Role of the gluten-free diet on neurological-EEG findings and sleep disordered breathing in children with celiac disease.

PubMed

Parisi, P; Pietropaoli, N; Ferretti, A; Nenna, R; Mastrogiorgio, G; Del Pozzo, M; Principessa, L; Bonamico, M; Villa, M P

2015-02-01

To determine whether celiac children are at risk for EEG-neurological features and sleep disordered breathing (SDB), and whether an appropriate gluten-free diet (GFD) influences these disorders. We consecutively enrolled 19 children with a new biopsy-proven celiac disease (CD) diagnosis. At CD diagnosis and after 6 months of GFD, each patient underwent a general and neurological examination, an electroencephalogram, a questionnaire about neurological features, and a validated questionnaire about SDB: OSA (obstructive sleep apnea) scores<0 predict normality; values>0 predict OSA. At CD diagnosis, 37% of patients complained headache that affected daily activities and 32% showed positive OSA score. The EEG examinations revealed abnormal finding in 48% of children. After 6 months of GFD headache disappeared in 72% of children and EEG abnormalities in 78%; all children showed negative OSA score. According to our preliminary data, in the presence of unexplained EEG abnormalities and/or other neurological disorders/SDB an atypical or silent CD should also be taken into account. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Adult fulminant subacute sclerosing panencephalitis: pathological and molecular studies--a case report.

PubMed

Souraud, J B; Faivre, A; Waku-Kouomou, D; Gaillard, T; Aouad, N; Meaudre, E; Wild, F T; Fouet, B; Soulard, R

2009-01-01

Subacute sclerosing panencephalitis is an uncommon progressive neurological disorder caused by a persistent defective measles virus, typically affecting children. We describe a case of fulminant subacute sclerosing panencephalitis in a 25-year-old male. Brain tissue biopsy showed histologic evidence of encephalitis with eosinophilic intranuclear inclusion bodies (Cowdry Type A and B), intracytoplasmic inclusion bodies, perivascular lymphoplasmacytic infiltration and gliosis. Immunohistochemical studies were positive using an anti-measles antibody. Reverse transcriptase-PCR detected measles virus RNA and phylogenetic analysis indicated a C2 genotype. The rare adult-onset form is often atypical and difficult to diagnose and should be included in the differential diagnosis of subacute "unexplained" neurological diseases and uncommon infectious disorders.

Review of somatic symptoms in post-traumatic stress disorder.

PubMed

Gupta, Madhulika A

2013-02-01

Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes.

The relationship between ataque de nervios and unexplained neurological symptoms: a preliminary analysis.

PubMed

Interian, Alejandro; Guarnaccia, Peter J; Vega, William A; Gara, Michael A; Like, Robert C; Escobar, Javier I; Díaz-Martínez, Angélica M

2005-01-01

Within somatization, unexplained neurological symptoms (UNSs) have been shown to mark a distinct subgroup with greater clinical severity. However, some UNSs resemble ataque de nervios somatic symptoms. This raises questions about cultural factors related to Hispanics with somatization characterized by UNSs. To examine cultural factors, preliminary analyses examined the relationship between Hispanic ethnicity, UNSs, and ataque de nervios. Data were obtained from 127 primary care patients (95 Hispanic, 32 European American) with somatization. The Composite International Diagnostic Interview provided somatization data, whereas the Primary Care Evaluation of Mental Disorders was used for data on Axis I disorders. Ataque de nervios was assessed via a proxy measure. Within each ethnic group, cross-tabs examined the relationship between ataque de nervios and multiple UNSs, and ataque de nervios and selected Axis I disorders. Only among Hispanics, a significant overlap was found between ataque de nervios and having four or more UNSs (p < .001), and ataque de nervios and a diagnosis of panic disorder (p = .05). Although equal percentages of European Americans and Hispanics experience multiple UNSs, these results show that the presentation of UNSs among some Hispanics may be qualitatively different, because it may involve features related to ataque de nervios. A diagnosis of panic disorder also appears to interact with cultural factors.

Neuropsychological function and memory suppression in conversion disorder.

PubMed

Brown, Laura B; Nicholson, Timothy R; Aybek, Selma; Kanaan, Richard A; David, Anthony S

2014-09-01

Conversion disorder (CD) is a condition where neurological symptoms, such as weakness or sensory disturbance, are unexplained by neurological disease and are presumed to be of psychological origin. Contemporary theories of the disorder generally propose dysfunctional frontal control of the motor or sensory systems. Classical (Freudian) psychodynamic theory holds that the memory of stressful life events is repressed. Little is known about the frontal (executive) function of these patients, or indeed their general neuropsychological profile, and psychodynamic theories have been largely untested. This study aimed to investigate neuropsychological functioning in patients with CD, focusing on executive and memory function. A directed forgetting task (DFT) using words with variable emotional valence was also used to investigate memory suppression. 21 patients and 36 healthy controls completed a battery of neuropsychological tests and patients had deficits in executive function and auditory-verbal (but not autobiographical) memory. The executive deficits were largely driven by differences in IQ, anxiety and mood between the groups. A subgroup of 11 patients and 28 controls completed the DFT and whilst patients recalled fewer words overall than controls, there were no significant effects of directed forgetting or valence. This study provides some limited support for deficits in executive, and to a lesser degree, memory function in patients with CD, but did not find evidence of altered memory suppression to support the psychodynamic theory of repression. © 2013 The British Psychological Society.

Sudden onset unexplained encephalopathy in infants: think of cannabis intoxication.

PubMed

Lavi, Eran; Rekhtman, David; Berkun, Yackov; Wexler, Isaiah

2016-03-01

The use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations. During the initial interview of caregivers, no history of exposure to neurotoxic agents was obtained. All three patients were subsequently diagnosed with cannabis intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC). The infants recovered with supportive care that included fluids and monitoring. The non-specific symptomatology of cannabis intoxication in infants together with the wide differential for unexplained acute onset encephalopathy may delay diagnosis and lead to inappropriate procedures and interventions such as antimicrobial treatments and imaging studies. Healthcare personnel of emergency rooms, urgent care centers, and general clinics should be aware of the potential risk of cannabis ingestion in young infants. A thorough medical history and toxic screen are warranted in all infants with unexplained decreased sensorium.

Headaches as a presenting symptom of linear morphea en coup de sabre.

PubMed

Polcari, Ingrid; Moon, Amanda; Mathes, Erin F; Gilmore, Elaine S; Paller, Amy S

2014-12-01

Linear morphea en coup de sabre (ECDS) is a form of localized scleroderma that predominantly affects the pediatric population, with a median age of 10 years at presentation. The existence of neurologic findings in association with ECDS has been well described in the literature. Here we describe 4 patients with ECDS who presented with headaches, which were typical migraines in 3 of the patients. The headaches preceded the onset of cutaneous findings by at least 6 months. Our patients' cases emphasize both the importance of recognizing headaches as a harbinger of ECDS and the necessity of performing thorough cutaneous examination in patients with unexplained headaches or other neurologic disease. Copyright © 2014 by the American Academy of Pediatrics.

Covert video monitoring in the assessment of medically unexplained symptoms in children.

PubMed

Wallace, Dustin P; Sim, Leslie A; Harrison, Tracy E; Bruce, Barbara K; Harbeck-Weber, Cynthia

2012-04-01

Diagnosis of medically unexplained symptoms (MUS) occurs after thorough evaluations have failed to identify a physiological cause for symptoms. However, families and providers may wonder if something has been missed, leading to reduced confidence in behavioral treatment. Confidence may be improved through the use of technology such as covert video monitoring to better assess functioning across settings. A 12-year-old male presented with progressive neurological decline, precipitated by chronic pain. After thorough evaluation and the failure of standard treatments (medical, rehabilitative, and psychological) covert video monitoring revealed that the patient demonstrated greater abilities when alone in his room. Negative reinforcement was used to initiate recovery, accompanied by positive reinforcement and a rehabilitative approach. Covert video monitoring assisted in three subsequent cases over the following 3 years. In certain complex cases, video monitoring can inform the assessment and treatment of MUS. Discussion includes ethical and practical considerations.

Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes.

PubMed

Oaklander, Anne Louise; Klein, Max M

2013-04-01

We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies.

Evidence of Small-Fiber Polyneuropathy in Unexplained, Juvenile-Onset, Widespread Pain Syndromes

PubMed Central

Klein, Max M.

2013-01-01

OBJECTIVE: We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. METHODS: Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. RESULTS: Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). CONCLUSIONS: More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies. PMID:23478869

External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: results of the SYNARR-Flash study.

PubMed

Locati, E T; Moya, A; Oliveira, M; Tanner, H; Willems, R; Lunati, M; Brignole, M

2016-08-01

SYNARR-Flash study (Monitoring of SYNcopes and/or sustained palpitations of suspected ARRhythmic origin) is an international, multicentre, observational, prospective trial designed to evaluate the role of external 4-week electrocardiogram (ECG) monitoring in clinical work-up of unexplained syncope and/or sustained palpitations of suspected arrhythmic origin. Consecutive patients were enrolled within 1 month after unexplained syncope or palpitations (index event) after being discharged from emergency room or hospitalization without a conclusive diagnosis. A 4-week ECG monitoring was obtained by external high-capacity loop recorder (SpiderFlash-T(®), Sorin) storing patient-activated and auto-triggered tracings. Diagnostic monitorings included (i) conclusive events with reoccurrence of syncope or palpitation with concomitant ECG recording (with/without arrhythmias) and (ii) events with asymptomatic predefined significant arrhythmias (sustained supraventricular or ventricular tachycardia, advanced atrio-ventricular block, sinus bradycardia <30 b.p.m., pauses >6 s). SYNARR-Flash study enrolled 395 patients (57.7% females, 56.9 ± 18.7 years, 28.1% with syncope, and 71.9% with palpitations) from 10 European centres. For syncope, the 4-week diagnostic yield was 24.5%, and predictors of diagnostic events were early start of recording (0-15 vs. >15 days after index event) (OR 6.2, 95% CI 1.3-29.6, P = 0.021) and previous history of supraventricular arrhythmias (OR 3.6, 95% CI 1.4-9.7, P = 0.018). For palpitations, the 4-week diagnostic yield was 71.6% and predictors of diagnostic events were history of recurrent palpitations (P < 0.001) and early start of recording (P = 0.001). The 4-week external ECG monitoring can be considered as first-line tool in the diagnostic work-up of syncope and palpitation. Early recorder use, history of supraventricular arrhythmia, and frequent previous events increased the likelihood of diagnostic events during the 4-week external ECG monitoring. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

B vitamins in the nervous system.

PubMed

Bender, D A

1984-01-01

The coenzyme functions of the B vitamins in intermediatry metabolism are well established; nevertheless, for none of them is it possible to determine precisely the connection between the biochemical lesions associated with deficiency and the neurological consequences. Although there is convincing evidence of a neurospecific role for thiamin and other B vitamins, in no case has this role been adequately described. Similarly, the neurochemical sequelae of intoxication by massive amounts of vitamins (so-called mega-vitamin therapy or orthomolecular medicine) remain largely unexplained.

Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis.

PubMed

Liu, Aihai; Zheng, Chao; Lang, Junzhe; Chen, Wenbing

2014-05-01

The objective of this study is to investigate and compare the effectiveness of letrozole and clomiphene citrate for improving fertility outcomes, including pregnancy rate, miscarriage rate, multiple pregnancy rate, and incidence rate of adverse events, number of dominant follicles, endometrial thickness at hCG day and serum E2 on hCG day. MEDLINE, EMBASE, CENTRAL, CNKI and CBMdisc databases were searched up to March 2013. Randomized controlled trials comparing letrozole with clomiphene in women with unexplained infertility were included. Pooled relative risk, mean difference and 95% confidence intervals were calculated. We found that there are no differences in pregnancy, miscarriage and multiple pregnancy rates, incidence rate of adverse events, number of dominant follicles (>18 mm) and endometrial thickness at hCG day in women with unexplained infertility between letrozole and clomiphene regimens. The mean (±standard deviation) concentration of serum E2 on hCG day was lower in those treated with letrozole than those with clomiphene. The subgroup of 2.5 mg letrozole displayed a statistically significant higher rate of clinical pregnancy as compared with 100 mg of clomiphene. The results of this study conclude that letrozole is as effective as clomiphene in women with unexplained infertility. Letrozole at a dose of 2.5 mg seems more effective. Further high-quality studies assessing the possible effectiveness of letrozole in selected groups of patients are warranted. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Current Care and Investigational Therapies in Achondroplasia.

PubMed

Unger, Sheila; Bonafé, Luisa; Gouze, Elvire

2017-04-01

The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia. This disease is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications. Achondroplasia is the most common non-lethal skeletal dysplasia. It is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications.

Brief resolved unexplained event - BRUE

MedlinePlus

... Allergic reactions A brain, nerve, or muscle disorder Child abuse Certain uncommon genetic disorders A specific cause of ... by a trained provider was needed Signs of child abuse If risk factors are present, testing that may ...

Neurological and cardiac complications in a cohort of children with end-stage renal disease.

PubMed

Albaramki, Jumana H; Al-Ammouri, Iyad A; Akl, Kamal F

2016-05-01

Adult patients with chronic kidney disease are at risk of major neurologic and cardiac complications. The purpose of this study is to review the neurological and cardiac complications in children with end-stage renal disease (ESRD). A retrospective review of medical records of children with ESRD at Jordan University Hospital was performed. All neurological and cardiac events were recorded and analyzed. Data of a total of 68 children with ESRD presenting between 2002 and 2013 were reviewed. Neurological complications occurred in 32.4%; seizures were the most common event. Uncontrolled hypertension was the leading cause of neurological events. Cardiac complications occurred in 39.7%, the most common being pericardial effusion. Mortality from neurological complications was 45%. Neurological and cardiac complications occurred in around a third of children with ESRD with a high mortality rate. More effective control of hypertension, anemia, and intensive and gentle dialysis are needed.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.

PubMed

Larkin, James; Chmielowski, Bartosz; Lao, Christopher D; Hodi, F Stephen; Sharfman, William; Weber, Jeffrey; Suijkerbuijk, Karijn P M; Azevedo, Sergio; Li, Hewei; Reshef, Daniel; Avila, Alexandre; Reardon, David A

2017-06-01

Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management. We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8-year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy ( n  = 22), noninfective meningitis ( n  = 5), encephalitis ( n  = 6), neuromuscular disorders ( n  = 3), and nonspecific adverse events ( n  = 7). Study drug was discontinued ( n  = 20), interrupted ( n  = 8), or unchanged ( n  = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1-170) and to resolution was 32 days (2-809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four cases resolved and one was fatal. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune-related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab. © AlphaMed Press 2017.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis

PubMed Central

Chmielowski, Bartosz; Lao, Christopher D.; Hodi, F. Stephen; Sharfman, William; Weber, Jeffrey; Suijkerbuijk, Karijn P. M.; Azevedo, Sergio; Li, Hewei; Reshef, Daniel; Avila, Alexandre; Reardon, David A.

2017-01-01

Abstract Background. Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune‐related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life‐threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment‐related encephalitis, and provide practical guidance on diagnosis and management. Methods. We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8‐year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol‐Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. Results. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–809+). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal. Conclusion. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. Implications for Practice. With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune‐related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab. PMID:28495807

In vitro Repair of Oxidative DNA Damage by Human Nucleotide Excision Repair System: Possible Explanation for Neurodegeneration in Xeroderma Pigmentosum Patients

NASA Astrophysics Data System (ADS)

Reardon, Joyce T.; Bessho, Tadayoshi; Kung, Hsiang Chuan; Bolton, Philip H.; Sancar, Aziz

1997-08-01

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20-30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.

Chiari I Malformation in Nephropathic Cystinosis

PubMed Central

Rao, Kavya I; Hesselink, John; Trauner, Doris A

2015-01-01

Objective To determine the relative incidence of Chiari I malformations in children with cystinosis compared with those in the general population. Study design Magnetic resonance imaging (MRI) scans were performed on 53 patients with nephropathic cystinosis and 120 controls, age range 3-18 years. Results Ten of 53 (18.9%) cystinosis patients had Chiari I or tonsillar ectopia, and only 2 of 120 controls (1.6%) had a similar finding. At least 2 of the patients had symptoms or signs thought to be related to the malformation, and one had surgical decompression. Two had an associated cervical syrinx. Conclusions Children with cystinosis have a 12-fold higher prevalence of Chiari I malformations than the general pediatric population. Chiari I malformations should be high on the differential diagnosis when individuals with cystinosis develop neurologic signs and symptoms, and MRI scans should be performed on children with cystinosis who present with new-onset headache, ataxia, incontinence, or other unexplained neurologic symptoms. PMID:26265281

Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.

PubMed

Jordan, Lori C; Roberts Williams, Dionna O; Rodeghier, Mark J; Covert Greene, Brittany V; Ponisio, Maria R; Casella, James F; McKinstry, Robert C; Noetzel, Michael J; Kirkham, Fenella J; Meier, Emily R; Fuh, Beng; McNaull, Melissa; Sarnaik, Sharada; Majumdar, Suvankar; McCavit, Timothy L; DeBaun, Michael R

2018-06-01

In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. © 2018 Wiley Periodicals, Inc.

Pediatric neurological syndromes and inborn errors of purine metabolism.

PubMed

Camici, Marcella; Micheli, Vanna; Ipata, Piero Luigi; Tozzi, Maria Grazia

2010-02-01

This review is devised to gather the presently known inborn errors of purine metabolism that manifest neurological pediatric syndromes. The aim is to draw a comprehensive picture of these rare diseases, characterized by unexpected and often devastating neurological symptoms. Although investigated for many years, most purine metabolism disorders associated to psychomotor dysfunctions still hide the molecular link between the metabolic derangement and the neurological manifestations. This basically indicates that many of the actual functions of nucleosides and nucleotides in the development and function of several organs, in particular central nervous system, are still unknown. Both superactivity and deficiency of phosphoribosylpyrophosphate synthetase cause hereditary disorders characterized, in most cases, by neurological impairments. The deficiency of adenylosuccinate lyase and 5-amino-4-imidazolecarboxamide ribotide transformylase/IMP cyclohydrolase, both belonging to the de novo purine synthesis pathway, is also associated to severe neurological manifestations. Among catabolic enzymes, hyperactivity of ectosolic 5'-nucleotidase, as well as deficiency of purine nucleoside phosphorylase and adenosine deaminase also lead to syndromes affecting the central nervous system. The most severe pathologies are associated to the deficiency of the salvage pathway enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase: the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to a clear impairment of mitochondrial functions. The assessment of hypo- or hyperuricemic conditions is suggestive of purine enzyme dysfunctions, but most disorders of purine metabolism may escape the clinical investigation because they are not associated to these metabolic derangements. This review may represent a starting point stimulating both scientists and physicians involved in the study of neurological dysfunctions caused by inborn errors of purine metabolism with the aim to find novel therapeutical approaches. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Studies of human sex ratios at birth may lead to the understanding of several forms of pathology.

PubMed

James, William H

2013-10-01

This article deals with the problem of the causes of the variation of sex ratio (proportion male) at birth. This problem is common to a number of areas in biology and medicine, for example, obstetrics, neurology/psychiatry, parasitology, virology, oncology, and teratology. It is established that there are signifi cantly biased, but unexplained, sex ratios in each of these fields. Yet workers in them (with the possible exception of virology) have regarded the problem as a minor loose end, irrelevant to the field's major problems. However, as far as I know, no one has previously noted that unexplained biased sex ratios occur, and thus pose (perhaps similar) problems, in all these fields. Here it is suggested that similar sorts of solutions apply in each. Further research is proposed for testing each solution. If the argument here is substantially correct across this range of topics, it may lead to an improved understanding not only of sex ratio but also of some of the pathologies in these specialties. Copyright © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.

Immune-related neurological toxicities among solid tumor patients treated with immune checkpoint inhibitors: a systematic review.

PubMed

Eltobgy, Mostafa; Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Decker, Michael; Abdel-Rahman, Omar

2017-07-01

Immune-related neurologic toxicities are uncommon but serious adverse events that may be associated with the use of immune checkpoint inhibitors. The objective of this review is to assess the incidence and risk of neurologic toxicities which are potentially immune-related and occur with immune checkpoint treatment of solid tumors. Areas covered: PubMed database has been searched till January 2017. Clinical trials, case series and case reports reporting the occurrence of immune-related neurologic toxicities in solid tumor patients treated with immune checkpoint inhibitors were included. Eighteen trials with 4469 participants were included. The most common neurologic toxicities reported with these agents included sensory and motor peripheral neuropathies. Moreover, 17 case reports describing immune-related neurological events occurring with 22 patients were included. Expert commentary: Immune-related neurological toxicities occur uncommonly in cancer patients treated immune checkpoint inhibitors. Further studies are needed to better describe the course of these events (i.e. time to onset, time to resolution and responsiveness to different immunosuppressives).

The possible role of opiates in women with chronic urinary retention: observations from a prospective clinical study.

PubMed

Panicker, Jalesh N; Game, Xavier; Khan, Shahid; Kessler, Thomas M; Gonzales, Gwen; Elneil, Sohier; Fowler, Clare J

2012-08-01

Urinary retention in women often presents a diagnostic difficulty, and the etiology may remain unidentified even after excluding structural and neurological causes. We evaluated a group of women referred to a specialist center with unexplained urinary retention. A total of 61 consecutive women with complete urinary retention were evaluated. Urological and neurological investigations locally had failed to identify a cause. Urethral pressure profile, sphincter volume measurement and in some cases urethral sphincter electromyography were performed to diagnose a primary disorder of sphincter relaxation (Fowler's syndrome). Mean patient age was 39 years (range 18 to 88). Following investigations, a probable etiology was identified in 25 (41%) women, the most common being Fowler's syndrome. Of the women 24 (39%) were being treated with opiates for various pain syndromes and in 13 no other cause of retention was identified. Opiates could be discontinued in only 2 patients, and both demonstrated improved sensations and voiding. The cause of urinary retention may remain unknown in spite of extensive investigations. Young women regularly using prescription opiates for various undiagnosed pain syndromes present a challenging clinical problem and this study suggests that iatrogenic causes should be considered if voiding difficulties emerge. An association between opiate use and constipation is well-known and, although urinary retention is a listed adverse event, it appears to be often overlooked in clinical practice. It is hypothesized that Fowler's syndrome is due to an up-regulation of spinal cord enkephalins and that exogenous opiates may compound any functional abnormalities predisposing young women to urinary retention. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Neural correlates of improvements in personality and behavior following a neurological event.

PubMed

King, Marcie L; Manzel, Kenneth; Bruss, Joel; Tranel, Daniel

2017-11-21

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maximal potential patent foramen diameter does not correlate with the type or frequency of the neurologic event prior to closure.

PubMed

Kutty, Shelby; Brown, Kimberly; Qureshi, Athar M; Latson, Larry A

2009-01-01

We analyzed our data on patients undergoing transcatheter patent foramen ovale (PFO) closure to determine if the maximal potential PFO diameter (MPPD) by balloon sizing correlates with important clinical characteristics in this population. We defined stroke as a focal neurologic deficit lasting >24 h, or focal deficit of shorter duration associated with permanent MRI/CT changes consistent with a focal infarction. Parameters analyzed included age, gender, anticoagulation, hypertension, smoking, MRI/CT findings and MPPD at catheterization. We specifically analyzed the type of neurologic event (stroke/transient ischemic attack, TIA), and number of recorded preceding clinical neurologic events. In 216 consecutive patients, 167 suffered a stroke. MRI/CT changes consistent with one or more embolic events were seen in 156 patients; 49 had a clinical TIA. There was no significant difference in MPPD between stroke (11.0 +/- 3.6 mm) and TIA groups (10.9 +/- 3.9 mm; 95% confidence interval for difference: -1.33 to 1.00). MPPD did not differ between MRI/CT-positive vs. -negative strokes, and had no correlation with the number of identified pre-closure clinical neurologic events. Continued investigation is needed to determine whether other PFO characteristics, or other anatomic/physiologic parameters, may be useful to identify patients at high risk for cryptogenic stroke/TIA, even before they have their first neurologic event. Copyright 2008 S. Karger AG, Basel.

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients: Report of Four Additional Cases and Review of Clinical, Diagnostic, and Therapeutic Features

PubMed Central

Winston, Drew J.; Vikram, Holenarasipur R.; Rabe, Ingrid B.; Dhillon, Gundeep; Mulligan, David; Hong, Johnny C.; Busuttil, Ronald W.; Nowicki, Marek J.; Mone, Thomas; Civen, Rachel; Tecle, Selam A.; Trivedi, Kavita K.; Hocevar, Susan N.

2017-01-01

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived. Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5–37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity. PMID:24827763

Donor-derived West Nile virus infection in solid organ transplant recipients: report of four additional cases and review of clinical, diagnostic, and therapeutic features.

PubMed

Winston, Drew J; Vikram, Holenarasipur R; Rabe, Ingrid B; Dhillon, Gundeep; Mulligan, David; Hong, Johnny C; Busuttil, Ronald W; Nowicki, Marek J; Mone, Thomas; Civen, Rachel; Tecle, Selam A; Trivedi, Kavita K; Hocevar, Susan N

2014-05-15

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

PREDICTING A THIRD PLANET IN THE KEPLER-47 CIRCUMBINARY SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinse, Tobias C.; Haghighipour, Nader; Kostov, Veselin B.

2015-01-20

We have studied the possibility that a third circumbinary planet in the Kepler-47 planetary system is the source of the single unexplained transiting event reported during the discovery of these planets. We applied the MEGNO technique to identify regions in the phase space where a third planet can maintain quasi-periodic orbits, and assessed the long-term stability of the three-planet system by integrating the entire five bodies (binary + planets) for 10 Myr. We identified several stable regions between the two known planets as well as a region beyond the orbit of Kepler-47c where the orbit of the third planet could bemore » stable. To constrain the orbit of this planet, we used the measured duration of the unexplained transit event (∼4.15 hr) and compared that with the transit duration of the third planet in an ensemble of stable orbits. To remove the degeneracy among the orbits with similar transit durations, we considered the planet to be in a circular orbit and calculated its period analytically. The latter places an upper limit of 424 days on the orbital period of the third planet. Our analysis suggests that if the unexplained transit event detected during the discovery of the Kepler-47 circumbinary system is due to a planetary object, this planet will be in a low eccentricity orbit with a semi-major axis smaller than 1.24 AU. Further constraining of the mass and orbital elements of this planet requires a re-analysis of the entire currently available data, including those obtained post-announcement of the discovery of this system. We present details of our methodology and discuss the implication of the results.« less

Pioneer Venus 12.5 km Anomaly Workshop Report, volume 1

NASA Technical Reports Server (NTRS)

Seiff, A.; Sromovsky, L.; Borucki, W.; Craig, R.; Juergens, D.; Young, R. E.; Ragent, B.

1995-01-01

A workshop was convened at Ames Research Center on September 28 and 29, 1993, to address the unexplained electrical anomalies experienced in December 1978 by the four Pioneer Venus probes below a Venus altitude of 12.5 km. These anomalies caused the loss of valuable data in the deep atmosphere, and, if their cause were to remain unexplained, could reoccur on future Venus missions. The workshop participants reviewed the evidence and studied all identified mechanisms that could consistently account for all observed anomalies. Both hardware problems and atmospheric interactions were considered. Based on a workshop recommendation, subsequent testing identified the cause as being an insulation failure of the external harness. All anomalous events are now explained.

Anti-ma2 paraneoplastic encephalitis in association with recurrent cervical cancer.

PubMed

Ney, Douglas E; Messersmith, Wells; Behbakht, Kian

2014-07-01

Paraneoplastic neurological syndromes are rare, and although they are frequently associated with gynecological malignancies, cervical cancer is a rare cause. The symptoms of anti-Ma2 encephalitis are diverse and often present prior to the diagnosis of malignancy. We report a case of a 37-year-old woman with a history of cervical cancer presenting with unexplained weight gain and vertical supranuclear gaze palsy. Magnetic resonance imaging of the brain revealed lesions within the bilateral hypothalami and midbrain. Anti-Ma2 antibodies were eventually found in the serum, prompting a search for malignancy. Recurrent metastatic cervical cancer was found in the retroperitoneal lymph nodes. This is the first report of cervical cancer in association with anti-Ma2 encephalitis, and highlights the need for a high degree of suspicion in patients with a cancer history presenting with neurological symptoms. The symptoms associated with anti-Ma2 encephalitis are diverse and typically precede the diagnosis of cancer in patients, and should trigger a search for an underlying malignancy.

