

PubMed

De Tina, Annalisa; Quattrin, Rosanna; Montina, Laura; Brusaferro, Silvio

2014-01-01

Over the past ten years there has been a progressive increase in accesses to services for paediatric emergency room, documented in Italy and abroad. The aim of the study is describe the sociodemographic, cultural, subjective and objective factors for non-urgent access to paediatric emergency service in an Italian region. It was adopted a descriptive survey of a sample of non-urgent accesses to two paediatric emergency room services in an Italian region during the period from February-March 2009, through the administration of questionnaires and the consultation of facilities databases. Half of the accesses to the paediatric emergency room are not urgent and are to be referred to the paediatric primary care. 80% of the users do not call for advice before coming to the emergency room. The convenience of the service, which accounts for more than 50% of the case, and the proximity from home are reasons to go to the emergency room. Approximately half of the accesses to the paediatric emergency department could be managed by primary care services. The convenience of the service, the self-referred and the proximity to home are emerging as the only influential factors reported by literature. In the future it should become crucial providing strategies for education/health information focused on non-urgent paediatric problems and offering people a call center phone service in order to filter and prevent the inappropriate accesses.

How Stable Is Coping in Patients with Neuropsychiatric Symptoms after Acquired Brain Injury? Changes in Coping Styles and Their Predictors in the Chronic Phase.

PubMed

Wolters Gregório, Gisela; Ponds, Rudolf W H M; Smeets, Sanne M J; Jonker, Frank; Pouwels, Climmy G J G; van Heugten, Caroline M

2016-04-01

The objective of the study was to examine changes in coping and their predictors in patients in the chronic phase after an acquired brain injury with prominent neuropsychiatric symptoms. Patients with brain injury were recruited from consecutive admissions to the outpatient clinics of four mental health centers in the Netherlands. Patients received psychoeducation and/or one or more individual treatment sessions that were not targeting coping styles. Forty-two patients and thirty-two significant others participated. Patients reported a significantly greater use of passive and avoidance coping than both the general population and patients with brain injury without neuropsychiatric symptoms. There were statistically significant increases in avoidance coping between T1 and T2 (t = 2.0; p < 0.05). Less neuropsychiatric symptoms at T1 were associated with increases in avoidance coping, and more neuropsychiatric symptoms were associated with decreases in avoidance coping (β = -3.3; p < 0.001). Patients' underestimation of their deficits at T1 was associated with greater increases in active coping (β = -2.33; p < 0.05) than were patients' accurate estimation and overestimation of deficits at T1. Self-reported executive functioning at T1 was not associated with changes in coping. In conclusion, avoidance coping increased in the chronic phase after brain injury. The changes in coping could partially be explained by the level of neuropsychiatric symptoms and the level of self-awareness but not by self-reported executive functioning, which should be considered in treatment programs.

Outcome of appendicectomy in children performed in paediatric surgery units compared with general surgery units.

PubMed

Tiboni, S; Bhangu, A; Hall, N J

2014-05-01

Appendicectomy for acute appendicitis in children may be performed in specialist centres by paediatric surgeons or in general surgery units. Service provision and outcome of appendicectomy in children may differ between such units. This multicentre observational study included all children (aged less than 16 years) who had an appendicectomy at either a paediatric surgery unit or general surgery unit. The primary outcome was normal appendicectomy rate (NAR). Secondary outcomes included 30-day adverse events, use of ultrasound imaging and laparoscopy, and consultant involvement in procedures. Appendicectomies performed in 19 paediatric surgery units (242 children) and 54 general surgery units (461 children) were included. Children treated in paediatric surgery units were younger and more likely to have a preoperative ultrasound examination, a laparoscopic procedure, a consultant present at the procedure, and histologically advanced appendicitis than children treated in general surgery units. The unadjusted NAR was significantly lower in paediatric surgery units (odds ratio (OR) 0.37, 95 per cent confidence interval 0.23 to 0.59; P < 0.001), and the difference persisted after adjusting for age, sex and use of preoperative ultrasound imaging (OR 0.34, 0.21 to 0.57; P < 0.001). Female sex and preoperative ultrasonography, but not age, were significantly associated with normal appendicectomy in general surgery units but not in paediatric surgery units in this adjusted model. The unadjusted 30-day adverse event rate was higher in paediatric surgery units than in general surgery units (OR 1.90, 1.18 to 3.06; P = 0.011). When adjusted for case mix and consultant presence at surgery, no statistically significant relationship between centre type and 30-day adverse event rate existed (OR 1.59, 0.93 to 2.73; P = 0.091). The NAR in general surgery units was over twice that in paediatric surgery units. Despite a more severe case mix, paediatric surgery units had a similar 30-day adverse event rate to general surgery units. Service provision differs between paediatric and general surgery units. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Paediatric case mix in a rural clinical school is relevant to future practice.

PubMed

Wright, Helen M; Maley, Moira A L; Playford, Denese E; Nicol, Pam; Evans, Sharon F

2017-11-29

Exposure to a representative case mix is essential for clinical learning, with logbooks established as a way of demonstrating patient contacts. Few studies have reported the paediatric case mix available to geographically distributed students within the same medical school. Given international interest in expanding medical teaching locations to rural contexts, equitable case exposure in rural relative to urban settings is topical. The Rural Clinical School of Western Australia locates students up to 3500 km from the urban university for an academic year. There is particular need to examine paediatric case mix as a study reported Australian graduates felt unprepared for paediatric rotations. We asked: Does a rural clinical school provide a paediatric case mix relevant to future practice? How does the paediatric case mix as logged by rural students compare with that by urban students? The 3745 logs of 76 urban and 76 rural consenting medical students were categorised by presenting symptoms and compared to the Australian Institute of Health and Welfare (AIHW) database Major Diagnostic Categories (MDCs). Rural and urban students logged core paediatric cases, in similar order, despite the striking difference in geographic locations. The pattern of overall presenting problems closely corresponded to Australian paediatric hospital admissions. Rural students logged 91% of cases in secondary healthcare settings; urban students logged 90% of cases in tertiary settings. The top four presenting problems were ENT/respiratory, gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made up 60% of all cases. Rural and urban students logged similar proportions of infants, children and adolescents, with a variety of case morbidity. Rural clinical school students logged a mix of core paediatric cases relevant to illnesses of Australian children admitted to public hospitals, with similar order and pattern by age group to urban students, despite major differences in clinical settings. Logged cases met the curriculum learning outcomes of graduates. Minor variations were readily addressed via recommendations about logging. This paper provides evidence of the legitimacy of student logs as useful tools in affirming appropriate paediatric case mix. It validates the rural clinical school context as appropriate for medical students to prepare for future clinical paediatric practice.

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study

PubMed Central

Zulfiqar, AA; Andres, E

2017-01-01

Objective: To investigate the association between pernicious anemia and other autoimmune diseases. Methods: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. Results: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. Conclusion: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b. PMID:29362601

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study.

PubMed

Zulfiqar, A A; Andres, E

2017-01-01

To investigate the association between pernicious anemia and other autoimmune diseases. This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

A systematic review of clinical pharmacist interventions in paediatric hospital patients.

PubMed

Drovandi, Aaron; Robertson, Kelvin; Tucker, Matthew; Robinson, Niechole; Perks, Stephen; Kairuz, Therése

2018-06-19

Clinical pharmacists provide beneficial services to adult patients, though their benefits for paediatric hospital patients are less defined. Five databases were searched using the MeSH terms 'clinical pharmacist', 'paediatric/paediatric', 'hospital', and 'intervention' for studies with paediatric patients conducted in hospital settings, and described pharmacist-initiated interventions, published between January 2000 and October 2017. The search strategy after full-text review identified 12 articles matching the eligibility criteria. Quality appraisal checklists from the Joanna Briggs Institute were used to appraise the eligible articles. Clinical pharmacist services had a positive impact on paediatric patient care. Medication errors intercepted by pharmacists included over- and under-dosing, missed doses, medication history gaps, allergies, and near-misses. Interventions to address these errors were positively received, and implemented by physicians, with an average acceptance rate of over 95%. Clinical pharmacist-initiated education resulted in improved medication understanding and adherence, improved patient satisfaction, and control of chronic medical conditions. This review found that clinical pharmacists in paediatric wards may reduce drug-related problems and improve patient outcomes. The benefits of pharmacist involvement appear greatest when directly involved in ward rounds, due to being able to more rapidly identify medication errors during the prescribing phase, and provide real-time advice and recommendations to prescribers. What is Known: • Complex paediatric conditions can require multiple pharmaceutical treatments, utilised in a safe manner to ensure good patient outcomes • The benefits of pharmacist interventions when using these treatments are well-documented in adult patients, though less so in paediatric patients What is New: • Pharmacists are adept at identifying and managing medication errors for paediatric patients, including incorrect doses, missed doses, and gaps in medication history • Interventions recommended by pharmacists are generally well-accepted by prescribing physicians, especially when recommendations can be made during the prescribing phase of treatment.

The educational challenge of Paediatric Virology: An interview with Professor of Neonatology Anne Greenough

PubMed Central

Mammas, Ioannis N.; Spandidos, Demetrios A.

2017-01-01

According to Professor Anne Greenough, Professor of Neonatology and Clinical Respiratory Physiology at the King's College London (London, UK), Paediatric Virology is indeed a rapidly increasing educational challenge. Professor Greenough, who in 1992 wrote her book on congenital, perinatal and neonatal infections, believes that during the past 3 decades, paediatric health professionals are becoming increasingly involved in specialised care and follow-up of paediatric patients with viral diseases, who require advanced medical care and innovative technological services. Moreover, she highlights the expected role of new vaccines and antiviral agents that are currently under investigation, as well as the impact of emerging viral diseases that require novel prevention strategies and therapeutic protocols. However, she notes that the number of Paediatric Virologists in any one country is likely to be small; hence, a separate paediatric subspecialty needs to be considered carefully. In the context of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece, on October 7th, 2017, Professor Greenough will give her plenary lecture on the impact of viral infections on the long term outcomes of prematurely born infants. PMID:29042914

Towards evidence-based medicine in specific grass pollen immunotherapy.

PubMed

Calderon, M; Mösges, R; Hellmich, M; Demoly, P

2010-04-01

When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality.

Neck pain in children: a retrospective case series.

PubMed

Cox, Jocelyn; Davidian, Christine; Mior, Silvano

2016-09-01

Spinal pain in the paediatric population is a significant health issue, with an increasing prevalence as they age. Paediatric patients attend for chiropractor care for spinal pain, yet, there is a paucity of quality evidence to guide the practitioner with respect to appropriate care planning. A retrospective chart review was used to describe chiropractic management of paediatric neck pain. Two researchers abstracted data from 50 clinical files that met inclusion criteria from a general practice chiropractic office in the Greater Toronto Area, Canada. Data were entered into SPSS 15 and descriptively analyzed. Fifty paediatric neck pain patient files were analysed. Patients' age ranged between 6 and 18 years (mean 13 years). Most (98%) were diagnosed with Grade I-II mechanical neck pain. Treatment frequency averaged 5 visits over 19 days; with spinal manipulative therapy used in 96% of patients. Significant improvement was recorded in 96% of the files. No adverse events were documented. Paediatric mechanical neck pain appears to be successfully managed by chiropractic care. Spinal manipulative therapy appears to benefit paediatric mechanical neck pain resulting from day-today activities with no reported serious adverse events. Results can be used to inform clinical trials assessing effectiveness of manual therapy in managing paediatric mechanical neck pain.

Music therapy as a non-pharmacological anxiolytic for paediatric radiotherapy patients.

PubMed

O'Callaghan, C; Sexton, M; Wheeler, G

2007-04-01

Outpatient radiotherapy treatment in the paediatric cancer patient can be a traumatic and an anxiety-provoking experience for both the patient and the family. Music therapy has been widely reported to have psychosocial, educational and physical benefits for the paediatric cancer patient. Using individual case reports, this paper shows the successful use of music therapy as a non-pharmacological anxiolytic in the paediatric radiotherapy, outpatient waiting room setting, by providing the patient and the family with a means of communication, self-expression and creativity.

Practising what we preach: A look at healthy active living policy and practice in Canadian paediatric hospitals

PubMed Central

Solh, Ziad; Adamo, Kristi B; Platt, Jennica L; Ambler, Kathryn; Boyd, Erin; Orrbine, Elaine; Cummings, Elizabeth; LeBlanc, Claire MA

2010-01-01

BACKGROUND: In the past 30 years, the rate of obesity has risen considerably among Canadian children. Paediatric hospitals are in a unique position to model healthy environments to Canadian children. OBJECTIVE: To obtain an overview of healthy active living (HAL) policy and practice in Canadian paediatric hospitals. METHODS: Working in partnership with the local Canadian Paediatric Society HAL champions and the Canadian Association of Paediatric Health Centres liaisons, a nationwide survey was conducted in 2006/2007 to identify healthy eating, physical activity and smoking cessation practices in all 16 Canadian paediatric academic hospitals. RESULTS: Policies addressing healthy eating and/or physical activity promotion were present in 50% of hospitals with a greater focus on nutrition. Wellness committees were created in 50% of the hospitals, most of which were recently established. Healthy food options were available in cafeterias, although they were often more expensive. Fast food outlets were present in 75% of hospitals. Although inpatient meals were designed by dietitians, 50% offered less nutritious replacement kids meals (ie, meal substitutions) on request. Options for play available to inpatients and outpatients were primarily sedentary, with screen-based activities and crafts predominating over active play. Physical activity promotion for staff focused on reduced membership fees to fitness centres and classes. CONCLUSION: Canadian paediatric hospitals do not adequately promote HAL for patients and staff. The present study findings suggest further effort is required to create necessary healthy lifestyle modifications in these institutions through Canadian Paediatric Society/Canadian Association of Paediatric Health Centres-led policy development and implementation initiatives. A national-level policy framework is required to regulate interhospital variability in policies and practices. PMID:22131867

Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients.

PubMed

Raouf, H E; Yassin, A S; Megahed, S A; Ashour, M S; Mansour, T M

2015-02-01

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt. © 2014 John Wiley & Sons Ltd.

What Evidence Underlies Clinical Practice in Paediatric Surgery? A Systematic Review Assessing Choice of Study Design.

PubMed

Allin, Benjamin; Aveyard, Nicholas; Campion-Smith, Timothy; Floyd, Eleanor; Kimpton, James; Swarbrick, Kate; Williams, Emma; Knight, Marian

2016-01-01

Identify every paediatric surgical article published in 1998 and every paediatric surgical article published in 2013, and determine which study designs were used and whether they were appropriate for robustly assessing interventions in surgical conditions. A systematic review was conducted according to a pre-specified protocol (CRD42014007629), using EMBASE and Medline. Non-English language studies were excluded. Studies were included if meeting population criteria and either condition or intervention criteria. Children under the age of 18, or adults who underwent intervention for a condition managed by paediatric surgeons when they were under 18 years of age. One managed by general paediatric surgeons. Used for treatment of a condition managed by general paediatric surgeons. Studies were classified according to whether the IDEAL collaboration recommended their design for assessing surgical interventions or not. Change in proportions between 1998 and 2013 was calculated. 1581 paediatric surgical articles were published in 1998, and 3453 in 2013. The most commonly used design, accounting for 45% of studies in 1998 and 46.8% in 2013, was the retrospective case series. Only 1.8% of studies were RCTs in 1998, and 1.9% in 2013. Overall, in 1998, 9.8% of studies used a recommended design. In 2013, 11.9% used a recommended design (proportion increase 2.3%, 95% confidence interval 0.5% increase to 4% increase, p = 0.017). A low proportion of published paediatric surgical manuscripts utilise a design that is recommended for assessing surgical interventions. RCTs represent fewer than 1 in 50 studies. In 2013, 88.1% of studies used a less robust design, suggesting the need for a new way of approaching paediatric surgical research.

The status of paediatric medicines initiatives around the world--What has happened and what has not?

PubMed

Hoppu, Kalle; Anabwani, Gabriel; Garcia-Bournissen, Facundo; Gazarian, Madlen; Kearns, Gregory L; Nakamura, Hidefumi; Peterson, Robert G; Sri Ranganathan, Shalini; de Wildt, Saskia N

2012-01-01

This review was conducted to examine the current status of paediatric medicines initiatives across the globe. The authors made a non-systematic descriptive review of current world situation. Two regions, the United States (US) and the European Union (EU), and the World Health Organization (WHO) have introduced strong paediatric initiatives to improve children's health through improving access to better paediatric medicines. The experience from the US initiative indicates that it is possible to stimulate development and study of paediatric medicines and provide important new information for improvement of paediatric therapy. The early results from the EU initiative are similarly encouraging. In Canada, Japan, Australia and other developed countries, specific paediatric medicines initiatives have been less extensive and weaker, with modest results. Disappointingly, current evidence suggests that results from clinical trials outside the US often do not benefit children in the country in which the trials were largely conducted. Pharmaceutical companies that have derived a financial benefit commensurate with the cost of doing the paediatric trials in one country do not seem to be making the results of these trials available to all countries if there is no financial incentive to the company. The WHO campaign 'make medicines child size' has produced substantive accomplishments in building improved foundations to improve mechanisms that will enhance children's access to critical medicines in resource-limited settings. However, practically all of this work has been performed using an amalgamation of short-term funding from a variety of sources as opposed to a sustained, programmatic commitment. Although much still needs to be done, it's clear that with concerted efforts and appropriate resources, change is possible but slow. Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.

The neuropsychiatric aspect of Addison's disease: a case report.

PubMed

Abdel-Motleb, Mohamed

2012-10-01

Chronic adrenal insufficiency, known as Addison's disease, presents with a constellation of symptoms and signs. The neuropsychiatric aspect of this condition is not fully understood and not much has been documented about it in the English literature. This article presents a case of a 41-year old male patient who presented initially with depression after a recent life stressor. After his condition escalated and therapy continued to fail, the medical team revised its diagnosis to Addison's disease. Neuropsychiatric symptoms could be the first presentation of Addison's disease, and thus should be kept in mind whenever such a case presents to the physician.

Anti-ganglioside antibodies in patients with systemic lupus erythematosus and neurological manifestations.

PubMed

Labrador-Horrillo, M; Martinez-Valle, F; Gallardo, E; Rojas-Garcia, R; Ordi-Ros, J; Vilardell, M

2012-05-01

Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller-Fisher syndrome, Guillain-Barré syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients.

Scaling-up essential neuropsychiatric services in Ethiopia: a cost-effectiveness analysis

PubMed Central

Strand, Kirsten Bjerkreim; Chisholm, Dan; Fekadu, Abebaw; Johansson, Kjell Arne

2016-01-01

Introduction There is an immense need for scaling-up neuropsychiatric care in low-income countries. Contextualized cost-effectiveness analyses (CEAs) provide relevant information for local policies. The aim of this study is to perform a contextualized CEA of neuropsychiatric interventions in Ethiopia and to illustrate expected population health and budget impacts across neuropsychiatric disorders. Methods A mathematical population model (PopMod) was used to estimate intervention costs and effectiveness. Existing variables from a previous WHO-CHOICE regional CEA model were substantially revised. Treatments for depression, schizophrenia, bipolar disorder and epilepsy were analysed. The best available local data on epidemiology, intervention efficacy, current and target coverage, resource prices and salaries were used. Data were obtained from expert opinion, local hospital information systems, the Ministry of Health and literature reviews. Results Treatment of epilepsy with a first generation antiepileptic drug is the most cost-effective treatment (US$ 321 per DALY adverted). Treatments for depression have mid-range values compared with other interventions (US$ 457–1026 per DALY adverted). Treatments for schizophrenia and bipolar disorders are least cost-effective (US$ 1168–3739 per DALY adverted). Conclusion This analysis gives the Ethiopian government a comprehensive overview of the expected costs, effectiveness and cost-effectiveness of introducing basic neuropsychiatric interventions. PMID:26491060

Biochemical correlates of neuropsychiatric illness in maple syrup urine disease

PubMed Central

Muelly, Emilie R.; Moore, Gregory J.; Bunce, Scott C.; Mack, Julie; Bigler, Don C.; Morton, D. Holmes; Strauss, Kevin A.

2013-01-01

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. Dietary management enables survival and reduces risk of acute crises. Liver transplantation has emerged as an effective way to eliminate acute decompensation risk. Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. We report the prevalence and characteristics of neuropsychiatric problems among 37 classical MSUD patients (ages 5–35 years, 26 on dietary therapy, 11 after liver transplantation) and explore their underlying mechanisms. Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. Using quantitative proton magnetic resonance spectroscopy, we found lower brain glutamate, N-acetylaspartate (NAA), and creatine concentrations in MSUD patients, which correlated with specific neuropsychiatric outcomes. Asymptomatic neonatal course and stringent longitudinal biochemical control proved fundamental to optimizing long-term mental health. Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. These findings may provide insight into general mechanisms of psychiatric illness. PMID:23478409

Sustainable Benefits of a Community Hospital-Based Paediatric Asthma Clinic.

PubMed

Kuzik, Brian A; Chen, Chee P; Hansen, Miriam J; Montgomery, Paula L

2017-01-01

In 2011, we reported that our paediatric asthma clinic (PAC) appeared to significantly reduce the burden of paediatric asthma in our community. Supported by these results, the PAC underwent a gradual threefold expansion while maintaining the same model of care. We now report on the outcome of that expansion and demonstrate that our PAC continues to significantly reduce the burden of paediatric asthma in our community. As previously, newly enrolled PAC patients continue to show a 12-month reduction in asthma-related emergency department (ED) visits and admissions exceeding 60% and 80%, respectively. This consistent short-term benefit, coupled with clinic expansion, has contributed to a significant improvement in our rate of paediatric asthma-related ED visits or hospitalizations when compared to other Ontario hospitals.

Novel pebbles in the mosaic of autoimmunity.

PubMed

Perricone, Carlo; Agmon-Levin, Nancy; Shoenfeld, Yehuda

2013-04-04

Almost 25 years ago, the concept of the 'mosaic of autoimmunity' was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are now looking at an era in which the players of autoimmunity have changed names and roles. In this issue of BMC Medicine, several aspects of autoimmunity have been addressed, suggesting that we are now at the forefront of autoimmunity science. Within the environmental factors generating autoimmunity are now included unsuspected molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are recognized as causal factors in the development of the autoimmune response. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), has been recently described. This is the new wind blowing within the branches of autoimmunity, adding knowledge to physicians for helping patients with autoimmune disease.

A Clinical Study of Phenomenology and Comorbidity of Paediatric Bipolar Disorder

ERIC Educational Resources Information Center

Gupta, Pavan Kumar; T., Sivakumar; Agarwal, Vivek; Sitholey, Prabhat

2012-01-01

Background: Considerable controversy exists regarding clinical presentation, diagnosis, and comorbidities especially with Attention Deficit Hyperactivity Disorder (ADHD), in paediatric Bipolar Disorder (BPD). Aims and objectives: To describe phenomenology and comorbidities of paediatric BPD. Method: 78 Subjects (6-16 years) attending child and…

Audit of availability and distribution of paediatric cardiology services and facilities in Nigeria

PubMed Central

Ekure, Ekanem N; Sadoh, Wilson E; Bode-Thomas, Fidelia; Yilgwan, Christopher S; Orogade, Adeola A; Animasahun, Adeola B; Ogunkunle, Oluwatoyin O; Omokhodion, Samuel I; Babaniyi, Iretiola; Anah, Maxwell U; Otaigbe, Barbara E; Olowu, Adebiyi; Okpokowuruk, Frances; Maduka, Ogechi C; Onakpoya, Uvie U; Adiele, Daberechi K; Sani, Usman. M; Asani, Mustapha; Daniels, Queennette; Uzodimma, Chinyere C; Duru, Chika O; Abdulkadir, Mohammad B; Afolabi, Joseph K; Okeniyi, John A

2017-01-01

Summary Background Paediatric cardiac services in Nigeria have been perceived to be inadequate but no formal documentation of availability and distribution of facilities and services has been done. Objective: To evaluate and document the currently available paediatric cardiac services in Nigeria. Methods In this questionnaire-based, cross-sectional descriptive study, an audit was undertaken from January 2010 to December 2014, of the personnel and infrastructure, with their distributions according to geopolitical zones of Nigeria. Results Forty-eight centres participated in the study, with 33 paediatric cardiologists and 31 cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were available in 45 (93.8%) centres while paediatric intensive care units were in 23 (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone had the majority of centres (20; 41.7%). Conclusions Available paediatric cardiac services in Nigeria are grossly inadequate and poorly distributed. Efforts should be intensified to upgrade existing facilities, establish new and functional centres, and train personnel. PMID:27701490

Audit of availability and distribution of paediatric cardiology services and facilities in Nigeria.

PubMed

Ekure, Ekanem N; Sadoh, Wilson E; Bode-Thomas, Fidelia; Orogade, Adeola A; Animasahun, Adeola B; Ogunkunle, Oluwatoyin O; Babaniyi, Iretiola; Anah, Maxwell U; Otaigbe, Barbara E; Olowu, Adebiyi; Okpokowuruk, Frances; Omokhodion, Samuel I; Maduka, Ogechi C; Onakpoya, Uvie U; Adiele, Daberechi K; Sani, Usman M; Asani, Mustapha; Yilgwan, Christopher S; Daniels, Queennette; Uzodimma, Chinyere C; Duru, Chika O; Abdulkadir, Mohammad B; Afolabi, Joseph K; Okeniyi, John A

Paediatric cardiac services in Nigeria have been perceived to be inadequate but no formal documentation of availability and distribution of facilities and services has been done. To evaluate and document the currently available paediatric cardiac services in Nigeria. In this questionnaire-based, cross-sectional descriptive study, an audit was undertaken from January 2010 to December 2014, of the personnel and infrastructure, with their distributions according to geopolitical zones of Nigeria. Forty-eight centres participated in the study, with 33 paediatric cardiologists and 31 cardiac surgeons. Echocardiography, electrocardiography and pulse oximetry were available in 45 (93.8%) centres while paediatric intensive care units were in 23 (47.9%). Open-heart surgery was performed in six (12.5%) centres. South-West zone had the majority of centres (20; 41.7%). Available paediatric cardiac services in Nigeria are grossly inadequate and poorly distributed. Efforts should be intensified to upgrade existing facilities, establish new and functional centres, and train personnel.

[Consensus document by the Spanish Society of Paediatric Infectious Diseases and the advisory committee on vaccines of the Spanish Paediatrics Association on vaccination in immunocompromised children].

PubMed

Mellado Peña, M J; Moreno-Pérez, D; Ruíz Contreras, J; Hernández-Sampelayo Matos, T; Navarro Gómez, M L

2011-12-01

Vaccination in immunocompromised infants, children and adolescents is a major aspect in the follow-up of this complex pathology in specific Paediatric Units. Vaccination is also an important prevention tool, as this can, to a certain extent, determine the morbidity and mortality in these patients. This consensus document was jointly prepared by Working Groups of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Paediatric Association, who are usually involved in updating the management of vaccinations in immunocompromised children, and reflects their opinions. The consensus specifically summarises indications for vaccination in the following special paediatric populations: Solid organ and haematopoietic transplant-recipients; primary immunodeficiency; asplenic children; non-previously transplanted immunocompromised patients; chronically ill patients; HIV-infected children and also the vaccines recommended for immunodeficient children who travel. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Paediatric Virology: A rapidly increasing educational challenge

PubMed Central

Mammas, Ioannis N.; Theodoridou, Maria; Kramvis, Anna; Thiagarajan, Prakash; Gardner, Sharryn; Papaioannou, Georgia; Melidou, Angeliki; Koutsaki, Maria; Kostagianni, Georgia; Achtsidis, Vassilis; Koutsaftiki, Chryssie; Calachanis, Marcos; Zaravinos, Apostolos; Greenough, Anne; Spandidos, Demetrios A.

2017-01-01

The ‘2nd Workshop on Paediatric Virology’, which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop. PMID:28352303

The 2017 Seventh World Congress of Paediatric Cardiology and Cardiac Surgery: "The Olympics of our Profession".

PubMed

Cohen, Mitchell I; Jacobs, Jeffrey P; Cicek, Sertac

2017-12-01

The 1st World Congress of Paediatric Cardiology was held in London, United Kingdom, in 1980, organised by Dr Jane Somerville and Prof. Fergus Macartney. The idea was that of Jane Somerville, who worked with enormous energy and enthusiasm to bring together paediatric cardiologists and surgeons from around the world. The 2nd World Congress of Paediatric Cardiology took place in New York in 1985, organised by Bill Rashkind, Mary Ellen Engle, and Eugene Doyle. The 3rd World Congress of Paediatric Cardiology was held in Bangkok, Thailand, in 1989, organised by Chompol Vongraprateep. Although cardiac surgeons were heavily involved in these early meetings, a separate World Congress of Paediatric Cardiac Surgery was held in Bergamo, Italy, in 1988, organised by Lucio Parenzan. Thereafter, it was recognised that surgeons and cardiologists working on the same problems and driven by a desire to help children would really rather meet together. A momentous decision was taken to initiate a Joint World Congress of Paediatric Cardiology and Cardiac Surgery. A steering committee was established with membership comprising the main organisers of the four separate previous Congresses and additional members were recruited in an effort to achieve numerical equality of cardiologists and surgeons and a broad geographical representation. The historic 1st "World Congress of Paediatric Cardiology and Cardiac Surgery" took place in Paris in June, 1993, organised by Jean Kachaner. The next was to be held in Japan, but the catastrophic Kobe earthquake in 1995 forced relocation to Hawaii in 1997. Then followed Toronto, Canada, 2001, organised by Bill Williams and Lee Benson; Buenos Aires, Argentina, 2005, organised by Horatio Capelli and Guillermo Kreutzer; Cairns, Australia, 2009, organised by Jim Wilkinson; Cape Town, South Africa, 2013, organised by Christopher Hugo-Hamman; and Barcelona, Spain, 2017, organised by Sertac Cicek. With stops in Europe (1993), Asia-Pacific (1997), North America (2001), South America (2005), Australia (2009), Africa (2013), and Europe again (2017), in 2021, The World Congress of Paediatric Cardiology and Cardiac Surgery will be held for the first time in the continental United States. 1 The 8th World Congress of Paediatric Cardiology and Cardiac Surgery will be held in Washington DC, United States of America, 19-24 September, 2021, and will be organised by Jeffrey P. Jacobs and Gil Wernovsky. Mitchell I. Cohen served as the Scientific Program Co-Chair for the 2017 World Congress of Paediatric Cardiology and Cardiac Surgery, and he will again serve as the Scientific Program Co-Chair for the 2021 World Congress of Paediatric Cardiology and Cardiac Surgery along with Kathyrn Dodds RN, MSN, CRNP. Information about the upcoming 8th World Congress of Paediatric Cardiology and Cardiac Surgery can be found at www.WCPCCS2021.org.

What Do We Know about Knowledge Brokers in Paediatric Rehabilitation? A Systematic Search and Narrative Summary

PubMed Central

Verrier, Molly C.; Landry, Michel D.

2014-01-01

ABSTRACT Purpose: To conduct a systematic review of the literature related to the use of knowledge brokers within paediatric rehabilitation, and specifically to determine (1) how knowledge brokers are defined and used in paediatric rehabilitation and (2) whether knowledge brokers in paediatric rehabilitation have demonstrably improved the performance of health care providers or organizations. Methods: The MEDLINE, CINAHL, EMBASE, and AMED databases were systematically searched to identify studies relating to knowledge brokers or knowledge brokering within paediatric rehabilitation, with no restriction on the study design or primary aim. Following review of titles and abstracts, those studies identified as potentially relevant were assessed based on the inclusion criteria that they: (1) examined some aspect of knowledge brokers/brokering in paediatric rehabilitation; (2) included sufficient descriptive detail on how knowledge brokers/brokering were used; and(3) were peer-reviewed and published in English. Results: Of 1513 articles retrieved, 4 met the inclusion criteria, 3 of which referenced the same knowledge broker initiative. Two papers used mixed methods, one qualitative methodology, and one case presentation. Because of the different methods used in the included studies, the findings are presented in a narrative summary. Conclusions: This study provides an overview of the limited understanding of knowledge brokers within paediatric rehabilitation. Knowledge broker initiatives introduced within paediatric rehabilitation have been anchored in different theoretical frameworks, and no conclusions can be drawn as to the optimum combination of knowledge brokering activities and methods, nor about optimal duration, for sustained results. PMID:24799751

Shared decision-making in the paediatric field: a literature review and concept analysis.

PubMed

Park, Eun Sook; Cho, In Young

2017-09-13

The concept of shared decision-making is poorly defined and often used interchangeably with related terms. The aim of this study was to delineate and clarify the concept of shared decision-making in the paediatric field. Rodgers and Knafl's evolutionary concept analysis was used to delineate and clarify the concept. Following a search of the CINAHL, PubMed and MEDLINE databases and online journals between 1995 and 2016, we included a total of 42 articles that referred to shared decision-making in the paediatric field. The attributes included active participation of the three: parents, children and health professionals; collaborative partnership; reaching a compromise; and common goal for child's health. Antecedents were existing several options with different possible outcomes; substantial decisional conflict; recognising child's health situations that decision-making is needed; and willingness to participate in decision-making. Finally, the consequences included decreased decisional conflict; mutual empowerment; improved child health status; and improved quality of paediatric health care. This study provides a theoretical understanding of the concept of shared decision-making in the paediatric field; furthermore, by integrating this concept into paediatric practice, it may help to reduce the gap between theory and practice. The analysis could also provide nursing researchers with insight into paediatric decision-making and establish a foundation to develop future interventions and situation-specific theory for promoting high-quality decision-making in the paediatric field. © 2017 Nordic College of Caring Science.

Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions.

PubMed

Jeong, Hae Woong; Her, Minyoung; Bae, Jong Seok; Kim, Seong-Kyu; Lee, Sung Won; Kim, Ho Kyun; Kim, Dongyook; Park, Nayoung; Chung, Won Tae; Lee, Sang Yeob; Choe, Jung-Yoon; Kim, In Joo

2015-05-01

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.

[A case of anti-LKM 1 positive autoimmune hepatitis accompanied by systemic lupus erythematosus].

PubMed

Choi, Dae Han; Kim, Hae Kyung; Park, Tae Il; John, Byung Min; Kang, Sung Hwan; Lee, Yoon Serk; Kim, Tae Hyun; Lee, Uh Joo; Lee, Tae Seung; Yoon, Gwi Ok

2008-03-01

Overlap of autoimmune hepatitis and systemic lupus erythematosus (SLE) is a comparatively rare condition. Although both autoimmune hepatitis and SLE can share common autoimmune features such as polyarthralgia, hypergammaglobulinemia and positive ANA, it has been considered as two different entities. We report a case of anti-LKM1 positive autoimmune hepatitis who developed SLE two years later. The presence of interface hepatitis with lymphoplasma cell infiltrates and rosette formation points to the autoimmune hepatitis rather than SLE hepatitis. Autoimmune hepatitis is infrequently accompanied by SLE, therefore, it could be recommended to investigate for SLE in patients with autoimmune hepatitis.

Paediatric Low-Vision Assessment and Management in a Specialist Clinic in the UK

ERIC Educational Resources Information Center

Lennon, Julie; Harper, Robert; Biswas, Sus; Lloyd, Chris

2007-01-01

This article presents a survey of the demographical, educational and visual functional characteristics of children attending a specialist paediatric low-vision assessment clinic at Manchester Royal Eye Hospital. Comprehensive data were collected retrospectively from children attending the paediatric low-vision clinic between January 2003 and…

How many procedures do UK paediatric trainees perform in their neonatal posts?

PubMed

Ramaiah, Sridhar M; Athiraman, Naveen; Tse, Yincent

2018-05-26

The UK training programme typically takes 8 years full time equivalent to become a paediatric consultant but can be shortened to as little as five years if deemed competent. At minimum trainees complete two six months posts in neonatology, one at level 1 Specialty training (ST 1-3) and another at level 2 training (ST 4-5) during their paediatric training programme. According to the Royal College of Paediatrics and Child Health curriculum (1), by end of ST 5 training year the competent paediatric registrar will 'be able to provide and lead basic and advanced neonatal resuscitation' and 'be able to intubate sick newborn infants without direct supervision. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Contribution to scientific research in paediatrics in The Netherlands: evaluation according to subspeciality over a 10-year period.

PubMed

Verberkmoes, J A; Monnens, L A; Vossen, J M; Weening, R S

1993-11-01

The board of the Dutch Paediatric Association requested a survey of the scientific research performed in all academic and non-academic paediatric hospitals, authorized to train medical doctors in paediatrics in the Netherlands. Contributions to the international and the Dutch scientific literature, in the form of regular publications, chapters in books, contributions to proceedings and Ph.D. theses were counted over two 5-year periods, i.e. 1981-1985 and 1986-1990. The quality of publications in the international journals was assessed using the average impact factor of the journals over the 10-year period. The number of publications in the international literature doubled during the observation period 1986-1990 compared to the period 1981-1985. Nevertheless, the quality of the publications remained the same. Metabolism, oncology/haematology, immunology/infectious diseases and cardiology are the subspecializations in which scientific research takes place in four or more academic paediatric hospitals. In total, 84 Ph.D. theses were produced in which a paediatrician was either the project leader (mostly a professor in paediatrics) or the investigator-in-charge. Insight into structure and major research efforts of paediatric hospitals in other countries of Europe may lead to exchange of views and, maybe, profitable co-operation.

Permeation studies through porcine small intestine of furosemide solutions for personalised paediatric administration.