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.

Contemporary outcomes for carotid endarterectomy at a large community-based academic health center.

PubMed

Long, Graham W; Nuthakki, Vijay; Bove, Paul G; Brown, O William; Shanley, Charles J; Bendick, Phillip J; Rimar, Steven; Kitzmiller, John; Zelenock, Gerald B

2007-05-01

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS) demonstrated the efficacy of carotid endarterectomy (CEA), but these studies were published 15 and 11 years ago, respectively. We hypothesized that present clinical results of CEA have improved compared with those reported by NASCET/ACAS. Every patient having CEA from January 1999 through December 2003 was reviewed as part of a continuous quality-assurance program. Patient demographics and risk factors were recorded; high-risk patients were identified using inclusion criteria for high-risk carotid stent trials. Primary end points recorded were all neurologic events, deaths, and myocardial infarctions (MIs). Outcomes were reported individually or as combined neurologic events and deaths (traditional NASCET/ACAS methodology) and, similar to recent carotid stent trials, individually, combined, and as a composite that included MI. A total of 1,927 CEAs were performed, 1,140 in men (59%) and 787 in women (41%). The average age was 72 +/- 9 years; 21% of patients were age 80 or older. Symptomatic patients accounted for 717 procedures (37%). Perioperative neurologic event, death, and MI occurred in 1.0%, 0.5%, and 1.3% of patients, respectively. The combined neurologic event and death rate was 1.3% (symptomatic = 1.8%, asymptomatic = 1.1%). High-risk patients comprised 54% of the cohort; the neurologic event and death rate for this group was 1.6%. The composite end point including MI was 3.4%. Severe coronary artery disease and prior ipsilateral CEA significantly correlated with a higher incidence of primary end point complications. In contemporary practice, the perioperative neurologic event rate is significantly less than reported in NASCET/ACAS. Perioperative death and MI rates were similar to those seen in NASCET/ACAS. Neurologic events and death rates were not different between high- and low-risk groups. These data may serve as a guide for the modern vascular specialist weighing open and endovascular options for treatment of carotid artery occlusive disease in both high- and low-risk patients.

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

PubMed

Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

2014-11-20

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

PubMed

Lutterloh, Emily; Likaka, Andrew; Sejvar, James; Manda, Robert; Naiene, Jeremias; Monroe, Stephan S; Khaila, Tadala; Chilima, Benson; Mallewa, Macpherson; Kampondeni, Sam D; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua G; Nygren, Benjamin; Tippett Barr, Beth; Demby, Austin; Phiri, Abel; Lungu, Rudia; Kaphiyo, James; Humphrys, Michael; Talkington, Deborah; Joyce, Kevin; Stockman, Lauren J; Armstrong, Gregory L; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Risk of Death in Infants Who Have Experienced a Brief Resolved Unexplained Event: A Meta-Analysis.

PubMed

Brand, Donald A; Fazzari, Melissa J

2018-06-01

To estimate an upper bound on the risk of death after a brief resolved unexplained event (BRUE), a sudden alteration in an infant's breathing, color, tone, or responsiveness, previously labeled "apparent life-threatening event" (ALTE). The meta-analysis incorporated observational studies of patients with ALTE that included data on in-hospital and post-discharge deaths with at least 1 week of follow-up after hospital discharge. Pertinent studies were identified from a published review of the literature from 1970 through 2014 and a supplementary PubMed query through February 2017. The 12 included studies (n = 3005) reported 12 deaths, of which 8 occurred within 4 months of the event. Applying a Poisson-normal random effects model to the 8 proximate deaths using a 4-month time horizon yielded a post-ALTE mortality rate of about 1 in 800, which constitutes an upper bound on the risk of death after a BRUE. This risk is about the same as the baseline risk of death during the first year of life. The meta-analysis therefore supports the return-home approach advocated in a recently published clinical practice guideline-not routine hospitalization-for BRUE patients who have been evaluated in the emergency department and determined to be at lower risk. Copyright © 2017 Elsevier Inc. All rights reserved.

[Application of single nucleotide polymorphism-microarray and target gene sequencing in the study of genetic etiology of children with unexplained intellectual disability or developmental delay].

PubMed

Gao, Z J; Jiang, Q; Cheng, D Z; Yan, X X; Chen, Q; Xu, K M

2016-10-02

Objective: To evaluate the application of single nucleotide polymorphism (SNP)-microarray and target gene sequencing technology in the clinical molecular genetic diagnosis of unexplained intellectual disability(ID) or developmental delay (DD). Method: Patients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and February 2016. The intellectual assessment of the patients was performed using 0-6-year-old pediatric examination table of neuropsychological development or Wechsler intelligence scale (>6 years). Patients with a DQ less than 49 or IQ less than 51 were included in this study. The patients were scanned by SNP-array for detection of genomic copy number variations (CNV), and the revealed genomic imbalance was confirmed by quantitative real time-PCR. Candidate gene mutation screening was carried out by target gene sequencing technology.Causal mutations or likely pathogenic variants were verified by polymerase chain reaction and direct sequencing. Result: There were 15 children with ID or DD enrolled, 9 males and 6 females. The age of these patients was 7 months-16 years and 9 months. SNP-array revealed that two of the 15 patients had genomic CNV. Both CNV were de novo micro deletions, one involved 11q24.1q25 and the other micro deletion located on 21q22.2q22.3. Both micro deletions were proved to have a clinical significance due to their association with ID, brain DD, unusual faces etc. by querying Decipher database. Thirteen patients with negative findings in SNP-array were consequently examined with target gene sequencing technology, genotype-phenotype correlation analysis and genetic analysis. Five patients were diagnosed with monogenic disorder, two were diagnosed with suspected genetic disorder and six were still negative. Conclusion: Sequential use of SNP-array and target gene sequencing technology can significantly increase the molecular genetic etiologic diagnosis rate of the patients with unexplained ID or DD. Combined use of these technologies can serve as a useful examinational method in assisting differential diagnosis of children with unexplained ID or DD.

[Multiple actinomycosis brain abscesses].

PubMed

Liotier, J; Venet, C; Chambonnière, M-L; Fournier, C; Fotso, M-J; Ewencsyk, I; Barral, F-G; Carricajo, A; Robert, F; Lucht, F; Mosnier, J-F; Zéni, F

2004-03-13

Actinomycosis is a subacute or chronic bacterial infection, which can affect immunocompetent or immunodeficient subjects. It most often occurs in cervico-facial or thoracic-abdominal locations. Central nervous system infection is rare but of severe prognosis. A 56 year-old woman with no history of immunodepression was admitted with unexplained fever, inappropriate behaviour, and spatial and temporal disorientation. The progressive worsening of the neurological signs let to coma and mechanical ventilation was required. Brain imaging showed multilocation cerebral abscesses. Stereotaxial biopsy permitted diagnosis of actinomycosis. Patient's outcome was favourable following appropriate dual antibiotherapy without surgical exeresis. When lacking bacteriologic identification, diagnosis of cerebral actinomycosis is performed by pathologic findings. Dual antibiotherapy allows full recover, even in the case of multilocation cerebral abscesses.

Anomalous cosmic ray interaction events for investigations in the SSC and Space Station era - 'Long lived she-devil phenomena'

NASA Technical Reports Server (NTRS)

Takahashi, Y.

1985-01-01

Observational data on anomalous cosmic-ray interaction events are compiled, classified, and briefly characterized. The events are divided into three groups: those confirmed by later observation or experiment, those shown to be the result of observational or analytical error, and those still unexplained. Among the phenomena in the latter group are magnetic-monopole candidates, fractionally charged particles, massive stable particles, anomalons, proton-decay and neutron-oscillation candidates, muon bundles, narrow showers, anomalous photons, fanlike phenomena, quark-gluon-plasma candidates, and anomalous long-range delta rays.

Anti-Ma2 Paraneoplastic Encephalitis in Association with Recurrent Cervical Cancer

PubMed Central

Messersmith, Wells; Behbakht, Kian

2014-01-01

Background Paraneoplastic neurological syndromes are rare, and although they are frequently associated with gynecological malignancies, cervical cancer is a rare cause. The symptoms of anti-Ma2 encephalitis are diverse and often present prior to the diagnosis of malignancy. Case Report We report a case of a 37-year-old woman with a history of cervical cancer presenting with unexplained weight gain and vertical supranuclear gaze palsy. Magnetic resonance imaging of the brain revealed lesions within the bilateral hypothalami and midbrain. Anti-Ma2 antibodies were eventually found in the serum, prompting a search for malignancy. Recurrent metastatic cervical cancer was found in the retroperitoneal lymph nodes. Conclusions This is the first report of cervical cancer in association with anti-Ma2 encephalitis, and highlights the need for a high degree of suspicion in patients with a cancer history presenting with neurological symptoms. The symptoms associated with anti-Ma2 encephalitis are diverse and typically precede the diagnosis of cancer in patients, and should trigger a search for an underlying malignancy. PMID:25045381

[Neuro-ophthalmology: the eye as a window to the brain].

PubMed

Kesler, Anat

2013-02-01

Neuro-ophthalmology focuses on the diagnosis and treatment of visual disorders related to the neurological system rather than the globe itself. Being a subspecialty of both neurology and ophthalmology, it requires specialized training and expertise in diseases of the eye, brain, nerves and muscles. Commonly encountered pathologies in neuro-ophthalmology include: optic neuropathies (such as optic neuritis and ischemic optic neuropathy), visual field loss (transient, constant, unexplained), transient visual loss, unspecified visual disturbances, diplopia, abnormal eye movements, thyroid eye disease, myasthenia gravis, anisocoria, and eyelid abnormalities. The current issue of "Harefuah" is dedicated to contemporary knowledge in neuro-opthalmology, and spans from studies of neuromyelitis optica (NMO), ischemic optic neuropathies, and optic neuropathies induced by phosphodiesterase inhibitors, to the management of sight-threatening carotid-cavernous fistulas, and more. These studies emphasize the importance of an interdisciplinary treatment team consisting of a neuro-ophthalmologist, a neuro-radiologist, and sometimes, even a neuro-surgeon. Such an approach may prove to be beneficial to the patient, by optimizing follow-up and treatment decisions. This issue emphasizes how a correct and timely diagnosis is of paramount significance in patients with neuro-ophthalmological disorders.

A safe and effective management strategy for blunt cerebrovascular injury: Avoiding unnecessary anticoagulation and eliminating stroke.

PubMed

Shahan, Charles P; Magnotti, Louis J; Stickley, Shaun M; Weinberg, Jordan A; Hendrick, Leah E; Uhlmann, Rebecca A; Schroeppel, Thomas J; Hoit, Daniel A; Croce, Martin A; Fabian, Timothy C

2016-06-01

Few injuries have produced as much debate with respect to management as have blunt cerebrovascular injuries (BCVIs). Recent work (American Association for the Surgery of Trauma 2013) from our institution suggested that 64-channel multidetector computed tomographic angiography (CTA) could be the primary screening tool for BCVI. Consequently, our screening algorithm changed from digital subtraction angiography (DSA) to CTA, with DSA reserved for definitive diagnosis of BCVI following CTA-positive study results or unexplained neurologic findings. The current study was performed to evaluate outcomes, including the potential for missed clinically significant BCVI, since this new management algorithm was adopted. Patients who underwent DSA (positive CTA finding or unexplained neurologic finding) over an 18-month period subsequent to the previous study were identified. Screening and confirmatory test results, complications, and BCVI-related strokes were reviewed and compared. A total of 228 patients underwent DSA: 64% were male, with mean age and Injury Severity Score (ISS) of 43 years and 22, respectively. A total of 189 patients (83%) had a positive screening CTA result. Of these, DSA confirmed injury in 104 patients (55%); the remaining 85 patients (45%) (false-positive results) were found to have no injury on DSA. Five patients (4.8%) experienced BCVI-related strokes, unchanged from the previous study (3.9%, p = 0.756); two were symptomatic at trauma center presentation, and three occurred while receiving appropriate therapy. No patient with a negative screening CTA result experienced a stroke. This management scheme using 64-channel CTA for screening coupled with DSA for definitive diagnosis was proven to be safe and effective in identifying clinically significant BCVIs and maintaining a low stroke rate. Definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients (false-positive results). No strokes resulted from injuries missed by CTA. Diagnostic study, level III.

Columbia River flow and drought since 1750.

Treesearch

Ze' ev Gedalof; David L. Peterson; Nathan J. Mantua

2004-01-01

A network of 32 drought sensitive tree-ring chronologies is used to reconstruct mean water year flow on the Columbia River at The Dalles, Oregon, since 1750. The reconstruction explains 30 percent of the variability in mean water year (October to September) flow, with a large portion of unexplained variance caused by underestimates of the most severe low flow events....

Investigations into the Power MOSFET SEGR Phenomenon and its Physical Mechanism

NASA Technical Reports Server (NTRS)

Swift, G. M.; Edmonds, L. E.; Miyahira, T.; Nichols, D. K.; Johnston, A. H.

1997-01-01

The state of understanding of the destructive SEGR event in power MOSFETs is relatively mature with large published efforts, both experimental and theoretical. However, gasps remain in the uderstanding of the phenomenon, including unexplained anomalies, emperical-only dependencies on some important device and incident ion physical parameters, and limited insight into latent effets.

Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked by symptoms that symbolized death in a patient with terminal stage stomach cancer: case report and review of the literature.

PubMed

Onishi, Hideki; Okuno, Shigeko; Yae, Suzu; Sairenji, Motonori; Onose, Masanari; Mizuno, Yasuhiro; Kawanishi, Chiaki

2006-03-01

We report here a terminally ill patient with stomach cancer who developed a brief psychotic disorder mimicking cerebrovascular attack after a short episode of nasal bleeding. Close examination of the patient revealed that nasal bleeding was an event that symbolized deterioration of the general condition leading to death for the patient. A 77-year-old male, who was diagnosed as having stomach cancer and was receiving palliative care, presented with tremor and insomnia just after a short episode of nasal bleeding and showed reduced response to stimuli mimicking cerebrovascular attack. Laboratory data were unremarkable. The next day, catatonic behavior developed. He had no history of psychiatric illness or drug or alcohol abuse. After receiving haloperidol, psychiatric symptoms disappeared and he returned to the previous level of functioning within 3 days. The patient explained that he had seen a patient whose general condition deteriorated after nasal bleeding and regarded nasal bleeding as a symptom of deteriorating general condition leading to death and thereafter became afraid of the nasal bleeding. Although, nasal bleeding is common and usually not severe in medical settings, for the patient, it was an event that symbolized deterioration of the general condition leading to death. Brief psychotic disorder in cancer patients is rare in the literature, although patients receiving terminal care share various kinds of psychological burden. Medical staff in the palliative care unit should be aware of the psychological distress experienced by each patient and consider brief psychotic disorder as part of the differential diagnosis when patients show unexplained neurological-like and/or psychiatric symptoms.

A novel mutation of laminin β2 (LAMB2) in two siblings with renal failure.

PubMed

Falix, Farah A; Bennebroek, Carlien A M; van der Zwaag, Bert; Lapid-Gortzak, Ruth; Florquin, Sandrine; Oosterveld, Michiel J S

2017-04-01

This report describes a novel mutation of LAMB2, the gene associated with Pierson syndrome (microcoria-congenital nephrosis syndrome), in two female siblings. The c.970T>C p.(Cys324Arg) mutation in the LAMB2 gene affects one of the eight highly conserved cysteine residues within the first EGF-like module of the laminin β2 protein. These residues form disulfide bonds in order to achieve a correct 3D structure of the protein. The reported phenotype is considered a relatively mild variant of Pierson syndrome and is associated with later-onset (18 months) therapy-resistant nephrotic syndrome leading to renal failure, and ocular abnormalities consisting of high myopia, microcoria, diverse retinal abnormalities, hence a low level of visual acuity. Importantly, the reported LAMB2 mutation was associated with normal neurological development in both siblings. this report presents the variability of the renal, ocular and neurological phenotypes associated with LAMB2 mutations and underscores the importance of ophthalmologic examination in all children with unexplained renal insufficiency or nephrotic syndrome. What is known • LAMB2 mutations are associated with Pierson syndrome • Pierson syndrome is associated with congenital nephrotic syndrome, microcoria and neurological deficits What is new • A novel mutation in the LAMB2 gene in two female siblings • Genotype and clinical phenotype description of a novel LAMB2 mutation.

Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe).

PubMed

Fantur, Michaela; Karall, Daniela; Scholl-Buergi, Sabine; Häberle, Johannes; Rauchenzauner, Markus; Fruehwirth, Martin

2013-01-01

Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C > T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case underlines that the diagnosis of a urea cycle defect should be considered in the differential diagnosis of recurrent idiopathic vomiting in combination with unexplained neurological symptoms also beyond the neonatal period due to the possibility of mild or atypical late-onset presentation (e.g. OTC deficiency in hemizygous males). Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

PubMed

Chapman, J; Rand, J H; Brey, R L; Levine, S R; Blatt, I; Khamashta, M A; Shoenfeld, Y

2003-01-01

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

The Incidence and Predictors of Early- and Mid-Term Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World Patients.

PubMed

Bosmans, Johan; Bleiziffer, Sabine; Gerckens, Ulrich; Wenaweser, Peter; Brecker, Stephen; Tamburino, Corrado; Linke, Axel

2015-07-21

Transcatheter aortic valve replacement (TAVR) enables treatment of high-risk patients with symptomatic aortic stenosis without open-heart surgery; however, the benefits are mitigated by the potential for neurological events. This study sought to determine the timing and causes of clinically relevant neurological events after self-expandable TAVR. We enrolled 1,015 patients, of whom 996 underwent TAVR with a self-expandable system at 44 TAVR-experienced centers in Europe, Colombia, and Israel. Neurological events were evaluated for 3 distinct time periods: periprocedural (0 to 1 days post TAVR); early (2 to 30 days); and late (31 to 730 days). In this real-world study, neurological events were first referred to the site neurologist and then reviewed by an independent neurologist. The overall stroke rate was 1.4% through the first day post-procedure, 3.0% at 30 days, and 5.6% at 2 years. There were no significant predictors of periprocedural stroke or stroke/transient ischemic attack (TIA) combined. Significant predictors of early stroke were acute kidney injury (p = 0.03), major vascular complication (p = 0.04), and female sex (p = 0.04). For stroke/TIA combined, prior atrial fibrillation (p = 0.03) and major vascular complication (p = 0.009) were predictive. Coronary artery bypass graft surgery was the only significant predictor of late stroke (p = 0.007) or late stroke/TIA (p = 0.06). Treatment of high-risk patients with aortic stenosis using a self-expandable system was associated with a low stroke rate at short- and long-term follow-up. Multivariable predictors of clinically relevant neurological events differed on the basis of the timing after TAVR. (CoreValve Advance International Post Market Study; NCT01074658). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cerebrovascular accidents after percutaneous coronary interventions from 2002 to 2014: Incidence, outcomes, and associated variables.

PubMed

Didier, Romain; Gaglia, Michael A; Koifman, Edward; Kiramijyan, Sarkis; Negi, Smita I; Omar, Al Fazir; Gai, Jiaxing; Torguson, Rebecca; Pichard, Augusto D; Waksman, Ron

2016-02-01

Cerebrovascular accident (CVA) and transient ischemic attack (TIA) related to percutaneous coronary intervention (PCI) are relatively rare complications, but they are associated with high morbidity and mortality. Given the evolution of both CVA risk and PCI techniques over time, this study was conducted to evaluate trends in CVA and TIA associated with PCI and to identify variables associated with neurologic events. Consecutive patients undergoing PCI at the Washington Hospital Center between January 2002 and June 2015 were included. Prespecified data were prospectively collected, including baseline and procedural characteristics, in-hospital outcomes, and 1-year mortality. The subjects who had a CVA or TIA during or immediately after PCI were compared with those without procedure-associated CVA or TIA. Overall, 25,626 patients were included in the study. The mean age was 65.0 ± 12.4 years, 16,949 (65.2%) were male, and 7,436 (28.6%) were African American. From 2002 to 2015, 110 neurologic events post-PCI were diagnosed (0.43%); this included 86 CVAs (0.34%) and 24 TIAs (0.09%). The annual rate of postprocedural neurologic events was 0.42% ± 0.12%. There were significant changes in baseline risk factors over time, with increasing age, incidence of insulin-dependent diabetes, and chronic kidney disease. Patients with neurologic events were more often African American (43.6% vs 28.6%, P < .001) with prior history of CVA (24.5% vs 7.8%, P < .001), chronic renal insufficiency (26.6% vs 15.2%, P < .001), and insulin-dependent diabetes (19.1% vs 12.4%, P = .03). Acute myocardial infarction (56% vs 30.4%, P < .001) and cardiogenic shock (20.2% vs 3%, P < .001) were also more common among patients with neurologic events post-PCI. After multivariable adjustment, use of an intraaortic balloon pump was strongly associated with neurologic events (odds ratio [OR] 4.9, 95% CI 2.7-8.8, P < .001), as was prior CVA (OR 2.4, 95% CI 1.4-4.4, P = .002) and African American race (OR 2.4, 95% CI 1.5-3.9, P < .001); there was a borderline association with the use of a thrombus extraction device (OR 1.7, 95% CI 0.9-3.2, P = .09). In-hospital mortality (20.0% vs 1.5%, P < .001) and 1-year mortality (45.0% vs 7.3%, P < .001) were also much higher in patients with neurologic events. Neurologic events post-PCI are associated with markedly worse in-hospital outcomes. The incidence of CVA and TIA post-PCI, however, remained stable over the last 12 years despite an increase in risk factors for CVA. Copyright © 2015 Elsevier Inc. All rights reserved.

The ALTE mysteries: who's to blame?

PubMed

Wickham, Sara

2016-02-01

In this column, Sara Wickham takes a sideways look at issues relevant to midwives, students, women and families, inviting us to sit down with a cup of tea and ponder what we think we know. A recent paper on apparent life-threatening events (ALTEs) in newborn babies brought to mind an experience from practice, the cause of which remains a mystery. As many similar events are unexplained, is it acceptable that there is a tendency in the literature to claim that skin-to-skin contact and breastfeeding are risk factors for ALTEs?

The black box in somatization: unexplained physical symptoms, culture, and narratives of trauma.

PubMed

Waitzkin, H; Magaña, H

1997-09-01

Stimulated by our clinical work with patients who manifest unexplained "somatoform" symptoms in the primary care setting, this article addresses a theoretical black box in our understanding of somatization: how does culture mediate severe stress to produce symptoms that cannot be explained by the presence of physical illness? Despite various problems in his explanation of hysteria, Freud broke new ground by emphasizing narratives of traumatic experiences in the development and treatment of unexplained physical symptoms. Except in anthropologically oriented cultural psychiatry, contemporary psychiatry has traveled away from a focus on narrative in the study of somatization. On the other hand, recent interest in narrative has spread across many intellectual disciplines, including the humanities and literary criticism, psychology, history, anthropology, and sociology. We operationally define narratives as attempts at storytelling that portray the interrelationships among physical symptoms and the psychologic, social, or cultural context of these symptoms. Regarding somatization and trauma, we focus on the ways that narrative integrates the cultural context with traumatic life events. In explaining the black box, we postulate that extreme stress (torture, rape, witnessing deaths of relatives, forced migration, etc.) is processed psychologically as a terrible, largely incoherent narrative of events too awful to hold in consciousness. Culture patterns the psychologic and somatic expression of the terrible narrative. Methodologically, we have developed some techniques for eliciting narratives of severe stress and somatic symptoms, which we illustrate with observations from an ongoing research project. In designing interventions to improve the care of somatizing patients, we are focusing on the creation of social situations where patients may feel empowered to express more coherent narratives of their prior traumatic experiences.

Physical Examination for the Academic Psychiatrist: Primer and Common Clinical Scenarios.

PubMed

Azzam, Pierre N; Gopalan, Priya; Brown, Jennifer R; Aquino, Patrick R

2016-04-01

As clinical psychiatry has evolved to mirror the patient care model followed in other medical specialties, psychiatrists are called upon increasingly to utilize general medical skills in routine practice. Psychiatrists who practice in academic settings are often required to generate broad differential diagnoses that include medical and neurologic conditions and, as a result, benefit from incorporating physical examination into their psychiatric assessments. Physical examination allows psychiatrists to follow and to teach patient-informed clinical practices and comprehensive treatment approaches. In this commentary, the authors encourage routine use of a targeted physical examination and outline common scenarios in which physical examination would be useful for the academic psychiatrist: delirium, toxidromes, and unexplained medical conditions (e.g., somatic symptom disorders).

Statistical Assessment of Cetacean Stranding Events in Cape Cod Area

NASA Technical Reports Server (NTRS)

Zellar, R.; Pulkkinen, A.; Moore, K.; Reeb, D.; Karakoylu, E.; Uritskaya, O.

2017-01-01

Cetacean (whales, dolphins and porpoises) mass strandings are a longstanding mystery in the field of marine biology that continue to be recorded in coastal environments around the world. For each of these events, anywhere from a few to several hundred otherwise healthy animals strand in onshore environments, often for no apparent reason. While the causes of these events remain unclear, anthropogenic and naturogenic mechanisms have been suggested. We present results of an inter-disciplinary study that draws expertise from space weather, marine mammal biology and ecology, and marine mammal stranding response. This study assessed 16 years of cetacean stranding events in the Cape Cod (Massachusetts, USA) area concurrently with a large dataset of meteorological, geophysical, biological, oceanographic and space weather data to produce inferences about possible causes for these unexplained events.

Statistical Assessment of Cetacean Stranding Events in Cape Cod (Massachusetts, USA) area.

NASA Astrophysics Data System (ADS)

Zellar, R.; Pulkkinen, A. A.; Moore, K.; Reeb, D.; Karakoylu, E.; Uritskaya, O.

2017-12-01

Cetacean (whales, dolphins and porpoises) mass strandings are a longstanding mystery in the field of marine biology that continue to be recorded in coastal environments around the world. For each of these events, anywhere from a few to several hundred otherwise healthy animals strand in onshore environments, often for no apparent reason. While the causes of these events remain unclear, anthropogenic and naturogenic mechanisms have been suggested. We present results of an inter-disciplinary study that draws expertise from space weather, marine mammal biology and ecology, and marine mammal stranding response. This study assessed 16 years of cetacean stranding events in the Cape Cod (Massachusetts, USA) area concurrently with a large dataset of meteorological, geophysical, biological, oceanographic and space weather data to produce inferences about possible causes for these unexplained events.

Cardiac events in football and strategies for first-responder treatment on the field.

PubMed

Schmied, Christian; Drezner, Jonathan; Kramer, Efraim; Dvorak, Jiri

2013-12-01

The incidence and outcomes of sudden cardiac arrest (SCA) and global strategies for prevention of sudden cardiac death (SCD) in football are not known. The aim of this study was to estimate the occurrence of cardiac events in football and to investigate the preventive measures taken among the Fédération International de Football Association (FIFA) member associations internationally. A questionnaire was sent to the member associations of FIFA. The first section addressed the previous events of SCA, SCD or unexplained sports-related sudden death within the last 10 years. Further questions focused on football player medical screening strategies and SCA resuscitation response protocols on the field. 126 of 170 questionnaires were returned (response rate 74.1%), and 103 questionnaires (60.6%) were completed sufficiently to include in further analysis. Overall, 107 cases of SCA/SCD and 5 unexplained football-associated sudden deaths were reported. These events occurred in 52 of 103 responding associations (50.5%). 23 of 112 (20.5%) footballers survived. 12 of 22 (54.5%) players treated with an available automated external defibrillators (AED) on the pitch survived. A national registry to monitor cardiac events was established in only 18.4% of the associations. Most associations (85.4%) provide regular cardiac screening for their national teams while 75% screen teams of the national leagues. An AED is available at all official matches in 68% of associations. National registries to accurately measure SCA/SCD in football are rare and greatly needed. Deficiencies in emergency preparations, undersupply of AEDs on the field during matches, and variability in resuscitation response protocols and training of team-staff members should be addressed to effectively prevent SCD in football.

Etiological diagnosis, prognostic significance and role of electrophysiological study in patients with Brugada ECG and syncope.

PubMed

Giustetto, Carla; Cerrato, Natascia; Ruffino, Enrico; Gribaudo, Elena; Scrocco, Chiara; Barbonaglia, Lorella; Bianchi, Francesca; Bortnik, Miriam; Rossetti, Guido; Carvalho, Paula; Riccardi, Riccardo; Castagno, Davide; Anselmino, Matteo; Bergamasco, Laura; Gaita, Fiorenzo

2017-08-15

Syncope is considered a risk factor for life-threatening arrhythmias in Brugada patients. Distinguishing a benign syncope from one due to ventricular arrhythmias is often difficult, unless an ECG is recorded during the episode. Aim of the study was to analyze the characteristics of syncopal episodes in a large population of Brugada patients and evaluate the role of electrophysiological study (EPS) and the prognosis in the different subgroups. One hundred ninety-five Brugada patients with history of syncope were considered. Syncope were classified as neurally mediated (group 1, 61%) or unexplained (group 2, 39%) on the basis of personal and family history, clinical features, triggers, situations, associated signs, concomitant therapy. Most patients underwent EPS; they received ICD or implantable loop-recorder on the basis of the result of investigations and physician's judgment. At 62±45months of mean follow-up, group 1 showed a significantly lower incidence of arrhythmic events (2%) as compared to group 2 (9%, p<0.001). Group 2 patients with positive EPS showed the highest risk of arrhythmic events (27%). No ventricular events occurred in subjects with negative EPS. Etiological definition of syncope in Brugada patients is important, as it allows identifying two groups with different outcome. Patients with unexplained syncope and ventricular fibrillation induced at EPS have the highest risk of arrhythmic events. Patients presenting with neurally mediated syncope showed a prognosis similar to that of the asymptomatic and the role of EPS in this group is unproven. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid clinical deterioration in an individual with Down syndrome.

PubMed

Jacobs, Julia; Schwartz, Alison; McDougle, Christopher J; Skotko, Brian G

2016-07-01

A small percentage of adolescents and young adults with Down syndrome experience a rapid and unexplained deterioration in cognitive, adaptive, and behavioral functioning. Currently, there is no standardized work-up available to evaluate these patients or treat them. Their decline typically involves intellectual deterioration, a loss of skills of daily living, and prominent behavioral changes. Certain cases follow significant life events such as completion of secondary school with friends who proceed on to college or employment beyond the individual with DS. Others develop this condition seemingly unprovoked. Increased attention in the medical community to clinical deterioration in adolescents and young adults with Down syndrome could provide a framework for improved diagnosis, evaluation, and treatment. This report presents a young adult male with Down syndrome who experienced severe and unexplained clinical deterioration, highlighting specific challenges in the systematic evaluation and treatment of these patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Current and emerging indications for implantable cardiac monitors.

PubMed

Giada, Franco; Bertaglia, Emanuele; Reimers, Bernhard; Noventa, Donatella; Raviele, Antonio

2012-09-01

Implantable cardiac monitors (ICMs) continuously monitor the patient's electrocardiogram and perform real-time analysis of the heart rhythm, for up to 36 months. The current clinical use of ICMs involves the evaluation of transitory symptoms of possible arrhythmic origin, such as unexplained syncope and palpitations. Moreover, ICMs can also be used for the evaluation of difficult cases of epilepsy and unexplained falls, though current indications for their application in these sectors are less clearly defined. Finally, the ability of new-generation ICMs to automatically record arrhythmic episodes suggests that these devices could also be used to study asymptomatic arrhythmias, and thus could be proposed for the long-term evaluation of the total (symptomatic and asymptomatic) arrhythmic burden in patients at risk of arrhythmic events. In particular, ICMs may have an emerging role in the management of patients with atrial fibrillation and in those at risk of ventricular arrhythmias. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Additional diagnostic value of implantable loop recorder in patients with initial diagnosis of real or apparent transient loss of consciousness of uncertain origin.

PubMed

Maggi, Roberto; Roberto, Maggi; Rafanelli, Martina; Martina, Rafanelli; Ceccofiglio, Alice; Alice, Ceccofiglio; Solari, Diana; Diana, Solari; Brignole, Michele; Michele, Brignole; Ungar, Andrea; Andrea, Ungar

2014-08-01

Non-syncopal transient loss of consciousness (T-LOC) encompasses disorders that sometimes resemble syncope, and the differential diagnosis with true syncope may be challenging. The implantable loop recorder (ILR) is potentially useful, but has never been systematically assessed. The aim of the study is to evaluate the diagnostic value of ILR in distinguishing syncope from non-syncopal forms of T-LOC. We implanted an ILR in 58 patients (mean age 71 ± 17 years, 25 males) who had had 4.6 ± 2.3 episodes of real or apparent T-LOC, in order to distinguishing epilepsy from syncope (#28), unexplained fall from syncope (#29), or functional pseudo-syncope from syncope (#1). During 20 ± 13 months of follow-up, 33 patients (57%) had a spontaneous event documented by ILR. A diagnosis of syncope was established by ILR documentation of an arrhythmia in 15 (26%) patients: an asystole of 6 s (IQR 4-10 s) duration was documented at the time of the spontaneous event in seven patients with initial suspicion of epilepsy and in five patients with unexplained fall; atrial tachyarrhythmia was documented at the time of the spontaneous event in 1 and 1 patient, respectively, and ventricular tachycardia in 1 patient with unexplained fall. Conversely, in another 18 patients, ILR monitoring documented no significant rhythm abnormalities at the time of T-LOC recurrence, thus excluding an arrhythmic syncope. Finally, ILR was unable to document any syncopal episode in 25 (43%) patients. Among the 15 patients with an established diagnosis of arrhythmic syncope, syncope recurred during follow-up in 2 of 11 patients who were on pacemaker therapy and in 3 of 4 patients who were on other therapies. Implantable loop recorder monitoring provides additional diagnostic value in 'difficult' patients with an initial diagnosis of non-syncopal real or apparent T-LOC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Phenotype in patients with intellectual disability and pathological results in array CGH.

PubMed

Caballero Pérez, V; López Pisón, F J; Miramar Gallart, M D; González Álvarez, A; García Jiménez, M C; García Iñiguez, J P; Orden Rueda, C; Gil Hernández, I; Fuertes Rodrigo, C; Fernando Martínez, R; Rodríguez Valle, A; Alcaine Villarroya, M J

Global developmental delay (GDD) and intellectual disability (ID) are frequent reasons for consultation in paediatric neurology departments. Nowadays, array comparative genomic hybridisation (array-CGH) is one of the most widely used techniques for diagnosing these disorders. Our purpose was to determine the phenotypic features associated with pathological results in this genetic test. We conducted a blind study of the epidemiological, clinical, anthropometric, and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH. Pathological results were found in 27.5% of the patients. Factors associated with pathological results in array-CGH were a family history of GDD/ID (OR = 12.1), congenital malformations (OR = 5.33), having more than 3 facial dysmorphic features (OR = 20.9), and hypotonia (OR = 3.25). Our findings are consistent with those reported by other published series. We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID/GDD. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies.

PubMed

Ludwig, Lea; Pasman, Joëlle A; Nicholson, Timothy; Aybek, Selma; David, Anthony S; Tuck, Sharon; Kanaan, Richard A; Roelofs, Karin; Carson, Alan; Stone, Jon

2018-04-01

Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder. We did a meta-analysis, with assessments of methodology, sources of bias, and sensitivity analyses. 34 case-control studies, with 1405 patients, were eligible. Studies were of moderate-to-low quality. The frequency of childhood and adulthood stressors was increased in cases compared with controls. Odds ratios (OR) were higher for emotional neglect in childhood (49% for cases vs 20% for controls; OR 5·6, 95% CI 2·4-13·1) compared with sexual abuse (24% vs 10%; 3·3, 2·2-4·8) or physical abuse (30% vs 12%; 3·9, 2·2-7·2). An association with stressful life events preceding onset (OR 2·8, 95% CI 1·4-6·0) was stronger in studies with better methods (interviews; 4·3, 1·4-13·2). Heterogeneity was significant between studies (I 2 21·1-90·7%). 13 studies that specifically ascertained that the participants had not had either severe life events or any subtype of maltreatment all found a proportion of patients with functional neurological disorder reporting no stressor. Stressful life events and maltreatment are substantially more common in people with functional neurological disorder than in healthy controls and patient controls. Emotional neglect had a higher risk than traditionally emphasised sexual and physical abuse, but many cases report no stressors. This outcome supports changes to diagnostic criteria in DSM-5; stressors, although relevant to the cause in many patients, are not a core diagnostic feature. This result has implications for ICD-11. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Apnea in the term infant.

PubMed

Patrinos, Mary Elaine; Martin, Richard J

2017-08-01

Whereas apnea of prematurity has been well defined and its pathophysiology extensively studied, apnea in the term infant remains a greater challenge. Unfortunately, clear diagnostic criteria are lacking and pathogenesis and management vary widely. In this review we have arbitrarily organized the discussion chronologically into earlier and later postnatal periods. In the first days of life, presumed apnea may reflect physiologic events such as positional or feeding etiologies, or may be a manifestation of serious pathophysiology, such as a seizure disorder. Beyond the neonatal period, presumed apnea may be characterized as a BRUE event (brief resolved unexplained event; formerly referred to as ALTE: apparent life-threatening event) and most frequently a precipitating event cannot be identified. Medical providers are left with somewhat of a dilemma regarding the need to hospitalize and/or work up such patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry.

PubMed

Schmidt, C; Hofmann, U; Kohlmüller, D; Mürdter, T; Zanger, U M; Schwab, M; Hoffmann, G F

2005-01-01

To evaluate the significance of inborn metabolic disorders of the pyrimidine degradation pathway, 450 children with unspecific neurological symptoms were comprehensively studied; 200 healthy children were recruited as controls. Uracil and thymine as well as their degradation products in urine were determined with an improved method based on reversed-phase HPLC coupled with electrospray ionization tandem mass spectrometry and detection by multiple-reaction monitoring using stable-isotope-labelled reference compounds as internal standards. From the results of the control group we established age-related reference ranges of all pyrimidine degradation products. In the patient group, two children with dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these was homozygous for the exon 14-skipping mutation of the DPYD gene. In addition, two patients with high uracil, dihydrouracil and beta-ureidopropionate were found to have ornithine transcarbamylase deficiency. In the urine of 9 patients, beta-alanine was markedly elevated owing to treatment with vigabatrin, an irreversible inhibitor of GABA transaminase, which interferes with beta-alanine breakdown. Four patients had exclusively high levels of beta-aminoisobutyrate (beta-AIB) due to a low activity of the D-beta-AIB-pyruvate aminotransferase, probably without clinical significance. In conclusion, quantitative investigation of pyrimidine metabolites in children with unexplained neurological symptoms, particularly epileptic seizures with or without psychomotor retardation, can be recommended as a helpful tool for diagnosis in clinical practice. Sensitive methods and age-related reference ranges enable the detection of partial enzyme deficiencies.

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

NASA Technical Reports Server (NTRS)

Clark, Jonathan B.; Riley, Terrence

2001-01-01

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or .0139% (4/28627). After review of the value of the EEG as a screening tool, the US Navy now uses EEG only for certain clinical indications (head injury, unexplained loss of consciousness, family history of epilepsy, and abnormal neurological exam). Currently the US Navy does not use EEG for screening for any flight applicant without a neurologic indication. In the US Navy, an electroencephalographic pattern is determined to be epileptiform by a neurologist.

Effects of space radiation on electronic microcircuits

NASA Technical Reports Server (NTRS)

Kolasinski, W. A.

1989-01-01

The single event effects or phenomena (SEP), which so far have been observed as events falling on one or another of the SE classes: Single Event Upset (SEU), Single Event Latchup (SEL) and Single Event Burnout (SEB), are examined. Single event upset is defined as a lasting, reversible change in the state of a multistable (usually bistable) electronic circuit such as a flip-flop or latch. In a computer memory, SEUs manifest themselves as unexplained bit flips. Since latchup is in general caused by a single event of short duration, the single event part of the SEL term is superfluous. Nevertheless, it is used customarily to differentiate latchup due to a single heavy charged particle striking a sensitive cell from more ordinary kinds of latchup. Single event burnout (SEB) refers usually to total instantaneous failure of a power FET when struck by a single particle, with the device shorting out the power supply. An unforeseen failure of these kinds can be catastrophic to a space mission, and the possibilities are discussed.

Deformity Angular Ratio Describes the Severity of Spinal Deformity and Predicts the Risk of Neurologic Deficit in Posterior Vertebral Column Resection Surgery.

PubMed

Wang, Xiao-Bin; Lenke, Lawrence G; Thuet, Earl; Blanke, Kathy; Koester, Linda A; Roth, Michael

2016-09-15

Retrospective review of prospectively collected data. To assess the value of the deformity angular ratio (DAR, maximum Cobb measurement divided by number of vertebrae involved) in evaluating the severity of spinal deformity, and predicting the risk of neurologic deficit in posterior vertebral column resection (PVCR). Although the literature has demonstrated that PVCR in spinal deformity patients has achieved excellent outcomes, it is still high risk neurologically. This study, to our knowledge, is the largest series of PVCR patients from a single center, evaluating deformity severity, and potential neurologic deficit risk. A total of 202 consecutive pediatric and adult patients undergoing PVCRs from November 2002 to September 2014 were reviewed. The DAR (coronal DAR, sagittal DAR, and total DAR) was used to evaluate the complexity of the deformity. The incidence of spinal cord monitoring (SCM) events was 20.5%. Eight patients (4.0%) had new neurologic deficits. Patients with a high total DAR (≥25) were significantly younger (20.3 vs. 29.0 yr, P = 0.001), had more severe coronal and sagittal deformities, were more myelopathic (33.3% vs. 11.7%, P = 0.000), needed larger vertebral resections (1.8 vs. 1.3, P = 0.000), and had a significantly higher rate of SCM events than seen in the low total DAR (<25) patients (41.1% vs. 10.8%; P = 0.000). Patients with a high sagittal DAR (≥15) also had a significantly higher rate of SCM events (34.0% vs. 15.1%, P = 0.005) and a greater chance of neurologic deficits postoperatively (12.5% vs. 0, P = 0.000). For patients undergoing a PVCR, the DAR can be used to quantify the angularity of the spinal deformity, which is strongly correlated to the risk of neurologic deficits. Patients with a total DAR greater than or equal to 25 or sagittal DAR greater than or equal to 15 are at much higher risk for intraoperative SCM events and new neurologic deficits. 3.

Comparison of Flow Impairment during Carotid Artery Stenting Using Two Types of Eccentric Filter Embolic Protection Devices.

PubMed

Nii, Kouhei; Tsutsumi, Masanori; Maeda, Hitoshi; Aikawa, Hiroshi; Inoue, Ritsuro; Eto, Ayumu; Sakamoto, Kimiya; Mitsutake, Takafumi; Hanada, Hayatsura; Kazekawa, Kiyoshi

2016-12-15

We investigated the angiographic findings and the clinical outcomes after carotid artery stenting (CAS) using two different, eccentric filter embolic protection devices (EPDs). Between July 2010 and August 2015, 175 CAS procedures were performed using a self-expandable closed-cell stent and a simple eccentric filter EPD (FilterWire EZ in 86 and Spider FX in 89 procedures). The angiographic findings (i.e., flow impairment and vasospasm) at the level of EPDs, neurologic events, and post-operative imaging results were compared between the FilterWire EZ and the Spider FX groups. The CAS was angiographically successful in all 175 procedures. However, the angiographs were obtained immediately after CAS-detected flow impairment in the distal internal carotid artery (ICA) in 11 (6.3%) and ICA spasms at the level of the EPD in 40 cases (22.9%). The incidence of these complications was higher with FilterWire EZ than Spider FX (ICA flow impairment of 10.5% vs. 2.2%, P = 0.03; vasospasm 30.2% vs. 15.7%, P = 0.03). There were nine neurologic events (5.1%); five patients were presented with transient ischemic attacks, three had minor strokes, and one had a major stroke. New MRI lesions were seen in 25 (29.1%) FilterWire-group and in 36 (40.4%) Spider-group patients. The neurologic events and new MRI lesions were not associated with the type of EPD used. Although the ICA flow impairment may result in neurologic events, there was no significant association between the FilterWire EZ and the Spider FX CAS with respect to the incidence of neurologic events by the prompt treatment such as catheter aspiration.

Disseminated toxoplasmosis in a patient with non-Hodgkin lymphoma.

PubMed

Herold, M A; Kühne, R; Vosberg, M; Ostheeren-Michaelis, S; Vogt, P; Karrer, U

2009-12-01

Toxoplasmosis is a well-recognized opportunistic disease in HIV-infected individuals that is caused by the reactivation of a previous infection, primarily in the central nervous system, during profound immunodeficiency. Toxoplasmosis has been described more rarely in patients with cancer and chemotherapy. We report a case of a patient with a history of chemotherapy for non-Hodgkin lymphoma who developed pain and progressive paresthesia of the right arm 6 weeks after remission. Relapsing lymphoma was suspected, and steroid and radiation treatment were initiated, but the patient died 5 days later due to multiple organ failure. Autopsy revealed disseminated toxoplasmosis. This case illustrates that toxoplasmosis should be suspected in patients with neoplastic disease, especially lymphomas, who present with unexplained neurologic, pulmonary, or febrile symptoms during or after chemotherapy.

Testing a symptom-based surveillance system at high-profile gatherings as a preparatory measure for bioterrorism.

PubMed

Osaka, K; Takahashi, H; Ohyama, T

2002-12-01

We tested symptom-based surveillance during the G8 conference in 2000 as a means of detecting outbreaks, including bio-terrorism attacks, promptly. Five categories of symptoms (skin and haemorrhagic, respiratory, gastrointestinal, neurological and unexplained) were adopted for the case definition of the surveillance. The surveillance began I week before the conference, and continued until 1 week after the conference ended. We could not detect any outbreaks during this surveillance. Compared to the existing diagnosis-based surveillance system, symptom-based surveillance has the advantages of timeliness and simplicity. However, poor specificity and difficulties in determining epidemic threshold were important limitations of this system. To increase the specificity of surveillance, it is essential to incorporate rapid laboratory diagnoses into the system.

Imaging screening of catastrophic neurological events using a software tool: preliminary results.

PubMed

Fernandes, A P; Gomes, A; Veiga, J; Ermida, D; Vardasca, T

2015-05-01

In Portugal, as in most countries, the most frequent organ donors are brain-dead donors. To answer the increasing need for transplants, donation programs have been implemented. The goal is to recognize virtually all the possible and potential brain-dead donors admitted to hospitals. The aim of this work was to describe preliminary results of a software application designed to identify devastating neurological injury victims who may progress to brain death and can be possible organ donors. This was an observational, longitudinal study with retrospective data collection. The software application is an automatic algorithm based on natural language processing for selected keywords/expressions present in the cranio-encephalic computerized tomography (CE CT) scan reports to identify catastrophic neurological situations, with e-mail notification to the Transplant Coordinator (TC). The first 7 months of this application were analyzed and compared with the standard clinical evaluation methodology. The imaging identification tool showed a sensitivity of 77% and a specificity of 66%; predictive positive value (PPV) was 0.8 and predictive negative value (PNV) was 0.7 for the identification of catastrophic neurological events. The methodology proposed in this work seems promising in improving the screening efficiency of critical neurological events. Copyright © 2015 Elsevier Inc. All rights reserved.

Patent Foramen Ovale: Association between the Degree of Shunt by Contrast Transesophageal Echocardiography and the Risk of Future Ischemic Neurologic Events

NASA Technical Reports Server (NTRS)

Stone, David A.; Godard, Joel; Godard, Joel; Corretti, mary C.; Kittner, Steven J.; Sample, Cindy; Price, Thomas R.; Plotnick, Gary D.

1996-01-01

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have patent foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt (220 microbubbles) and group 2 (n = 18) with a "small" degree of shunt (23 but <20 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p= 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patent foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk for subsequent adverse neurologic events compared with patients with a small degree of shunt.

How many published cases of serious adverse events after yellow fever vaccination meet Brighton Collaboration diagnostic criteria?

PubMed

Thomas, Roger E; Spragins, Wendy; Lorenzetti, Diane L

2013-12-16

To perform a systematic review of all serious adverse events (SAEs) after yellow fever vaccination and to assess them according to Brighton Collaboration criteria. Nine electronic databases were searched with the terms "yellow fever vaccine" and "adverse events" to 10 July 2013 (no language/date limits). Two reviewers independently assessed studies, entered data, and assessed cases with Brighton Collaboration criteria. One hundred and thirty-one cases met Brighton Collaboration criteria: 32 anaphylaxis, 41 neurologic (one death), 56 viscerotropic (24 deaths), and 2 both neurologic and viscerotropic criteria. All SAEs occurred following first yellow fever (YF) vaccination. Two additional cases which met Brighton Collaboration criteria were proven due to wild virus. An additional 345 cases were presented with insufficient detail to meet Brighton Collaboration criteria:173 neurological, 68 viscerotropic (24 deaths), 67 anaphylaxis, and 34 cases from a UK database and 3 from a Swiss database described as "serious adverse events" but not further classified into neurologic or viscerotropic. A further 253 cases were excluded as presenting insufficient data to be regarded as yellow fever vaccine (YFV) related SAEs. One hundred and thirty-one cases met Brighton Collaboration criteria for serious adverse events after yellow fever vaccination. Another 345 cases did not meet Brighton criteria and 253 were excluded as presenting insufficient data to be regarded as serious adverse events after YFV. There are likely to be cases in areas that are remote or with insufficient diagnostic resources that are neither correctly assessed nor not published. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of case volume on outcome and performance of targeted temperature management in out-of-hospital cardiac arrest survivors.

PubMed

Lee, Seung Joon; Jeung, Kyung Woon; Lee, Byung Kook; Min, Yong Il; Park, Kyu Nam; Suh, Gil Joon; Kim, Kyung Su; Kang, Gu Hyun

2015-01-01

This study aimed to determine the effect of case volume on targeted temperature management (TTM) performance, incidence of adverse events, and neurologic outcome in comatose out-of-hospital cardiac arrest (OHCA) survivors treated with TTM. We used a Web-based, multicenter registry (Korean Hypothermia Network registry), to which 24 hospitals throughout the Republic of Korea participated to study adult (≥18 years) comatose out-of-hospital cardiac arrest patients treated with TTM between 2007 and 2012. The primary outcome was neurologic outcome at hospital discharge. The secondary outcomes were inhospital mortality, TTM performance, and adverse events. We extracted propensity-matched cohorts to control for bias. Multivariate logistic regression analysis was performed to assess independent risk factors for neurologic outcome. A total of 901 patients were included in this study; 544 (60.4%) survived to hospital discharge, and 248 (27.5%) were discharged with good neurologic outcome. The high-volume hospitals initiated TTM significantly earlier and had lower rates of hyperglycemia, bleeding, hypotension, and rebound hyperthermia. However, neurologic outcome and inhospital mortality were comparable between high-volume (27.7% and 44.6%, respectively) and low-volume hospitals (21.1% and 40.5%) in the propensity-matched cohorts. The adjusted odds ratio for the high-volume hospitals compared with low-volume hospitals was 1.506 (95% confidence interval, 0.875-2.592) for poor neurologic outcome. Higher TTM case volume was significantly associated with early initiation of TTM and lower incidence of adverse events. However, case volume had no association with neurologic outcome and inhospital mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders.

PubMed

Perez, David L; Matin, Nassim; Barsky, Arthur; Costumero-Ramos, Victor; Makaretz, Sara J; Young, Sigrid S; Sepulcre, Jorge; LaFrance, W Curt; Keshavan, Matcheri S; Dickerson, Bradford C

2017-06-01

Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified. © 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.

Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms

PubMed Central

Harms, Klaus; Lunnan, Asbjørn; Hülter, Nils; Mourier, Tobias; Vinner, Lasse; Andam, Cheryl P.; Marttinen, Pekka; Fridholm, Helena; Hansen, Anders Johannes; Hanage, William P.; Nielsen, Kaare Magne; Willerslev, Eske; Johnsen, Pål Jarle

2016-01-01

In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome. PMID:27956618

The beginnings of the Southern Child/Pediatric Neurology Society.

PubMed

Dyken, Paul Richard; Bodensteiner, John B

2015-04-01

The founding and early development of the Southern Pediatric Neurology Society was in many ways parallel to that of the Child Neurology Society. The organization started out as the Southern Child Neurology Society but the name was changed at the time of incorporation so as to avoid confusion of identity and purpose with the larger Child Neurology Society. Although there are archives of early days and the later development of the Southern Pediatric Neurology Society, the details have never been set down in a narrative explaining the events that led to the development of the organization. In this paper, we try to produce a written record of the history of the founding and early development of the Southern Pediatric Neurology Society. © The Author(s) 2014.

Magnetic resonance imaging for cerebral lesions during minimal invasive mitral valve surgery: study protocol for a randomized controlled trial.

PubMed

Barbero, Cristina; Ricci, Davide; Cura Stura, Erik; Pellegrini, Augusto; Marchetto, Giovanni; ElQarra, Suad; Boffini, Massimo; Passera, Roberto; Valentini, Maria Consuelo; Rinaldi, Mauro

2017-02-21

Recent data have highlighted a higher rate of neurological injuries in minimal invasive mitral valve surgery (MIMVS) compared with the standard sternotomy approach; therefore, the role of specific clamping techniques and perfusion strategies on the occurrence of this complication is a matter of discussion in the medical literature. The purpose of this trial is to prospectively evaluate major, minor and silent neurological events in patients undergoing right mini-thoracotomy mitral valve surgery using retrograde perfusion and an endoaortic clamp or a transthoracic clamp. A prospective, blinded, randomized controlled study on the rate of neurological embolizations during MIMVS started at the University of Turin in June 2014. Major, minor and silent neurological events are being investigated through standard neurological evaluation and magnetic resonance imaging assessment. The magnetic resonance imaging protocol includes conventional sequences for the morphological and quantitative assessment and nonconventional sequences for the white matter microstructural evaluation. Imaging studies are performed before surgery as baseline assessment and on the third postoperative day and, in patients who develop postoperative ischemic lesions, after 6 months. Despite recent concerns raised about the endoaortic setting with retrograde perfusion, we expect to show equivalence in terms of neurological events of this technique compared with the transthoracic clamp in a selected cohort of patients. With the first results expected in December 2016 the findings would be of help in confirming the efficacy and safety of MIMVS. ClinicalTrials.gov, Identifier: NCT02818166 . Registered on 8 February 2016 - trial retrospectively registered.

Medically Unexplained Symptoms

MedlinePlus

WRIISC War Related Illness and Injury Study Center Office of Public Health Department of Veterans Affairs MEDICALLY UNEXPLAINED SYMPTOMS A RESOURCE FOR VETERANS, SERVICE MEMBERS, AND THEIR FAMILIES Medically Unexplained ...

Health hazard evaluation report HETA 84-419-1697, USGS Laboratory, Doraville, Georgia. [Benzene, methylene chloride, hexane, and acetone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rondinelli, R.; Wilcox, T.; Roper, P.