PubMed

Provenza, N; Calpena, A C; Mallandrich, M; Sánchez, A; Egea, M A; Clares, B

2014-11-20

Personalized medicine is a challenging research area in paediatric drug design since no suitable pharmaceutical forms are currently available. Furosemide is an anthranilic acid derivative used in paediatric practice to treat cardiac and pulmonary disorders in premature infants and neonates. However, it is not commercialized in suitable dosage forms for paediatrics. Elaborating new paediatric formulations when no commercial forms are available is a common practice in pharmacy laboratories; amongst these, oral liquid formulations are the most common. We developed two extemporaneous paediatric oral solutions of furosemide (pure powder). The characterization and stability study were also performed. Parameters such as organoleptic characteristics, rheology, pH, content of active substance, and microbial stability were evaluated at three temperatures for two months. Evaluation of all these parameters showed that both solutions were stable for 60 days at 4 and 25 °C. Moreover, ex vivo studies were performed to evaluate the permeation behaviour of developed solutions through porcine small intestine to evaluate the potential paediatric biological parameters influencing the bioavailability and efficacy. A validated spectrofluorometric method was also used for this purpose. Our results guarantee a correct dosification, administration and potential efficacy of furosemide when is formulated in liquid oral forms for the treatment of cardiac and pulmonary disorders in children. Copyright © 2014 Elsevier B.V. All rights reserved.

Are TB control programmes in South Asia ignoring children with disease? A situational analysis.

PubMed

Shakoor, Sadia; Qamar, Farah Naz; Mir, Fatima; Zaidi, Anita; Hasan, Rumina

2015-02-01

Paediatric tuberculosis (TB) has long been an evasive entity for public health practitioners striving to control the disease. Owing to difficulty in diagnosis of paediatric TB, incidence estimates based on current case detection fall short of actual rates. The four high-burden countries in South Asia (SA-HBC)-Afghanistan, Pakistan, India and Bangladesh-alone account for >75% of missed TB cases worldwide. It follows that these countries are also responsible for a large although unmeasured proportion of missed paediatric cases. In view of current Millennium Development Goals recommending a scale-up of paediatric TB detection and management globally, there is a dire need to improve paediatric TB programmes in these high-burden countries. Inherent problems with diagnosis of paediatric TB are compounded by programmatic and social barriers in SA-HBC. We have reviewed the current situation of TB control programmes in SA-HBC countries based on published statistics and performed a strengths, weaknesses, opportunities and threats situational analysis with a view towards identifying critical issues operant in the region posing barriers to improving paediatric TB control. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Paediatric conscious sedation: views and experience of specialists in paediatric dentistry.

PubMed

Woolley, S M; Hingston, E J; Shah, J; Chadwick, B L

2009-09-26

The objectives were three-fold: to investigate the level of conscious sedation training received prior to and during specialist training in paediatric dentistry; to establish the use of conscious sedation during and following specialisation; and to determine the attitudes of specialists in paediatric dentistry to conscious sedation. A self-administered postal questionnaire was sent to all specialists in paediatric dentistry registered with the General Dental Council in January 2008. Non-responders were contacted again after a four-week period. A response rate of 60% was achieved. Of the 122 respondents, 67 (55%) had received sedation training as an undergraduate; 89 (75%) had been trained during specialisation. All respondents performed dental treatment under sedation as a trainee and the majority used nitrous oxide inhalation sedation (NOIS). Over 90% of respondents felt that NOIS should be available to all children, both in appropriate primary care settings and in hospitals. One hundred and twenty-one (99%) respondents thought that all trainees in paediatric dentistry should have sedation training. The most popular form of sedation amongst specialists in paediatric dentistry was NOIS. However, some of the respondents felt that children should have access to other forms of sedation in both the primary care and hospital settings. Additional research on other forms of sedation is required to evaluate their effectiveness and safety.

Non-operative advances: what has happened in the last 50 years in paediatric surgery?

PubMed

Holland, Andrew J A; McBride, Craig A

2015-01-01

Paediatric surgeons remain paediatric clinicians who have the unique skill set to treat children with surgical problems that may require operative intervention. Many of the advances in paediatric surgical care have occurred outside the operating theatre and have involved significant input from medical, nursing and allied health colleagues. The establishment of neonatal intensive care units, especially those focusing on the care of surgical infants, has greatly enhanced the survival rates and long-term outcomes of those infants with major congenital anomalies requiring surgical repair. Educational initiatives such as the advanced trauma life support and emergency management of severe burns courses have facilitated improved understanding and clinical care. Paediatric surgeons have led with the non-operative management of solid organ injury following blunt abdominal trauma. Nano-crystalline burn wound dressings have enabled a reduced frequency of painful dressing changes in addition to effective antimicrobial efficacy and enhanced burn wound healing. Burns care has evolved so that many children may now be treated almost exclusively in an ambulatory care setting or as day case-only patients, with novel technologies allowing accurate prediction of burn would outcome and planning of elective operative intervention to achieve burn wound closure. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

The european paediatric legislation: benefits and perspectives

PubMed Central

2010-01-01

Background The lack of availability of appropriate medicines for children is an extensive and well known problem. Paediatricians and Physicians who take care of the paediatric population are primarily exposed to cope with this negative situation very often as more than half of the children are prescribed off-label or unlicensed medicines. Discussion Medicinal products used to treat this population should be subjected to ethical research of high quality and be explicitly authorised for use in children as it happens in adults. For that reason, and following the US experience, the European Paediatric Regulation has been amended in January 2007 by the European Commission. The objective of the Paediatric Regulation is to improve the development of high quality and ethically researched medicines for children aged 0 to 17 years, to facilitate the availability of information on the use of medicines for children, without subjecting children to unnecessary trials, or delaying the authorisation of medicines for use in adults. Summary The Paediatric Regulation is dramatically changing the regulatory environment for paediatric medicines in Europe and is fuelling an increased number of clinical trials in the paediatric population. Nevertheless, there are some risks and pitfalls that need to be anticipated and controlled in order to ensure that children will ultimately benefit from this European initiative. PMID:20716337

Potential Usefulness of the Kampo Medicine Yokukansan, Containing Uncaria Hook, for Paediatric Emotional and Behavioural Disorders: A Case Series

PubMed Central

2013-01-01

Background. Paediatric emotional and behavioural disorders (EBD) are relatively common diseases. Although nonpharmacologic and pharmacologic treatments are utilized in these cases, it is sometimes difficult to manage the symptoms of EBD. Historically, Uncaria hook has been used for treating nighttime crying and convulsions in children. Recent clinical studies have demonstrated that the Kampo medicine Yokukansan (YKS), which contains Uncaria hook, is efficacious for behaviour disorders in Alzheimer's disease patients. Herein, we investigated the clinical efficacy and safety of YKS in a series of cases with paediatric EBD. Patients and Methods. We retrospectively reviewed all paediatric patients who sought Japanese Kampo therapy at our outpatient clinics between April 1, 2012, and April 30, 2013; we selected patients who were diagnosed with paediatric EBD and were treated with YKS. Results. After screening all candidates, 3 patients were eligible for this analysis. Their average age was 11.6 years (range 10–13 years). All 3 patients responded very well to YKS within 1 month. No drug-related adverse events were observed during the course of YKS treatment. Conclusion. Yokukansan may be efficacious for paediatric EBD. We believe these results warrant further evaluation of the clinical efficacy and safety of Yokukansan for paediatric EBD in a carefully designed, double-blind, randomized clinical study. PMID:24204394

Neurobiological and Neuropsychiatric Effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS)

PubMed Central

Maninger, Nicole; Wolkowitz, Owen M.; Reus, Victor I.; Epel, Elissa S.; Mellon, Synthia H.

2009-01-01

DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed. PMID:19063914

A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders

PubMed Central

Jiang, Peng; Scarpa, Joseph R.; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D.; Hao, Ke; Summa, Keith C.; Yang, He S.; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H.; Turek, Fred W.; Kasarskis, Andrew

2016-01-01

SUMMARY Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multi-level organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J×A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests the interplay between sleep, stress, and neuropathology emerge from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework to interrogate the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. PMID:25921536

Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.

PubMed

McConnell, Michael J; Moran, John V; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A; Fasching, Liana; Flasch, Diane A; Freed, Donald; Ganz, Javier; Jaffe, Andrew E; Kwan, Kenneth Y; Kwon, Minseok; Lodato, Michael A; Mills, Ryan E; Paquola, Apua C M; Rodin, Rachel E; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A; Shin, Joo Heon; Song, Saera; Straub, Richard E; Thorpe, Jeremy; Weinberger, Daniel R; Urban, Alexander E; Zhou, Bo; Gage, Fred H; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G; Kidd, Jeffrey M; Park, Peter J; Pevsner, Jonathan; Vaccarino, Flora M

2017-04-28

Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. Copyright © 2017, American Association for the Advancement of Science.

The Sequelae of Acute Purulent Meningitis in Childhood

PubMed Central

Hutchison, Patricia A.; Kovacs, Michael C.

1963-01-01

Of a series of 122 children suffering from acute purulent meningitis at the Children's Hospital, Winnipeg, in the years 1952-56, 12 (9.8%) succumbed, all deaths occurring in those 12 months of age or less. Fortyone of the survivors were re-studied 2.5 to 7.5 years after their acute illness to assess the nature and incidence of sequelae, the relationship of sequelae to the severity of the acute illness, and the correlation between the various methods of identifying sequelae. Five children exhibited psychiatric evidence of organic brain damage; seven, neurological abnormality; 11, electroencephalographic abnormality. Three had defective intelligence and nine psychological test evidence of organic brain damage. Children with sequelae tended to have several abnormal test results, the total number with neuropsychiatric and/or psychological sequelae being 11 (26%). There was a positive correlation between the severity of the acute illness and the presence of neuropsychiatric sequelae; also between neuropsychiatric sequelae, defective intelligence and psychological evidence of brain damage. No correlation existed between the electroencephalographic abnormality and neuropsychiatric defect. PMID:13955939

Lost in translation: neuropsychiatric drug development.

PubMed

Becker, Robert E; Greig, Nigel H

2010-12-08

Recent studies have identified troubling method and practice lapses in neuropsychiatric drug developments. These problems have resulted in errors that are of sufficient magnitude to invalidate clinical trial data and interpretations. We identify two potential sources for these difficulties: investigators selectively choosing scientific practices for demonstrations of efficacy in human-testing phases of drug development and investigators failing to anticipate the needs of practitioners who must optimize treatment for the individual patient. When clinical investigators neglect to use clinical trials as opportunities to test hypotheses of disease mechanisms in humans, the neuropsychiatric knowledge base loses both credibility and scope. When clinical investigators do not anticipate the need to translate discoveries into applications, the practitioner cannot provide optimal care for the patient. We conclude from this evidence that clinical trials, and other aspects of neuropsychiatric drug development, must adopt more practices from basic science and show greater responsiveness to conditions of clinical practice. We feel that these changes are necessary to overcome current threats to the validity and utility of studies of neurological and psychiatric drugs.

Transitioning young adults from paediatric to adult care and the HIV care continuum in Atlanta, Georgia, USA: a retrospective cohort study.

PubMed

Hussen, Sophia A; Chakraborty, Rana; Knezevic, Andrea; Camacho-Gonzalez, Andres; Huang, Eugene; Stephenson, Rob; Del Rio, Carlos

2017-09-01

The transition from paediatric to adult HIV care is a particularly high-risk time for disengagement among young adults; however, empirical data are lacking. We reviewed medical records of 72 youth seen in both the paediatric and the adult clinics of the Grady Infectious Disease Program in Atlanta, Georgia, USA, from 2004 to 2014. We abstracted clinical data on linkage, retention and virologic suppression from the last two years in the paediatric clinic through the first two years in the adult clinic. Of patients with at least one visit scheduled in adult clinic, 97% were eventually seen by an adult provider (median time between last paediatric and first adult clinic visit = 10 months, interquartile range 2-18 months). Half of the patients were enrolled in paediatric care immediately prior to transition, while the other half experienced a gap in paediatric care and re-enrolled in the clinic as adults. A total of 89% of patients were retained (at least two visits at least three months apart) in the first year and 56% in the second year after transition. Patients who were seen in adult clinic within three months of their last paediatric visit were more likely to be virologically suppressed after transition than those who took longer (Relative risk (RR): 1.76; 95% confidence interval (CI): 1.07-2.9; p  = 0.03). Patients with virologic suppression (HIV-1 RNA below the level of detection of the assay) at the last paediatric visit were also more likely to be suppressed at the most recent adult visit (RR: 2.3; 95% CI: 1.34-3.9; p  = 0.002). Retention rates once in adult care, though high initially, declined significantly by the second year after transition. Pre-transition viral suppression and shorter linkage time between paediatric and adult clinic were associated with better outcomes post-transition. Optimizing transition will require intensive transition support for patients who are not virologically controlled, as well as support for youth beyond the first year in the adult setting.

Cannabidiol, neuroprotection and neuropsychiatric disorders.

PubMed

Campos, Alline C; Fogaça, Manoela V; Sonego, Andreza B; Guimarães, Francisco S

2016-10-01

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions. It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets. In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders. Copyright © 2016. Published by Elsevier Ltd.

Effects of early-life malnutrition on neurodevelopment and neuropsychiatric disorders and the potential mechanisms.

PubMed

Yan, Xintian; Zhao, Xinzhi; Li, Juxue; He, Lin; Xu, Mingqing

2018-04-20

Lines of evidence have demonstrated that early-life malnutrition is highly correlated with neurodevelopment and adulthood neuropsychiatric disorders, while some findings are conflicting with each other. In addition, the biological mechanisms are less investigated. We systematically reviewed the evidence linking early-life nutrition status with neurodevelopment and clinical observations in human and animal models. We summarized the effects of special nutritious on neuropsychiatric disorders and explored the underlying potential mechanisms. The further understanding of the biological regulation of early-life nutritional status on neurodevelopment might shed light on precision nutrition at an integrative systems biology framework. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration.

PubMed

Starkman, Monica N

2013-09-01

This article reviews the neuropsychiatric presentations elicited by spontaneous hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with Cushing disease and syndrome develop a depressive syndrome: irritable and depressed mood, decreased libido, disrupted sleep and cognitive decrements. Exogenous short-term glucocorticoid administration may elicit a hypomanic syndrome with mood, sleep and cognitive disruptions. Treatment options are discussed. Brain imaging and neuropsychological studies indicate elevated cortisol and other glucocorticoids are especially deleterious to hippocampus and frontal lobe. The research findings also shed light on neuropsychiatric abnormalities in conditions that have substantial subgroups exhibiting elevated and dysregulated cortisol: aging, major depressive disorder and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Derivation of new diagnostic reference levels for neuro-paediatric computed tomography examinations in Switzerland.

PubMed

Wagner, Franca; Bize, Julie; Racine, Damien; Le Coultre, Regis; Francis, Verdun; Trueb, Philipp; Treier, Reto

2018-05-22

Definition of new national diagnostic reference levels (DRLs) for volume computed tomography dose index (CTDIvol) and dose length product (DLP) for neuro-paediatric CT examinations depending on the medical indication. Methods: Paediatric cranial CT data sets acquired between January 2013 and December 2016 were retrospectively collected between July 2016 and March 2017 from the eight largest university and cantonal hospitals that perform most of the neuro-paediatric CTs in Switzerland. A consensus review of CTDIvol and DLP was undertaken for the three defined anatomical regions: brain, facial bone and petrous bone; each with and without contrast medium application. All indications for cranial CT imaging in paediatrics were assigned to one of these three regions. Descriptive statistical analysis of the distribution of the median values for CTDIvol and DLP yielded minimum, maximum, 25th percentile (1st quartile), median (2nd quartile) and 75th percentile (3rd quartile). New DRLs for neuro-paediatric CT examinations in Switzerland were based on the 75th percentiles of the distributions of the median values of all eight centres. Where appropriate, values were rounded such that the DRLs increase or at least remain constant as the age of the patient increases. Results: Our results revealed DRLs for CTDIvol and DLP up to 20% lower than the DRLs used so far in Switzerland and elsewhere in Europe. Conclusions: This study provides Swiss neuro-paediatric CT DRL values to establish optimum conditions for paediatric cranial CT examinations. Periodic national updates of DRLs, following international comparisons, are essential. . Creative Commons Attribution license.

How Much of the Paediatric Core Curriculum Do Medical Students Remember?

ERIC Educational Resources Information Center

Sullivan, Peter B.; Gregg, Nicky; Adams, Emily; Rodgers, Caroline; Hull, Jeremy

2013-01-01

Few educational studies have investigated how well information learned by medical students is retained over time. The primary aim of this study was to investigate how much of the paediatric core curriculum undergraduates remembered a year after originally passing their paediatrics examination. In addition, we looked at whether students'…

Helicobacter pylori and autoimmune disease: Cause or bystander

PubMed Central

Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

2014-01-01

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

PubMed Central

Robertson, Donald; Rodger, Jennifer; Martin-Iverson, Mathew T.

2016-01-01

The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease. PMID:27936175

Scaling-up essential neuropsychiatric services in Ethiopia: a cost-effectiveness analysis.

PubMed

Strand, Kirsten Bjerkreim; Chisholm, Dan; Fekadu, Abebaw; Johansson, Kjell Arne

2016-05-01

There is an immense need for scaling-up neuropsychiatric care in low-income countries. Contextualized cost-effectiveness analyses (CEAs) provide relevant information for local policies. The aim of this study is to perform a contextualized CEA of neuropsychiatric interventions in Ethiopia and to illustrate expected population health and budget impacts across neuropsychiatric disorders. A mathematical population model (PopMod) was used to estimate intervention costs and effectiveness. Existing variables from a previous WHO-CHOICE regional CEA model were substantially revised. Treatments for depression, schizophrenia, bipolar disorder and epilepsy were analysed. The best available local data on epidemiology, intervention efficacy, current and target coverage, resource prices and salaries were used. Data were obtained from expert opinion, local hospital information systems, the Ministry of Health and literature reviews. Treatment of epilepsy with a first generation antiepileptic drug is the most cost-effective treatment (US$ 321 per DALY adverted). Treatments for depression have mid-range values compared with other interventions (US$ 457-1026 per DALY adverted). Treatments for schizophrenia and bipolar disorders are least cost-effective (US$ 1168-3739 per DALY adverted). This analysis gives the Ethiopian government a comprehensive overview of the expected costs, effectiveness and cost-effectiveness of introducing basic neuropsychiatric interventions. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Effects of Herbal Medicine (Gan Mai Da Zao Decoction) on Several Types of Neuropsychiatric Disorders in an Animal Model: A Systematic Review: Herbal medicine for animal studies of neuropsychiatric diseases.

PubMed

Kim, Su Ran; Lee, Hye Won; Jun, Ji Hee; Ko, Byoung-Seob

2017-03-01

Gan Mai Da Zao (GMDZ) decoction is widely used for the treatment of various diseases of the internal organ and of the central nervous system. The aim of this study is to investigate the effects of GMDZ decoction on neuropsychiatric disorders in an animal model. We searched seven databases for randomized animal studies published until April 2015: Pubmed, four Korean databases (DBpia, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, and Research Information Sharing Service), and one Chinese database (China National Knowledge Infrastructure). The randomized animal studies were included if the effects of GMDZ decoction were tested on neuropsychiatric disorders. All articles were read in full and extracted predefined criteria by two independent reviewers. From a total of 258 hits, six randomized controlled animal studies were included. Five studies used a Sprague Dawley rat model for acute psychological stress, post-traumatic stress disorders, and unpredictable mild stress depression whereas one study used a Kunming mouse model for prenatal depression. The results of the studies showed that GMDZ decoction improved the related outcomes. Regardless of the dose and concentration used, GMDZ decoction significantly improved neuropsychiatric disease-related outcomes in animal models. However, additional systematic and extensive studies should be conducted to establish a strong conclusion.