1986-05-01

The U.S. Geological Survey National Water Quality Laboratory, Doraville, Georgia requested an evaluation of physical complaints reported by employees to determine possible work related causes. Laboratory workers, in general, complained of physical symptoms which were irritative (rash, sore throat, nose or sinus irritation), neurological (numbness, muscle weakness) and nonspecific (dizziness, headache, emotional swings, insomnia, muscle aching, fatigue). Reported exposure to solvents such as benzene, methylene chloride, hexane and acetone were positively related with light headedness or dizziness, numbness, unexplained muscle weakness and muscle aching. Air sampling did not reveal any remarkable exposure to chemical contaminants. The authors conclude that nomore » relationship could be established between chemical exposures and antinuclear antibody positivity. Exposure to chemicals measured by air sampling were below occupational health exposure limits.« less

Rigor, Reproducibility and in vitro CSF assays: The Devil in the Details

PubMed Central

Moody, Olivia A.; Talwar, Sahil; Jenkins, Meagan A.; Freeman, Amanda A.; Trotti, Lynn Marie; García, Paul S.; Bliwise, Donald; Lynch, Joseph W.; Cherson, Brad; Hernandez, Eric M; Feldman, Neil; Saini, Prabhjyot; Rye, David B.; Jenkins, Andrew

2017-01-01

Divergent results and misinterpretation of non-significant findings remain problematic in science – especially in retrospective, hypothesis generating, translational research.1 When such divergence occurs, it is imperative that the cause of the divergence be established. In their recent paper in Annals of Neurology, Dauvilliers et al2 challenged our earlier finding that cerebrospinal fluid (CSF) from some patients with unexplained excessive daytime sleepiness enhances the activation of GABAA receptors (GABAA-R)3. They present data from 15 subjects in which they were unable to find evidence of enhanced activation of GABAA receptors. Here we: 1) establish how flaws in Dauvilliers’ experimental design account for this difference; 2) present new data demonstrating the robustness and reproducibility of our methods and 3) summarize the clinical promise of GABAA-R antagonism in treating IH and related disorders. PMID:28440033

Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.

PubMed

Craig, J B; Jackson, D V; Moody, D; Cruz, J M; Pope, E K; Powell, B L; Spurr, C L; Capizzi, R L

1984-10-01

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.

Heterogeneous Pulmonary Phenotypes Associated With Mutations in the Thyroid Transcription Factor Gene NKX2-1

PubMed Central

Deterding, Robin R.; Wert, Susan E.; White, Frances V.; Dishop, Megan K.; Alfano, Danielle N.; Halbower, Ann C.; Planer, Benjamin; Stephan, Mark J.; Uchida, Derek A.; Williames, Lee D.; Rosenfeld, Jill A.; Lebel, Robert Roger; Young, Lisa R.; Cole, F. Sessions; Nogee, Lawrence M.

2013-01-01

Background: Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome. To characterize the spectrum of associated pulmonary phenotypes, we identified individuals with mutations in NKX2-1 whose primary manifestation was respiratory disease. Methods: Retrospective and prospective approaches identified infants and children with unexplained diffuse lung disease for NKX2-1 sequencing. Histopathologic results and electron micrographs were assessed, and immunohistochemical analysis for surfactant-associated proteins was performed in a subset of 10 children for whom lung tissue was available. Results: We identified 16 individuals with heterozygous missense, nonsense, and frameshift mutations and five individuals with heterozygous, whole-gene deletions of NKX2-1. Neonatal RDS was the presenting pulmonary phenotype in 16 individuals (76%), interstitial lung disease in four (19%), and pulmonary fibrosis in one adult family member. Altogether, 12 individuals (57%) had the full triad of neurologic, thyroid, and respiratory manifestations, but five (24%) had only pulmonary symptoms at the time of presentation. Recurrent respiratory infections were a prominent feature in nine subjects. Lung histopathology demonstrated evidence of disrupted surfactant homeostasis in the majority of cases, and at least five cases had evidence of disrupted lung growth. Conclusions: Patients with mutations in NKX2-1 may present with pulmonary manifestations in the newborn period or during childhood when thyroid or neurologic abnormalities are not apparent. Surfactant dysfunction and, in more severe cases, disrupted lung development are likely mechanisms for the respiratory disease. PMID:23430038

Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1.

PubMed

Hamvas, Aaron; Deterding, Robin R; Wert, Susan E; White, Frances V; Dishop, Megan K; Alfano, Danielle N; Halbower, Ann C; Planer, Benjamin; Stephan, Mark J; Uchida, Derek A; Williames, Lee D; Rosenfeld, Jill A; Lebel, Robert Roger; Young, Lisa R; Cole, F Sessions; Nogee, Lawrence M

2013-09-01

Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome. To characterize the spectrum of associated pulmonary phenotypes, we identified individuals with mutations in NKX2-1 whose primary manifestation was respiratory disease. Retrospective and prospective approaches identified infants and children with unexplained diffuse lung disease for NKX2-1 sequencing. Histopathologic results and electron micrographs were assessed, and immunohistochemical analysis for surfactant-associated proteins was performed in a subset of 10 children for whom lung tissue was available. We identified 16 individuals with heterozygous missense, nonsense, and frameshift mutations and five individuals with heterozygous, whole-gene deletions of NKX2-1. Neonatal RDS was the presenting pulmonary phenotype in 16 individuals (76%), interstitial lung disease in four (19%), and pulmonary fibrosis in one adult family member. Altogether, 12 individuals (57%) had the full triad of neurologic, thyroid, and respiratory manifestations, but five (24%) had only pulmonary symptoms at the time of presentation. Recurrent respiratory infections were a prominent feature in nine subjects. Lung histopathology demonstrated evidence of disrupted surfactant homeostasis in the majority of cases, and at least five cases had evidence of disrupted lung growth. Patients with mutations in NKX2-1 may present with pulmonary manifestations in the newborn period or during childhood when thyroid or neurologic abnormalities are not apparent. Surfactant dysfunction and, in more severe cases, disrupted lung development are likely mechanisms for the respiratory disease.

Unexplained somatic symptoms during major depression: prevalence and clinical impact in a national sample of Italian psychiatric outpatients.

PubMed

Perugi, Giulio; Canonico, Pier Luigi; Carbonato, Paolo; Mencacci, Claudio; Muscettola, Giovanni; Pani, Luca; Torta, Riccardo; Vampini, Claudio; Fornaro, Michele; Parazzini, Fabio; Dumitriu, Arina

2011-01-01

The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. 'Unexplained' somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1-5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment. Copyright © 2011 S. Karger AG, Basel.

The molecular autopsy: an indispensable step following sudden cardiac death in the young?

PubMed Central

Boczek, Nicole J.; Tester, David J.; Ackerman, Michael J.

2013-01-01

Annually thousands of sudden deaths involving young individuals (< 35 years of age) remain unexplained following a complete medicolegal investigation that includes an autopsy. In fact, epidemiological studies have estimated that over half of sudden deaths involving previously healthy young individuals have no morphological abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy, leaving investigators to only speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation, through the use of a cardiological and genetic evaluation of first- or second-degree relatives and/or a molecular autopsy, may pinpoint the underlying mechanism attributing to the sudden death and allow for the identification of living family members with the pathogenic substrate that renders them vulnerable to an increased risk for cardiac events, including sudden death. PMID:22993115

Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life

PubMed Central

Ramsdell, John S.

2010-01-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. PMID:22069654

Neurological disease rises from ocean to bring model for human epilepsy to life.

PubMed

Ramsdell, John S

2010-07-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages.

A Review of Neurogenic Stunned Myocardium

PubMed Central

Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

2017-01-01

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. PMID:28875040

The medically unexplained revisited.

PubMed

Eriksen, Thor Eirik; Kirkengen, Anna Luise; Vetlesen, Arne Johan

2013-08-01

Medicine is facing wide-ranging challenges concerning the so-called medically unexplained disorders. The epidemiology is confusing, different medical specialties claim ownership of their unexplained territory and the unexplained conditions are themselves promoted through a highly complicated and sophisticated use of language. Confronting the outcome, i.e. numerous medical acronyms, we reflect upon principles of systematizing, contextual and social considerations and ways of thinking about these phenomena. Finally we address what we consider to be crucial dimensions concerning the landscape of unexplained "matters"; fatigued being, pain-full being and dys-ordered being, all expressive momentums of an aesthetic of resistance.

The usefulness of carotid sinus massage in different patient groups.

PubMed

Kumar, Narasimhan Pradeep; Thomas, Alan; Mudd, Paul; Morris, Robert O; Masud, Tahir

2003-11-01

to determine the positive yield of carotid sinus massage in different patient groups: unexplained syncope, falls, dizziness and controls. observational study. teaching hospital. we studied consecutive patients over the age of 60 years referred to the 'falls clinic' with a history of unexplained syncope, unexplained falls and unexplained dizziness. We also studied asymptomatic control subjects recruited from a general practice register aged 60 years and over. All patients and control subjects underwent a full clinical assessment (comprehensive history and detailed clinical examination including supine and erect blood pressure measurements) and 12-lead electrocardiography. We performed carotid sinus massage in the supine position for 5 seconds separately on both sides followed by repeating the procedure in the upright positions using a motorised tilt table. Heart rate and blood pressure were recorded using a cardiac monitor and digital plethysmography respectively. The test was considered positive if carotid sinus massage produced asystole with more than a 3 second pause (cardioinhibitory type of carotid sinus syndrome), or a fall in systolic blood pressure of more than 50 mmHg in the absence of significant cardioinhibition (vasodepressor type of carotid sinus syndrome) or where there was evidence of both vasodepressor and cardio-inhibition as above (mixed type). we studied 44 asymptomatic control subjects and 221 symptomatic patients (130 with unexplained syncope, 41 with unexplained falls and 50 with unexplained dizziness). In the overall symptomatic patient group, the positive yield (any type of carotid sinus syndrome) was 17.6% (95% CI = 12.7-22.5). The positive yield in men (26.3% (95% CI = 16.4-36.2)) was twice that in women (13.1% (95% CI = 7.6-18.6)) (P = 0.014). Overall any type of carotid sinus syndrome was present in 22.3% (n = 29) of the syncope group, 17.1% (n = 7) in the unexplained fallers group and 6% (n = 3) in the dizziness group. We also found that no women with unexplained dizziness had a positive carotid sinus massage test. None of the controls demonstrated a positive response. None of the subjects suffered any complications during or after the test. the positive yield of carotid sinus massage in symptomatic patients was 17.6% with the yield in men being twice that in women. None of the asymptomatic control subjects demonstrated a positive response. The yields in unexplained syncope and unexplained falls patients were around 4-fold and 3-fold higher respectively than in unexplained dizziness patients. The positive yield in women with unexplained dizziness (without a definite history of syncope and falls) is zero. Hence, carotid sinus massage in older adults should particularly be targeted at patients with unexplained syncope and unexplained falls.

Comorbid Normal Pressure Hydrocephalus with Parkinsonism: A Clinical Challenge and Call for Awareness.

PubMed

Cucca, A; Biagioni, M C; Sharma, K; Golomb, J; Gilbert, R M; Di Rocco, A; Fleisher, J E

2018-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson's disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.

A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis.

PubMed

Häusler, Martin; Aksoy, Ayse; Alber, Michael; Altunbasak, Sakir; Angay, Aydan; Arsene, Oana Tarta; Craiu, Dana; Hartmann, Hans; Hiz-Kurul, Semra; Ichiyama, Takashi; Iliescu, Catrinel; Jocic-Jakubi, Bosanka; Korinthenberg, Rudolf; Köse, Gülsen; Lukban, Marissa B; Ozkan, Mehpare; Patcheva, Iliyana; Teichler, Jens; Vintan, Mihaela; Yaramis, Ahmet; Yarar, Coskun; Yis, Uluc; Yuksel, Deniz; Anlar, Banu

2015-12-01

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome. Georg Thieme Verlag KG Stuttgart · New York.

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.

PubMed

Guthrie, T C; Nelson, D A

1995-03-01

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures. Over 80% of MS patients develop a panoply of neurological signs during hyperthermia, 60% of which are "new" to that patient. The literature contains a number of unexplained paradoxical responses of MS patients during induced hyperthermia. These challenge the current hypothesis that, in MS, hyperthermia induces a heat-linked neuro-blockade of partially demyelinated axons. Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending. Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent neurological deficits after hyperthermia. The etiology of HR may be multifactorial. This includes heat itself, effects of serum calcium, blockade of ion channels, circulatory changes, heat shock proteins, and unidentified humoral substances. Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of demyelination.

Somatic complications of epilepsy surgery over 25 years at a single center.

PubMed

Gooneratne, Inuka K; Mannan, Shahidul; de Tisi, Jane; Gonzalez, Juan C; McEvoy, Andrew W; Miserocchi, Anna; Diehl, Beate; Wehner, Tim; Bell, Gail S; Sander, Josemir W; Duncan, John S

2017-05-01

Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. We reviewed the prospectively maintained records of adults who underwent epilepsy surgery at our center between 1990 and 2014 to identify peri/postsurgical adverse events. These were categorized into neurological deficits and those related to surgery (e.g. wound infections). Neurological deficits were categorized as expected or unexpected and into transient (≤3 months) or persistent (>3 months), RESULTS: There were 911 procedures with no peri-operative deaths. Persistent neurological adverse events were seen following 157 (17.2%) procedures. The most common persistent expected complication was quadrantanopia after temporal lobe resections (72/764, 9.4%). Unexpected persistent neurological complications occurred in 20 procedures (2.2%) and included: quadrantanopia (6, 0.7%); hemianopia (2, 0.2%); hemi/mono-paresis/sensory loss (9, 1%); dysphasia (10, 1%); frontalis muscle weakness (2, 0.2%); and oculomotor weakness (1, 0.1%). 106 surgery related adverse events occurred in 83 procedures, with severe infections requiring bone-flap removal in 24 (2.6%) procedures and intracranial infections in 8 (0.9%). The risk of post-resective severe infection increased by 4 fold (OR 4.32, 95% CI 2.1-8.9, p<0.001) with use of subdural EEG monitoring prior to resection. In consequence, in August 2011 we introduced antibiotic coverage in all individuals undergoing intracranial monitoring. Also, after August 2011 there was greater use of Stereo-EEG (SEEG) than subdural (OR 9.0 CI 0.36-224.2, p=0.18ns). One complicated by severe infection. Other surgical complications included haematoma (0.3%), hydrocephalus (0.3%) and CSF leak (1.2%). None had permanent complications. Adverse event rates are similar to other series. Epilepsy surgery carries well defined surgical and neurological risks. The risks of somatic adverse events, in addition to neuropsychiatric and neuropsychological complications need to be made clear to individuals considering this treatment option. Copyright © 2017 Elsevier B.V. All rights reserved.

Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke

PubMed Central

Coulombe, Janie; Li, Linxin; Ganesh, Aravind; Silver, Louise; Rothwell, Peter M.

2017-01-01

Background and Purpose— Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap. Methods— Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale. Results— Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12–1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36–1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90–1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82–1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke. Conclusions— We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies. PMID:28798261

Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke.

PubMed

Renoux, Christel; Coulombe, Janie; Li, Linxin; Ganesh, Aravind; Silver, Louise; Rothwell, Peter M

2017-10-01

Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap. Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale. Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12-1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36-1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90-1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82-1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke. We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies. Copyright © 2017 The Author(s).

Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation

PubMed Central

Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano

2016-01-01

Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive—Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post—Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. Conclusions: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper. PMID:26924998

Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

PubMed

Castelnuovo, Gianluca; Giusti, Emanuele M; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A M; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G; Wiederhold, Brenda; Tamburin, Stefano

2016-01-01

It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper.

Causality Assessment of Serious Neurologic Adverse Events Following 2009 H1N1 Vaccination

PubMed Central

Williams, S Elizabeth; Pahud, Barbara A; Vellozzi, Claudia; Donofrio, Peter D; Dekker, Cornelia L; Halsey, Neal; Klein, Nicola P; Baxter, Roger P; Marchant, Colin D; LaRussa, Philip S; Barnett, Elizabeth D; Tokars, Jerome I; McGeeney, Brian E; Sparks, Robert C; Aukes, Laurie L.; Jakob, Kathleen; Coronel, Silvia; Sejvar, James J; Slade, Barbara A; Edwards, Kathryn M

2016-01-01

Background Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009–10 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) Network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. Methods Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1st 2009 and March 31st 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. Results 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as “possibly” related (33%), 108 as “unlikely” related (51%), and 20 as “unrelated” (9%) to H1N1 vaccination; none were classified as “probable” or “definite” and 12 were unclassifiable (6%). Conclusion The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment. PMID:21893148

Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders.

PubMed

Espay, Alberto J; Aybek, Selma; Carson, Alan; Edwards, Mark J; Goldstein, Laura H; Hallett, Mark; LaFaver, Kathrin; LaFrance, W Curt; Lang, Anthony E; Nicholson, Tim; Nielsen, Glenn; Reuber, Markus; Voon, Valerie; Stone, Jon; Morgante, Francesca

2018-06-04

Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, unnecessary and costly evaluations, and poor outcomes. Functional Neurological Symptom Disorder/Conversion Disorder was adopted by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, replacing the term psychogenic with functional and removing the criterion of psychological stress as a prerequisite for FND. A diagnosis can now be made in an inclusionary manner by identifying neurological signs that are specific to FNDs without reliance on presence or absence of psychological stressors or suggestive historical clues. The new model highlights a wider range of past sensitizing events, such as physical trauma, medical illness, or physiological/psychophysiological events. In this model, strong ideas and expectations about these events correlate with abnormal predictions of sensory data and body-focused attention. Neurobiological abnormalities include hypoactivation of the supplementary motor area and relative disconnection with areas that select or inhibit movements and are associated with a sense of agency. Promising evidence has accumulated for the benefit of specific physical rehabilitation and psychological interventions alone or in combination, but clinical trial evidence remains limited. Functional neurological disorders are a neglected but potentially reversible source of disability. Further research is needed to determine the dose and duration of various interventions, the value of combination treatments and multidisciplinary therapy, and the therapeutic modality best suited for each patient.

[Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma].

PubMed

Cauro, F; Houtteville, J P; Mesnil, J L; Guarnieri, J

2002-03-01

Juvenile xanthogranuloma is one of the most common non-langerhan cell histiocytoses in children. Usually cutaneous, there are disseminated forms. However, neurological localizations remain exceptional. We report the case of a cerebellar localization, associated with cutaneous and pulmonary lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was associated with vinblastin chemotherapy, that led to total regression of the cutaneous and pulmonary lesions, neurological stabilization, without recurrence on the control IRM, after a period of 7 years. This is the second reported case of histologically documented cerebellar juvenile xanthogranuloma. In the event of cutaneous juvenile xanthogranuloma, the neurological examination must be attentive and supplemented, in case of any suspicion, by medical imaging. We believe that surgical treatment of neurological juvenile xanthogranuloma is necessary, in the event of symptomatic lesions and accessible to surgery. No consensus has been reached on subsequent treatments (radiotherapy, chemotherapy) and must be discussed according to the clinical profile and data in the literature.

The clinical spectrum of unruptured intracranial aneurysms.

PubMed

Raps, E C; Rogers, J D; Galetta, S L; Solomon, R A; Lennihan, L; Klebanoff, L M; Fink, M E

1993-03-01

A retrospective study was performed to delineate the clinical characteristics of symptomatic unruptured aneurysms. Patient histories, operative reports, and angiograms in 111 patients with 132 unruptured aneurysms were reviewed. Tertiary care university hospital. One hundred eleven patients with 132 unruptured intracranial aneurysms were studied. There were 85 women and 26 men, with a mean age of 51.2 years (age range, 11 to 77 years). Many patients were referred by community neurologists and neurosurgeons for further evaluation and neurosurgical management. Fifty-four symptomatic patients were identified. Group 1 (n = 19; mean aneurysm diameter, 2.1 cm) had acute symptoms: ischemia (n = 7), headache (n = 7), seizure (n = 3), and cranial neuropathy (n = 2). Group 2 (n = 35; mean aneurysm diameter, 2.2 cm) had chronic symptoms attributed to mass effect: headache (n = 18), visual loss (n = 10), pyramidal tract dysfunction (n = 4), and facial pain (n = 3). Group 3 (n = 57; mean aneurysm diameter, 1.1 cm) had asymptomatic aneurysms. Acute severe headache, comparable to subarachnoid hemorrhage headache, but without nuchal rigidity, was associated with the following mechanisms: aneurysm thrombosis, localized meningeal inflammation, and unexplained. Unruptured aneurysms may be misdiagnosed as optic neuritis or migraine, or serve as a nidus for cerebral thromboembolic events. Internal carotid artery and posterior circulation aneurysms were more likely to cause focal symptoms from mass effect than were anterior cerebral artery and middle cerebral artery aneurysms. Weeks to years may elapse before their diagnosis. The absence of subarachnoid blood does not exclude an aneurysm as a cause for acute or chronic neurologic symptoms.

Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry

PubMed Central

Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Kenny, Michael J.; Inder, Terrie; Pfister, Robert H.; Raju, Tonse; Soll, Roger F.

2012-01-01

BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. OBJECTIVES: To identify antecedents in a large registry of infants who had NE. METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of ≥36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of ≤3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of ≥37.5°C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained. PMID:23071210

Neurologic dysfunction in hypothyroid, hyperlipidemic Labrador Retrievers.

PubMed

Vitale, Christina L; Olby, Natasha J

2007-01-01

Hypothyroidism has been associated with a variety of neurologic signs, but the mechanism for this association is not completely understood. Hypothyroidism also is associated with hyperlipidemia that predisposes to atherosclerosis, increased blood viscosity, and thromboembolic events. The objective is to characterize neurologic signs potentially associated with hyperlipidemia and atherosclerosis in canine hypothyroidism. This study used dogs referred to North Carolina State University Veterinary Teaching Hospital for evaluation of neurologic signs. A retrospective study was conducted in which medical records of dogs with neurologic signs and a diagnosis of hypothyroidism and hyperlipidemia were reviewed. Details of the history, presenting signs, results of routine blood tests, thyroid tests, cerebrospinal fluid (CSF) analysis and diagnostic imaging, and response to therapy were compiled. Three Labrador Retrievers and one Labrador Retriever cross fit the inclusion criteria. All dogs were hypothyroid and severely hyperlipidemic. Neurologic signs included tetraparesis, central and peripheral vestibular signs, facial paralysis, and paraparesis. Two dogs had an acute history and rapid resolution of signs consistent with an infarct, the presence of which was confirmed in 1 of the dogs by magnetic resonance imaging. Two dogs had chronic histories of cranial neuropathies and paraparesis. One of these dogs had evidence of iliac thrombosis and atherosclerosis on ultrasound examination. All dogs improved with thyroid hormone supplementation. Labrador Retrievers may be predisposed to the development of severe hyperlipidemia in association with hypothyroidism. One possible consequence of severe hyperlipidemia is the development of neurologic signs due to atherosclerosis and thromboembolic events.

Neurologic Complications in Infective Endocarditis

PubMed Central

Morris, Nicholas A.; Matiello, Marcelo; Samuels, Martin A.

2014-01-01

Neurologic complications of infective endocarditis (IE) are common and frequently life threatening. Neurologic events are not always obvious. The prediction and management of neurologic complications of IE are not easily approached algorithmically, and the impact they have on timing and ability to surgically repair or replace the affected valve often requires a painstaking evaluation and joint effort across multiple medical disciplines in order to achieve the best possible outcome. Although specific recommendations are always tailored to the individual patient, there are some guiding principles that can be used to help direct the decision-making process. Herein, we review the pathophysiology, epidemiology, manifestations, and diagnosis of neurological complications of IE and further consider the impact they have on clinical decision making. PMID:25360207

Fibromyalgia and seizures.

PubMed

Tatum, William O; Langston, Michael E; Acton, Emily K

2016-06-01

The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described.

Multi-Center Retrospective Evaluation of Screw and Polymethylmethacrylate Constructs for Atlantoaxial Fixation in Dogs.

PubMed

Stout Steele, Megan W; Hodshon, Amy W; Hopkins, Andrew L; Tracy, Gaemia M; Cohen, Noah D; Kerwin, Sharon C; Boudreau, C Elizabeth; Thomas, William B; Mankin, Joseph M; Levine, Jonathan M

2016-10-01

To evaluate outcome and adverse events following ventral stabilization of the atlantoaxial (AA) joint in dogs with clinical AA subluxation using screw/polymethymethacrylate (PMMA) constructs in a retrospective, multi-center cohort study. Historical cohort study. 35 client-owned dogs. Medical records from 3 institutions were reviewed to identify dogs with AA subluxation treated with ventral screw and PMMA constructs. Data on signalment, pre- and postoperative neurologic status, imaging performed, and adverse events were retrieved. Neurologic examination data were abstracted to generate a modified Frankel score at admission, discharge, and re-examination. Telephone interview of owners >180 days postoperative was conducted. Thirty-five dogs with AA subluxation treated with ventral screw/PMMA constructs were included. Most dogs were young (median age 1 year), small breed dogs with acute onset of neurologic signs (median duration 22.5 hours). Most dogs were non-ambulatory at the time of admission (median modified Frankel score 3). Adverse events were identified in 15/35 dogs including 9 dogs with major adverse events. Four dogs required a second surgery due to vertebral canal violation (n = 2) or implant failure (n = 2). Re-examination at 4-6 weeks postoperative reported 15/28 dogs with improved neurologic status and 19/28 dogs were ambulatory. Telephone follow-up was available for 23/35 dogs with 23/23 reported as ambulatory (median follow-up 390 days). Ventral application of screw and PMMA constructs for AA subluxation, as described here, is associated with clinical improvement in the majority of dog. Major adverse events are infrequent and the technique is considered relatively safe. © Copyright 2016 by The American College of Veterinary Surgeons.

Altered autonomic nervous system activity in women with unexplained recurrent pregnancy loss.

PubMed

Kataoka, Kumie; Tomiya, Yumi; Sakamoto, Ai; Kamada, Yasuhiko; Hiramatsu, Yuji; Nakatsuka, Mikiya

2015-06-01

Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL). Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale. The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups. The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Suffocation and poisoning--the hard-hitting side of Munchausen syndrome by proxy.

PubMed

Vennemann, B; Bajanowski, T; Karger, B; Pfeiffer, H; Köhler, H; Brinkmann, B

2005-03-01

Munchausen syndrome by proxy (MSBP) is a severe and difficult to diagnose form of child abuse characterised by the simulation, aggravation or production of symptoms of illness in a child by an adult. MSBP often leads to multiple hospitalisations and has a high mortality and long-term morbidity. This study describes the cases of 5 families with 8 children affected who presented with unexplained neurological or gastrointestinal symptoms or even loss of consciousness. All were victims of poisoning or suffocation by their mothers. Two of those children died and were initially diagnosed as SIDS or natural death, respectively. They were only recognised as MSBP victims after another sibling had fallen ill with similar symptoms. The cases are discussed in consideration of the relevant literature. In addition warning signs of this forensically relevant syndrome and a strategy for the management of suspected MSBP cases are described.

Degos disease: a new simulator of non-accidental injury.

PubMed

Moss, Celia; Wassmer, Evangeline; Debelle, Geoff; Hackett, Scott; Goodyear, Helen; Malcomson, Roger; Ryder, Clive; Sgouros, Spyros; Shahidullah, Hossain

2009-08-01

Recent high-profile cases have made paediatricians very aware of the serious implications of either missing or wrongly diagnosing non-accidental injury. Subdural fluid collections in non-mobile infants usually represent haemorrhage caused by non-accidental injury. We report a 6-month-old male who presented to the Accident and Emergency Department of Birmingham Heartlands Hospital with bilateral subdural fluid collections and skin ulcers resembling cigarette burns. Non-accidental injury was considered to be the most likely diagnosis. However, while under observation in hospital, the child's neurological condition deteriorated with progressive cerebral infarctions, and serial photographs of the skin lesions showed failure to heal. The revised diagnosis, confirmed histologically, was Degos disease, an extremely rare and often fatal occlusive vasculopathy. The child was treated palliatively and died 8 weeks after presentation. This report informs doctors of a new simulator of non-accidental injury to be considered in infants with otherwise unexplained subdural fluid collections.

Niemann-Pick type B in adulthood.

PubMed

Simões, Rita Gonçalves; Maia, Helena

2015-02-05

Niemann-Pick disease (NPD) is a rare group of autosomal recessive disorders associated with intracellular deposition of sphingomyelin. NPD type B is a milder form, generally later in onset, with a good prognosis for survival into adulthood and usually with no neurological abnormalities. The authors describe the case of a 52-year-old man who presented with unexplained pancytopenia and splenomegaly. He was admitted to emergency splenectomy due to pathological splenic rupture. The histological findings showed diffuse histiocytosis, suggesting lysosomal storage disease. The NPD was confirmed when residual activity of acid sphingomyelinase in peripheral blood leucocytes and cultured skin fibroblasts was detected. Besides lipid abnormalities, the patient also had lipid interstitial pneumonia. There is no treatment for NPD. Management is based on surveillance and supportive care. The patient has reached the sixth decade of life with no symptoms and, despite the pneumonia and splenectomy, he still has a fairly healthy life. 2015 BMJ Publishing Group Ltd.

Overtraining Syndrome

PubMed Central

Kreher, Jeffrey B.; Schwartz, Jennifer B.

2012-01-01

Context: Fatigue and underperformance are common in athletes. Understanding overtraining syndrome (OTS) is helpful in the evaluation, management, and education of athletes. Evidence Acquisition: Relevant articles in English were searched with OVID (1948-2011) and PubMed using the following keywords: overtraining syndrome, overtraining, overreaching, unexplained underperformance, staleness, pathophysiology, management, treatment, evaluation. Bibliographies were reviewed for additional resources. Results: OTS appears to be a maladapted response to excessive exercise without adequate rest, resulting in perturbations of multiple body systems (neurologic, endocrinologic, immunologic) coupled with mood changes. Many hypotheses of OTS pathogenesis are reviewed, and a clinical approach to athletes with possible OTS (including history, testing, and prevention) is presented. Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS. PMID:23016079

Alligator diet in relation to alligator mortality on Lake Griffin, FL

USGS Publications Warehouse

Rice, A.N.; Ross, J.P.; Woodward, A.R.; Carbonneau, D.A.; Percival, H.F.

2007-01-01

Alligator mississippiensis (American Alligators) demonstrated low hatch-rate success and increased adult mortality on Lake Griffin, FL, between 1998 and 2003. Dying Lake Griffin alligators with symptoms of poor motor coordination were reported to show specific neurological impairment and brain lesions. Similar lesions were documented in salmonines that consumed clupeids with high thiaminase levels. Therefore, we investigated the diet of Lake Griffin alligators and compared it with alligator diets from two lakes that exhibited relatively low levels of unexplained alligator mortality to see if consumption of Dorosoma cepedianum (gizzard shad) could be correlated with patterns of mortality. Shad in both lakes Griffin and Apopka had high levels of thiaminase and Lake Apopka alligators were consuming greater amounts of shad relative to Lake Griffin without showing mortality rates similar to Lake Griffin alligators. Therefore, a relationship between shad consumption alone and alligator mortality is not supported.

Building-associated neurological damage modeled in human cells: a mechanism of neurotoxic effects by exposure to mycotoxins in the indoor environment.

PubMed

Karunasena, Enusha; Larrañaga, Michael D; Simoni, Jan S; Douglas, David R; Straus, David C

2010-12-01

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.

Weight loss and decubitus duodenal ulcer in Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion.

PubMed

Martino, Tommaso; Melchionda, Donato; Tonti, Paolo; De Francesco, Vincenzo; Lalla, Alessandra; Specchio, Luigi Maria; Avolio, Carlo

2016-12-01

Apparently, unexplained weight loss is a common symptom experienced by patients affected by Parkinson's disease, especially in those treated by levodopa-carbidopa infusion gel (LCIG) with a poor control of dyskinesias. Weight loss is considered part of gastrointestinal dysfunction seen in patients affected by Parkinson's disease, along with gastroparesis and reduced bowel peristalsis. In patients treated with LCIG, weight loss needs to be accurately evaluated, because of possible underlying life-threatening adverse events, like duodenum decubitus ulcer.

Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit.

PubMed

Honey, Brooke L; Harrison, Donald L; Gormley, Andrew K; Johnson, Peter N

2010-01-01

Dexmedetomidine is an α(2)-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events. Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose. Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events. Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

Our experience with the aetiological diagnosis of global developmental delay and intellectual disability: 2006-2010.

PubMed

López-Pisón, J; García-Jiménez, M C; Monge-Galindo, L; Lafuente-Hidalgo, M; Pérez-Delgado, R; García-Oguiza, A; Peña-Segura, J L

2014-09-01

Global developmental delay (GDD) and intellectual disability (ID) are common reasons for consultation in paediatric neurology. Results from aetiological evaluations of children with GDD/ID vary greatly, and consequently, there is no universal consensus regarding which studies should be performed. We review our experience with determining aetiological diagnoses for children with GDD/ID who were monitored by the paediatric neurology unit over the 5-year period between 2006 and 2010. During the study period, 995 children with GDD/ID were monitored. An aetiological diagnosis was established for 309 patients (31%), but not in 686 (69%), despite completing numerous tests. A genetic cause was identified in 142 cases (46% of the total aetiologies established), broken down as 118 cases of genetic encephalopathy and 24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile spasms/West syndrome, or visual deficit, but more difficult in cases of autism spectrum disorders. Genetic studies provide an increasing number of aetiological diagnoses, and they are also becoming the first step in diagnostic studies. Array CGH (microarray-based comparative genomic hybridisation) is the genetic test with the highest diagnostic yield in children with unexplained GDD/ID. The cost-effectiveness of complementary studies seems to be low if there are no clinically suspected entities. However, even in the absence of treatment, aetiological diagnosis is always important in order to provide genetic counselling and possible prenatal diagnosis, resolve family (and doctors') queries, and halt further diagnostic studies. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies.

PubMed

Yarmohammadi, Hale; Cunningham-Rundles, Charlotte

2017-10-01

Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. To describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. In a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. Twenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7-76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm 3 (range 4-294/mm 3 ) and 219 ± 258/mm 3 (range 7-630/mm 3 ), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. The pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Acoustic reflectors are visible in the right heart during radiofrequency ablation of varicose veins.

PubMed

Sounderajah, V; Moore, H M; Thapar, A; Lane, T R A; Fox, K; Franklin, I J; Davies, A H

2015-09-01

Cerebrovascular events have been noted after foam sclerotherapy for varicose veins. One hypothesis is migration of microemboli to the brain through a cardiac septal defect. The aim of this study was to identify whether acoustic reflectors are found in the right side of the heart during radiofrequency ablation of varicose veins, as neurological events are not reported during these procedures. Transthoracic echocardiography was performed during local anaesthetic radiofrequency ablation (VNUS ClosureFast) of the great saphenous vein in 14 patients. An apical view was captured at the start of the procedure, during each cycle of heating and at 1 min post-treatment. Patients were monitored for 1 h. Video loops were read by an independent cardiologist. The presence of acoustic reflectors was classified as: 0 = absent, 1 = occasional, 2 = stream, 3 = complete opacification. Loops were of diagnostic quality in 11/14 (79%) patients. After the second cycle of heating, acoustic reflectors moving through the right heart were seen in 5/11 (45%) patients. These were classified as grade 1 in four patients and grade 2 in one patient. No acoustic reflectors were seen in the left heart. No neurological symptoms were reported. Acoustic reflectors in the right heart are a common finding during radiofrequency ablation of varicose veins. Considering the prevalence of cardiac septal defects (17%), more neurological events would be expected if these particles were indeed responsible for these events. Further work is required to elicit the mechanisms underlying neurological complications following sclerotherapy. © The Author(s) 2014.

Neurologic adverse events associated with smallpox vaccination in the United States – response and comment on reporting of headaches as adverse events after smallpox vaccination among military and civilian personnel

PubMed Central

Schumm, Walter R

2006-01-01

Background Accurate reporting of adverse events occurring after vaccination is an important component of determining risk-benefit ratios for vaccinations. Controversy has developed over alleged underreporting of adverse events within U.S. military samples. This report examines the accuracy of adverse event rates recently published for headaches, and examines the issue of underreporting of headaches as a function of civilian or military sources and as a function of passive versus active surveillance. Methods A report by Sejvar et al was examined closely for accuracy with respect to the reporting of neurologic adverse events associated with smallpox vaccination in the United States. Rates for headaches were reported by several scholarly sources, in addition to Sejvar et al, permitting a comparison of reporting rates as a function of source and type of surveillance. Results Several major errors or omissions were identified in Sejvar et al. The count of civilian subjects vaccinated and the totals of both civilians and military personnel vaccinated were reported incorrectly by Sejvar et al. Counts of headaches reported in VAERS were lower (n = 95) for Sejvar et al than for Casey et al (n = 111) even though the former allegedly used 665,000 subjects while the latter used fewer than 40,000 subjects, with both using approximately the same civilian sources. Consequently, rates of nearly 20 neurologic adverse events reported by Sejvar et al were also incorrectly calculated. Underreporting of headaches after smallpox vaccination appears to increase for military samples and for passive adverse event reporting systems. Conclusion Until revised or corrected, the rates of neurologic adverse events after smallpox vaccinated reported by Sejvar et al must be deemed invalid. The concept of determining overall rates of adverse events by combining small civilian samples with large military samples appears to be invalid. Reports of headaches as adverse events after smallpox vaccination appear to be have occurred much less frequently using passive surveillance systems and by members of the U.S. military compared to civilians, especially those employed in healthcare occupations. Such concerns impact risk-benefit ratios associated with vaccines and weigh against making vaccinations mandatory, without informed consent, even among military members. Because of the issues raised here, adverse event rates derived solely or primarily from U.S. Department of Defense reporting systems, especially passive surveillance systems, should not be used, given better alternatives, for making public health policy decisions. PMID:17096855

Hypoxic Adaptation during Development: Relation to Pattern of Neurological Presentation and Cognitive Disability

ERIC Educational Resources Information Center

Kirkham, Fenella J.; Datta, Avijit K.

2006-01-01

Children with acute hypoxic-ischaemic events (e.g. stroke) and chronic neurological conditions associated with hypoxia frequently present to paediatric neurologists. Failure to adapt to hypoxia may be a common pathophysiological pathway linking a number of other conditions of childhood with cognitive deficit. There is evidence that congenital…

Analysis of Wind Tunnel Polar Replicates Using the Modern Design of Experiments

NASA Technical Reports Server (NTRS)

Deloach, Richard; Micol, John R.

2010-01-01

The role of variance in a Modern Design of Experiments analysis of wind tunnel data is reviewed, with distinctions made between explained and unexplained variance. The partitioning of unexplained variance into systematic and random components is illustrated, with examples of the elusive systematic component provided for various types of real-world tests. The importance of detecting and defending against systematic unexplained variance in wind tunnel testing is discussed, and the random and systematic components of unexplained variance are examined for a representative wind tunnel data set acquired in a test in which a missile is used as a test article. The adverse impact of correlated (non-independent) experimental errors is described, and recommendations are offered for replication strategies that facilitate the quantification of random and systematic unexplained variance.

A "Neurological Emergency Trolley" reduces turnaround time for high-risk medications in a general intensive care unit.

PubMed

Ajzenberg, Henry; Newman, Paula; Harris, Gail-Anne; Cranston, Marnie; Boyd, J Gordon

2018-02-01

To reduce medication turnaround times during neurological emergencies, a multidisciplinary team developed a neurological emergency crash trolley in our intensive care unit. This trolley includes phenytoin, hypertonic saline and mannitol, as well as other equipment. The aim of this study was to assess whether the cart reduced turnaround times for these medications. In this retrospective cohort study, medication delivery times for two year epochs before and after its implementation were compared. Eligible patients were identified from our intensive care unit screening log. Adults who required emergent use of phenytoin, hypertonic saline or mannitol while in the intensive care unit were included. Groups were compared with nonparametric analyses. 33-bed general medical-surgical intensive care unit in an academic teaching hospital. Time to medication administration. In the pre-intervention group, there were 43 patients with 66 events. In the post-intervention group, there were 45 patients with 80 events. The median medication turnaround time was significantly reduced after implementation of the neurological emergency trolley (25 vs. 10minutes, p=0.003). There was no statistically significant difference in intensive care or 30-day survival between the two cohorts. The implementation of a novel neurological emergency crash trolley in our intensive care unit reduced medication turnaround times. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2011-07-01

To assess the reporting rates of serious adverse events attributable to yellow fever vaccination with 17D and 17DD strains as reported in pharmacovigilance databases, and assess reasons for differences in reporting rates. We searched 9 electronic databases for peer reviewed and grey literature (government reports, conferences), in all languages. Reference lists of key studies were also reviewed to identify additional studies. We identified 2,415 abstracts, of which 472 were selected for full text review. We identified 15 pharmacovigilance databases which reported adverse events attributed to yellow fever vaccination, of which 10 contributed data to this review with about 107,600,000 patients (allowing for overlapping time periods for the studies of the US VAERS database), and the data are very heavily weighted (94%) by the Brazilian database. The estimates of serious adverse events form three groups. The estimates for Australia were low at 0/210,656 for "severe neurological disease" and 1/210,656 for YEL-AVD, and also low for Brazil with 9 hypersensitivity events, 0.23 anaphylactic shock events, 0.84 neurologic syndrome events and 0.19 viscerotropic events cases/million doses. The five analyses of partly overlapping periods for the US VAERS database provide an estimate of 3.6/cases per million YEL-AND in one analysis and 7.8 in another, and 3.1 YEL-AVD in one analysis and 3.9 in another. The estimates for the UK used only the inclusive term of "serious adverse events" not further classified into YEL-And or YEL-AND and reported 34 "serious adverse events." The Swiss database used the term "serious adverse events" and reported 7 such events (including 4 "neurologic reactions") for a reporting rate of 25 "serious adverse events"/million doses. Reporting rates for serious adverse events following yellow fever vaccination are low. Differences in reporting rates may be due to differences in definitions, surveillance system organisation, methods of reporting cases, administration of YFV with other vaccines, incomplete information about denominators, time intervals for reporting events, the degree of passive reporting, access to diagnostic resources, and differences in time periods of reporting.

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

PubMed

Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

2016-07-13

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

Conversion, Factitious Disorder and Malingering: A Distinct Pattern or a Continuum?

PubMed

Galli, Silvio; Tatu, Laurent; Bogousslavsky, Julien; Aybek, Selma

2018-01-01

This chapter is aimed at highlighting the recent findings concerning physiopathology, diagnosis, and management of conversion, factitious disorder, and malingering. Conversion disorder is the unintentional production of neurological symptom, whereas malingering and factitious disorder represent the voluntary production of symptoms with internal or external incentives. They have a close history and this has been frequently confounded. Practitioners are often confronted to medically unexplained symptoms; they represent almost 30% of neurologist's consultation. The first challenge is to detect them, and recent studies have confirmed the importance of "positive" clinical bedside signs based on incoherence and discordance, such as the Hoover's sign for the diagnosis of conversion disorder. Functional neuroimaging has allowed a better understanding of the pathophysiology, and highlighted abnormal cerebral activation patterns in conversion disorder in relation to motor, emotional, and limbic networks, different from feigners. This supports the theory evoked by Charcot of a "psychodynamic lesion," which is also reflected by the new term introduced in the DSM-5: functional neurological disorder. Multidisciplinary therapy is recommended with behavioral cognitive therapy, antidepressant to treat frequent comorbid anxiety or depression, and physiotherapy. Factitious disorder and malingering should be clearly delineated from conversion disorder. Factitious disorder should be considered as a mental illness and more research on its physiopathology and treatment is needed, when malingering is a non-medical condition encountered in medico-legal cases. © 2018 S. Karger AG, Basel.

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial

PubMed Central

2013-01-01

Background Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Methods Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Results Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Conclusions Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. Trial registration ISRCTN69856593 PMID:23496872

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

PubMed

Maitland, Kathryn; George, Elizabeth C; Evans, Jennifer A; Kiguli, Sarah; Olupot-Olupot, Peter; Akech, Samuel O; Opoka, Robert O; Engoru, Charles; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Brent, Bernadette; Nteziyaremye, Julius; Mpoya, Ayub; Prevatt, Natalie; Dambisya, Cornelius M; Semakula, Daniel; Ddungu, Ahmed; Okuuny, Vicent; Wokulira, Ronald; Timbwa, Molline; Otii, Benedict; Levin, Michael; Crawley, Jane; Babiker, Abdel G; Gibb, Diana M

2013-03-14

Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. ISRCTN69856593.

Pancreatic Cancer in Pregnancy Presenting with Thromboembolic Events: Case Report and Review of the Literature.

PubMed

Wakefield, Brian W; Masterson, Crystal M C; Borges, Manuel T; Hurt, K Joseph

2018-06-08

Stroke and hepatic vein thrombosis are highly associated with neoplasia but are extremely rare events in young, pregnant women. Rare and recurrent thrombotic events in pregnancy increase the suspicion for occult malignancy. We describe the case of a healthy 31-year-old G2P1 who presented with visual changes and dysarthria during pregnancy. Imaging showed cerebral infarcts. Her thrombophilia evaluation was negative. During delivery, she was diagnosed with fulminant Budd-Chiari Syndrome. Hepatic ultrasound suggested malignancy or metastasis, and postpartum CT scan and biopsy confirmed the diagnosis of Stage IV pancreatic cancer. Although rare in pregnancy, a new diagnosis of malignancy should be considered in patients with recurrent unexplained hypercoagulable complications. We propose an evidence-based algorithm for evaluation of occult malignancy in pregnancy based upon this case and review of the literature. © 2018 S. Karger AG, Basel.

Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion.

PubMed

Talavage, Thomas M; Nauman, Eric A; Breedlove, Evan L; Yoruk, Umit; Dye, Anne E; Morigaki, Katherine E; Feuer, Henry; Leverenz, Larry J

2014-02-15

Head trauma and concussion in football players have recently received considerable media attention. Postmortem evidence suggests that accrual of damage to the brain may occur with repeated blows to the head, even when the individual blows fail to produce clinical symptoms. There is an urgent need for improved detection and characterization of head trauma to reduce future injury risk and promote development of new therapies. In this study we examined neurological performance and health in the presence of head collision events in high school football players, using longitudinal measures of collision events (the HIT(™) System), neurocognitive testing (ImPACT(™)), and functional magnetic resonance imaging MRI (fMRI). Longitudinal assessment (including baseline) was conducted in 11 young men (ages 15-19 years) participating on the varsity and junior varsity football teams at a single high school. We expected and observed subjects in two previously described categories: (1) no clinically-diagnosed concussion and no changes in neurological behavior, and (2) clinically-diagnosed concussion with changes in neurological behavior. Additionally, we observed players in a previously undiscovered third category, who exhibited no clinically-observed symptoms associated with concussion, but who demonstrated measurable neurocognitive (primarily visual working memory) and neurophysiological (altered activation in the dorsolateral prefrontal cortex [DLPFC]) impairments. This new category was associated with significantly higher numbers of head collision events to the top-front of the head, directly above the DLPFC. The discovery of this new category suggests that more players are suffering neurological injury than are currently being detected using traditional concussion-assessment tools. These individuals are unlikely to undergo clinical evaluation, and thus may continue to participate in football-related activities, even when changes in brain physiology (and potential brain damage) are present, which will increase the risk of future neurological injury.

Increased Anti-HSP60 and Anti-HSP70 Antibodies in Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Matsuda, Miwa; Sasaki, Aiko; Shimizu, Keiko; Kamada, Yasuhiko; Noguchi, Soichi; Hiramatsu, Yuji; Nakatsuka, Mikiya

2017-06-01

　Vascular dysfunction has been reported in women with recurrent pregnancy loss (RPL). We investigated the severity of vascular dysfunction in non-pregnant women with RPL and its correlation with anti-heat shock protein (HSP) antibodies that are known to induce arteriosclerosis. We measured the serum anti-HSP60 antibodies, anti-HSP70 antibodies, and anti-phospholipid antibodies (APA) in 68 women with RPL and 29 healthy controls. Among the women with RPL, 14 had a diagnosis of antiphospholipid syndrome (APS), and in the remaining 54, the causes for RPL were unexplained. Compared to the controls, the brachial-ankle pulse wave velocity (baPWV), carotid augmentation index (cAI), and uterine artery pulsatility index (PI) were all significantly higher in the women with both APS and unexplained RPL. Compared to the controls, the anti-HSP60 antibody levels were significantly higher in the APA-positive group of women with unexplained RPL, and the anti-HSP70 antibody levels were significantly higher in APS and APA-positive group of women with unexplained RPL. However, the anti-HSP60 and anti-HSP70 antibody levels did not correlate with the values of baPWV or cAI. Our results demonstrated anti-HSP60 and anti-HSP70 antibodies are increased in women with unexplained RPL. Further studies are needed to elucidate the roles of anti-HSP antibodies and their pathophysiology in unexplained RPL.

Self-imagining enhances recognition memory in memory-impaired individuals with neurological damage.

PubMed

Grilli, Matthew D; Glisky, Elizabeth L

2010-11-01

The ability to imagine an elaborative event from a personal perspective relies on several cognitive processes that may potentially enhance subsequent memory for the event, including visual imagery, semantic elaboration, emotional processing, and self-referential processing. In an effort to find a novel strategy for enhancing memory in memory-impaired individuals with neurological damage, we investigated the mnemonic benefit of a method we refer to as self-imagining-the imagining of an event from a realistic, personal perspective. Fourteen individuals with neurologically based memory deficits and 14 healthy control participants intentionally encoded neutral and emotional sentences under three instructions: structural-baseline processing, semantic processing, and self-imagining. Findings revealed a robust "self-imagination effect (SIE)," as self-imagination enhanced recognition memory relative to deep semantic elaboration in both memory-impaired individuals, F(1, 13) = 32.11, p < .001, η2 = .71; and healthy controls, F(1, 13) = 5.57, p < .05, η2 = .30. In addition, results indicated that mnemonic benefits of self-imagination were not limited by severity of the memory disorder nor were they related to self-reported vividness of visual imagery, semantic processing, or emotional content of the materials. The findings suggest that the SIE may depend on unique mnemonic mechanisms possibly related to self-referential processing and that imagining an event from a personal perspective makes that event particularly memorable even for those individuals with severe memory deficits. Self-imagining may thus provide an effective rehabilitation strategy for individuals with memory impairment.

Disturbed EEG sleep, paranoid cognition and somatic symptoms identify veterans with post-traumatic stress disorder

PubMed Central

Rothman, Lorne; Kleinman, Robert; Rhind, Shawn G.; Richardson, J. Donald

2016-01-01

Background Chronic post-traumatic stress disorder (PTSD) behavioural symptoms and medically unexplainable somatic symptoms are reported to occur following the stressful experience of military combatants in war zones. Aims To determine the contribution of disordered EEG sleep physiology in those military combatants who have unexplainable physical symptoms and PTSD behavioural difficulties following war-zone exposure. Method This case-controlled study compared 59 veterans with chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and psychological treatments. All had standardised EEG polysomnography, computerised sleep EEG cyclical alternating pattern (CAP) as a measure of sleep stability, self-ratings of combat exposure, paranoid cognition and hostility subscales of Symptom Checklist-90, Beck Depression Inventory and the Wahler Physical Symptom Inventory. Statistical group comparisons employed linear models, logistic regression and chi-square automatic interaction detection (CHAID)-like decision trees. Results Veterans with PTSD were more likely than those without PTSD to show disturbances in non-rapid eye movement (REM) and REM sleep including delayed sleep onset, less efficient EEG sleep, less stage 4 (deep) non-REM sleep, reduced REM and delayed onset to REM. There were no group differences in the prevalence of obstructive sleep apnoeas/hypopnoeas and periodic leg movements, but sleep-disturbed, non-PTSD military had more EEG CAP sleep instability. Rank order determinants for the diagnosis of PTSD comprise paranoid thinking, onset to REM sleep, combat history and somatic symptoms. Decision-tree analysis showed that a specific military event (combat), delayed onset to REM sleep, paranoid thinking and medically unexplainable somatic pain and fatigue characterise chronic PTSD. More PTSD veterans reported domestic and social misbehaviour. Conclusions Military combat, disturbed REM/non-REM EEG sleep, paranoid ideation and medically unexplained chronic musculoskeletal pain and fatigue are key factors in determining PTSD disability following war-zone exposure. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:29018561

Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

2013-02-01

To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P< .001) and cortical presentations (P< .001); CASPR2 IgG was associated with peripheral motor excitability (P= .009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

Insights From LGI1 and CASPR2 Potassium Channel Complex Autoantibody Subtyping

PubMed Central

Klein, Christopher J.; Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; O’Toole, Orna; Quek, Amy; Pittock, Sean J.

2014-01-01

Objective: To determine, in patients identified as sero-positive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Design: Retrospective cohort study. Setting: Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. Patients: A total of 54853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. Results: From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54 853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (P<.001) and cortical presentations (P<.001); CASPR2 IgG was associated with peripheral motor excitability (P=.009). However, neither autoantibody was pathognomonic for a specific neurologic presentation or correlated significantly with cancer. Neurologic phenotypes were diverse. Cerebrocortical manifestations (including cognitive impairment and seizures) were recorded in 76% of patients with LGI1 IgG alone (n=46) and 29% with CASPR2 IgG alone (n=28). Peripheral motor hyperexcitability was found in 21% of patients with CASPR2 IgG alone and 6.5% of patients with LGI1 IgG alone. Conclusions: The study emphasizes diverse and overlapping neurologic phenotypes across a range of VGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined. PMID:23407760

Discordant transsexualism in male monozygotic twins: neuroanatomical and psychological differences.

PubMed

Andreazza, Tahiana Signorini; Costa, Angelo Brandelli; Massuda, Raffael; Salvador, Jaqueline; Silveira, Esalba Maria; Piccon, Felipe; Carvalho, Renata; Fontanari, Anna Martha Vaitses; Koff, Walter; Belmonte-de-Abreu, Paulo; Lobato, Maria Inês Rodrigues

2014-02-01

One monozygotic male twin pair discordant for transsexualism is described. Both twins were interviewed and tested with the Wechsler Adult Intelligence Scale battery for cognitive functions and they underwent magnetic resonance imaging to measure the volumes of specific cerebral structures. Interviews with the twins and their mother indicated no unusual medical or life history events that could have had a causal role in the emergence of the disorder. Both cognitive function testing and neuroimaging detected differences between the twins that could be related to unexplained epigenetic effects and exogenous hormone usage.

Clinical Usefulness of SPECT-CT in Patients with an Unexplained Pain in Metal on Metal (MOM) Total Hip Arthroplasty.

PubMed

Berber, Reshid; Henckel, Johann; Khoo, Michael; Wan, Simon; Hua, Jia; Skinner, John; Hart, Alister

2015-04-01

SPECT-CT is increasingly used to assess painful knee arthroplasties. The aim of this study was to evaluate the clinical usefulness of SPECT-CT in unexplained painful MOM hip arthroplasty. We compared the diagnosis and management plan for 19 prosthetic MOM hips in 15 subjects with unexplained pain before and after SPECT-CT. SPECT-CT changed the management decision in 13 (68%) subjects, Chi-Square=5.49, P=0.24. In 6 subjects (32%) pain remained unexplained however the result reassured the surgeon to continue with non-operative management. SPECT-CT should be reserved as a specialist test to help identify possible causes of pain where conventional investigations have failed. It can help reassure surgeons making management decisions for patients with unexplained pain following MOM hip arthroplasty. Copyright © 2014 Elsevier Inc. All rights reserved.

Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet.

PubMed

Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D; Elsea, Sarah H

2017-01-01

Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation.

Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet

PubMed Central

Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D.

2017-01-01

Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation. PMID:28961260

Negative life events have detrimental effects on in-vitro fertlization outcome.