Introduction to "Diversity of Child Health Care in Europe: A Study of the European Paediatric Association/Union of National European Paediatric Societies and Associations".

PubMed

Ehrich, Jochen; Namazova-Baranova, Leyla; Pettoello-Mantovani, Massimo

2016-10-01

The field of pediatrics in Europe is characterized by the diversities, variations, and heterogeneities of child health care services provided in 53 European countries with more than 200 million children below 18 years of age. Managing the health care of infants, children, and adolescents in Europe requires balancing clinical aims, research findings, and socioeconomic goals within a typical environment characterized by cultural and economic complexity and large disparity in availability, affordability, and accessibility of pediatric care. Since its foundation in 1976, the European Paediatric Association-Union of National European Paediatric Societies and Associations has worked to improve both medical care of all children and cooperation of their caretakers in Europe. Such a report has been conceived in the strong belief that broadening of the intellectual basis of the European Paediatric Association-Union of National European Paediatric Societies and Associations and creating a multidisciplinary society will be necessary to reduce fragmentation of pediatrics and tackle the legal, economic, and organizational challenges of child health care in Europe. Copyright © 2016 Elsevier Inc. All rights reserved.

Paediatric manpower.

PubMed Central

Liberman, M M; Bellman, M H

1982-01-01

Two investigations of paediatric manpower in England, Wales, and Northern Ireland were carried out, each using a different method. The first survey located registrars and senior registrars and checked on their occupational status 3 years later in order to see which ones had been promoted. Loss factors--such as emigration, retirement for personal reasons, part-time training, or transfer to general practice, community paediatrics, or other medical specialties--were examined closely. The second survey was a cross-sectional analysis of the entire paediatric establishment. It examined in particular the distribution of consultants and registrars. Using figures from survey 2 and loss factors from survey 1, a model of the paediatric career structure could be constructed. This showed that the present career pyramid would be unable to absorb the current number of registrars in training. There is an urgent need for a comprehensive registration scheme for registrars, especially those with honorary contracts, who are not currently included in official records. Paediatrics is unique in having a high proportion of women for whom there is little opportunity of reconciling career aspirations with family commitments. PMID:7125690

Causes, mechanisms and management of paediatric osteoporosis.

PubMed

Mäkitie, Outi

2013-08-01

Osteoporosis, a skeletal disorder characterized by compromised bone strength and an increased risk of fractures, is an important paediatric disorder that involves almost all paediatric subspecialties. Osteogenesis imperfecta is the most common form of childhood-onset primary osteoporosis, but several other forms are also known. Secondary osteoporosis is caused by an underlying chronic illness or its treatment. The most common causes of secondary osteoporosis include chronic systemic inflammation, glucocorticoid use and neuromuscular disabilities. The skeletal sequelae can present in childhood as low-energy peripheral and vertebral fractures, or become evident in adulthood as low bone mass and an increased propensity to develop osteoporosis. Management should aim at prevention, as interventions to treat symptomatic osteoporosis in the paediatric age group are scarce. Bisphosphonates are the principal pharmacological agents that can be used in this setting, but data on their efficacy and safety in paediatric populations remain inadequate, especially in patients with secondary osteoporosis. Consequently, it is important to understand the potential skeletal effects of paediatric illnesses and their therapies in order to institute effective and timely prevention of skeletal complications.

Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Tay, Sen Hee; Mak, Anselm

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. PMID:25955648

Epileptic syndrome in systemic lupus erythematosus and neuronal autoantibody associations.

PubMed

Kampylafka, E I; Alexopoulos, H; Fouka, P; Moutsopoulos, H M; Dalakas, M C; Tzioufas, A G

2016-10-01

We investigated systemic lupus erythematosus (SLE) patients with epilepsy, a major and organic neurological symptom. Our aim was to test patients for the autoimmune epilepsy-associated antibodies anti-GAD, anti-NMDAR, anti-AMPAR1/2, anti-GABABR and anti-VGKC. We tested sera from ten SLE patients with current or previous episodes of epileptic seizures. In addition, sera were tested for staining on primary hippocampal neurons. The patients' clinical and neuroimaging profile, disease activity and accumulated damage scores and therapeutic regimens administered were recorded, and correlations were evaluated. Patients were negative for all anti-neuronal autoantibodies tested, and showed no staining on primary hippocampal cells, which suggests the absence of autoantibodies against neuronal cell surface antigens. Epileptic seizures were all tonic-clonic, and all patients had high disease activity (mean SLE Damage Acticity Index score 19.3 ± 7.3). Six patients had minor or no brain magnetic resonance imaging findings, and three had major findings. 9/10 patients received immunosuppression for 5 ± 4 months, while anti-convulsive treatment was administered to all patients (4.2 ± 3 years). Our results suggest that the majority of SLE-related epileptic seizures cannot be attributed to the action of a single antibody against neuronal antigens. Studies with larger neuropsychiatric SLE populations and stricter inclusion criteria are necessary to verify these findings. © The Author(s) 2016.

Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves' Disease: Case Report and Review of the Literature.

PubMed

Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia

2017-07-01

Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.

The PANDAS subgroup of tic disorders and childhood-onset obsessive-compulsive disorder.

PubMed

Martino, Davide; Defazio, Giovanni; Giovannoni, Gavin

2009-12-01

Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive-compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A beta-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a recent exposure to GABHS might be a risk factor for the onset of tics and obsessive-compulsive symptoms. However, further evidence from longitudinal prospective research is needed to verify whether a temporal association between GABHS infections and symptom exacerbations is a useful and reliable criterion for the diagnosis of PANDAS. In addition, preliminary results suggest that the PANDAS spectrum might be enlarged to include attention deficit/hyperactivity disorder. Although a number of immunological biomarkers have been proposed as markers of the PANDAS variant, at present, none of these has been conclusively proved useful to diagnose and monitor disease course in children with a suspicion of PANDAS. Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted.

Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome

PubMed Central

Merheb, V.; Ding, A.; Murphy, T.; Dale, R.C.

2011-01-01

Objective: To test the hypothesis that Sydenham chorea (SC) immunoglobulin G (IgG) autoantibodies bind to specific neuronal surface proteins, whereas IgG from patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) or Tourette syndrome (TS) do not bind to neuronal surface proteins. Methods: We used live differentiated SH-SY5Y cells, which have neuronal and dopaminergic characteristics. Using flow cytometry, we measured serum IgG cell surface binding in patients with SC (n = 11), PANDAS (n = 12), and TS (n = 11), and compared the findings to healthy controls (n = 11) and other neurologic controls (n = 11). In order to determine the specificity of binding to neuronal antigens, we also used a non-neuronal cell line, HEK 293. Results: The mean IgG cell surface binding was significantly higher in the SC group compared to all other groups (p < 0.001). By contrast, there was no difference between the PANDAS or TS groups and the controls. Using the non-neuronal HEK-293 cells, there was no significant difference in IgG cell surface binding between any groups. Conclusions: Serum autoantibodies that bind to neuronal cell surface antigens are present in SC, but not in PANDAS or TS. These findings strengthen the hypothesis that SC is due to a pathogenic autoantibody, but weaken the autoantibody hypothesis in PANDAS and TS. PMID:21411742

Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome.

PubMed

Brilot, F; Merheb, V; Ding, A; Murphy, T; Dale, R C

2011-04-26

To test the hypothesis that Sydenham chorea (SC) immunoglobulin G (IgG) autoantibodies bind to specific neuronal surface proteins, whereas IgG from patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) or Tourette syndrome (TS) do not bind to neuronal surface proteins. We used live differentiated SH-SY5Y cells, which have neuronal and dopaminergic characteristics. Using flow cytometry, we measured serum IgG cell surface binding in patients with SC (n = 11), PANDAS (n = 12), and TS (n = 11), and compared the findings to healthy controls (n = 11) and other neurologic controls (n = 11). In order to determine the specificity of binding to neuronal antigens, we also used a non-neuronal cell line, HEK 293. The mean IgG cell surface binding was significantly higher in the SC group compared to all other groups (p < 0.001). By contrast, there was no difference between the PANDAS or TS groups and the controls. Using the non-neuronal HEK-293 cells, there was no significant difference in IgG cell surface binding between any groups. Serum autoantibodies that bind to neuronal cell surface antigens are present in SC, but not in PANDAS or TS. These findings strengthen the hypothesis that SC is due to a pathogenic autoantibody, but weaken the autoantibody hypothesis in PANDAS and TS.

EAP viewpoint on unpublished data from paediatric clinical trials.

PubMed

Schrier, L; Illy, K; Valiulis, A; Wyder, C; Stiris, T

2018-02-01

European children and paediatricians rely heavily on the fair, complete and timely publication of data obtained from paediatric randomised controlled trials (RCTs). Selective publication and reporting of paediatric RCTs is common practice. Industry-sponsored trials are more likely to remain unpublished, and take longer to get published compared with trials sponsored by others. However, also academic sponsors contribute to inefficiencies in publishing clinical data. Publication bias violates the ethical obligation that investigators have towards study participants, leads to considerable inefficiencies in research and a waste of financial and human resources, and has the potential to distort evidence for treatment approaches. The European Academy of Paediatrics (EAP) therefore actively supports initiatives that increase the public dissemination of paediatric clinical trial data. The EAP will raise awareness about the guidelines for Good Publication Practice among European paediatricians and subspecialty societies.

Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Zaidi, Habib

2014-03-01

PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes to a better understanding of the factors influencing patient-specific radiation dose calculation.

Gait and Lower Limb Observation of Paediatrics (GALLOP): development of a consensus based paediatric podiatry and physiotherapy standardised recording proforma.

PubMed

Cranage, Simone; Banwell, Helen; Williams, Cylie M

2016-01-01

Paediatric gait and lower limb assessments are frequently undertaken in podiatry and physiotherapy clinical practice and this is a growing area of expertise within Australia. No concise paediatric standardised recording proforma exists to assist clinicians in clinical practice. The aim of this study was to develop a gait and lower limb standardised recording proforma guided by the literature and consensus, for assessment of the paediatric foot and lower limb in children aged 0-18 years. Expert Australian podiatrists and physiotherapists were invited to participate in a three round Delphi survey panel using the online Qualtrics(©) survey platform. The first round of the survey consisted of open-ended questions on paediatric gait and lower limb assessment developed from existing templates and a literature search of standardised lower limb assessment methods. Rounds two and three consisted of statements developed from the first round responses. Questions and statements were included in the final proforma if 70 % or more of the participants indicated consensus or agreement with the assessment method and if there was support within the literature for paediatric age-specific normative data with acceptable reliability of outcome measures. There were 17 of the 21 (81 %) participants who completed three rounds of the survey. Consensus was achieved for 41 statements in Round one, 54 statements achieved agreement in two subsequent rounds. Participants agreed on 95 statements relating to birth history, developmental history, hip measurement, rotation of the lower limb, ankle range of motion, foot posture, balance and gait. Assessments with acceptable validity and reliability were included within the final Gait and Lower Limb Observation of Paediatrics (GALLOP) proforma. The GALLOP proforma is a consensus based, systematic and standardised way to collect information and outcome measures in paediatric lower limb assessment. This standardised recording proforma will assist professions to collect information in a standardised format based on best evidence assessment methods whilst aiding consistency in communication between health professionals.

Severe systemic autoimmune disease associated with Epstein-Barr virus infection.

PubMed

Sevilla, Julián; del Carmen Escudero, Maria; Jiménez, Raquel; González-Vicent, Marta; Manzanares, Javier; García-Novo, Dolores; Madero, Luis

2004-12-01

Infection with Epstein-Barr virus (EBV) has been associated with different autoimmune manifestations. The authors describe a girl who developed a severe systemic autoimmune disease with severe autoimmune hemolytic anemia, mild autoimmune thrombopenia, antineutrophil antibodies, and fatal autoimmune hepatitis after EBV infection. Despite immunosuppressive treatment and ultimately liver transplantation, this patient could not overcome her clinical condition and died. The etiopathogenesis of this complex disease and the association with EBV infection is discussed.

Clues to immune tolerance: The monogenic autoimmune syndromes

PubMed Central

Waterfield, Michael; Anderson, Mark S.

2010-01-01

Autoimmune disease affects a significant proportion of the population. The etiology of most autoimmune diseases is largely unknown, but it is thought to be multifactorial with both environmental and genetic influences. Rare monogenic autoimmune diseases, however, offer an invaluable window into potential disease mechanisms. In this review, we will discuss the autoimmune polyglandular syndrome (APS1), the immunedysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), and autoimmune lymphoproliferative syndrome (ALPS). Significantly, the information gained from the study of these diseases has provided new insights into more common autoimmune disease and have yielded new diagnostics and therapeutic opportunities. PMID:20969580

Autoimmunity and autoimmune co-morbidities in psoriasis.

PubMed

Furue, Kazuhisa; Ito, Takamichi; Tsuji, Gaku; Kadono, Takafumi; Nakahara, Takeshi; Furue, Masutaka

2018-05-01

Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis. © 2018 John Wiley & Sons Ltd.

Autoimmunity and Gastric Cancer

PubMed Central

Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

2018-01-01

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

Explosion of autoimmune diseases and the mosaic of old and novel factors

PubMed Central

Agmon-Levin, Nancy; Lian, Zhexiong; Shoenfeld, Yehuda

2011-01-01

In recent decades, an enormous effort has been made to elucidate the pathogenesis of autoimmune and autoinflammatory diseases. Autoimmunity is a multifactorial process in which genetic, immunological, environmental and hormonal factors play in concert, together representing what was termed years ago the ‘mosaic of autoimmunity'. To date, more than 80 systemic and organ-specific autoimmune diseases have been defined, and their cumulative burden is substantial, both medically and financially. Furthermore, the burden of autoimmune and autoinflammatory diseases is rising, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. In this issue of the journal, additional aspects of autoimmunity are detailed. Immune dysregulation and loss of self-tolerance are the cornerstones of autoimmunity. PMID:21358666

Frequency of autoimmune diseases in myasthenia gravis: a systematic review.

PubMed

Mao, Zhi-Feng; Yang, Long-Xiu; Mo, Xue-An; Qin, Chao; Lai, Yong-Rong; He, Ning-Yu; Li, Tong; Hackett, Maree L

2011-03-01

The course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%-14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and anti-acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Sexual Abuse Allegations by Children with Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Lindblad, Frank; Lainpelto, Katrin

2011-01-01

All Swedish court cases from 2004 and 2006 concerning alleged child sexual abuse (sexual harassment excluded) were identified through criminal registers. Fourteen cases (one boy) concerned a child with a neuropsychiatric disorder. The diagnostic groups were mental retardation (10 cases), autism (three cases), and ADHD (one case). Psychiatric…

The Double Helix Takes the Witness Stand: Behavioral and Neuropsychiatric Genetics in Court

PubMed Central

Appelbaum, Paul S.

2014-01-01

Summary Data on neuropsychiatric and behavioral genetics have attracted legal interest, as attorneys explore their use in criminal and civil cases. These developments may assist judges and juries in making difficult judgments—but they bring substantial risk of misinterpretation and misuse. PMID:24908480

Pattern of paediatric trauma in Sokoto, North West Nigeria.

PubMed

Oboirien, Muhammad

2013-01-01

Paediatric trauma has become a major cause of mortality, disability and socioeconomic burden in developing countries and the World Health Organization (WHO) projects that by 2020 it will be the leading disease globally. This study described the pattern of paediatric injuries seen at a regional trauma center in North West, Nigeria. Trauma centre of a tertiary hospital in North-Western Nigeria. A retrospective look at the trauma register for records of paediatric trauma from January to December 2010 was performed. Information obtained include age and sex, causes and pattern of injury. The limit of 16 years was set for paediatric in our centre. The numbers of paediatric trauma seen over the 12-month period were 567 out of a total of 3984 trauma cases representing 14.2%. The number of males was 407(71.8%) and females were 160(28.2%) with M: F ratio of 2.5:1. The mean age was 7.77 and standard deviation of 0.19. Road Traffic Accidents (RTA) and Domestic injuries representing 44.8 and 42.0%, respectively, were the commonest causes of injuries. Laceration and bruises, head injuries including extremities were the commonest types of injuries seen. Road traffic accidents and domestic injuries as common causes of paediatric trauma need to be 'addressed by the authorities' so as to reduce the burden of trauma on the vulnerable children in our society.

Single institution experience of paediatric melanoma in Victoria, Australia.

PubMed

Le, Quynh; Norris, Diana; McClean, Catriona A; Mcguiness, Myra; Meani, Rowena; Kelly, John W; Pan, Yan

2017-05-01

Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years. A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method. A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (< 12 years of age). Ten patients developed nodal metastatic disease, eight of which progressed to visceral metastatic disease. The 5-year melanoma-specific survival rate was 96.8%. This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients. © 2016 The Australasian College of Dermatologists.

Career choices for paediatrics: national surveys of graduates of 1974-2002 from UK medical schools.

PubMed

Turner, G; Lambert, T W; Goldacre, M J; Turner, Steve

2007-05-01

Knowledge of UK doctors' career intentions and pathways is essential for understanding future workforce requirements. The aim of this study was to report career choices for and career progression in paediatrics in the UK. Postal questionnaire surveys of qualifiers from all UK medical schools in nine qualification years since 1974. In total, 74% (24 621/33 412) and 73% (20 720/28 459) of doctors responded at 1 and 3 years after graduation. Choices for paediatrics 1 year after qualifying fell from 7.8% of 1974 graduates to 5.0% of 1983 graduates, increased to 7.2% of 1993 graduates, and since the level has remained fairly constant. Approximately twice the percentage of women graduates than men graduates indicated a long-term career choice for paediatrics. A total of 44% of those who chose paediatrics 1 year after graduation were working in it 10 years after qualifying. Experience of the subject as a student, and enthusiasm/commitment: what I really want to do, affected long-term career choices more for paediatrics than for other medical careers. The proportion of junior doctors wishing to become paediatricians has not changed much during the last 30 years. The planned increase in the number of medical school graduates is necessary to increase the number of UK-trained consultant paediatricians. Medical students who experience enthusiastic and stimulating training in paediatrics may be more likely to become paediatricians.

Survey on sedation in paediatric dentistry: a global perspective.