PubMed

Yilmaz, Nafiye; Kahyaoglu, İnci; İnal, Hasan Ali; Görkem, Ümit; Devran, Aysun; Mollamahmutoglu, Leyla

2015-09-01

The aim of this study was to investigate the effect of negative life events on in-vitro-fertilization (IVF) outcome. Depression and negative life events were measured using Beck Depression Inventory (BDI) and List of Recent Events in 83 women attending the IVF clinic of a tertiary research and education hospital with the diagnosis of unexplained infertility between January 2013 and August 2013. Demographic features, stimulation parameters, depression scores, and negative life events of pregnant and non-pregnant participants were compared and the relation between negative life events, depression scores, and IVF outcome was investigated. Women who did not achieve a pregnancy experienced more negative life events than women who became pregnant (77.2% vs. 23.1%) (p > 0.001). The number of patients with moderate-to-severe depression (BDI scores > 16) was higher in the non-pregnant group than pregnant group (49.1% vs. 26.9%), however the difference was not statistically significant (p = 0.057). Clinical pregnancy showed a significant moderate negative correlation with the number of negative life events (r = -0.513, p = 0.001), but the correlation between clinical pregnancy and BDI scores was not statistically significant (r = -0.209, p = 0.059). Stressful life events have a negative influence on the quality of life, which eventually affects in IVF outcome, possibly through maladaptive lifestyle behavior.

Interprofessional Collaboration with Immune Checkpoint Inhibitor Therapy: the Roles of Gastroenterology, Endocrinology and Neurology.

PubMed

Seery, Virginia

2017-11-01

To discuss immune checkpoint inhibitor therapy and identify opportunities for interprofessional collaboration in the management of toxicities in the areas of gastroenterology, endocrinology, and neurology. Published research and education articles in oncology, nursing, and various specialties. The use of immune checkpoint inhibitors is expanding; timely management of toxicity is critical for positive patient outcomes. There are many opportunities for interprofessional collaboration in the diagnosis and treatment of immune-related adverse events. Nurses play key roles in recognizing immune-related adverse events, providing patient education, and helping to facilitate interprofessional collaboration. Copyright © 2017 Elsevier Inc. All rights reserved.

Rechallenging With Intrathecal Methotrexate After Developing Subacute Neurotoxicity in Children With Hematologic Malignancies.

PubMed

Badke, Colleen; Fleming, Amy; Iqbal, Asneha; Khilji, Ohmed; Parhas, Sophia; Weinstein, Joanna; Morgan, Elaine; Hijiya, Nobuko

2016-04-01

Methotrexate is associated with neurologic side effects. It is recommended that patients who developed neurotoxicity be rechallenged with methotrexate, but little is known about the safety of this approach. We performed a chart review to identify patients who received high-dose or intrathecal (IT) methotrexate. Twenty-one of 298 patients (7%) experienced neurologic symptoms attributed to methotrexate treatment in the premaintenance phase. Seventeen of these patients were rechallenged with IT methotrexate and 13 (76%) had no further neurotoxic events. No patients rechallenged during maintenance (n = 9) experienced recurrence of neurotoxic events. It is safe to rechallenge with IT methotrexate in maintenance. © 2015 Wiley Periodicals, Inc.

Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

PubMed Central

Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

2014-01-01

Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

Laparoscopy In Unexplained Abdominal Pain: Surgeon's Perspective.

PubMed

Abdullah, Muhammad Tariq; Waqar, Shahzad Hussain; Zahid, Muhammad Abdul

2016-01-01

Unexplained abdominal pain is a common but difficult presenting feature faced by the clinicians. Such patients can undergo a number of investigations with failure to reach any diagnosis. The objective of this study was to evaluate the use of laparoscopy in the diagnosis and management of patients with unexplained abdominal pain. This cross-sectional study was conducted at Pakistan Institute of Medical Sciences Islamabad from January 2009 to December 2013. This study included 91 patients of unexplained abdominal pain not diagnosed by routine clinical examination and investigations. These patients were subjected to diagnostic laparoscopy for evaluation of their conditions and to confirm the diagnosis. These patients presented 43% of patients undergoing investigations for abdominal pain. Patients diagnosed with gynaecological problems were excluded to see surgeon's perspective. The findings and the outcomes of the laparoscopy were recorded and data was analyzed. Unexplained abdominal pain is common in females than in males. The most common laparoscopic findings were abdominal tuberculosis followed by appendicitis. Ninety percent patients achieved pain relief after laparoscopic intervention. Laparoscopy is both beneficial and safe in majority of patients with unexplained abdominal pain. General surgeons should acquire training and experience in laparoscopic surgery to provide maximum benefit to these difficult patients.

Medical marijuana in neurology.

PubMed

Benbadis, Selim R; Sanchez-Ramos, Juan; Bozorg, Ali; Giarratano, Melissa; Kalidas, Kavita; Katzin, Lara; Robertson, Derrick; Vu, Tuan; Smith, Amanda; Zesiewicz, Theresa

2014-12-01

Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ(9)-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS 'depressants' and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand.

Health care utilization of mexican patients with medically unexplained physical symptoms.

PubMed

Rodriguez González, Azucena Maribel; Ramírez Aranda, José Manuel; de Los Santos Reséndiz, Homero; Lara Duarte, María Yolanda; Pazaran Zanella, Santiago Oscar; Méndez López, Jafet Felipe; Gil Alfaro, Issa; Islas Ruz, Félix Gilberto; Navarrete Floriano, Gloria; Guillen Salomón, Edith; Texon Fernández, Obdulia; Cruz Duarte, Silvia; Romo Salazar, Juan Carlos; Pérez Ruiz, Claudia Elsa; López Salas, Sara de Jesús; Benítez Amaya, Lizbeth; Zapata Gallardo, Javier Nahum

2016-09-30

To determine the prevalence of medically unexplained physical symptoms and the characteristics and use of health services in a group of patients with medically unexplained physical symptoms and a group of patients with other illnesses. This was a cross-sectional, retrospective and multicenter study. We included 1,043 patients over 18 years of age from 30 primary care units of a government health institution, in 11 states of Mexico, attended by 39 family physicians. The prevalence of medically unexplained physical symptoms was determined and both groups with or without symptoms were compared with regard to drug use, laboratory and other studies, leaves of absence, and referrals in the last six months. The group with medically unexplained physical symptoms was diagnosed using the Patient Health Questionnaire and the diagnostic criteria of Reid et al . Emergency or terminal illnesses were excluded. The chi square test was used with a statistical significance of p < 0.05. Medically unexplained physical symptoms was diagnosed in 73 patients (7.0%). The majority were women (91.8%); their predominant symptom was from the gastrointestinal system in 56 (76.7%). This group had a greater use of clinical studies and referrals to other services (mean 1.1 vs. 0.5; p <0.0001 and 0.6 vs. 0.8; p < 0.01, respectively). The prevalence of medically unexplained physical symptoms was low, but with a greater impact on some health services. This could represent an overload in medical costs.

Risks of presurgical embolization of feeding arteries in 137 intracranial meningeal tumors.

PubMed

Law-ye, Bruno; Clarençon, Frédéric; Sourour, Nader-Antoine; Di Maria, Federico; Jean, Betty; Bonneville, Fabrice; Biondi, Alessandra; Iosif, Christina; Navarro, Soledad; Cornu, Philippe; Chiras, Jacques

2013-04-01

Embolization of extra-axial tumors has shown its effectiveness in reducing perisurgical blood loss. However, the complication rate of this procedure is poorly reported. We aimed to evaluate the rate of procedure-related complications and their risk factors. From 1998 to 2011, 193 consecutive patients (141 females, 52 males; mean age = 52.9 years) were referred to our institution for presurgical embolization of an extra-axial tumor (meningiomas: n = 178; solitary fibrous tumors: n = 3; other: n = 12). Of 193 patients, 137 (71 %) underwent 141 embolizations (by microparticles: n = 133; by glue: n = 8). The remaining 56 patients (29 %) were not embolized due to unstable catheterization or dangerous anastomosis. Occurrence of neurological deficit was systematically assessed during and after embolization. The risk factors of procedure-related neurological complications were evaluated. Neither intratumoral hemorrhage nor procedure-related death was reported. Two of the 137 patients (1.5 %) had ischemic events with permanent neurological deficit after microparticles embolization. One patient had cortical blindness and one had hemiparesis. Both complications involved the vertebrobasilar system. The first patient had direct intratumoral anastomosis between the middle and the posterior meningeal arteries (PMA); the second one had reflux in the vertebral artery during particles injection in the PMA. Occurrence of ischemic complication was not related to the size of the microparticles. Though embolization of meningeal tumors is considered as a safe technique, serious neurological complications may occur. Opening of dangerous anastomosis or uncontrolled reflux caused two neurological complications (1.5 %). The size of the microparticles was not associated with the occurrence of neurological event.

Television image of a large upward electrical discharge above a thunderstorm system

NASA Technical Reports Server (NTRS)

Franz, R. C.; Nemzek, R. J.; Winckler, J. R.

1990-01-01

A low light-level TV camera is used to obtain an unusual image of luminous electrical discharge over a thunderstorm 250 km from the observation site. The image is presented and the discharge in the image is described. It is suggested that the image is probably due to two localized electric charge concentrations at the cloud tops. The hazard of these discharges for aircraft and rocket launches is examined. Consideration is given to the possibility that these discharges may account for unexplained photometric observations of distant lightning events that show a low rise rate of the luminous pulse and no electromagnetic sferic pulse like that in cloud-to-earth lightning strokes. The photometric events of this type that occurred on September 22-23, 1989 during hurricane Hugo are noted.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

PubMed

Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E M; Bender Atik, Ruth; Bloemenkamp, Kitty W M; Brady, Rebecca; Briley, Annette L; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin J; Eapen, Abey; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A M; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark D; Khalaf, Yacoub; Goddijn, Mariette; Regan, Lesley; Rai, Rajendra

2015-11-26

Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

Neurologic complications of vaccinations.

PubMed

Miravalle, Augusto A; Schreiner, Teri

2014-01-01

This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

Self-Imagining Enhances Recognition Memory in Memory-Impaired Individuals with Neurological Damage

PubMed Central

Grilli, Matthew D.; Glisky, Elizabeth L.

2010-01-01

Objective The ability to imagine an elaborative event from a personal perspective relies on a number of cognitive processes that may potentially enhance subsequent memory for the event, including visual imagery, semantic elaboration, emotional processing, and self-referential processing. In an effort to find a novel strategy for enhancing memory in memory-impaired individuals with neurological damage, the present study investigated the mnemonic benefit of a method we refer to as “self-imagining” – or the imagining of an event from a realistic, personal perspective. Method Fourteen individuals with neurologically-based memory deficits and fourteen healthy control participants intentionally encoded neutral and emotional sentences under three instructions: structural-baseline processing, semantic processing, and self-imagining. Results Findings revealed a robust “self-imagination effect” as self-imagination enhanced recognition memory relative to deep semantic elaboration in both memory-impaired individuals, F (1, 13) = 32.11, p < .001, η2 = .71, and healthy controls, F (1, 13) = 5.57, p < .05, η2 = .30. In addition, results indicated that mnemonic benefits of self-imagination were not limited by severity of the memory disorder nor were they related to self-reported vividness of visual imagery, semantic processing, or emotional content of the materials. Conclusions The findings suggest that the self-imagination effect may depend on unique mnemonic mechanisms possibly related to self-referential processing, and that imagining an event from a personal perspective makes that event particularly memorable even for those individuals with severe memory deficits. Self-imagining may thus provide an effective rehabilitation strategy for individuals with memory impairment. PMID:20873930

Cross-cultural differences in the epidemiology of unexplained fatigue syndromes in primary care.

PubMed

Skapinakis, Petros; Lewis, Glyn; Mavreas, Venetsanos

2003-03-01

Unexplained fatigue has been extensively studied but most of the samples used were from Western countries. To present international data on the prevalence of unexplained fatigue and fatigue as a presenting complaint in primary care. Method Secondary analysis of the World Health Organization study of psychological problems in general health care. A total of 5438 primary care attenders from 14 countries were assessed with the Composite International Diagnostic Interview. The prevalence of unexplained fatigue of 1-month duration differed across centres, with a range between 2.26 (95% CI 1.17-4.33) and 15.05 (95% CI 10.85-20.49). Subjects from more-developed countries were more likely to report unexplained fatigue but less likely to present with fatigue to physicians compared with subjects from less developed countries. In less-developed countries fatigue might be an indicator of unmet psychiatric need, but in more-developed countries it is probably a symbol of psychosocial distress.

Listeria monocytogenes: a foodborne pathogen.

PubMed Central

Farber, J M; Losos, J Z

1988-01-01

Listeriosis, caused by Listeria monocytogenes, appears to be increasing in incidence worldwide. The disease is of great concern to the food industry. A recent outbreak in California was linked to the consumption of Mexican-style soft cheese and involved more than 300 cases, 30% of which were fatal. L. monocytogenes can be found in a variety of dairy products, leafy vegetables, fish and meat products. It can grow in refrigerated foods and is more heat resistant than most vegetative microbes. The epidemiologic features of listeriosis are poorly understood, and the minimum infectious dose is unknown. Those predisposed to listeriosis include immunocompromised people and pregnant women and their fetuses. Meningitis, spontaneous abortion and septicemia are the primary manifestations of the disease. Early recognition is critical for successful treatment, and ampicillin is the preferred drug. Listeriosis should be considered in any febrile patient with neurologic symptoms of unknown origin, as well as in women with unexplained recurrent miscarriages, premature labour or fetal death. A food source should be the prime suspect if any isolated case or outbreak occurs. PMID:3124948

Study of the Dynamics of Transcephalic Cerebral Impedance Data during Cardio-Vascular Surgery

NASA Astrophysics Data System (ADS)

Atefi, S. R.; Seoane, F.; Lindecrantz, K.

2013-04-01

Postoperative neurological deficits are one of the risks associated with cardio vascular surgery, necessitating development of new techniques for cerebral monitoring. In this study an experimental observation regarding the dynamics of transcephalic Electrical Bioimpedance (EBI) in patients undergoing cardiac surgery with and without extracorporeal circulation (ECC) was conducted to investigate the potential use of electrical Bioimpedance for cerebral monitoring in cardio vascular surgery. Tetrapolar transcephalic EBI measurements at single frequency of 50 kHz were recorded prior to and during cardio vascular surgery. The obtained results show that the transcephalic impedance decreases in both groups of patients as operation starts, however slight differences in these two groups were also observed with the cerebral impedance reduction in patients having no ECC being less common and not as pronounced as in the ECC group. Changes in the cerebral impedance were in agreement with changes of haematocrit and temperature. The origin of EBI changes is still unexplained however these results encourage us to continue investigating the application of electrical bioimpedance cerebral monitoring clinically.

"White Cord Syndrome" of Acute Hemiparesis After Posterior Cervical Decompression and Fusion for Chronic Cervical Stenosis.

PubMed

Antwi, Prince; Grant, Ryan; Kuzmik, Gregory; Abbed, Khalid

2018-05-01

"White cord syndrome" is a very rare condition thought to be due to acute reperfusion of chronically ischemic areas of the spinal cord. Its hallmark is the presence of intramedullary hyperintense signal on T2-weighted magnetic resonance imaging sequences in a patient with unexplained neurologic deficits following spinal cord decompression surgery. The syndrome is rare and has been reported previously in 2 patients following anterior cervical decompression and fusion. We report an additional case of this complication. A 68-year-old man developed acute left-sided hemiparesis after posterior cervical decompression and fusion for cervical spondylotic myelopathy. The patient improved with high-dose steroid therapy. The rare white cord syndrome following either anterior cervical decompression and fusion or posterior cervical decompression and fusion may be due to ischemic-reperfusion injury sustained by chronically compressed parts of the spinal cord. In previous reports, patients have improved following steroid therapy and acute rehabilitation. Copyright © 2018 Elsevier Inc. All rights reserved.

An update in recurrent spontaneous abortion.

PubMed

Pandey, Manoj Kumar; Rani, Reena; Agrawal, Suraksha

2005-07-01

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The etiology of recurrent spontaneous abortion is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Reasonably accepted etiologic causes include, genetics, anatomical, endocrine, placental anomalies, hormonal problems, infection, smoking and alcohol consumption, exposure to environmental factors, psychological trauma and stressful life event, certain coagulation and immunoregulatory protein defects. Detection of an abnormality in any of these areas may result into specific therapeutic measures, with varying degrees of success. However, the majority of cases of RSA remains unexplained and is found to be associated with certain autoimmune (APA, ANA, ACA, ATA, AECA) and alloimmune (APCA, Ab2, MLR-Bf) antibodies that may play major role in the immunologic failure of pregnancy and may lead to abortion. Alteration in the expression of HLA-G molecules, T-helper-1 (Th-1) pattern of cytokines and natural killer (NK) cells activity may also induce abortion. Various forms of treatment like antithrombotic therapies such as aspirin and heparin, intravenous immunoglobulin (IVIg) therapy, immunotherapy with paternal lymphocytes and vitamin D3 therapy are effective mode of treatment for unexplained cause of fetal loss in women with RSA.

Case Study on the Effect of Word Repetition Method Supported by Neurological Affecting Model on Fluent Reading

ERIC Educational Resources Information Center

Duran, Erol

2013-01-01

This research is a case study which is a qualitative study model and named as example event as well. The purpose of this research is determining the effect of word repetitive reading method supported with neurological affecting model on fluent reading. In this study, False Analysis Inventory was used in order to determine the student's oral…

Medically unexplained visual loss in a specialist clinic: a retrospective case-control comparison.

PubMed

O'Leary, Éanna D; McNeillis, Benjamin; Aybek, Selma; Riordan-Eva, Paul; David, Anthony S

2016-02-15

To compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. Case-control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro-ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30 months (SD=67 months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. Seventy-two percent (n=36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n=20), premorbid psychiatric (27%, n=13) as well as functional (24%, n=12) diagnoses and psychotropic medication usage (22%, n=11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n=9; 18%). Medically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression.

PubMed

Blokhuis, Gijsbert J; Bleeker-Rovers, Chantal P; Diender, Marije G; Oyen, Wim J G; Draaisma, Jos M Th; de Geus-Oei, Lioe-Fee

2014-10-01

Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression. All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis. FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively. FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value.

Common and unique associated factors for medically unexplained chronic widespread pain and chronic fatigue☆

PubMed Central

McBeth, J.; Tomenson, B.; Chew-Graham, C.A.; Macfarlane, G.J.; Jackson, J.; Littlewood, A.; Creed, F.H.

2015-01-01

Objective Chronic widespread pain and chronic fatigue share common associated factors but these associations may be explained by the presence of concurrent depression and anxiety. Methods We mailed questionnaires to a randomly selected sample of people in the UK to identify participants with chronic widespread pain (ACR 1990 definition) and those with chronic fatigue. The questionnaire assessed sociodemographic factors, health status, healthcare use, childhood factors, adult attachment, and psychological stress including anxiety and depression. To identify persons with unexplained chronic widespread pain or unexplained chronic fatigue; we examined participant's medical records to exclude medical illness that might cause these symptoms. Results Of 1443 participants (58.0% response rate) medical records of 990 were examined. 9.4% (N = 93) had unexplained chronic widespread pain and 12.6% (N = 125) had unexplained chronic fatigue. Marital status, childhood psychological abuse, recent threatening experiences and other somatic symptoms were commonly associated with both widespread pain and fatigue. No common effect was found for few years of education and current medical illnesses (more strongly associated with chronic widespread pain) or recent illness in a close relative, neuroticism, depression and anxiety scores (more strongly associated with chronic fatigue). Putative associated factors with a common effect were associated with unexplained chronic widespread pain or unexplained chronic fatigue only when there was concurrent anxiety and/or depression. Discussion This study suggests that the associated factors for chronic widespread pain and chronic fatigue need to be studied in conjunction with concurrent depression/anxiety. Clinicians should be aware of the importance of concurrent anxiety or depression. PMID:26652592

Making sense of medically unexplained symptoms in general practice: a grounded theory study

PubMed Central

2013-01-01

Background General practitioners often encounter patients with medically unexplained symptoms. These patients share many common features, but there is little agreement about the best diagnostic framework for describing them. Aims This study aimed to explore how GPs make sense of medically unexplained symptoms. Design Semi-structured interviews were conducted with 24 GPs. Each participant was asked to describe a patient with medically unexplained symptoms and discuss their assessment and management. Setting The study was conducted among GPs from teaching practices across Australia. Methods Participants were selected by purposive sampling and all interviews were transcribed. Iterative analysis was undertaken using constructivist grounded theory methodology. Results GPs used a variety of frameworks to understand and manage patients with medically unexplained symptoms. They used different frameworks to reason, to help patients make sense of their suffering, and to communicate with other health professionals. GPs tried to avoid using stigmatising labels such as ‘borderline personality disorder’, which were seen to apply a ‘layer of dismissal’ to patients. They worried about missing serious physical disease, but managed the risk by deliberately attending to physical cues during some consultations, and focusing on coping with medically unexplained symptoms in others. They also used referrals to exclude serious disease, but were wary of triggering a harmful cycle of uncoordinated care. Conclusion GPs were aware of the ethical relevance of psychiatric diagnoses, and attempted to protect their patients from stigma. They crafted helpful explanatory narratives for patients that shaped their experience of suffering. Disease surveillance remained an important role for GPs who were managing medically unexplained symptoms. PMID:24427176

Sperm chromatin structure assay results in Nigerian men with unexplained infertility

PubMed Central

Kolade, Charles Oluwabukunmi

2015-01-01

Objective Several publications have established a relationship between sperm DNA damage and male factor infertility, based on data from America, Europe, and Asia. This study aimed to compare the extent of sperm DNA damage in sperm samples from Nigerian men with unexplained infertility and in sperm samples from a fertile group composed of sperm donors who had successfully impregnated a female partner naturally or through assisted conception. Methods A total of 404 men underwent male fertility evaluation at Androcare Laboratories and Cryobank participated in this study. Semen analysis and a sperm chromatin structure assay (SCSA) were performed on all subjects. Results The men in the unexplained infertility group were slightly older than the men in the fertile sperm group (36±10 years vs. 32±6 years, p=0.051). No significant difference was observed between the two groups in semen analysis parameters (p≥0.05). Men in the unexplained infertility group with normal semen parameters had a significantly higher DNA fragmentation index (DFI) than men in the fertile sperm group (27.5%±7.0% vs. 14.1%±5.3%, p<0.05). In the unexplained infertility group, 63% of the men had a DFI greater than 20%, compared to 4% in the fertile sperm group. In the unexplained infertility group, 15.2% of the subjects had a DFI greater than 30%, compared to 1% in the fertile sperm group. Conclusion Our study showed that the SCSA may be a more reliable predictor of fertility potential than traditional semen analysis in cases of unexplained infertility. PMID:26473109

Characteristics of patients contacting a center for undiagnosed and rare diseases.

PubMed

Mueller, Tobias; Jerrentrup, Andreas; Bauer, Max Jakob; Fritsch, Hans Walter; Schaefer, Juergen Rolf

2016-06-21

Little is known about the characteristics of patients seeking help from dedicated centers for undiagnosed and rare diseases. However, information about their demographics, symptoms, prior diagnoses and medical specialty is crucial to optimize these centers' processes and infrastructure. Using a questionnaire, structured information from 522 adult patients contacting a center for undiagnosed and rare diseases was obtained. The information included basic sociodemographic data (age, gender, insurance status), previous hospital admissions, primary symptoms of complaint and previously determined diagnosis. The majority of patients completing the questionnaire were female, 300 (57 %) vs. 222 men (43 %). The median age was 52 years (range 18-92). More than half, 309 (59 %), of our patients had never been admitted to a university hospital. Common diagnoses included other soft tissue disorders, not classified elsewhere (ICD M79, n = 63, 15.3 %), somatoform disorders (ICD F45, n = 51, 12.3 %) and other polyneuropathies (ICD G62, n=36, 8.7 %). The most frequent symptoms were general weakness (n = 180, 36.6 %) followed by arthralgia (n = 124, 25.2 %) and abdominal discomfort (n = 113, 23.0 %). The majority of patients had either internal medicine (81.3 %) and/or neurologic (37.6 %) health problems. Pain-associated diagnoses and the typical "unexplained" medical conditions (chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome) are frequent among people contacting a center dedicated to undiagnosed diseases. The chief symptoms are mostly unspecific. An interdisciplinary organizational approach involving mainly internal medicine, neurology and psychiatry/psychosomatic care is needed.

Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum.

PubMed

van Karnebeek, Clara D M; Tiebout, Sylvia A; Niermeijer, Jikkemien; Poll-The, Bwee Tien; Ghani, Aisha; Coughlin, Curtis R; Van Hove, Johan L K; Richter, Jost Wigand; Christen, Hans Juergen; Gallagher, Renata; Hartmann, Hans; Stockler-Ipsiroglu, Sylvia

2016-06-01

Pyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of α-aminoadipic semialdehyde/pyrroline 6' carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported. We present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions. The phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of α-aminoadipic semialdehyde/pyrroline 6' carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Birth asphyxia: pathophysiologic events and fetal adaptive changes.

PubMed

Woods, J R

1983-06-01

We have made significant advances toward understanding birth asphyxia and its effects upon neurologic development in the newborn and infant. The fetus is well adapted to compensate for moderate alterations in oxygen delivery. However, near lethal hypoxemia, prolonged exposure, and survival result in cell death and permanent neurologic sequelae. Neuroelectrical measurements such as the EEG and visual evoked potential provide insight into the acute alterations in nerve transmission during asphyxia, and in the recovery phase may ultimately provide information for long-term prognosis. These measurements are limited, however, by their inability once lost to distinguish cell inactivity from cell death. Permanent neurologic damage from asphyxia appears now to be a complex process in which severe hypoxemia precipitates a cascade of events leading to glycolysis, glycogenolysis, hypotension, and ultimately the accumulation of high concentrations of lactate at the cell level. As a consequence, cellular and extracellular fluid shifts produce cerebral edema, further impairment of cerebral circulation, and ultimately cell death. Clinical studies have helped to identify the newborn at high risk for neurologic impairment, but a cause-effect relationship remains unclear. That birth asphyxia can produce severe neurologic damage and death is generally accepted. Moreover, improper resuscitation of a severely depressed newborn increases the chance of permanent sequelae. The important clinical question is: Can one alter the natural course of asphyxia as has been alluded to through pharmacologic and ventilator manipulation? Answers to this question will depend upon continued study of the mechanisms of asphyctic damage in the central nervous system.

Post-marketing safety evaluation of a tetanus toxoid, reduced diphtheria toxoid and 3-component acellular pertussis vaccine administered to a cohort of adolescents in a United States health maintenance organization.

PubMed

Klein, Nicola P; Hansen, John; Lewis, Edwin; Lyon, Liisa; Nguyen, Bessie; Black, Steven; Weston, Wayde M; Wu, Sterling; Li, Ping; Howe, Barbara; Friedland, Leonard R

2010-07-01

Prelicensure clinical studies may not include sufficient numbers of subjects to assess the potential for rare postvaccination adverse events. The aim of this postlicensure study (NCT00297856) was to evaluate uncommon outcomes following vaccination with a tetanus, reduced-antigen-content diphtheria, and acellular pertussis vaccine (Tdap, Boostrix GlaxoSmithKline) in a large adolescent cohort. We monitored safety outcomes among 13,427 10 to 18-year-old adolescents enrolled in the Northern California Kaiser Permanente Health Care Plan who received Tdap vaccination as part of their normal health care. Subjects were evaluated using self-control analysis comparing days 0 to 29 to days 30 to 59 postvaccination for neurologic events, hematologic events and allergic reactions. We evaluated new onset chronic illnesses within 6 months of Tdap vaccination by comparing with historical Td controls matched for age at vaccination, season, sex, and geographic area. We also compared the incidence of events of interest between the Tdap and historical cohorts as exploratory analyses. No increased risk for medically attended neurologic (odds ratio [OR], 0.962; 95% confidence interval [CI], 0.533-1.733) or allergic reactions (OR, 1.091; 95% CI, 0.441-2.729) was observed following Tdap vaccination when comparing the first 30 postvaccination days to the second 30 postvaccination days. There was one hematologic event within 30 days of Tdap, compared with 0 events within days 30 to 59 (P = 1.0). When compared with matched historical Td recipients, no increase in new onset chronic illnesses (OR, 0.634; 95% CI, 0.475-0.840) was seen after Tdap. No deaths occurred in the Tdap cohort during the study. This study provides no evidence for an increased risk for neurologic, hematologic, allergic events, or new onset of chronic illnesses among adolescents vaccinated with Tdap.

Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

PubMed Central

Sozda, Christopher N.; Larson, Michael J.; Kaufman, David A.S.; Schmalfuss, Ilona M.; Perlstein, William M.

2011-01-01

Continuous monitoring of one’s performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. PMID:21756946

Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study.

PubMed

Sozda, Christopher N; Larson, Michael J; Kaufman, David A S; Schmalfuss, Ilona M; Perlstein, William M

2011-10-01

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. Copyright © 2011 Elsevier B.V. All rights reserved.

[Transcient ischemic attack, a rare manifestation of Eagle syndrome].

PubMed

Usseglio, J; Montoro, F Macian; Martin, S; Lerat, J; Laloze, J; Taibi, A; Brie, J

2016-12-01

Clinical presentation of Eagle syndrome (ES) is very variable and non-specific, making its diagnosis difficult. It is usually limited to pain. Transient neurological manifestations are exceptional. We report one case in which the diagnosis of ES has been made based on neurological events occurring during left anterolateral head bending, without pain. A 47-year-old man presented with transient neurological events progressing since two years, half-right body paresthesia and reduced field of vision on the left side type, triggered by left anterolateral head flexion and regressive in neutral position. Transcranial Doppler and CT angiography of the supra-aortic trunks were performed in neutral position and in right and left head rotation that showed a disruption of the left sylvian flow and an extrinsic compression of the left internal carotid artery, due to a musculoskeletal impediment involving the lower end of the temporal styloid process. Complete recovering was achieved after surgical resection of this process. A control CT angiography confirmed the cessation of the compression. ES has non-specific and highly variable clinical manifestations making diagnosis difficult or leading to misdiagnosis. ES should be considered in any transient neurological deficit, especially when occurring during head rotation. Treatment relies on surgical resection of the excessively long styloid process. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Great majority of recombination events in Arabidopsis are gene conversion events

PubMed Central

Yang, Sihai; Yuan, Yang; Wang, Long; Li, Jing; Wang, Wen; Liu, Haoxuan; Chen, Jian-Qun; Hurst, Laurence D.; Tian, Dacheng

2012-01-01

The evolutionary importance of meiosis may not solely be associated with allelic shuffling caused by crossing-over but also have to do with its more immediate effects such as gene conversion. Although estimates of the crossing-over rate are often well resolved, the gene conversion rate is much less clear. In Arabidopsis, for example, next-generation sequencing approaches suggest that the two rates are about the same, which contrasts with indirect measures, these suggesting an excess of gene conversion. Here, we provide analysis of this problem by sequencing 40 F2 Arabidopsis plants and their parents. Small gene conversion tracts, with biased gene conversion content, represent over 90% (probably nearer 99%) of all recombination events. The rate of alteration of protein sequence caused by gene conversion is over 600 times that caused by mutation. Finally, our analysis reveals recombination hot spots and unexpectedly high recombination rates near centromeres. This may be responsible for the previously unexplained pattern of high genetic diversity near Arabidopsis centromeres. PMID:23213238

Trousseau's syndrome in a patient with advanced stage gastric cancer.

PubMed

Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

2015-09-14

Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.

Characteristics of Patients Referred to a Pediatric Infectious Diseases Clinic With Unexplained Fever.

PubMed

Statler, Victoria A; Marshall, Gary S

2016-09-01

Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lower FOXO3 mRNA expression in granulosa cells is involved in unexplained infertility.

PubMed

Yamamoto, Hikaru; Yamashita, Yoshiki; Saito, Natsuho; Hayashi, Atsushi; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

2017-06-01

The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/μL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013. Real-time PCR was carried out using mRNA extracted from granulosa cells retrieved from mature follicles. We compared FOXO1 and FOXO3 mRNA expression ratios in granulosa cells between the unexplained infertility group and the male infertility group. The relation between FOXO1 and FOXO3 mRNA expression ratios in granulosa cells and assisted reproduction technology clinical outcome was also examined. FOXO3 mRNA expression ratio was significantly lower in the unexplained infertility group than in the male infertility group. Moreover, FOXO3 mRNA expression ratio showed a positive correlation with both the number of retrieved oocytes and serum anti-Müllerian hormone level. A positive correlation was also identified between FOXO1 mRNA expression and total dose of hMG. As well, the number of retrieved oocytes in the unexplained infertility group was statistically lower than that in the male infertility group. A lower FOXO3 mRNA expression in granulosa cells leads to poor oocyte development in patients with unexplained infertility undergoing controlled ovarian stimulation for in vitro fertilization-embryo transfer. © 2017 Japan Society of Obstetrics and Gynecology.

Late-time X-ray signatures of compact binary mergers: potential counterparts of gravitational wave events

NASA Astrophysics Data System (ADS)

Tanvir, Nial

2017-09-01

Merging compact binaries (NS-NS or NS-BH) offer the best prospects for detection of EM signals accompanying gravitational wave (GW) events. They may be seen as bright short-GRBs (SGRBs), but this is likely to be rare due to beaming. Alternatively, more isotropic near-IR emission is predicted to result from the 'kilonova' produced by radioactive decay of neutron star ejecta. However, recent XMM observations have shown unexplained excess X-ray emission several days post-burst in two low-z SGRBs. This may indicate ongoing engine activity which both enhances the nIR emission, and crucially provides a potential new isotropic X-ray signature of compact binary mergers. We propose a detailed study of a further z<0.35 SGRB, to explore this phenomenon and inform future searches for GW counterparts.

Maternal serum amyloid A level as a novel marker of primary unexplained recurrent early pregnancy loss.

PubMed

Ibrahim, Moustafa I; Ramy, Ahmed R; Abdelhamid, Ahmed S; Ellaithy, Mohamed I; Omar, Amna; Harara, Rany M; Fathy, Hayam; Abolouz, Ashraf S

2017-03-01

To assess maternal serum amyloid A (SAA) levels among women with primary unexplained recurrent early pregnancy loss (REPL). A prospective study was conducted among women with missed spontaneous abortion in the first trimester at Ain Shams University Maternity Hospital, Cairo, Egypt, between January 21 and December 25, 2014. Women with at least two consecutive primary unexplained REPLs and no previous live births were enrolled. A control group was formed of women with no history of REPL who had at least one previous uneventful pregnancy with no adverse outcomes. Serum samples were collected to measure SAA levels. The main outcome was the association between SAA and primary unexplained REPL. Each group contained 96 participants. Median SAA level was significantly higher among women with REPL (50.0 μg/mL, interquartile range 26.0-69.0) than among women in the control group (11.6 μg/mL, interquartile range 6.2-15.5; P<0.001). The SAA level was an independent indicator of primary unexplained REPL, after adjusting for maternal age and gestational age (odds ratio 1.12, 95% confidence interval 1.06-1.19; P<0.001). Elevated SAA levels found among women with primary unexplained REPL could represent a novel biomarker for this complication of pregnancy. © 2016 International Federation of Gynecology and Obstetrics.

HIGH-RISK GASTRIC PATHOLOGY AND PREVALENT AUTOIMMUNE DISEASES IN PATIENTS WITH PERNICIOUS ANEMIA.

PubMed

Hughes, Jing W; Muegge, Brian D; Tobin, Garry S; Litvin, Marina; Sun, Lulu; Saenz, Jose B; Gyawali, C Prakash; McGill, Janet B

2017-11-01

Pernicious anemia (PA) develops from atrophic gastritis due to autoimmune destruction of parietal cells and results in achlorhydria, vitamin B12 and iron deficiencies, anemia, neurologic deficits, and premalignant and malignant stomach lesions. We report the presentation, diagnosis and gastric complications of PA in patients from an endocrinology practice. Thirty-four patients (31 female, 3 male) with PA who underwent esophagogastroduodenoscopy (EGD) or gastrectomy were identified. Pertinent clinical, laboratory, and pathology findings were reviewed and summarized. The mean age of patients was 58.6 ± 14.2 years; the onset of PA was age 50.2 ± 15.3 years. Anemia reflected vitamin B12 and/or iron deficiencies. Parietal cell antibodies (PCA) were detected in 97% of patients, and intrinsic factor blocking antibody (IFBA) was found in 52%. Fasting gastrin and chromogranin A levels were elevated (1,518.0 ± 1,588.3 pg/mL, and 504.9.1 ± 1,524.9 ng/mL respectively). Autoimmune or immunologic diseases (AIDs) were present in 32/34 patients. Stomach pathology showed premalignant or malignant lesions in 26 patients, including gastric neuroendocrine tumors (GNETs) in 6 and adenocarcinoma in 1. One patient presented with neurologic symptoms and subacute combined degeneration of the posterior column of the spinal cord. PA should be suspected in patients with unexplained anemia or neurologic symptoms. The diagnosis of PA relies on fasting gastrin and gastric auto-antibody testing, in addition to hematologic evaluation. EGD with measurement of gastric pH and biopsies of the fundus and antrum identifies patients with achlorhydria, atrophic gastritis, and premalignant and malignant stomach lesions. EGD surveillance of patients with high-risk stomach lesions is recommended. AID = autoimmune or immunologic disease; EGD = esophagogastroduodenoscopy; GNET = gastric neuroendocrine tumor; IFBA = intrinsic factor blocking antibody; PA = pernicious anemia; PCA = parietal cell antibody; T1D = type 1 diabetes.

Multi-symptom illnesses, unexplained illness and Gulf War Syndrome

PubMed Central

Ismail, Khalida; Lewis, Glyn

2006-01-01

Explanatory models for the increased prevalence of ill health in Gulf veterans compared to those not deployed to the Gulf War 1990–1991 remain elusive. This article addresses whether multi-symptom reporting in Gulf veterans are types of medically unexplained symptoms and whether the alleged Gulf War Syndrome is best understood as a medically unexplained syndrome. A review of the epidemiological studies, overwhelmingly cross-sectional, describing ill health was conducted including those that used factor analysis to search for underlying or latent clinical constructs. The overwhelming evidence was that symptoms in Gulf veterans were either in keeping with currently defined psychiatric disorders such as depression and anxiety or were medically unexplained. The application of factor analysis methods had varied widely with a risk of over interpretation in some studies and limiting the validity of their findings. We concluded that ill health in Gulf veterans and the alleged Gulf War Syndrome is best understood within the medically unexplained symptoms and syndromes constructs. The cause of increased reporting in Gulf veterans are still not clear and requires further inquiry into the interaction between sociological factors and symptomatic distress. PMID:16687260

Definition and epidemiology of unexplained infertility.

PubMed

Gelbaya, Tarek A; Potdar, Neelam; Jeve, Yadava B; Nardo, Luciano G

2014-02-01

The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.

Retrospective Validation of a Surveillance System for Unexplained Illness and Death: New Haven County, Connecticut

PubMed Central

Kluger, Michael D.; Sofair, Andre N.; Heye, Constance J.; Meek, James I.; Sodhi, Rajesh K.; Hadler, James L.

2001-01-01

Objectives. This study investigated retrospective validation of a prospective surveillance system for unexplained illness and death due to possibly infectious causes. Methods. A computerized search of hospital discharge data identified patients with potential unexplained illness and death due to possibly infectious causes. Medical records for such patients were reviewed for satisfaction of study criteria. Cases identified retrospectively were combined with prospectively identified cases to form a reference population against which sensitivity could be measured. Results. Retrospective validation was 41% sensitive, whereas prospective surveillance was 73% sensitive. The annual incidence of unexplained illness and death due to possibly infectious causes during 1995 and 1996 in the study county was conservatively estimated to range from 2.7 to 6.2 per 100 000 residents aged 1 to 49 years. Conclusions. Active prospective surveillance for unexplained illness and death due to possibly infectious causes is more sensitive than retrospective surveillance conducted through a published list of indicator codes. However, retrospective surveillance can be a feasible and much less labor-intensive alternative to active prospective surveillance when the latter is not possible or desired. PMID:11499106

Is the long-term prognosis of transient ischemic attack or minor ischemic stroke affected by the occurrence of nonfocal symptoms?

PubMed

Compter, Annette; van der Worp, H Bart; van Gijn, Jan; Kappelle, L Jaap; Koudstaal, Peter J; Algra, Ale

2014-05-01

In patients with a transient ischemic attack or ischemic stroke, nonfocal neurological symptoms, such as confusion and nonrotatory dizziness, may be associated with a higher risk of vascular events. We assessed the relationship between nonfocal symptoms and the long-term risk of vascular events or death in patients with a transient ischemic attack or minor ischemic stroke. We related initial symptoms with outcome events in 2409 patients with a transient ischemic attack (n=723) or minor ischemic stroke (n=1686), included in the Life Long After Cerebral ischemia cohort. All patients underwent a standardized interview on the occurrence of focal and nonfocal neurological symptoms during the qualifying event. The primary outcome was the composite of any stroke, myocardial infarction, or vascular death. Secondary outcomes were all-cause death, vascular death, cardiac death, myocardial infarction, and stroke. Hazard ratios were calculated with Cox regression. Focal symptoms were accompanied by nonfocal symptoms in 739 (31%) patients. During a mean follow-up of 10.1 years, the primary outcome occurred in 1313 (55%) patients. There was no difference in the risk of the primary outcome between patients with both focal and nonfocal symptoms and patients with focal symptoms alone (adjusted hazard ratio, 0.97; 95% confidence interval, 0.86-1.09; P=0.60). The risk of each of the secondary outcomes was also similar in both groups. About one third of the patients with a transient ischemic attack or minor ischemic stroke has both focal and nonfocal neurological symptoms. Nonfocal symptoms are not associated with an increased long-term risk of vascular events or death. This trial was not registered because enrollment began before July 1, 2005.

Effectiveness of a Blended Multidisciplinary Intervention for Patients with Moderate Medically Unexplained Physical Symptoms (PARASOL): Protocol for a Cluster Randomized Clinical Trial.

PubMed

van Westrienen, Paula Elisabeth; Pisters, Martijn F; Toonders, Suze Aj; Gerrits, Marloes; Veenhof, Cindy; de Wit, Niek J

2018-05-08

Medically unexplained physical symptoms are an important health problem in primary care, with a spectrum from mild to chronic. The burden of chronic medically unexplained physical symptoms is substantial for patients, health care professionals, and society. Therefore, early identification of patients with moderate medically unexplained physical symptoms is needed in order to prevent chronicity. The preventive screening of medically unexplained physical symptoms (PRESUME) screening method was developed using data from the electronic medical record of the patients' general practitioner and demonstrated its prognostic accuracy to identify patients with moderate medically unexplained physical symptoms. In the next step, we developed a proactive blended and integrated mental health and physical therapy intervention program (PARASOL) to reduce complaints of moderate medically unexplained physical symptoms, stimulate self-management, and prevent chronicity. The primary objective of this study is to investigate the effectiveness of the blended PARASOL intervention on the impact of symptoms and quality of life in patients with moderate medically unexplained physical symptoms compared with usual care. Secondary objectives are to study the effect on severity of physical and psychosocial symptoms, general health, physical behavior, illness perception, and self-efficacy in patients with moderate medically unexplained physical symptoms as well as to determine the cost-effectiveness of the program. This paper presents the study protocol of a multicenter cluster randomized clinical trial. Adult patients with moderate medically unexplained physical symptoms will be identified from electronic medical record data using the PRESUME screening method and proactively recruited for participation in the study. Cluster randomization will be performed at the level of the participating health care centers. In total 248 patients with moderate medically unexplained physical symptoms (124 patients per arm) are needed. The PARASOL intervention is a 12-week blended primary care program consisting of 4 face-to-face consultations with the mental health nurse and 5 physical therapy sessions, supplemented with a Web-based program. The Web-based program contains (1) information modules and videos on self-management and educative themes, (2) videos and instructions on prescribed home exercises, and (3) assignments to gradually increase the physical activity. The program is directed at patients' perception of symptoms as well as modifiable prognostic risk factors for chronicity using therapeutic neuroscience education. It encourages self-management, as well as an active lifestyle using a cognitive behavioral approach and graded activity. Primary outcomes are impact of symptoms and quality of life. Secondary outcomes are severity of physical and psychosocial symptoms, general health, physical behavior, illness perceptions, self-efficacy, and cost-effectiveness. All measurements will be performed at baseline, 3 and 12 months after baseline. Retrospective cost questionnaires will also be sent at 6 and 9 months after baseline and these will be used for the cost-effectiveness analysis. The intervention has been developed, and the physical therapists and mental health nurses in the participating experimental health care centers have received two days of training on the content of the blended PARASOL intervention. The recruitment of health care centers started in June 2016 and inclusion of patients began in March 2017. Follow-up assessments of patients are expected to be completed in March 2019. This study is the first randomized clinical trial to determine the effectiveness (including cost-effectiveness) of a proactive, blended, and integrated mental health and physical therapy care program for patients with moderate medically unexplained physical symptoms. The findings will help to improve the treatment for patients with moderate medically unexplained physical symptoms and prevent chronicity. Netherlands Trial Register NTR6755; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6755 (Archived by WebCite at http://www.webcitation.org/6ywporY7u). ©Paula Elisabeth van Westrienen, Martijn F Pisters, Suze AJ Toonders, Marloes Gerrits, Cindy Veenhof, Niek J de Wit. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.05.2018.

Anxiety, depression, suicidal ideation, and stressful life events in non-cardiac adolescent chest pain: a comparative study about the hidden part of the iceberg.

PubMed

Eliacik, Kayi; Kanik, Ali; Bolat, Nurullah; Mertek, Hilal; Guven, Baris; Karadas, Ulas; Dogrusoz, Buket; Bakiler, Ali Rahmi

2017-08-01

Chest pain in adolescents is rarely associated with cardiac disease. Adolescents with medically unexplained chest pain usually have high levels of anxiety and depression. Psychological stress may trigger non-cardiac chest pain. This study evaluated risk factors that particularly characterise adolescence, such as major stressful events, in a clinical population. The present study was conducted on 100 adolescents with non-cardiac chest pain and 76 control subjects. Stressful life events were assessed by interviewing patients using a 36-item checklist, along with the Children's Depression Inventory and Spielberger's State-Trait Anxiety Inventory for children, in both groups. Certain stressful life events, suicidal thoughts, depression, and anxiety were more commonly observed in adolescents with non-cardiac chest pain compared with the control group. Moreover, binary logistic regression analysis showed that trouble with bullies, school-related problems, and depression may trigger non-cardiac chest pain in adolescents. Non-cardiac chest pain on the surface may point to the underlying psychosocial health problems such as depression, suicidal ideas, or important life events such as academic difficulties or trouble with bullies. The need for a psychosocial evaluation that includes assessment of negative life events and a better management have been discussed in light of the results.

Biofeedback: Making the Science Real

PubMed Central

Baker, Robert A.; Newland, Richard F.; Bennetts, Jayme

2009-01-01

Abstract: Neurological deficits such as stroke and subtle psychological, cognitive, and behavioral changes are known risks associated with cardiac surgery. These altered neurologic outcomes have a significant impact on patients and their quality of life postoperatively. Perioperative events, such as cerebral embolism and decrease in cerebral oxygenation and hypoperfusion have been identified as factors causal in producing adverse neurologic outcomes. More importantly, a number of mechanisms related to operative techniques have been found to cause these adverse events. Identifying practices associated with adverse outcomes and implementing practice changes may benefit clinical outcomes for cardiac surgery patients. Standardizing techniques among clinicians will also achieve continuous quality improvement in the process of care. Optimal intra-operative management systems contribute significantly to ensuring good patient outcomes (i.e., avoiding neurological injury in patients which is an important cause of post-operative morbidity and mortality). Groom and colleagues (2004) have developed a system to obtain a thorough understanding and redesign of the process of care associated with cardiac surgery. They have developed a system that simultaneously measures some embolic activity, cerebral oxygen saturation, and physiologic parameters, as well as uses a video recording device during cardiac surgery. To date, the evaluation of this methodology in a rigorous, prospective manner has not been reported. Our aim is to conduct a randomised clinical trial to evaluate the influence of continuous quality improvement in cardiac surgery using biofeedback (i.e., real time information on physiologic functioning from an integrated monitoring system) to reduce the incidence of potentially adverse events during surgery. By achieving the outcomes of this project, we plan to be able to not only introduce change in our own practice, but provide a framework for other units to introduce change. PMID:20092086

[Neurologic manifestations associated with antiphospholipid antibodies. Or what remains of neurolupus?].

PubMed

Hachulla, E; Leys, D; Deleume, J F; Pruvo, J P; Devulder, B

1995-01-01

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. Central nervous system involvement in SLE is multifactorial, thrombotic events, antineuronal antibodies, hypertension, infection, side effects of drugs etc. Antiphospholipid antibodies may play a role in focal neurological manifestations in SLE. In the absence of SLE, different neurological symptoms are well associated with antiphospholipid antibodies including stroke, seizures, dementia, migraine, ocular ischemia, chorea, transverse myelopathy, cerebral phlebitis. Other association are more controversal like Guillain Barré syndrome, motor neuron disease, communicating hydrocephalus. In all patients with antiphospholipid antibodies with neurological involvement, cerebral MRI may be performed with an echocardiographic study because a possible association with Libman and Sacks endocarditis, valve dysfunction or cardiac thrombus source of cerebral ischemia.

Financial impact of adopting implantable loop recorder diagnostic for unexplained syncope compared with conventional diagnostic pathway in Portugal.

PubMed

Providência, Rui; Candeias, Rui; Morais, Carlos; Reis, Hipólito; Elvas, Luís; Sanfins, Vitor; Farinha, Sara; Eggington, Simon; Tsintzos, Stelios

2014-05-06

To estimate the short- and long-term financial impact of early referral for implantable loop recorder diagnostic (ILR) versus conventional diagnostic pathway (CDP) in the management of unexplained syncope (US) in the Portuguese National Health Service (PNHS). A Markov model was developed to estimate the expected number of hospital admissions due to US and its respective financial impact in patients implanted with ILR versus CDP. The average cost of a syncope episode admission was estimated based on Portuguese cost data and landmark papers. The financial impact of ILR adoption was estimated for a total of 197 patients with US, based on the number of syncope admissions per year in the PNHS. Sensitivity analysis was performed to take into account the effect of uncertainty in the input parameters (hazard ratio of death; number of syncope events per year; probabilities and unit costs of each diagnostic test; probability of trauma and yield of diagnosis) over three-year and lifetime horizons. The average cost of a syncope event was estimated to be between 1,760€ and 2,800€. Over a lifetime horizon, the total discounted costs of hospital admissions and syncope diagnosis for the entire cohort were 23% lower amongst patients in the ILR group compared with the CDP group (1,204,621€ for ILR, versus 1,571,332€ for CDP). The utilization of ILR leads to an earlier diagnosis and lower number of syncope hospital admissions and investigations, thus allowing significant cost offsets in the Portuguese setting. The result is robust to changes in the input parameter values, and cost savings become more pronounced over time.

Somatization disorders in dermatology.

PubMed

Gupta, Madhulika A

2006-02-01

This paper reviews a wide range of somatization-related symptoms that are encountered in dermatology. These include the unexplained cutaneous sensory syndromes especially the cutaneous dysesthesias associated with pain, numbness and pruritus; traumatic memories in post-traumatic stress disorder (PTSD) which are experienced on a sensory level as 'body memories' and may present as local or generalized pruritic states, urticaria and angioedema; and unexplained flushing reactions and profuse perspiration, in addition to unexplained exacerbations of stress-reactive dermatoses such as psoriasis and atopic eczema secondary to the autonomic hyperarousal in PTSD; classic 'pseudoneurologic' symptoms associated with dissociation including unexplained loss of touch or pain, in addition to the self-induced dermatoses such as dermatitis artefacta and trichotillomania that are encountered with dissociative states; and body dysmorphic disorder where the patient often presents with a somatic preoccupation involving the skin or hair.

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation

PubMed Central

Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Cesar, Sergi; Mademont, Irene; Mates, Jesus; Pérez-Serra, Alexandra; Coll, Monica; Pico, Ferran; Iglesias, Anna; Tirón, Coloma; Allegue, Catarina; Carro, Esther; Gallego, María Ángeles; Ferrer-Costa, Carles; Hospital, Anna; Bardalet, Narcís; Borondo, Juan Carlos; Vingut, Albert; Arbelo, Elena; Brugada, Josep; Castellà, Josep; Medallo, Jordi; Brugada, Ramon

2016-01-01

Background Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Methods and Findings Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Conclusions Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk. PMID:27930701

Screening for Chlamydia trachomatis in Egyptian women with unexplained infertility, comparing real-time PCR techniques to standard serology tests: case control study.

PubMed

Abdella, Rana M A; Abdelmoaty, Hatem I; Elsherif, Rasha H; Sayed, Ahmed Mahmoud; Sherif, Nadine Alaa; Gouda, Hisham M; El Lithy, Ahmed; Almohamady, Maged; Abdelbar, Mostafa; Hosni, Ahmed Naguib; Magdy, Ahmed; Ma, Youssef

2015-06-02

To study the prevalence of Chlamydia infection in women with primary and secondary unexplained infertility using ELISA technique for antibody detection and real time, fully automated PCR for antigen detection and to explore its association with circulating antisperm antibodies (ASA). A total of 50 women with unexplained infertility enrolled in this case control study and a control group of 44 infertile women with a known cause of infertility. Endocervical specimens were collected for Chlamydia antigen detection using PCR and serum samples for antibodies detection. Circulating anti-sperm antibodies were detected using sperm antibody Latex Agglutination tests. The overall prevalence of Chlamydial infection in unexplained infertility cases as detected by both ELISA and PCR was 40 % (20/50). The prevalence of current Chlamydial genital infection as detected by real-time PCR was only 6.0 % (3/50); two of which were also IgM positive. Prevalence of ASA was 6.0 % (3/50); all were sero-negative for anti-C.trachomatis IgM and were PCR negative. The incidence of Chlamydial infection in Egyptian patients with unexplained infertility is relatively high. In the setting of fertility investigations; screening for anti. C.trachomatis antibodies using ELISA, and treatment of positive cases should be considered. The presence of circulating ASA does not correlate with the presence of old or current Chlamydia infection in women with unexplained infertility.

Devices for Ambulatory Monitoring of Sleep-Associated Disorders in Children with Neurological Diseases.

PubMed

Ulate-Campos, Adriana; Tsuboyama, Melissa; Loddenkemper, Tobias

2017-12-25

Good sleep quality is essential for a child's wellbeing. Early sleep problems have been linked to the later development of emotional and behavioral disorders and can negatively impact the quality of life of the child and his or her family. Sleep-associated conditions are frequent in the pediatric population, and even more so in children with neurological problems. Monitoring devices can help to better characterize sleep efficiency and sleep quality. They can also be helpful to better characterize paroxysmal nocturnal events and differentiate between nocturnal seizures, parasomnias, and obstructive sleep apnea, each of which has a different management. Overnight ambulatory detection devices allow for a tolerable, low cost, objective assessment of sleep quality in the patient's natural environment. They can also be used as a notification system to allow for rapid recognition and prompt intervention of events like seizures. Optimal monitoring devices will be patient- and diagnosis-specific, but may include a combination of modalities such as ambulatory electroencephalograms, actigraphy, and pulse oximetry. We will summarize the current literature on ambulatory sleep devices for detecting sleep disorders in children with neurological diseases.

Adverse events associated with poor neurological outcome during targeted temperature management and advanced critical care after out-of-hospital cardiac arrest.