PubMed

Wilson, Stephen; Alcaino, Eduardo A

2011-09-01

Paediatric dentists receive training in sedation during their advanced education training, but evidence suggests that this training varies widely. The purpose of this study was to survey members of the International Association of Paediatric Dentistry (IAPD) and the European Academy of Paediatric Dentistry (EAPD) on their opinion on pharmacological and other behavioural management techniques and their training related to provision of oral health care of paediatric patients in the dental setting. A request was made for access to the IAPD and EAPD membership email addresses. The responses were recorded anonymously and data uploaded into spss (version 9) and analysed using descriptive analysis and chi-square with and without tabulation processes. A total of 311 respondents of 1973 targeted individuals answered the survey. The response rate was 16%. The majority of the respondents came from the continent of Europe, Asia, and the Americas. The most frequent type of sedation was general anaesthesia (52% of the respondents), followed by nitrous oxide (46%) and then oral sedation (44%). At least 91% of the respondents indicated that they were interested in the development of continuing education on the topic of sedation. Paediatric dentists around the world use relatively few behaviour management techniques, including pharmacological management. There is a definite interest in continuing education in the area of sedation. The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

Current views and advances on Paediatric Virology: An update for paediatric trainees

PubMed Central

MAMMAS, IOANNIS N.; GREENOUGH, ANNE; THEODORIDOU, MARIA; KRAMVIS, ANNA; CHRISTAKI, ILIANA; KOUTSAFTIKI, CHRYSSIE; KOUTSAKI, MARIA; PORTALIOU, DIMITRA M.; KOSTAGIANNI, GEORGIA; PANAGOPOULOU, PARASKEVI; SOURVINOS, GEORGE; SPANDIDOS, DEMETRIOS A.

2016-01-01

Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop. PMID:26889211

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study.

PubMed

Grønbæk, Lisbet; Vilstrup, Hendrik; Pedersen, Lars; Christensen, Kaare; Jepsen, Peter

2018-06-06

It is widely believed that autoimmune hepatitis accumulates in families, but the degree of familial clustering has not been clarified. We conducted a population-based study on the family occurrence of autoimmune hepatitis. Through Danish nationwide registries we identified 8,582 first-degree and 9,230 second-degree relatives of index patients diagnosed with autoimmune hepatitis in 1994-2015; and 64 co-twins of index patients diagnosed with autoimmune hepatitis in 1977-2011. For first- and second-degree relatives we calculated the sex- and age-adjusted standardized incidence ratio of autoimmune hepatitis relative to the general population, and we calculated the cumulative risk, i.e. the cumulative incidence, of developing autoimmune hepatitis from the time of the index patient's diagnosis. For co-twins, we estimated the standardized incidence ratio and the concordance rate of autoimmune hepatitis. In first-degree relatives, there were six incident autoimmune hepatitis diagnoses during 64,020 years of follow-up: the standardized incidence ratio was 4.9 (95% CI 1.8-10.7), and the 10-year cumulative risk was 0.10% (95% CI 0.04-0.23). In the second-degree relatives, there were no incident autoimmune hepatitis diagnoses (expected number assuming incidence rate as in the Danish general population = 0.8). In the co-twins, there was one incident autoimmune hepatitis diagnosis during 1,112 years of follow-up, and the standardized incidence ratio was 53.9 (95% CI 1.4-300.4). The probandwise concordance rate, a measure of heritability, was higher in monozygotic than in dizygotic twins (8.7% [95% CI 1.1-28.0] vs. 0%). This nationwide study indicates that only first-degree relatives of index patients with autoimmune hepatitis are at increased risk of autoimmune hepatitis from the time of the index patient's diagnosis, but the absolute risk is very low. Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune hepatitis accumulates in families. We studied the family members of patients with autoimmune hepatitis from the entire Danish population. We found that autoimmune hepatitis does accumulate in families, but the risk of autoimmune hepatitis in the family members is very low. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Multi-loci diagnosis of acute lymphoblastic leukaemia with high-throughput sequencing and bioinformatics analysis.

PubMed

Ferret, Yann; Caillault, Aurélie; Sebda, Shéhérazade; Duez, Marc; Grardel, Nathalie; Duployez, Nicolas; Villenet, Céline; Figeac, Martin; Preudhomme, Claude; Salson, Mikaël; Giraud, Mathieu

2016-05-01

High-throughput sequencing (HTS) is considered a technical revolution that has improved our knowledge of lymphoid and autoimmune diseases, changing our approach to leukaemia both at diagnosis and during follow-up. As part of an immunoglobulin/T cell receptor-based minimal residual disease (MRD) assessment of acute lymphoblastic leukaemia patients, we assessed the performance and feasibility of the replacement of the first steps of the approach based on DNA isolation and Sanger sequencing, using a HTS protocol combined with bioinformatics analysis and visualization using the Vidjil software. We prospectively analysed the diagnostic and relapse samples of 34 paediatric patients, thus identifying 125 leukaemic clones with recombinations on multiple loci (TRG, TRD, IGH and IGK), including Dd2/Dd3 and Intron/KDE rearrangements. Sequencing failures were halved (14% vs. 34%, P = 0.0007), enabling more patients to be monitored. Furthermore, more markers per patient could be monitored, reducing the probability of false negative MRD results. The whole analysis, from sample receipt to clinical validation, was shorter than our current diagnostic protocol, with equal resources. V(D)J recombination was successfully assigned by the software, even for unusual recombinations. This study emphasizes the progress that HTS with adapted bioinformatics tools can bring to the diagnosis of leukaemia patients. © 2016 John Wiley & Sons Ltd.

Advances in paediatrics in 2016: current practices and challenges in allergy, autoimmune diseases, cardiology, endocrinology, gastroenterology, infectious diseases, neonatology, nephrology, neurology, nutrition, pulmonology.

PubMed

Caffarelli, Carlo; Santamaria, Francesca; Di Mauro, Dora; Mastrorilli, Carla; Montella, Silvia; Bernasconi, Sergio

2017-09-16

This review reports main progresses in various pediatric issues published in Italian Journal of Pediatrics and in international journals in 2016. New insights in clinical features or complications of several disorders may be useful for our better understanding. They comprise severe asthma, changing features of lupus erythematosus from birth to adolescence, celiac disease, functional gastrointestinal disorders, Moebius syndrome, recurrent pneumonia. Risk factors for congenital heart defects, Kawasaki disease have been widely investigated. New diagnostic tools are available for ascertaining brucellosis, celiac disease and viral infections. The usefulness of aCGH as first-tier test is confirmed in patients with neurodevelopmental disorders. Novel information have been provided on the safety of milk for infants. Recent advances in the treatment of common disorders, including neonatal respiratory distress syndrome, hypo-glycemia in newborns, atopic dermatitis, constipation, cyclic vomiting syndrome, nephrotic syndrome, diabetes mellitus, regurgitation, short stature, secretions in children with cerebral palsy have been reported. Antipyretics treatment has been updated by national guidelines and studies have excluded side effects (e.g. asthma risk during acetaminophen therapy). Vaccinations are a painful event and several options are reported to prevent this pain. Adverse effects due to metabolic abnormalities are reported for second generation antipsychotic drugs.

Association of systemic-onset juvenile idiopathic arthritis and celiac disease - a case report.

PubMed

Michelin, Cintia Maria; Aikawa, Nadia Emi; Diniz, João Carlos; Jesus, Adriana Almeida; Koda, Yu Kar; Silva, Clovis Artur

2011-01-01

In a 28-year period, 5508 patients were followed at our Paediatric Rheumatology Division and 712 (13%) patients had juvenile idiopathic arthritis (JIA) (ILAR criteria). One (0.14%) of them had association with celiac disease (CD), with predominance of gastrointestinal manifestations and this case was described herein. A 10-years-old female patient was hospitalized with persistent fever, weight loss, asthenia, anorexia and an evanescent pink macular rash. After one week, she presented arthritis of left knee and ankle with duration of 75 days. The initial laboratory exams revealed anemia and elevation of inflammatory markers. Immunological tests were positive for anti-endomysial antibodies IgA and anti-thyroglobulin antibody. The diagnosis of systemic JIA was established and indomethacin (2.0 mg/kg/day) was started with improvement of arthritis. The patient evolved with vomiting, diarrhea and abdominal pain and upper gastrointestinal barium study showed areas of small bowel dilatation and thickening of folds, suggestive of malabsorption syndrome. Colonoscopy was normal and small intestinal biopsy was compatible with CD. We reported a case of a rare association of early diagnosis of systemic JIA occurring simultaneously with CD. This study reinforces the importance of taking into account the possible association of organ-specific autoimmune diseases during JIA course.

[Antonino Longo: the school of Concetti and the birth of paediatrics in Catania].

PubMed

Farnetani, I; Farnetani, F

2007-12-01

The biography of Antonino Longo gives us the opportunity to gain knowledge in, even in everyday life, Luigi Concetti's school of paediatrics in Rome, the state of the art in some infectious diseases,and the reality of paediatrics in Catania where Longo founded University teachings and organised health care for children.

[The pathogenesis and regulation of autoimmunity].

PubMed

Miyake, Sachiko

2008-06-01

The pathogenesis of autoimmunity has been studied extensively using animal models and genome-wide genetic analysis. Moreover, recent advance in the therapy for the autoimmune diseases using molecular-targeted drugs has provided us a lot of information in the pathogenesis of human autoimmune diseases. In this review, we overviewed the recent progress in the study of autoimmunity including central tolerance, regulatory cells and cytokines. Finally, we discuss the relationship of innate immunity and adoptive immunity in the context of autoimmunity.

Comparison of the quality of night paediatric urgent care in rural and urban areas of Lublin Province, eastern Poland - Appraisals by parents of children requiring medical attention.

PubMed

Kołłątaj, Barbara; Kołłątaj, Witold; Wrzołek, Katarzyna; Karwat, Irena Dorota; Klatka, Maria

2017-03-31

 Introduction. The quality of primary medical care for children in Poland is unsatisfactory. In the ranking known as 'the European Health Consumer Index', Poland (taking the patient point of view on healthcare quality) is classified on the 27th position out of the 33 possible. The unsolved problems concern inter alia the quality and availability of night paediatric urgent care. The aim was assessing the quality as well as the level of satisfaction with the night paediatric urgent care in the Lublin Province of eastern Poland. The materials for this study consisted of 540 parents of children aged 6-16 years benefiting from night paediatric urgent medical assistance in Lublin Province. The survey was conducted using the Original Survey Questionnaire. Inhabitants of the Lublin Province (regardless of place of residence) generally assessed the quality and accessibility of night paediatric urgent care facilities as only satisfactory. Inhabitants living in rural areas have worse access to night paediatric urgent care facilities because of having to travel greater distances, and receive less comprehensive medical assistance than inhabitants living in more urbanized areas, and they are more often referred to hospital emergency departments. During the past five years, both the availability and quality of night paediatric urgent care did not change significantly. Inhabitants of the Lublin Province (regardless of place of residence) generally assessed the quality as well as accessibility of night paediatric urgent care facilities as only satisfactory. Rural residents have more reasons for dissatisfaction than urban dwellers. Both the quality and availability of such medical care needs to be improved.

Family-centred care in the paediatric intensive care unit: an integrative review of the literature.

PubMed

Butler, Ashleigh; Copnell, Beverley; Willetts, Georgina

2014-08-01

To review extant research on family-centred care in a paediatric intensive care environment and identify gaps in the literature. Family-centred care is currently a core concept in paediatric nursing, focusing on the premise that families are central to a child's well-being, and as such, should be included as equal members of the child's healthcare team. Due to the nature of critical care, family-centred care may be challenging to implement and maintain. An integrative literature review. The review was conducted using the Cumulative Index to Nursing and Allied Health Literature, PubMed, OVID MEDLINE and Google Scholar databases, from 1990 to present. The search focused on the following terms: 'p(a)ediatric critical care', 'paediatric intensive care unit', 'family cent(e)red care', 'parental needs', 'family presence' and 'family/nurse roles'. Additionally, the search was limited to studies conducted in a developed country and published in English. Eighteen studies were included in the review. The results demonstrated that implementing family-centred care into a paediatric intensive care environment posed several challenges. The discrepancy between nurses' and parents' perception of their roles, the reluctance of medical staff to share potentially negative or rapidly changing information, restrictive family presence and poor understanding of family needs emerged as the key difficulties. No studies evaluated strategies to improve family-centred care practice. Family-centred care presents many challenges in a paediatric intensive care environment; however, nurses are uniquely positioned to foster relationships with families, encourage accurate and honest information sharing and advocate for families to be present when they choose. This review outlines the extant research to enhance awareness of the unique state of family-centred care in paediatric intensive care and makes recommendations for future research. © 2013 John Wiley & Sons Ltd.

"Not such a kid thing anymore": Young adults' perspectives on transfer from paediatric to adult cardiology care.

PubMed

Catena, G; Rempel, G R; Kovacs, A H; Rankin, K N; Muhll, I V; Mackie, A S

2018-03-25

Transfer of adolescents with congenital heart disease from paediatric cardiology providers to specialized adult congenital heart disease (ACHD) care providers is becoming a standard practice. However, some paediatric cardiologists continue to provide care for their patients into adult life. Little is known about the perspectives of young adult patients who have been transferred to ACHD clinics versus those who continue to receive their cardiology care in paediatric settings. Content and thematic analysis of structured telephone interviews with 21 young adults age 18-25 (13 transferred to ACHD clinic and 8 who had not transferred) was conducted to identify similarities and differences in patient characteristics of those in ACHD versus paediatric settings. There were no appreciable differences in gender, age, heart disease type, and independence between those transferred to ACHD care versus those not transferred. Participants in both groups were aware of differences between the paediatric and ACHD care settings and providers, with some favouring the familiarity offered by the paediatric setting and providers. Participants had varying views on parental involvement in their care; most of them had attended clinic appointments on their own. Those who had transferred to ACHD care acknowledged that it would take time to adjust to new relationships. Positive perspectives on actual or anticipated transfer to ACHD care included a growing sense of autonomy and responsibility, as well as access to reproductive information relevant to ACHD patients. The absence of patient characteristics distinguishing those in ACHD care versus those still followed in paediatric care suggests that system, provider, and parent factors, rather than patient factors, may account for patients' perspectives on transfer to ACHD care. © 2018 John Wiley & Sons Ltd.

A survey of specialist paediatric dental services in Sweden: results from 2003, and trends since 1983.

PubMed

Klingberg, G; Dahllöf, G; Erlandsson, A-L; Grindefjord, M; Hallström-Stalin, U; Koch, G; Lundin, S-A

2006-03-01

The child population in Sweden has changed dramatically during the last 20 years. Changes have also occurred within the Public Dental Service (PDS), regarding the provision of dental care to children and adolescents. All these changes may affect the referral pattern and provision of specialist dental care for children and adolescents. The primary aim of this study was to survey the services provided by specialists in paediatric dentistry in Sweden during 2003. A secondary aim was to compare the results with previous surveys. A Web-based survey was sent to all 34 specialist paediatric dentistry clinics and was answered by all clinics. Data were compared with results from the surveys performed in 1983, 1989, and 1996. The number of paediatric dentists had been relatively constant over the last 20 years, whereas the number of children referred to paediatric dentists had increased by 28% since 1983. It was estimated that 1.3% of all children in Sweden are treated at a specialist paediatric dental clinic in 2003. Dental treatment need in combination with behaviour management problems (BMP) was the main reason for referral and occurred in 37% of all referrals. The proportion of medically compromised children/children with disabilities had increased from 6% in 1983 to 22% in 2003. The number of patients treated using sedation and general anaesthesia had increased since 1983, and particularly since 1996. Despite improvements in dental health among children and adolescents in Sweden during the last 20 years, an increasing number of children are referred for specialist paediatric dental treatment. There is an urgent need to increase the number of specialist paediatric dentists in Sweden in order to ensure the continuation of high quality of dental care for children and adolescents.

Development of a subspecialty cardiology curriculum for paediatric registrars in Malawi: Implementation of a long-distance hybrid model.

PubMed

Newberry, Laura; Kennedy, Neil; Greene, Elizabeth A

2016-06-01

Malawi has a high burden of paediatric cardiac disease but a limited number of health providers familiar with these chronic diseases. Given the rising number of Malawian postgraduate paediatric trainees at the University of Malawi College of Medicine, we sought to remedy this lack of basic cardiology training with a long-distance, module-based curriculum that could be utilised independently, as needed, with on-site teaching. We also wished to evaluate the initial modules for utility and improvement in knowledge and confidence in each topic. After an initial site visit to determine curriculum needs, online modules with interactive evaluations and quizzes were developed by a paediatric cardiologist in the United States, in collaboration with paediatric registrar training directors in Malawi. This online interactive curriculum was followed by several site visits to Malawi, by the United States-based paediatric cardiologist, to provide bedside teaching, case-based discussions and hands-on skill training in cardiac ultrasound and electrocardiogram interpretation. Evaluation of the curriculum model included post-module quizzes on cardiac topics as well as registrar self-assessments regarding confidence in content areas. The average post-module quiz score was 93.6%. Repeat testing with the same questions four months later yielded an average score of 78%, with a range from 60 to 100%. Pre- and post-module registrar self-assessment regarding confidence in content areas showed a substantial gain in knowledge and confidence mean. In their qualitative feedback, registrars noted that the modules were helpful in studying for their certifying examinations, and all four of the registrars sitting Part I of their Malawian and South African paediatric certifying examinations passed. Our innovative hybrid approach, combining online educational modules with in-person teaching visits, is a useful approach in expanding paediatric cardiology subspecialty education in Malawi.

A mixed methods evaluation of paediatric trainee preparedness to manage cardiopulmonary arrests.

PubMed

Walsh, Órla; Lydon, Sinéad; O'Connor, Paul

2017-12-01

Paediatric cardiopulmonary arrest (CPA) survival rates are strongly linked to the training of the doctors responding to the event. This study sought to characterise the level of experience in managing CPAs among paediatric trainees and to investigate the nontechnical (NTS) required to effectively lead a paediatric CPA team. A mixed-methods research design was used. For the quantitative phase, a questionnaire was developed to assess training, confidence, and experiences related to CPA management. During the qualitative phase, 17 paediatric trainees participated in a series of critical incident technique (CIT) interviews to explore the NTS used during the management of paediatric CPAs. A total of 56 of 131 (37.1% response rate) trainees responded to the preparedness questionnaire. A total of 48.2% of respondents expressed low confidence in their skill as a team leader during the management of a CPA. The CIT interviews highlighted deficiencies in specific NTS (identifying options, prioritising, and identifying and utilising resources). Our results indicate that there is a desire for more training in CPA management among paediatric trainees, in particular as a team leader, which includes a focus on key NTS. What is Known • Levels of preparedness to be a paediatric cardiopulmonary arrests team member/leader are generally lower than desirable. • The importance of nontechnical skills to the effective performance of adult cardiopulmonary arrests teams has been identified. What is New • Levels of preparedness to be a cardiopulmonary arrests team member were higher than reported in US studies. • There is a need for greater training in cardiopulmonary arrest management which includes a focus on key nontechnical skills to include identifying options, prioritising, identifying and utilising resources.

Sources of funding for adult and paediatric CT procedures at a metropolitan tertiary hospital: How much do Medicare statistics really cover?

PubMed

Hayton, Anna; Wallace, Anthony; Johnston, Peter

2015-12-01

The radiation dose to the Australian paediatric population as a result of medical imaging is of growing concern, in particular the dose from CT. Estimates of the Australian population dose have largely relied on Medicare Australia statistics, which capture only a fraction of those imaging procedures actually performed. The fraction not captured has been estimated using a value obtained for a survey of the adult population in the mid-1990s. To better quantify the fraction of procedures that are not captured by Medicare Australia, procedure frequency and funding data for adult and paediatric patients were obtained from a metropolitan tertiary teaching and research hospital. Five calendar years of data were obtained with a financial class specified for each individual procedure. The financial classes were grouped to give the percentage of Medicare Australia billable procedures for both adult and paediatric patients. The data were also grouped to align with the Medicare Australia age cohorts. The percentage of CT procedures billable to Medicare Australia increased from 16% to 28% between 2008 and 2012. In 2012, the percentage billable for adult and paediatric patients was 28% and 33%, respectively; however, many adult CT procedures are performed at stand-alone clinics, which bulk bill. Using Medicare Australia statistics alone, the frequency of paediatric CT procedures performed on the Australian paediatric population will be grossly under estimated. A correction factor of 4.5 is suggested for paediatric procedures and 1.5 for adult procedures. The fraction of actual procedures performed that are captured by Medicare Australia will vary with time. © 2015 The Royal Australian and New Zealand College of Radiologists.

Interleukins for the paediatric pulmonologist.

PubMed

Rozycki, Henry J; Zhao, Wei

2014-03-01

Interleukins are critical immune modulators and since their first description in 1977, there has been a steady increase in the recognition of their roles in many paediatric respiratory diseases. This basic and clinical knowledge is now maturing into both approved and investigational therapies aimed at blocking or modifying the interleukin response. The purpose of this review is to bring up to date what is known about interleukin function in paediatric pulmonology, focusing on nine important lung conditions. This is followed by summaries about 18 interleukins which have been associated with these paediatric pulmonary conditions. Throughout, emphasis is placed on where interventions have been tested. Over the next several years, it is likely that many more treatments based on interleukin biology and function will become available and understanding the basis for these therapies will allow the practicing paediatric pulmonologist to take appropriate advantage of them. Copyright © 2013 Elsevier Ltd. All rights reserved.

The relevance of the Goudge inquiry to the practice of child protection/forensic paediatrics.

PubMed

Skellern, Catherine; Donald, Terence

2014-10-01

In 2008 Ontario, Canada the Goudge Inquiry arose following increasing concerns about practices surrounding forensic pathology and the investigation of paediatric deaths. Some of the considerations and recommendations have relevance to child protection/forensic paediatricians, particularly in relation to their responsibilities in opinion formulation and as expert witnesses. By examining the Inquiry recommendations, this paper applies them in relation to child protection/forensic paediatrics by discussing forensic medicine and its legal context, how interpretation of published reports and data should be used in opinion formulation; issues of 'diagnosis' versus 'opinion'; issues specific to child protection paediatrics; quality control; aspects of report writing and terminological considerations. It concludes with an adaptation of key recommendations directly from those of Goudge, applied to the context of paediatric forensic medicine undertaken in child protection assessments. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Who are the PDCO?

PubMed

Dempsey, E M; Connolly, K

2014-02-01

In January 2007, the Paediatric Regulation entered into force and established the Paediatric Committee (PDCO) within the European Medicines Agency. The goal of the PDCO is to improve the health of the children of Europe by increasing high-quality research for medicinal products and promoting the development and authorization of such medicines at the EU level. A major function of the PDCO is to formulate and authorize Paediatric Investigation Plans and Paediatric Use Marketing Authorisations. The EU's Seventh Framework Programme for Research has facilitated the establishment of consortia whose ultimate goal is to answer important clinical questions involving medicines commonly used "off-label", in children. The benefits of these consortia include enhanced collaboration amongst paediatricians, scientists and small to medium enterprises whose ultimate goal is to obtain an authorization for a new indication or formulation for use in the paediatric population. It will be interesting in a number of years time to measure the success of this very important European initiative.

Recent developments in neonatal and paediatric emergencies.

PubMed

Turner, Nigel M

2011-07-01

The present article is intended as an update for anaesthesiologists on recent developments in life-threatening paediatric emergencies and paediatric resuscitation. It is assumed that the reader has at least a basic knowledge of the general principles of emergency medicine, such as the ABCDE-approach and the principle of 'treat first what kills first'; and also that the reader is familiar with the anatomical, physiological and psychological differences between adults and children. The article begins with a description of the background to paediatric emergencies followed by a description of a widely used systematic approach to the assessment of the seriously ill child. In the second half of the article, the principles of the initial treatment for acute, life-threatening problems in children and paediatric resuscitation are discussed with reference to the recent literature. The article ends with a discussion of the changes in latest guidelines for resuscitation of babies at birth.

Negotiating identity at the intersection of paediatric and genetic medicine: the parent as facilitator, narrator and patient.

PubMed

Dimond, Rebecca

2014-01-01

This article identifies a significant transformation in the role and identity of parents accompanying their child to clinic. This shift is a product of the intersection between paediatric and genetic medicine, where parents play a critical role in providing information about their child, family and ultimately, about themselves. To provide a context for this matrix, two broad areas of sociological inquiry are highlighted. The first is explanations of the role a parent plays in paediatric medicine and the second is the diagnostic process in paediatric genetics and the implications for parent and child identities. Drawing from an ethnographic study of clinical consultations, attention is paid to the changing role of parenthood and the extended role of patienthood in paediatric genetic medicine. © 2013 The Author. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

Complicating autoimmune diseases in myasthenia gravis: a review

PubMed Central

Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

2015-01-01

Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

CHALLENGES IN PHENOTYPE DEFINITION IN THE WHOLE-GENOME ERA: MULTIVARIATE MODELS OF MEMORY AND INTELLIGENCE

PubMed Central

SABB, F. W.; BURGGREN, A. C.; HIGIER, R. G.; FOX, J.; HE, J.; PARKER, D. S.; POLDRACK, R. A.; CHU, W.; CANNON, T. D.; FREIMER, N. B.; BILDER, R. M.

2009-01-01

Refining phenotypes for the study of neuropsychiatric disorders is of paramount importance in neuroscience. Poor phenotype definition provides the greatest obstacle for making progress in disorders like schizophrenia, bipolar disorder, Attention Deficit/Hyperactivity Disorder (ADHD), and autism. Using freely available informatics tools developed by the Consortium for Neuropsychiatric Phenomics (CNP), we provide a framework for defining and refining latent constructs used in neuroscience research and then apply this strategy to review known genetic contributions to memory and intelligence in healthy individuals. This approach can help us begin to build multi-level phenotype models that express the interactions between constructs necessary to understand complex neuropsychiatric diseases. PMID:19450667

[Neuropsychiatric coaching of an adult with Asperger syndrome].

PubMed

Sihvonen, Janne

2011-01-01

Asperger syndrome is a lifelong neurodevelopmental condition. The major features of the syndrome include problems in social interaction and communication, narrow interests and stereotyped behaviour. Cognitive abilities are usually within normal. The syndrome potentially leads to a diminished level of life management in adulthood. Neuropsychiatric coaching is a solution-focused and practically oriented process of interventions for clients with neurodevelopmental problems. The methods include forms of evaluation and self reflection, structuring, guidance and visualization aids. Coaching does not exclude simultaneous therapeutic elements. The effectiveness has not yet been established by research, but the experiences reported have been encouraging. Neuropsychiatric coaching is recommended for adults with Asperger syndrome to rehabilitate life management skills.

Genetic variation associated with cardiovascular risk in autoimmune diseases

PubMed Central

Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio

2017-01-01

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122

Chronic Liver Diseases in Children: Clinical Profile and Histology.

PubMed

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage liver disease and fulminant hepatic failure and the only way to prevent and treat these patients is by liver transplantation.

The role of sex and gender in neuropsychiatric disorders.

PubMed

Thibaut, Florence

2016-12-01

The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.

Neuropsychiatric Sequelae of Acute Epidemic Encephalitis in Children

ERIC Educational Resources Information Center

Ebaugh, Franklin G.

2007-01-01

In reviewing the enormous number of articles on all phases of acute epidemic encephalitis one cannot help being impressed by the lack of attention paid to children who have suffered from this disease. This is especially true of the important neuropsychiatric sequelae. During the past few months, seventeen patients have been referred to the…

Project CARE: A Randomized Controlled Trial of a Behavioral Intervention Group for Alzheimer's Disease Caregivers

ERIC Educational Resources Information Center

Gonyea, Judith G.; O'Connor, Maureen K.; Boyle, Patricia A.

2006-01-01

Purpose: The neuropsychiatric symptoms associated with Alzheimer's disease are a major contributor to caregiver distress and burden. Despite recent efforts to teach caregivers skills to manage neuropsychiatric symptoms and reduce burden, there continues to be limited evidence that these strategies have helped caregivers of individuals with…

Neuropsychiatric symptoms and quality of life in patients in the final phase of dementia.

PubMed

Koopmans, Raymond T C M; van der Molen, Marloes; Raats, Monique; Ettema, Teake P

2009-01-01

To assess neuropsychiatric symptoms and quality of life in a group of patients in the final phase of dementia. All patients with dementia (n = 216) residing on dementia special care units of two Dutch nursing homes were included in the study provided they met the criteria for the final phase of dementia. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory Nursing Home version (NPI-NH) and the Cohen Mansfield Agitation Inventory (CMAI). Quality of life was assessed with the QUALIDEM. Of the 216 dementia patients 39 met the criteria for the final phase of dementia. The patients showed a specific pattern of behaviours with a high prevalence of apathy, agitation and behaviours that were mainly observed during morning care such as making strange noises, grabbing, performing repetitious mannerism, spitting, hitting, screaming and pushing. Overall quality of life of these patients in the final phase of dementia was moderate. In this small sample, patients in the final phase of dementia show specific behavioural problems, that mainly should be addressed with psychosocial interventions. (c) 2008 John Wiley & Sons, Ltd.

Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin

PubMed Central

Theoharides, Theoharis C.; Stewart, Julia M.; Hatziagelaki, Erifili; Kolaitis, Gerasimos

2015-01-01

Brain “fog” is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain “fog” characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as “minimal cognitive impairment,” an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain “fog” in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain “fog.” PMID:26190965

A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

PubMed

Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

2015-05-05

Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neuropsychiatric Symptoms in Posterior Cortical Atrophy and Alzheimer Disease

PubMed Central

Crutch, Sebastian J.; Franco-Macías, Emilio; Gil-Néciga, Eulogio

2016-01-01

Background: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by early progressive visual dysfunction in the context of relative preservation of memory and a pattern of atrophy mainly involving the posterior cortex. The aim of the present study is to characterize the neuropsychiatric profile of PCA. Methods: The Neuropsychiatric Inventory was used to assess 12 neuropsychiatric symptoms (NPS) in 28 patients with PCA and 34 patients with typical Alzheimer disease (AD) matched by age, disease duration, and illness severity. Results: The most commonly reported NPS in both groups were depression, anxiety, apathy, and irritability. However, aside from a trend toward lower rates of apathy in patients with PCA, there were no differences in the percentage of NPS presented in each group. All those patients presenting visual hallucinations in the PCA group also met diagnostic criteria for dementia with Lewy bodies (DLB). Auditory hallucinations were only present in patients meeting diagnosis criteria for DLB. Conclusion: Prevalence of the 12 NPS examined was similar between patients with PCA and AD. Hallucinations in PCA may be helpful in the differential diagnosis between PCA-AD and PCA-DLB. PMID:26404166

[Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

  The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

Multifactorial Determinants of the Neurocognitive Effects of Electroconvulsive Therapy

PubMed Central

McClintock, Shawn M.; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G.; Krystal, Andrew D.; Lisanby, Sarah H.

2014-01-01

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper is to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the utility of this important and widely used intervention tool for neuropsychiatric diseases. PMID:24820942

Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

PubMed

McClintock, Shawn M; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G; Krystal, Andrew D; Lisanby, Sarah H

2014-06-01

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.

The awareness of childhood autism among residents of neuropsychiatric and other disciplines of a research and training hospital in Istanbul, Turkey.

PubMed

Hidiroglu, Seyhan; Lüleci, Nimet Emel; Karavus, Melda; Tanriover, Ozlem; Bayar, Elif Samiye; Karavus, Ahmet

2018-02-01

To assess the awareness of childhood autism among physicians undergoing residency training in various disciplines. This cross-sectional study was conducted at a research and training hospital in Istanbul, Turkey, in February 2013 and comprised physicians undergoing residency training in various disciplines. Data was collected through a self-administered questionnaire. Questions about "awareness on autism" were prepared in the light of "Knowledge about Childhood Autism among Health Workers questionnaire. Of the 128 physicians, 122(95.3%) were aware that the most known characteristic of childhood autism was "failure to build-up friendship". All of the 29(22.66%) physicians at the neuropsychiatric disciplines were aware that "autism can be a genetic disorder", whereas, in other disciplines 69(69.7) physicians had that awareness. Besides, 15(51.7%) of the residents of the neuropsychiatric disciplines thought that "autism can be associated with childhood epilepsy", while 32(32.3%) physicians of other disciplines gave a similar answer (p=0.057). The awareness on childhood autism of residents belonging to the non- neuropsychiatric disciplines was moderate.

The Autoimmune Ecology.

PubMed

Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

2016-01-01

Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

Information Seeking Behaviour of Parents of Paediatric Patients for Clinical Decision Making: The Central Role of Information Literacy in a Participatory Setting

ERIC Educational Resources Information Center

Kostagiolas, Petros; Martzoukou, Konstantina; Georgantzi, Georgia; Niakas, Dimitris

2013-01-01

Introduction: This study investigated the information seeking behaviour and needs of parents of paediatric patients and their motives for seeking Internet-based information. Method: A questionnaire survey of 121 parents was conducted in a paediatric clinic of a Greek university hospital. Analysis: The data were analysed using SPSS; descriptive…

Framework conditions facilitating paediatric clinical research

PubMed Central

2011-01-01

The use of unlicensed and "off-label" medicines in children is widespread. Between 50-80% of the medicines currently administered to children have neither been tested nor authorized for their use in the paediatric population which represents approximately 25% of the whole European population. On 26 January 2007, entered into force the European Regulation of Paediatric Medicines. It aims at the quality of research into medicines for children but without subjecting the paediatric population to unnecessary clinical trial. This article addresses ethical and legal issues arising from the regulation and makes recommendations for the framework conditions facilitating the development of clinical research with children. PMID:21345195

Prebiotics as a modulator of gut microbiota in paediatric obesity.

PubMed

Nicolucci, A C; Reimer, R A

2017-08-01

This review highlights our current understanding of the role of gut microbiota in paediatric obesity and the potential role for dietary manipulation of the gut microbiota with prebiotics in managing paediatric obesity. The aetiology of obesity is multifactorial and is now known to include microbial dysbiosis in the gut. Prebiotics are non-digestible carbohydrates which selectively modulate the number and/or composition of gut microbes. The goal of prebiotic consumption is to restore symbiosis and thereby confer health benefits to the host. There is convincing evidence that prebiotics can reduce adiposity and improve metabolic health in preclinical rodent models. Furthermore, there are several clinical trials in adult humans highlighting metabolic and appetite-regulating benefits of prebiotics. In paediatric obesity, however, there are very limited data regarding the potential role of prebiotics as a dietary intervention for obesity management. As the prevalence of paediatric obesity and obesity-associated comorbidities increases globally, interventions that target the progression of obesity from an early age are essential in slowing the obesity epidemic. This review emphasizes the need for further research assessing the role of prebiotics, particularly as an intervention in effectively managing paediatric obesity. © 2016 World Obesity Federation.

Per capita increase in hospital presentations and admissions among children since the 1990s.

PubMed

Hardy, Andrew; Fuller, David G; Forrester, Mike; Anderson, Kym P; Cooper, Chris; Jenner, Bernard; Marshall, Isaac; Mccloskey, Kate; Sanderson, Christine; Standish, Jane; Vuillermin, Peter

2016-10-01

Data regarding temporal trends in per capita paediatric hospital presentations and admissions are required to inform health system and workforce planning. Emergency Department (ED) presentations and admissions to the University Hospital Geelong among patients aged 0 to 16 years over a 12-month period (2012-2013) were determined by review of hospital records and then compared with similar data collected during 1996/1997. 1 During each period, the Geelong region was serviced by a single ED, enabling us to estimate per capita presentation and admission rates. Since 1996/1997, per capita paediatric presentations to the ED increased from 643 to 1837 per 10 000 (186%; 95% confidence interval 181% to 191%). Moreover, the proportion of paediatric ED presentations resulting in hospital admission increased from 12.3% to 18.3% (49%; 95% confidence interval 39% to 59%). There has been a substantial absolute and per capita increase in paediatric ED presentations and hospital admissions since the 1990s. These trends place an increasing burden on the public hospital system, and strategies are required to promote paediatric acute care in the ambulatory setting. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Paediatric investigation plans for pain: painfully slow!

PubMed

Davies, Elin H; Ollivier, Cecile M; Saint Raymond, Agnes

2010-11-01

To examine the early impact of the Paediatric Regulation, which entered into force in Europe on 27 January 2007, on the development of pharmaceutical drugs in the therapeutic field of pain submitted to the Paediatric Committee (PDCO) and to the European Medicines Agency (EMA). Paediatric Investigations Plans (PIPs) submitted with a Decision (outcome) reached between September 2007 and March 2010 were included in the analysis. Of the 17 Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3 were withdrawn by the applicants, 8 were granted a full waiver from development, and 1 resulted in a negative opinion. Decisions as issued included 15 clinical trials, with at least 1,282 children to be recruited into studies across five different products. Neonates were included in four of the products. The small number of submissions indicates a lack of new drugs being developed for the management of pain. Ethical concerns that too many vulnerable children will be recruited into clinical trials must be balanced against limiting the number of off-label prescribing and obtaining age-appropriate information on paediatric use. Now is an opportune time for clinicians, academics, learned societies and industry to collaborate for the benefit of children in pain.

Is optimal paddle force applied during paediatric external defibrillation?

PubMed

Bennetts, Sarah H; Deakin, Charles D; Petley, Graham W; Clewlow, Frank

2004-01-01

Optimal paddle force minimises transthoracic impedance; a factor associated with increased defibrillation success. Optimal force for the defibrillation of children < or =10 kg using paediatric paddles has previously been shown to be 2.9 kgf, and for children >10 kg using adult paddles is 5.1 kgf. We compared defibrillation paddle force applied during simulated paediatric defibrillation with these optimal values. 72 medical and nursing staff who would be expected to perform paediatric defibrillation were recruited from a University teaching hospital. Participants, blinded to the nature of the study, were asked to simulate defibrillation of an infant manikin (9 months of age) and a child manikin (6 years of age) using paediatric or adult paddles, respectively, according to guidelines. Paddle force (kgf) was measured at the time of simulated shock and compared with known optimal values. Median paddle force applied to the infant manikin was 2.8 kgf (max 9.6, min 0.6), with only 47% operators attaining optimal force. Median paddle force applied to the child manikin was 3.8 kgf (max 10.2, min 1.0), with only 24% of operators attaining optimal force. Defibrillation paddle force applied during paediatric defibrillation often falls below optimal values.

Community engagement for paediatric MDR-TB clinical trials: principles to support ethical trial implementation.

PubMed

Hoddinott, G; Staples, S; Brown, R; Simwinga, M; Mubekapi-Musadaidzwa, C; Hesseling, A C; Hendricks, G; De Koker, P; McKenna, L

2018-05-01

The paediatric tuberculosis (TB) prevention and treatment landscape is moving into a new and exciting era, with knowledge from clinical trials offering real benefit to children. Community engagement is key to optimising the success of these trials. However, the clinical profile, epidemiology and social perceptions for paediatric multidrug-resistant TB (MDR-TB) complicate the operationalisation of this community engagement. We reflect on a diversity of recent experiences attempting to implement this type of research and the community engagement around it. We describe four recommendations and argue that these should guide the implementation of the community engagement agenda in the new landscape of paediatric MDR-TB clinical trials. Specifically, we argue for 1) dynamic, long-term continuity in community engagement platforms; 2) tiers of TB and research literacy; 3) multiple separate and joint platforms for holding 'stakes'; and 4) addressing the social/structural implications of family participation. We conclude that community-level stakeholders, such as health workers, parents and children, are willing to collaborate in paediatric MDR-TB clinical trials. Using these recommendations, there is considerable opportunity for effective community engagement in this new era of paediatric MDR-TB research.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

PubMed

Penazzato, Martina; Lewis, Linda; Watkins, Melynda; Prabhu, Vineet; Pascual, Fernando; Auton, Martin; Kreft, Wesley; Morin, Sébastien; Vicari, Marissa; Lee, Janice; Jamieson, David; Siberry, George K

2018-02-01

Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets. © 2018 World Health Organization; licensee IAS.

Development of a core set of quality indicators for paediatric primary care practices in Europe, COSI-PPC-EU.

PubMed

Ewald, Dominik A; Huss, Gottfried; Auras, Silke; Caceres, Juan Ruiz-Canela; Hadjipanayis, Adamos; Geraedts, Max

2018-06-01

Paediatric ambulatory healthcare systems in Europe are, because of historical reasons, diverse and show strikingly different outcomes. All across Europe, the benchmarking of structures, processes and outcomes could reveal opportunities for improving Paediatric Primary Care (PPC). The aim of this study was to develop a set of Quality Indicators (QIs) to assess and monitor PPC in Europe. In a three-step process, we used the available external evidence and European expert consensus in a modified RAND/UCLA Appropriateness Method (RAM) to develop an indicator set. (1) A broad literature and online research of published QI and guidelines yielded an inventory of 1516 QI. (2) A collaborative panel of paediatric senior experts from the European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Paediatricians (ECPCP) from 15 European countries participated in a first consensus process to reduce the initial indicator inventory by eliminating not PPC-focused indicators and duplicates. (3) In a second consensus process, the panel rated the QI regarding validity and feasibility. The final QI set "COSI-PPC-EU" consists of 42 indicators in five categories of PPC: (A) health promotion/prevention/screening (13 QI), (B) acute care (9 QI), (C) chronic care (8 QI), (D) practice management (3 QI) and (E) patient safety (9 QI). COSI-PPC-EU represents a consented set of a limited number of valid quality indicators for the application in paediatric primary care in different healthcare systems throughout Europe. What is Known: • Paediatric ambulatory healthcare systems in Europe are diverse and show strikingly different outcomes. • There are known gaps in quality performance measures of paediatric primary care in Europe. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. What is New: • A set of 42 quality indicators for primary paediatric care in Europe was developed in a multi-country collaborative effort. The method combined a systematic literature review and a consensus process among European paediatric experts. • The quality indicator set can facilitate quality improvement of PPC. After studying the feasibility, providers can use COSI-PPC-EU to monitor, compare and improve performance of practices, regions and countries.

[Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

PubMed

Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

2007-01-01

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina.

PubMed

Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge

2014-01-01

Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6-1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders.

The effects of participation in leisure activities on neuropsychiatric symptoms of persons with cognitive impairment: a cross-sectional study.

PubMed

Chiu, Yi-Chen; Huang, Chien-Ying; Kolanowski, Ann M; Huang, Hsiu-Li; Shyu, Yeaing Lotus; Lee, Shu-Hwa; Lin, Ching-Rong; Hsu, Wen-Chuin

2013-10-01

People with cognitive impairment have been shown to engage in few structured activities. During periods of unoccupied time or boredom, these patients most likely manifest neuropsychiatric symptoms. The purposes of this study were to (1) describe the leisure-activity indicators (variety in leisure activities, appraisal of each activity's restorative function, and leisure dysfunction, i.e. failure to appreciate the importance of restorative aspects of leisure activity), of community-dwelling older Taiwanese adults with cognitive impairment, and (2) explore the relationships between these indicators and neuropsychiatric symptoms in this population. Cross-sectional. Memory disorder and geriatric psychiatric clinics of two hospitals in northern Taiwan. Patient-family caregiver dyads (N=60). Patients' dementia severity, based on Clinical Dementia Rating scores, was 0.5-2.0. Family caregivers completed the Chinese Neuropsychiatric Inventory to assess patients' behavioral problems and the Restorative Activity Questionnaire to assess patients' participation in leisure activities, restorative experience, and leisure dysfunction. On average, patients participated in approximately five individual leisure activities, but very few group leisure activities. The top three leisure activities were watching TV, taking a walk, and talking to relatives and friends. The leisure activities in which participants least commonly engaged were fishing, attending cultural exhibitions, and chess/card playing. All leisure-activity indicators were significantly correlated with disease stage, global cognitive function, and neuropsychiatric symptoms. Two leisure-activity indicators (leisure dysfunction and restorative experiences) were significantly correlated with depressive symptoms. Only leisure dysfunction significantly and consistently predicted neuropsychiatric symptoms. These results can be used by home health or community health nurses to design tailored leisure-activity plans for improving the care quality of patients with cognitive impairment. Health professionals can develop leisure-education programmes to emphasize the value of leisure pursuit and to modify attitudes toward participating in leisure activities. Finally, parks and recreational agencies may re-examine their services and facilities to meet the increasing needs of this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association of neuropsychiatric symptoms and sub-syndromes with cognitive impairment in community-dwelling Asian elderly.

PubMed

Xu, Xin; Ang, Seow Li; Hilal, Saima; Chan, Qun Lin; Wong, Tien Yin; Venketasubramanian, Narayanaswamy; Ikram, Mohammad Kamran; Chen, Christopher Li-Hsian

2015-11-01

To investigate the presence of neuropsychiatric symptoms (NPS) and sub-syndromes in elderly community-dwelling Asians with varying severity of cognitive impairment. Chinese and Malay participants (n = 613) from the Epidemiology of Dementia in Singapore (EDIS) Study aged ≥ 60 years underwent clinical examination, neuropsychological testing, and NPS assessment using the Neuropsychiatric Inventory (NPI). Diagnosis of no cognitive impairment (NCI), cognitive impairment-no dementia (CIND), including CIND-mild and CIND-moderate, and dementia were made using established criteria. A significant increase in the numbers of NPS was observed accompanying with increasing severity of cognitive impairment (p < 0.001). Compared to those with NCI/CIND-mild, participants with CIND-moderate [Odds ratio (OR): 4.2, 95% confidence interval (CI): 1.8-10.0] or dementia [OR: 9.2, 95% CI: 2.3-36.0] were more likely to have two or more neuropsychiatric sub-syndromes. Participants with CIND-moderate were more likely to have hyperactivity [OR: 2.0, 95% CI: 1.0-3.8] and apathy [OR: 2.9, 95% CI: 1.0-8.4] sub-syndromes, whereas patients with dementia were more likely to have psychosis [OR: 6.9, 95% CI: 2.4-20.1], affective (OR: 8.7, 95% CI: 1.8-42.9), and hyperactivity (OR: 5.4, 95% CI: 1.8-16.1). Furthermore, executive dysfunction and visual memory impairment were associated with the presence of three neuropsychiatric sub-syndromes; whist language and visuomotor speed impairment were related to the presence of two sub-syndromes. By contrast, impairment in attention, verbal memory, and visuoconstruction were not associated with any of the sub-syndromes. The presence of NPS and sub-syndromes increase with increasing severities of cognitive impairment, and different neuropsychiatric syndromes are associated with specific impairment on cognitive domains in community-dwelling Asian elderly.

The emerging trend of non-operative treatment in paediatric type I open forearm fractures.

PubMed

Zhang, H; Fanelli, M; Adams, C; Graham, J; Seeley, M

2017-08-01

Open fractures are considered an orthopaedic emergency and are generally an indication for operative debridement. Recent studies have questioned this approach for the management of Gustilo-Anderson Type I open fractures in the paediatric population. This meta-analysis studies the non-operative management of Type I open paediatric forearm fractures. An Ovid MEDLINE and PubMed database literature search was performed for studies that involved a quantified number of Gustilo-Anderson Type I open forearm fractures in the paediatric population, which were treated without operative intervention. A fixed-effect meta-analysis, weighting each study based on the number of patients, and a pooled estimate of infection risk (with 95% confidence interval (CI)) was performed. The search results yielded five studies that were eligible for inclusion. No included patients had operative debridement and all were treated with antibiotics. The number of patients in each study ranged from 3 to 45, with a total of 127 paediatric patients in the meta-analysis. The infection rate was 0% for all patients included. The meta-analysis estimated a pooled infection risk of 0% (95% CI 0 to 2.9). The five included studies had a total of 127 patients with no cases of infection after non-operative management of Type I open paediatric forearm fractures. The infection rate of Type I fractures among operatively managed patients is 1.9%. The trend in literature towards non-operative treatment of paediatric Type I open fractures holds true in this meta-analysis.

Trends and patterns of computed tomography scan use among children in The Netherlands: 1990-2012.

PubMed

Meulepas, Johanna M; Smets, Anne M J B; Nievelstein, Rutger A J; Gradowska, Patrycja; Verbeke, Jonathan; Holscher, Herma C; Rutten, Matthieu J C M; Kieft, Mariëtte; Ronckers, Cécile M; Hauptmann, Michael

2017-06-01

To evaluate trends and patterns in CT usage among children (aged 0-17 years) in The Netherlands during the period 1990-2012. Lists of electronically archived paediatric CT scans were requested from the Radiology Information Systems (RIS) of Dutch hospitals which reported >10 paediatric CT scans annually in a survey conducted in 2010. Data included patient identification, birth date, gender, scan date and body part scanned. For non-participating hospitals and for years prior to electronic archiving in some participating hospitals, data were imputed by calendar year and hospital type (academic, general with <500 beds, general with ≥ 500 beds). Based on 236,066 CT scans among 146,368 patients performed between 1990 and 2012, estimated annual numbers of paediatric CT scans in The Netherlands increased from 7,731 in 1990 to 26,023 in 2012. More than 70 % of all scans were of the head and neck. During the last decade, substantial increases of more than 5 % per year were observed in general hospitals with fewer than 500 beds and among children aged 10 years or older. The estimated number of paediatric CT scans has more than tripled in The Netherlands during the last two decades. • Paediatric CT in The Netherlands has tripled during the last two decades. • The number of paediatric CTs increased through 2012 in general hospitals. • Paediatric CTs continued to increase among children aged 10 years or older.

Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation.

PubMed

Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Queudeville, Manon; Feucht, Judith; Blaeschke, Franziska; Schlegel, Patrick; Feuchtinger, Tobias; Lang, Peter; Müller, Ingo; Handgretinger, Rupert; Heinz, Werner J

2017-07-01

Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients. This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT. They were analysed for efficacy, feasibility and the safety of posaconazole. Out of 63 patients, 31 received posaconazole oral suspension and 32 received posaconazole tablets up to 200 days after transplantation. Analyses of the posaconazole trough levels were determined. No possible, probable or proven invasive fungal infection was observed in either group. Posaconazole trough levels were significantly higher in the tablet group than in the suspension group at all analysed time points. Drug-related adverse events were similarly low in both groups. Posaconazole tablets are effective in preventing invasive fungal infections in paediatric patients. As early as day 3 after starting posaconazole tablets, over 50% of the posaconazole trough levels were >500 ng/mL, while this was observed on day 14 after start with posaconazole suspension. The administration of posaconazole tablets was safe, effective and feasible as antifungal prophylaxis in paediatric patients after HSCT.

Comparative Study on Knowledge About Autism Spectrum Disorder Among Paediatric and Psychiatric Nurses in Public Hospitals in Kumasi, Ghana.

PubMed

Sampson, Wireko-Gyebi; Sandra, Ashiagbor Emelia

2018-01-01

Despite the existence of autism spectrum disorder in Ghana, few studies have provided the necessary information on the phenomenon. These studies have mostly focused on speech and language therapy for children and modification of classroom environment for children with autism spectrum disorder. This approach has resulted in a paucity of knowledge on nurse's knowledge of autism spectrum disorder in Ghana. The study sought to assess the knowledge of paediatric and psychiatric on autism spectrum disorder. In this study, 130 paediatric and 93 psychiatric nurses sampled from five public hospitals in the Kumasi Metropolis participated in the survey. The Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire was employed to assess their knowledge of autism spectrum disorder. It emerged from the study that psychiatric nurses were more knowledgeable on autism spectrum disorder than paediatric nurses in general and specifically on each of the four domains on the KCAHW questionnaire. However, the level of knowledge on autism spectrum disorder among both groups of nurses remains low. Apart from the previous encounter, there were no significant differences between paediatric and psychiatric nurses' gender, age, marital status, working experience and their knowledge. In view of the findings, it will be appropriate for autism spectrum disorder to be included in the clinical training curriculum as well as the continuous professional education for both paediatric and psychiatric nurses. This will go a long way in helping paediatric and psychiatric nurses to increase their knowledge of autism spectrum disorder.

Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC).

PubMed

Kneyber, Martin C J; de Luca, Daniele; Calderini, Edoardo; Jarreau, Pierre-Henri; Javouhey, Etienne; Lopez-Herce, Jesus; Hammer, Jürg; Macrae, Duncan; Markhorst, Dick G; Medina, Alberto; Pons-Odena, Marti; Racca, Fabrizio; Wolf, Gerhard; Biban, Paolo; Brierley, Joe; Rimensberger, Peter C

2017-12-01

Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children. The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms. The Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with "strong agreement". The final iteration of the recommendations had none with equipoise or disagreement. These recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.

Catalysing the development and introduction of paediatric drug formulations for children living with HIV: a new global collaborative framework for action.

PubMed

Penazzato, Martina; Watkins, Melynda; Morin, Sébastien; Lewis, Linda; Pascual, Fernando; Vicari, Marissa; Lee, Janice; Hargreaves, Sally; Doherty, Meg; Siberry, George K

2018-05-01

Progress in the development and introduction of paediatric formulations for key infectious diseases is poor in low-income and middle-income countries (LMICs). Although major steps have been made in the scale-up of antiretroviral medicines in LMICs, the development and deployment of formulations for infants and children is suboptimal. Of the children living with HIV globally (most in Africa), only 43% are receiving antiretroviral therapy (ART), many with suboptimal formulations. These shortfalls pose a series of challenges to meeting global treatment targets of 1·6 million children (aged 0-14 years) on ART by the end of 2018 (95% coverage) and to ensuring that 95% of those on ART are virologically suppressed. The Global Accelerator for Paediatric Formulations (GAP-f) has been developed to accelerate research, development, regulatory filing, introduction, and uptake of prioritised paediatric antiretrovirals in age-appropriate formulations by 2020, with innovative, strategic, and sustainable financing. The GAP-f will build on existing efforts to maximise coordination and alignment of policy makers, research networks, regulatory agencies, funding organisations, and manufacturers in paediatric HIV and other paediatric diseases, including tuberculosis, viral hepatitis, and other infectious diseases. Paediatric drug development and scale-up will require special efforts to bring greater visibility and new solutions to ensure that children in LMICs have access to effective and appropriate treatment options. Copyright © 2018 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Autoimmunity and primary immunodeficiency: two sides of the same coin?

PubMed

Schmidt, Reinhold E; Grimbacher, Bodo; Witte, Torsten

2017-12-19

Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

PubMed

Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

2015-10-01

Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.

Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

PubMed Central

Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

2015-01-01

Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

Microwave frequency electromagnetic fields (EMFs) produce widespread neuropsychiatric effects including depression.

PubMed

Pall, Martin L

2016-09-01

Non-thermal microwave/lower frequency electromagnetic fields (EMFs) act via voltage-gated calcium channel (VGCC) activation. Calcium channel blockers block EMF effects and several types of additional evidence confirm this mechanism. Low intensity microwave EMFs have been proposed to produce neuropsychiatric effects, sometimes called microwave syndrome, and the focus of this review is whether these are indeed well documented and consistent with the known mechanism(s) of action of such EMFs. VGCCs occur in very high densities throughout the nervous system and have near universal roles in release of neurotransmitters and neuroendocrine hormones. Soviet and Western literature shows that much of the impact of non-thermal microwave exposures in experimental animals occurs in the brain and peripheral nervous system, such that nervous system histology and function show diverse and substantial changes. These may be generated through roles of VGCC activation, producing excessive neurotransmitter/neuroendocrine release as well as oxidative/nitrosative stress and other responses. Excessive VGCC activity has been shown from genetic polymorphism studies to have roles in producing neuropsychiatric changes in humans. Two U.S. government reports from the 1970s to 1980s provide evidence for many neuropsychiatric effects of non-thermal microwave EMFs, based on occupational exposure studies. 18 more recent epidemiological studies, provide substantial evidence that microwave EMFs from cell/mobile phone base stations, excessive cell/mobile phone usage and from wireless smart meters can each produce similar patterns of neuropsychiatric effects, with several of these studies showing clear dose-response relationships. Lesser evidence from 6 additional studies suggests that short wave, radio station, occupational and digital TV antenna exposures may produce similar neuropsychiatric effects. Among the more commonly reported changes are sleep disturbance/insomnia, headache, depression/depressive symptoms, fatigue/tiredness, dysesthesia, concentration/attention dysfunction, memory changes, dizziness, irritability, loss of appetite/body weight, restlessness/anxiety, nausea, skin burning/tingling/dermographism and EEG changes. In summary, then, the mechanism of action of microwave EMFs, the role of the VGCCs in the brain, the impact of non-thermal EMFs on the brain, extensive epidemiological studies performed over the past 50 years, and five criteria testing for causality, all collectively show that various non-thermal microwave EMF exposures produce diverse neuropsychiatric effects. Copyright © 2015 The Author. Published by Elsevier B.V. All rights reserved.

Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring.

PubMed

Nahum Sacks, Kira; Friger, Michael; Shoham-Vardi, Ilana; Abokaf, Hanaa; Spiegel, Efrat; Sergienko, Ruslan; Landau, Daniella; Sheiner, Eyal

2016-09-01

The reported rates of gestational diabetes mellitus are constantly escalating and little is known about long-term complications in the offspring. Evidence from the field of epigenetics strongly advocates the need for research on the neuropsychiatric complications in offspring prenatally exposed to gestational diabetes mellitus. We sought to assess whether in utero exposure to gestational diabetes mellitus increases the risk of long-term neuropsychiatric morbidity in the offspring. A population-based cohort study compared the incidence of hospitalizations due to neuropsychiatric disease between singletons exposed and unexposed to gestational diabetes mellitus. Deliveries occurred in the years 1991 through 2014 in a regional tertiary medical center. Perinatal deaths, multiple gestations, mothers with pregestational diabetes or lack of prenatal care, and children with congenital malformations were excluded from the study. A multivariate generalized estimating equation logistic regression model analysis was used to control for confounders and for maternal clusters. During the study period 231,271 deliveries met the inclusion criteria; 5.4% of the births were to mothers diagnosed with gestational diabetes mellitus (n = 12,642), of these 4.3% had gestational diabetes type A1 (n = 10,076) and 1.1% had gestational diabetes type A2 (n = 2566). During the follow-up period, a significant linear association was noted between the severity of the gestational diabetes (no gestational diabetes, gestational diabetes mellitus A1, gestational diabetes mellitus A2) and neuropsychiatric disease of the offspring (1.02% vs 1.36% vs 1.68%, respectively, P < .001). A Kaplan-Meier curve demonstrated that children born to women with gestational diabetes mellitus had higher cumulative incidence of neuropsychiatric morbidity. Using a generalized estimating equation multivariable logistic regression model, controlling for time-to-event, maternal age, gestational age at delivery, maternal obesity, maternal preeclampsia and fertility treatments, maternal gestational diabetes mellitus was found to be an independent risk factor for long-term neuropsychiatric disease of the offspring (gestational diabetes mellitus A1 [adjusted odds ratio, 1.83; 95% confidence interval, 1.53-2.19] and gestational diabetes mellitus A2 [adjusted odds ratio, 1.64; 95% confidence interval, 1.18-2.27]). Within the limits of our database, our findings also point to a possible association between in utero exposure to gestational diabetes mellitus and autistic spectrum disorder of the offspring (adjusted odds ratio, 4.44; 95% confidence interval, 1.55-12.69), which was found significant also after controlling for time-to-event, maternal age, gestational age at delivery, and offspring weight at birth. Exposure to maternal gestational diabetes mellitus is an independent risk factor for long-term neuropsychiatric morbidity in the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of abnormal autoimmune function on reproduction: maternal and fetal consequences.

PubMed

Gleicher, Norbert; Weiner, Rebecca; Vietzke, Mary

2006-11-01

The impact of abnormal autoimmune function on reproductive success has remained a highly controversial issue. This is, at least partially, due to the relative lack of demographic data from women with established autoimmune diseases. We, therefore, investigated 163 women with proven autoimmune diseases and 73 controls in a demographic study of reproductive success and impact of abnormal autoimmunity on pregnancy and offspring. Women with autoimmune diseases experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses (p=0.05). Offspring from women with autoimmune diseases demonstrated a significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR 3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with autoimmune diseases exhibited a trend towards lower cesarean section delivery during their own birth and a significantly increased prevalence of disease in vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune diseases impair female fecundity even before the diseases become clinically overt. Offspring are at increased risk to develop autoimmune diseases, though they may differ from those of their mothers. This risk appears to correlate with mode of delivery and may be the consequence of varying cell traffic dynamics with vaginal and cesarean section deliveries.

Autoimmune myelofibrosis. A steroid-responsive cause of bone marrow fibrosis associated with systemic lupus erythematosus.

PubMed

Paquette, R L; Meshkinpour, A; Rosen, P J

1994-05-01

Autoimmune myelofibrosis is an uncommon disorder in which patients present with anemia and thrombocytopenia in conjunction with limited clinical manifestations of autoimmune disease or an exacerbation of previously established SLE. The presence of leukoerythroblastosis in a patient with SLE may suggest the presence of myelofibrosis. Conversely, the absence of splenomegaly in a patient with presumed idiopathic myelofibrosis may suggest an autoimmune etiology. Patients with autoimmune myelofibrosis universally have a positive ANA test and frequently have either elevated anti-DNA titers or a positive LE cell preparation. Because physical manifestations of autoimmune disease may not be evident at presentation, all patients found to have myelofibrosis should have an ANA test. Peripheral blood cytopenias in autoimmune myelofibrosis frequently respond to glucocorticoids but regression of bone marrow fibrosis may be incomplete. Hematologic response to treatment parallels that of the associated autoimmune disease.

[Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

PubMed

Krysiak, Robert; Okopień, Bogusław

2015-01-01

Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

The effectiveness of telemedicine for paediatric retrieval consultations: rationale and study design for a pragmatic multicentre randomised controlled trial.

PubMed

Armfield, Nigel R; Coulthard, Mark G; Slater, Anthony; McEniery, Julie; Elcock, Mark; Ware, Robert S; Scuffham, Paul A; Bensink, Mark E; Smith, Anthony C

2014-11-11

In many health systems, specialist services for critically ill children are typically regionalised or centralised. Studies have shown that high-risk paediatric patients have improved survival when managed in specialist centres and that volume of cases is a predictor of care quality. In acute cases where distance and time impede access to specialist care, clinical advice may be provided remotely by telephone. Emergency retrieval services, attended by medical and nursing staff may be used to transport patients to specialist centres. Even with the best quality retrieval services, stabilisation of the patient and transport logistics may delay evacuation to definitive care. Several studies have examined the use of telemedicine for providing specialist consultations for critically ill children. However, no studies have yet formally examined the clinical effectiveness and economic implications of using telemedicine in the context of paediatric patient retrieval. The study is a pragmatic, multicentre randomised controlled trial running over 24 months which will compare the use of telemedicine with the use of the telephone for paediatric retrieval consultations between four referring hospitals and a tertiary paediatric intensive care unit. We aim to recruit 160 children for whom a specialist retrieval consultation is required. The primary outcome measure is stabilisation time (time spent on site at the referring hospital by the retrieval team) adjusted for initial risk. Secondary outcome measures are change in patient's physiological status (repeated measure, two time points) scored using the Children's Emergency Warning Tool; change in diagnosis (repeated measure taken at three time points); change in destination of retrieved patients at the tertiary hospital (general ward or paediatric intensive care unit); retrieval decision, and length of stay in the Paediatric Intensive Care Unit for retrieved patients. The trial has been approved by the Human Research Ethics Committees of Children's Health Services Queensland and The University of Queensland, Australia. Health services are adopting telemedicine, however formal evidence to support its use in paediatric acute care is limited. Generalisable evidence is required to inform clinical use and health system policy relating to the effectiveness and economic implications of the use in telemedicine in paediatric retrieval. Australian and New Zealand Clinical Trials Registry ACTRN12612000156886 .

[Contribution of Anales de Pediatría to the international visibility of Spanish paediatric research in the Web of Science (2010-2014)].

PubMed

Abad-García, María Francisca; González-Teruel, Aurora; Solís Sánchez, Gonzalo

2016-12-01

To describe the role of Anales de Pediatría in highlighting Spanish paediatric research, and to identify the journals with which it competes internationally. Spanish paediatric articles, including those from Anales de Pediatría were identified using the Paediatrics category of the Science Citation Index (2010-2014), and their volume and document type was analysed. For original articles and review articles, the year, the citation and journal of publication was studied. The journals were classified as general and specialised. The productivity of general journals was analysed according to their language, JCR quartile, and article access. A total of 2,701 Spanish paediatric papers were identified, accounting for 2.8% of the paediatrics world output. More than two-thirds (68%) of papers were articles that received an average number of 4.97 citations per article. The 965 papers published in Anales de Pediatría accounted for 38.7% of the Spanish paediatric output, and for 1% of the paediatric world publications. A mean of 1.03 citations per article were received for 439 (45.4%) articles and reviews. Of the 106 journals identified, 82 were classified as specialised (1,196 articles) and 24 as general (741 articles). Anales de Pediatría published 60% of the articles in general journals. The rest of articles (309) were published in general journals published in English (82.8%), with a best position in the JCR ranking (83.4%) and mainly by subscription (73.8%). Anales de Pediatría plays an important role in providing international visibility to a large volume of Spanish scientific production in paediatrics. The results presented are a still only a snapshot of this role that could be used in the near future for assessing its evolution and the changes that could be made in order to improve its quality, positioning and competitiveness. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

To change or not to change - translating and culturally adapting the paediatric version of the Moral Distress Scale-Revised (MDS-R).

PubMed

Af Sandeberg, Margareta; Wenemark, Marika; Bartholdson, Cecilia; Lützén, Kim; Pergert, Pernilla

2017-02-20

Paediatric cancer care poses ethically difficult situations that can lead to value conflicts about what is best for the child, possibly resulting in moral distress. Research on moral distress is lacking in paediatric cancer care in Sweden and most questionnaires are developed in English. The Moral Distress Scale-Revised (MDS-R) is a questionnaire that measures moral distress in specific situations; respondents are asked to indicate both the frequency and the level of disturbance when the situation arises. The aims of this study were to translate and culturally adapt the questionnaire to the context of Swedish paediatric cancer care. In doing so we endeavoured to keep the content in the Swedish version as equivalent to the original as possible but to introduce modifications that improve the functional level and increase respondent satisfaction. The procedure included linguistic translation and cultural adaptation of MDS-R's paediatric versions for Physicians, Nurses and Other Healthcare Providers to the context of Swedish paediatric cancer care. The process of adjustment included: preparation, translation procedure and respondent validation. The latter included focus group and cognitive interviews with healthcare professionals in paediatric cancer care. To achieve a Swedish version with a good functional level and high trustworthiness, some adjustments were made concerning design, language, cultural matters and content. Cognitive interviews revealed problems with stating the level of disturbance hypothetically and items with negations caused even more problems, after having stated that the situation never happens. Translation and cultural adaptation require the involvement of various types of specialist. It is difficult to combine the intention to keep the content as equivalent to the original as possible with the need for modifications that improve the functional level and increase respondent satisfaction. The translated and culturally adapted Swedish MDS-R seems to have equivalent content as well as improved functional level and respondent satisfaction. The adjustments were made to fit paediatric cancer care but it could be argued that the changes are relevant for most areas of paediatric care of seriously ill patients.

[Diagnostics and treatment of polyglandular syndrome of adults].

PubMed

Larina, A A; Shapoval'iants, O S; Mazurina, N V; Troshina, E A

2012-01-01

Autoimmune polyendocrine syndromes (APS) are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune diseases. APS comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS type 1) and a more common adult type with (APS 2) or without adrenal failure (APS 3). The first clinical manifestations of APS 1 usually occur in childhood whereas APS 2 mostly occurs during the third and fourth decades of life. The third type has been described in adults that, contrary to types 1 and 2, does not involve the adrenal cortex. No clinical differences between types 2 and 3 have been described except the absence of adrenal failure. Type 4 APS is a rare syndrome characterized by the combination of autoimmune conditions not falling into the above categories. It consists of adrenal failure with one or more minor autoimmune disorders barring major components of type 1 and 2 APS. Usually, autoimmune polyendocrine syndrome of adults manifests itself as one of the major autoimmune diseases (such as adrenal failure, Grave's disease, or type 1 diabetes) and minor autoimmune disorders (vitiligo, alopecia) preceding the development of autoimmune deficiency of major endocrine glands. This article describes a patient with type 3 APS, who developed type 1 diabetes. Grave's disease and vitiligo. The development of the syndrome started from vitiligo in the chidhood. Moreover, the patient suffered primary sterility and presented with progressive diabetic nephropathy of autoimmune origin. It is concluded that patients with a single autoimmune component of polyendocrine syndrome should be screened to exclude other autoimmune endocrine disorders.

Autoimmune Disease Prevalence in a Multiple Sclerosis Cohort in Argentina

PubMed Central

Farez, Mauricio F.; Balbuena Aguirre, María E.; Varela, Francisco; Köhler, Alejandro A.

2014-01-01

Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6–1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders. PMID:25170425

Neuropsychiatric Disorders Associated with Streptococcal Infection: A Case-Control Study among Privately Insured Children

ERIC Educational Resources Information Center

Leslie, Douglas L.; Kozma, Laura; Martin, Andres; Landeros, Angeli; Katsovich, Liliya; King, Robert A.; Leckman, James F.

2008-01-01

The link between streptococcal infections and the onset of a variety of neuropsychiatric disorders is studied using a national sample of privately insured children. Findings suggest that patients with new-onset of obsessive-compulsive disorder, Tourette syndrome or tic orders were more likely to have been diagnosed with streptococcal infections in…

Narrative Skills, Cognitive Profiles and Neuropsychiatric Disorders in 7-8-Year-Old Children with Late Developing Language

ERIC Educational Resources Information Center

Miniscalco, Carmela; Hagberg, Bibbi; Kadesjo, Bjorn; Westerlund, Monica; Gillberg, Christopher

2007-01-01

Background: A community-representative sample of screened and clinically examined children with language delay at 2.5 years of age was followed up at school age when their language development was again examined and the occurrence of neuropsychiatric/neurodevelopmental disorder (attention deficit/hyperactivity disorder (ADHD) and/or autism…

Psychiatric Disorders and Intellectual Functioning throughout Development in Velocardiofacial (22q11.2 Deletion) Syndrome

ERIC Educational Resources Information Center

Green, Tamar; Gothelf, Doron; Glaser, Bronwyn; Debbane, Martin; Frisch, Amos; Kotler, Moshe; Weizman, Abraham; Eliez, Stephan

2009-01-01

Objective: Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample.…

Autism, ADHD, Mental Retardation and Behavior Problems in 100 Individuals with 22q11 Deletion Syndrome

ERIC Educational Resources Information Center

Niklasson, Lena; Rasmussen, Peder; Oskarsdottir, Solveig; Gillberg, Christopher

2009-01-01

This study assessed the prevalence and type of associated neuropsychiatric problems in children and adults with 22q11 deletion syndrome. One-hundred consecutively referred individuals with 22q11 deletion syndrome were given in-depth neuropsychiatric assessments and questionnaires screens. Autism spectrum disorders (ASDs) and/or attention…

A Comprehensive Rehabilitation Approach in a Patient With Serious Neuropsychiatric Systemic Lupus Erythematosus.

PubMed

Ko, Yong Jae; Lee, Yang Gyun; Park, Ji Woong; Ahn, Sung Ho; Kwak, Jin Myoung; Choi, Yoon-Hee

2016-08-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves the central and peripheral nervous system in patients with systemic lupus erythematosus (SLE). It is essential to specify the problems faced by patients with NPSLE because it causes diverse disabilities and impairs quality of life. After performing a comprehensive evaluation, tailored management should be provided for the patient's specific problems. We report here the case of a 30-year-old female with SLE who experienced serious neuropsychiatric symptoms cerebral infarction followed by posterior reversible encephalopathy syndrome and peripheral polyneuropathy. We systemically assessed the patient using the International Classification of Functioning, Disability and Health model as a clinical problem-solving tool and provided comprehensive rehabilitation by focusing on her problems.

Chinese version of the treatment of autoimmune bullous disease quality of life questionnaire: Reliability and validity.

PubMed

Chen, Guo; Yang, Baoqi; Zhang, Zhaoxia; Yang, Qing; Yan, Xiaoxiao; Murrell, Dédée F; Zhang, Furen

2018-01-01

Treatments for autoimmune blistering disease carry significant risks of medical complications and can affect the patient's quality of life. Recently, the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was developed in Australia. The objective of this study was to evaluate the reliability and validity of the Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire in Chinese patients with autoimmune blistering diseases. The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was produced by forward-backward translation and cross-cultural adaptation of the original English version. Autoimmune blistering disease patients recruited in the study self-administered the Chinese Treatment of Autoimmune Bullous Disease Quality of Life questionnaire, the Dermatology Life Quality Index and the 36-item Short-Form Health Survey. Reliability of the Chinese Treatment of Autoimmune Bullous Disease Quality of Life was evaluated using internal consistency and test-retest (days 0 and 7) methods. Validity was analyzed by face, content, construct, convergent and discriminant validity measures. A total of 86 autoimmune blistering disease patients were recruited for the study. Cronbach's alpha coefficient was 0.883 and the intraclass correlation coefficient was 0.871. Face and content validities were satisfactory. Convergent validity testing revealed correlation coefficients of 0.664 for the Treatment of Autoimmune Bullous Disease Quality of Life and Dermatology Life Quality Index and -0.577 for the Treatment of Autoimmune Bullous Disease Quality of Life and 36-item Short-Form Health Survey. With respect to discriminant validity, no significant differences were observed in the Treatment of Autoimmune Bullous Disease Quality of Life scores of men and women (t = 0.251, P = 0.802), inpatients and outpatients (t = 0.447, P = 0.656), patients on steroids and steroid-sparing medications (t = 0.672, P = 0.503) and patients with different autoimmune blistering disease subtypes (F = 0.030, P = 0.971). Illiterate patients were excluded from the study. The patients were from a single hospital and most of their conditions were in a relatively stable status. The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire is a reliable and valid instrument to measure treatment burden and to serve as an end point in clinical trials in Chinese autoimmune blistering disease patients.

The Autoimmune Ecology

PubMed Central

Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A.; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

2016-01-01

Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures – internal and external – across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied. PMID:27199979

[Spanish Society of Pediatric Infectious Diseases, Spanish Society of Paediatric Clinical Immunology and Allergy, Spanish Association of Paediatric Primary Care, and the Spanish Society of Extra-hospital Paediatrics and Primary Health Care consensus document on antibiotic treatment in penicillin or amoxicillin allergy].

PubMed

Baquero-Artigao, Fernando; Michavila, Antonio; Suárez-Rodriguez, Ángeles; Hernandez, Anselmo; Martínez-Campos, Leticia; Calvo, Cristina

2017-02-01

The suspected allergy to beta-lactam antibiotics, especially penicillin and amoxicillin, is the most frequent reason for consultation in Child Allergy Units. In this consensus document, the clinical and diagnostic criteria of allergic reactions are described, as well as alternative antibiotic treatment for the most common infections diagnosed in paediatrics for patients with known or suspected allergy. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Paediatric Pain Management: Using Complementary and Alternative Medicine.

PubMed

Evans, Subhadra; Tsao, Jennie C I; Zeltzer, Lonnie K

2008-09-01

Children undergo acute painful procedures and many also experience chronic pain.Due to their developing systems, infants and children may be at greater risk than adults for protracted pain sensitivity.There is a need to manage acute and chronic paediatric pain to reduce children's suffering and to prevent future pain problems.Consistent with a biopsychosocial perspective, complementary and alternative medicine (CAM) should be considered in management of acute and chronic paediatric pain.Although research is limited for paediatric pain, CAM interventions receiving the most empirical attention include hypnotherapy, acupuncture and music therapy. Evidence also exists for the therapeutic benefits of yoga, massage, humor therapy and the use of certain biological based therapies.