PubMed

Kim, Young-Min; Youn, Chun Song; Kim, Soo Hyun; Lee, Byung Kook; Cho, In Soo; Cho, Gyu Chong; Jeung, Kyung Woon; Oh, Sang Hoon; Choi, Seung Pill; Shin, Jong Hwan; Cha, Kyoung-Chul; Oh, Joo Suk; Yim, Hyeon Woo; Park, Kyu Nam

2015-07-22

The aim of this study was to investigate the association of adverse events (AEs) during targeted temperature management (TTM) and other AEs and concomitant treatments during the advanced critical care period with poor neurological outcome at hospital discharge in adult out-of-hospital cardiac arrest (OHCA) patients. This was a retrospective study using Korean Hypothermia Network registry data of adult OHCA patients treated with TTM in 24 teaching hospitals throughout South Korea from 2007 to 2012. Demographic characteristics, resuscitation and post-resuscitation variables, AEs, and concomitant treatments during TTM and the advanced critical care were collected. The primary outcome was poor neurological outcome, defined as a cerebral performance category (CPC) score of 3-5 at hospital discharge. The AEs and concomitant treatments were individually entered into the best multivariable predictive model of poor neurological outcome to evaluate the associations between each variable and outcome. A total of 930 patients, including 704 for whom a complete dataset of AEs and covariates was available for multivariable modeling, were included in the analysis; 476 of these patients exhibited poor neurological outcome [CPC 3 = 50 (7.1%), CPC 4 = 214 (30.4%), and CPC 5 = 212 (30.1%)]. Common AEs included hyperglycemia (45.6%), hypokalemia (31.3%), arrhythmia (21.3%) and hypotension (29%) during cooling, and hypotension (21.6%) during rewarming. Bleeding (5%) during TTM was a rare AE. Common AEs during the advanced critical care included pneumonia (39.6%), myoclonus (21.9%), seizures (21.7%) and hypoglycemia within 72 hours (23%). After adjusting for independent predictors of outcome, cooling- and rewarming-related AEs were not significantly associated with poor neurological outcome. However, sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care were associated with poor neurological outcome [adjusted odds ratios (95% confidence intervals) of 3.12 (1.40-6.97), 3.72 (1.93-7.16), 4.02 (2.04-7.91), 2.03 (1.09-3.78), and 1.69 (1.03-2.77), respectively]. Alternatively, neuromuscular blocker use was inversely associated with poor neurological outcome (0.48 [0.28-0.84]). Cooling- and rewarming-related AEs were not associated with poor neurological outcome at hospital discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during the advanced critical care period were associated with poor neurological outcome at hospital discharge in our study.

Unexplained Cases of Allergic Reactions Linked to Red Meat

MedlinePlus

... that starts after being bitten by a lone star tick may cause unexplained cases of recurrent anaphylaxis. ... after eating meat. Previous studies have linked lone star tick bites to this unusual food allergy. The ...

Percutaneous closure of patent foramen ovale in patients with presumed paradoxical embolism: periprocedural results and midterm risk of recurrent neurologic events.

PubMed

Balbi, Manrico; Casalino, Laura; Gnecco, Giovanni; Bezante, Gian Paolo; Pongiglione, Giacomo; Marasini, Maurizio; Del Sette, Massimo; Barsotti, Antonio

2008-08-01

To report our data on selected patients with previous paradoxical embolism who underwent transcatheter patent foramen ovale (PFO) closure. Between July 2001 and July 2007, percutaneous PFO closure was performed on 128 patients (65 women, mean age: 46 +/- 12.8 years). Patent foramen ovale closure was recommended for secondary prevention in patients with previous transient ischemic attacks (52.5%), stroke (46%), or peripheral embolism (1.5%). Implantation was successful in all patients, and at the end of intervention, complete PFO closure was achieved in 70.3% of them. There were no "major" complications (ie, deaths, device embolization or thrombosis, need for cardiac surgery). The overall incidence of complications (mostly hemorrhagic) was 7%. The mean follow-up period was 32 months. Complete closure had been achieved in 78.4% and in 82.5% of patients at the third month of transesophageal echocardiography examination and at the sixth month of transcranial Doppler examination, respectively. There were no recurrent thromboembolic events during the follow-up period. Percutaneous closure of PFO is a feasible procedure, but it is not a risk-free technique. However, in correctly selected patients (ie, large PFO and those at risk for neurologic relapse), nearly complete PFO closure seems to provide protection from future neurologic ischaemic events at midterm follow-up.

The Molecular Autopsy: Should the Evaluation Continue After the Funeral?

PubMed Central

Tester, David J.; Ackerman, Michael J.

2012-01-01

Sudden cardiac death (SCD) is one of the most common causes of death in developed countries, with most SCDs involving the elderly, and structural heart disease evident at autopsy. Each year, however, thousands of sudden deaths involving individuals younger than 35 years of age remain unexplained after a comprehensive medicolegal investigation that includes an autopsy. In fact, several epidemiologic studies have estimated that at least 3% and up to 53% of sudden deaths involving previously healthy children, adolescents, and young adults show no morphologic abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation through either a cardiologic and genetic evaluation of first- or second-degree relatives or a molecular autopsy may elucidate the underlying mechanism contributing to the sudden death and allow for identification of living family members with the pathogenic substrate that renders them vulnerable, with an increased risk for cardiac events including syncope, cardiac arrest, and sudden death. PMID:22307399

Anticipating smallpox and monkeypox outbreaks: complications of the smallpox vaccine.

PubMed

Abrahams, Brian C; Kaufman, David M

2004-09-01

The recent outbreak in the Midwest of monkeypox, as well as the continued fears of a terrorist-induced epidemic of smallpox, prompted the authors' review of the literature regarding past and current experiences with smallpox vaccination. The smallpox vaccine, which is highly effective in preventing the spread of both these orthopoxvirus infectious illnesses, might be administered to numerous health care workers and, in the event of a smallpox attack, millions of other citizens. However, vaccinees would be at risk for several vaccine-related neurologic complications. According to prior reports, neurologic complications have occurred in 2.5 per million US individuals, with the most common being postvaccinal encephalomyelitis (PVEM). In older children and adults, PVEM causes stupor and coma, seizures, paraparesis, and other neurologic and mental abnormalities, and, in 16% of cases, permanent neurologic sequelae. The overall mortality rate of neurologic complications is approximately 1.5 per million vaccinees. Risk factors for PVEM were age younger than 1 year and no previous smallpox vaccination, but not a prior episode of PVEM or other preexisting neurologic illnesses. Neither the current smallpox vaccination campaigns in Israel nor the one in the United States has had comparable complications, but the US campaign has been associated with myocarditis and myopericarditis. Although the potential neurologic complications of the smallpox vaccine must be weighed against the threat of monkeypox and smallpox, current experience with vaccination suggests it carries a very low risk of neurologic complications and does not lead to exacerbations of chronic neurologic illnesses.

Historical model for editor and Office of Research Integrity cooperation in handling allegations, investigation, and retraction in a contentious (Abbs) case of research misconduct.

PubMed

Price, Alan R; Daroff, Robert B

2015-01-01

Cooperation between a journal editor and the federal Office of Research Integrity (ORI) in addressing investigations of research misconduct, each performing their own responsibilities while keeping each other informed of events and evidence, can be critical to the professional and regulatory resolution of a case. This paper describes the history of one of ORI's most contentious investigations that involved falsification of research on Parkinson's disease patients by James Abbs, Professor of Neurology, University of Wisconsin, published in the journal Neurology, which was handled cooperatively by the authors, who were the chief ORI investigator and the Editor-in-Chief of Neurology, respectively.

Gardner-Diamond syndrome: Difficulties in the management of patients with unexplained medical symptoms

PubMed Central

Meeder, Robert; Bannister, Susan

2006-01-01

The case of an adolescent girl who presented with unexplained bruising is reported. Subsequent investigations failed to elucidate an organic etiology. The diagnosis of Gardner-Diamond syndrome – a syndrome of predictable bruising preceded by pain and warmth at the bruise site, often associated with physical or psychosocial stress – was made. In the present report, the authors use their experience with this rare syndrome to highlight some important ethical and practical considerations with regard to investigation, treatment and communication in illnesses with unexplained medical symptoms. PMID:19030312

A case of anorexia nervosa in an elderly man.

PubMed

Malik, Fahd; Wijayatunga, Uditha; Bruxner, George M

2014-06-01

To explore aspects of anorexia nervosa occurring in older populations, especially men, by reviewing the literature and presenting a case study of an elderly man with unexplained vomiting and weight loss. The literature is reviewed and an illustrative case study of an elderly man with unexplained vomiting and weight loss is described. Anorexia nervosa is an uncommon cause of unexplained weight loss in the elderly, but may be under-recognized and associated with a high level of mortality. © The Royal Australian and New Zealand College of Psychiatrists 2014.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY): concept, design and rationale.

PubMed

Fanning, Jonathon P; Wesley, Allan J; Platts, David G; Walters, Darren L; Eeles, Eamonn M; Seco, Michael; Tronstad, Oystein; Strugnell, Wendy; Barnett, Adrian G; Clarke, Andrew J; Bellapart, Judith; Vallely, Michael P; Tesar, Peter J; Fraser, John F

2014-04-05

The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY): concept, design and rationale

PubMed Central

2014-01-01

Background The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. Methods The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. Discussion The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification. PMID:24708720

Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and ranavirus in Russia.

PubMed

Reshetnikov, Andrey N; Chestnut, Tara; Brunner, Jesse L; Charles, Kaylene; Nebergall, Emily E; Olson, Deanna H

2014-08-11

In a population of the European common toad Bufo bufo from a rural pond in the region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained mass mortality events involving larvae and metamorphs have been observed over a monitoring period of >20 yr. We tested toads from this and a nearby site for the emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus (Rv). Both pathogens were detected, and at the rural pond site, with the above-noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens. Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25 and 55%, respectively). This is the first confirmation of these pathogens in Russia. Questions remain as to the origins of these pathogens in Russia and their roles in documented mass mortality events.

Congenital portosystemic shunt: characterization of a multisystem disease.

PubMed

Sokollik, Christiane; Bandsma, Robert H J; Gana, Juan C; van den Heuvel, Meta; Ling, Simon C

2013-06-01

Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome.

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

PubMed

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

Cause of death and predictors of mortality in a community-based cohort of people with epilepsy.

PubMed

Keezer, Mark R; Bell, Gail S; Neligan, Aidan; Novy, Jan; Sander, Josemir W

2016-02-23

The risk of premature mortality is increased in people with epilepsy. The reasons for this and how it may relate to epilepsy etiology remain unclear. The National General Practice Study of Epilepsy is a prospective, community-based cohort that includes 558 people with recurrent unprovoked seizures of whom 34% died during almost 25 years of follow-up. We assessed the underlying and immediate causes of death and their relationship to epilepsy etiology. Psychiatric and somatic comorbidities of epilepsy as predictors of mortality were scrutinized using adjusted Cox proportional hazards models. The 3 most common underlying causes of death were noncerebral neoplasm, cardiovascular, and cerebrovascular disease, accounting for 59% (111/189) of deaths, while epilepsy-related causes (e.g., sudden unexplained death in epilepsy) accounted for 3% (6/189) of deaths. In 23% (43/189) of individuals, the underlying cause of death was directly related to the epilepsy etiology; this was significantly more likely if death occurred within 2 years of the index seizure (percent ratio 4.28 [95% confidence interval 2.63-6.97]). Specific comorbidities independently associated with increased risk of mortality were neoplasms (primary cerebral and noncerebral neoplasm), certain neurologic diseases, and substance abuse. Comorbid diseases are important causes of death, as well as predictors of premature mortality in epilepsy. There is an especially strong relationship between cause of death and epilepsy etiology in the first 2 years after the index seizure. Addressing these issues may help stem the tide of premature mortality in epilepsy. © 2016 American Academy of Neurology.

Clinical Manifestations, Outcomes, and Etiologies of Perinatal Stroke in Taiwan: Comparisons between Ischemic, and Hemorrhagic Stroke Based on 10-year Experience in A Single Institute.

PubMed

Lee, Chien-Chung; Lin, Jainn-Jim; Lin, Kuang-Lin; Lim, Wai-Ho; Hsu, Kai-Hsiang; Hsu, Jen-Fu; Fu, Ren-Huei; Chiang, Ming-Chou; Chu, Shih-Ming; Lien, Reyin

2017-06-01

Perinatal stroke is a common cause of established neurological sequelae. Although several risk factors have been identified, many questions regarding causes and clinical outcomes remain unanswered. This study investigated the clinical manifestations and outcomes of perinatal stroke and identified its etiologies in Taiwan. We searched the reports of head magnetic resonance imaging and computed tomography performed between January 2003 and December 2012. The medical records of enrolled infants with perinatal stroke were also reviewed. Thirty infants with perinatal stroke were identified; 10 infants had perinatal arterial ischemic stroke (PAIS) and 20 had perinatal hemorrhagic stroke (PHS). Neonatal seizure was the most common manifestation and presented in 40% of infants with PAIS and 50% of infants with PHS. All survivors with PAIS and 77% of the surviving infants with PHS developed neurological sequelae. Acute seizure manifestation was associated with poststroke epilepsy in infants with PHS but not in infants with PAIS (86% vs. 0%, p=0.005). PAIS was mostly caused by dysfunctional hemostasis (20%) and embolism (20%), whereas PHS was mostly attributable to birth asphyxia (30%). Perinatal stroke is associated with high mortality and morbidity rates in infants. Clinically, it can be difficult to distinguish PAIS and PHS. One should keep a high level of suspicion, especially for PHS, if infants develop unexplained seizure, cyanosis, conscious change, anemia, and/or thrombocytopenia. A systematic diagnostic approach is helpful in identifying the etiologies of perinatal stroke. Copyright © 2016. Published by Elsevier B.V.

Gestational age of pregnancy loss in women with unexplained recurrent miscarriage.

PubMed

Ticconi, Carlo; Giuliani, Emma; Sorge, Roberto; Patrizi, Lodovico; Piccione, Emilio; Pietropolli, Adalgisa

2016-03-01

The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% (n = 136) experienced miscarriages within a 1-week range of GA and 53.4% (n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient. © 2015 Japan Society of Obstetrics and Gynecology.

Unexplained chronic leukopenia treated with oral iron supplements.

PubMed

Abuirmeileh, Ayman; Bahnassi, Anas; Abuirmeileh, Amjad

2014-04-01

A 67-year-old woman known to have iron deficiency anemia and persistent unexplained chronic leukopenia was cared for by our medical center for about 16 years. During this period she was examined thoroughly and diagnosed to have chronic idiopathic neutropenia (also known as chronic benign neutropenia). Her iron deficiency was attributed to nutritional factors and she was non-compliant with her oral iron supplements. The patient fully received her iron supplement medication by nursing staff for two and a half months during an unexpected prolonged hospital stay after her suffering an acute ischemic cerebrovascular accident. An astonishing outcome was that in addition to having her iron deficiency anemia treated, her long-term unexplained neutropenia was also corrected. Some patients diagnosed with chronic idiopathic neutropenia and clinically present as having unexplained chronic neutropenia might actually be suffering from a form of not yet described iron deficiency induced neutropenia.

Neurological adverse events associated with vaccination.

PubMed

Piyasirisilp, Sucheep; Hemachudha, Thiravat

2002-06-01

Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

[The assesment of cranio-cerebral injuries in the aspect of neurological, psychiatric and certification criteria].

PubMed

Maksymowicz, Krzysztof; Piechocki, Dariusz; Drozd, Radosław

2005-01-01

In this paper an effort has been made to explain and systemize the notions of encephalopathy, psycho organic syndrome, characteropathy, seen as consequences of cranio-cerebral injuries, and regarding neurological, psychiatric and certificating criteria. The main aim of this classification is to define the necessary conditions needed to confirm or exclude the presence of neurological changes mentioned above. The conditions should be acceptable from the neurological, psychiatric and certificating points of view. The certificating experience of the authors shows that there are vast differences among criteria applied by neurologists, psychiatrists and certificating doctors in assessing the consequences of cranio-cerebral injuries. Moreover, in the above paper various injury and disease factors have been presented and discussed. Although they do not remain in any causal connection with the assessed event, they have a significant influence on the final result of the medical certification.

Therapists' experiences and perceptions of teamwork in neurological rehabilitation: critical happenings in effective and ineffective teamwork.

PubMed

Suddick, Kitty M; De Souza, Lorraine H

2007-12-01

This paper reports the second part of an exploratory study into occupational therapists' and physiotherapists' perceptions and experiences of teamwork in neurological rehabilitation: the factors that were thought to influence effective and ineffective teamwork, and the meaning behind effective and ineffective teamwork in neurological rehabilitation. The study was undertaken through semi-structured interviews of 10 therapists from three different neurological rehabilitation teams based in the United Kingdom, and used the critical incident technique. Through analysis of the data, several main themes emerged regarding the perceived critical happenings in effective and ineffective teamwork. These were: team events and characteristics, team members' characteristics, shared and collaborative working practices, communication, specific organizational structures, environmental, external, and patient and family-related factors. Effective and ineffective team-work was perceived to impact on a number of levels: having implications for the team, the patient, individual team members, and the neurological rehabilitation service. The study supported the perceived value of team work within neurological rehabilitation. It also indicated the extensive and variable factors that may influence the team-working process as well as the complex and diverse nature of the process.

Unexplained cough: it is time to rule out Sjogren's syndrome.

PubMed

Koslow, Matthew; Kivity, Shaye; Vishnevskia-Dai, Vicktoria; Ben-Dov, Issahar

2018-05-01

Sjogren's syndrome is associated with chronic cough, but sicca symptoms are missing from cough evaluation guidelines. We evaluated patients with unexplained cough for undiagnosed Sjogren's syndrome. Patients referred to our pulmonary clinic (Sheba Medical Center, 2009 to 2012) with unexplained cough and concomitant dry eyes were selected for evaluation. Unexplained cough was defined as chronic cough of unknown etiology despite algorithm-based evaluation and treatment. Patients were evaluated in a dedicated clinic by a pulmonologist, rheumatologist, and ophthalmologist specializing in autoimmune disease. Patients completed the Leicester Cough Questionnaire, spirometry, antibody testing for anti Ro/La, ophthalmologic examination with visual acuity, eyelid, ocular surface fluorescein staining, tear break-up time and Schirmer's test, full slit lamp, and fundus examinations. Four-year follow-up was conducted by telephone questionnaire. We identified 24 patients among which 22 (21 females) agreed for evaluation. Eight patients (36%), seven initially, and one during follow-up were diagnosed with Sjogren's syndrome (SS) (six secondary and two primary SS). At 4-year follow-up, cough tended to persist and improve in only 37% with SS. These include 2 (Scl and RA) who received rituximab and 1 (stage 1 sarcoidosis) with spontaneous improvement. In contrast, cough improved in most (64%) patients without SS; the majority (eight/nine) report intensified disease-specific treatment (five allergic and three GERD). We describe patients in whom unexplained chronic cough was associated with dry eyes. Focused workup revealed undiagnosed Sjogren's syndrome in 36%. Dry eyes, with or without SS, is under-recognized and should be added to diagnostic algorithms for unexplained cough.

Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli: A Meta-Analysis

PubMed Central

Mossbridge, Julia; Tressoldi, Patrizio; Utts, Jessica

2012-01-01

This meta-analysis of 26 reports published between 1978 and 2010 tests an unusual hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: (1) randomly ordered presentations of arousing vs. neutral stimuli, or (2) guessing tasks with feedback (correct vs. incorrect). Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity, and blood oxygenation level dependent (BOLD) activity. To avoid including data hand-picked from multiple different analyses, no post hoc experiments were considered. The results reveal a significant overall effect with a small effect size [fixed effect: overall ES = 0.21, 95% CI = 0.15–0.27, z = 6.9, p < 2.7 × 10−12; random effects: overall (weighted) ES = 0.21, 95% CI = 0.13–0.29, z = 5.3, p < 5.7 × 10−8]. Higher quality experiments produced a quantitatively larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p > 0.05) was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviorally relevant events. We conclude that to further examine this currently unexplained anticipatory activity, multiple replications arising from different laboratories using the same methods are necessary. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones), remains to be determined. PMID:23109927

Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic testing.

PubMed

Giannopoulos, Georgios; Kossyvakis, Charalampos; Panagopoulou, Vasiliki; Tsiachris, Dimitrios; Doudoumis, Konstantinos; Mavri, Maria; Vrachatis, Dimitrios; Letsas, Konstantinos; Efremidis, Michael; Katsivas, Apostolos; Lekakis, John; Deftereos, Spyridon

2017-05-01

Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly. The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT). This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms. Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders. In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause). Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Neurological deficits in the life and works of Frida Kahlo.

PubMed

Budrys, Valmantas

2006-01-01

World-famous Mexican painter Frida Kahlo is an impressive example of an artist whose entire life and creativity were extremely influenced by chronic, severe illness. Many of her best-known works depict her physical and mental suffering. She was one of those very uncommon artists who dared to show their nude, sick body. This article describes biographical events and works of Frida Kahlo that are closely related to neurology: congenital anomaly (spina bifida), poliomyelitis, spine injury, neuropathic pain.

Widespread activity of multiple lineages of Usutu virus, western Europe, 2016

PubMed Central

Cadar, Daniel; Lühken, Renke; van der Jeugd, Henk; Garigliany, Mutien; Ziegler, Ute; Keller, Markus; Lahoreau, Jennifer; Lachmann, Lars; Becker, Norbert; Kik, Marja; Oude Munnink, Bas B; Bosch, Stefan; Tannich, Egbert; Linden, Annick; Schmidt, Volker; Koopmans, Marion P; Rijks, Jolianne; Desmecht, Daniel; Groschup, Martin H; Reusken, Chantal; Schmidt-Chanasit, Jonas

2017-01-01

In the summer of 2016, Belgium, France, Germany and the Netherlands reported widespread Usutu virus (USUV) activity based on live and dead bird surveillance. The causative USUV strains represented four lineages, of which two putative novel lineages were most likely recently introduced into Germany and spread to other western European countries. The spatial extent of the outbreak area corresponded with R0 values > 1. The occurrence of the outbreak, the largest USUV epizootic registered so far in Europe, allowed us to gain insight in how a recently introduced arbovirus with potential public health implications can spread and become a resident pathogen in a naïve environment. Understanding the ecological and epidemiological factors that drive the emergence or re-emergence of USUV is critical to develop and implement timely surveillance strategies for adequate preventive and control measures. Public health authorities, blood transfusion services and clinicians in countries where USUV was detected should be aware of the risk of possible USUV infection in humans, including in patients with unexplained encephalitis or other neurological impairments, especially during late summer when mosquito densities peak. PMID:28181903

Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea.

PubMed

Hosp, Christine; Naumann, Markus K; Hamm, Henning

2016-02-01

Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bayés syndrome and acute cardioembolic ischemic stroke.

PubMed

Arboix, Adrià; Martí, Lucía; Dorison, Sebastien; Sánchez, María José

2017-03-16

Bayés syndrome is an under-recognized clinical condition characterized by advanced interatrial block. Bayés syndrome is a subclinical disease that manifests electrocardiographically as a prolonged P wave duration > 120 ms with biphasic morphology ± in the inferior leads. The clinical relevance of Bayés syndrome lies in the fact that is a clear arrhythmological syndrome and has a strong association with supraventricular arrhythmias, particularly atypical atrial flutter and atrial fibrillation. Likewise, Bayés syndrome has been recently identified as a novel risk factor for non-lacunar cardioembolic ischemic stroke and vascular dementia. Advanced interatrial block can be a risk for embolic stroke due to its known sequelae of left atrial dilation, left atrial electromechanical dysfunction or atrial tachyarrhythmia (paroxysmal or persistent atrial fibrillation), conditions predisposing to thromboembolism. Bayés syndrome may be responsible for some of the unexplained ischemic strokes and shall be considered and investigated as a possible cause for cryptogenetic stroke. In summary, Bayés syndrome is a poorly recognized cardiac rhythm disorder with important cardiologic and neurologic implications.

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2010 CFR

2010-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2013 CFR

2013-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2014 CFR

2014-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2011 CFR

2011-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2012 CFR

2012-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

Unexplained Absences and Risk of Death and Injury Among Nursing Home Residents: A Systematic Review.

PubMed

Woolford, Marta H; Weller, Carolina; Ibrahim, Joseph E

2017-04-01

Unexplained absence of nursing home (NH) residents is one of the most challenging issues related to the care of older people. The aim of this review was to examine the death and injury outcomes of unexplained absence of NH residents. We searched MEDLINE, CINAHL, EMBASE, PsycINFO, AgeLine, and Cochrane Library to identify qualitative and quantitative studies published in the English language. Data on death and injury were collated, and aggregate proportions were calculated where possible. Nine studies were identified; most (n = 6) were conducted in the United States. Persons with dementia formed the study population in all studies. There were 1440 individual unexplained absences reported across the 9 studies. We calculated a rate of 82 deaths and 61 injuries per 1000 incidents of unexplained absence. Extreme temperatures were the most common cause of death. Most individuals left by foot, and were found within a 1-mile radius of place last seen in green vegetation and waterways. This review provides valuable insight into death and injury outcomes. Further studies are recommended to improve understanding and prevent adverse outcomes. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Physician Satisfaction in Treating Medically Unexplained Symptoms.

PubMed

Brauer, Simon G; Yoon, John D; Curlin, Farr A

2017-05-01

To determine whether treating conditions having medically unexplained symptoms is associated with lower physician satisfaction and higher ascribed patient responsibility, and to determine whether higher ascribed patient responsibility is associated with lower physician satisfaction in treating a given condition. We surveyed a nationally representative sample of 1504 US primary care physicians. Respondents were asked how responsible patients are for two conditions with more-developed medical explanations (depression and anxiety) and two conditions with less-developed medical explanations (chronic back pain and fibromyalgia), and how much satisfaction they experienced in treating each condition. We used Wald tests to compare mean satisfaction and ascribed patient responsibility between medically explained conditions and medically unexplained conditions. We conducted single-level and multilevel ordinal logistic models to test the relation between ascribed patient responsibility and physician satisfaction. Treating medically unexplained conditions elicited less satisfaction than treating medically explained conditions (Wald P < 0.001). Physicians attribute significantly more patient responsibility to the former (Wald P < 0.005), although the magnitude of the difference is small. Across all four conditions, physicians reported experiencing less satisfaction when treating symptoms that result from choices for which patients are responsible (multilevel odds ratio 0.57, P = 0.000). Physicians experience less satisfaction in treating conditions characterized by medically unexplained conditions and in treating conditions for which they believe the patient is responsible.

Myocardial Bridge and Acute Plaque Rupture.

PubMed

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

Vaccinations and multiple sclerosis.

PubMed

Gout, O

2001-04-01

Two problems must be considered in regard to the relationship between vaccinations and MS: Do vaccinations favour the first attack of MS? Do they increase the short- or long-term risk in patients with known disease? Answers to these questions are difficult due to the paucity of reported cases, our ignorance of the precise frequency of neurological adverse events in vaccines based on prospective studies, and finally by the lack of a well established pathophysiology. In most instances, the role of the vaccine is based on a temporal link between the injection and the onset of neurological disease, and more rarely to a positive reintroduction. Acute disseminated encephalomyelitis (ADEM), a monophasic and multifocal illness of the white and grey matter, has been observed following various viral or bacterial infections as well as vaccine injections for diseases such as pertussis, tetanus and yellow fever. The similarities between ADEM and experimental allergic encephalitis (EAE) are suggestive of an immunological process. In addition to the dramatic presentation of ADEM, more limited white matter involvement, such as optic neuritis or myelitis, has been reported following vaccine injections, and has occasionally been counted as the first attack of MS. In France, 25 million inhabitants, almost half of the population, were vaccinated against hepatitis B (HB) between 1991 and 1999. Several hundred cases of an acute central demyelinating event following HB vaccination were reported to the pharmacovigilance unit, leading to a modification of vaccination policy in the schools and the initiation of several studies designed to examine the possible relationship between the vaccine and the central demyelinating events. The results of these studies failed to establish the causality of the HB vaccine. Nevertheless, molecular mimicry between HB antigen(s) and one or more myelin proteins, or a non-specific activation of autoreactive lymphocytes, could constitute possible pathogenetic mechanisms for these adverse neurological events.

Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology.

PubMed

da Costa Souza, Paola; Dondo, Patrícia Suemi; Souza, Gabriela; Lopes, Deborah; Moscardi, Marcel; de Miranda Martinho, Vinicius; de Mattos Lourenço, Rodolfo Daniel; Prieto, Tabatha; Balancin, Marcelo Luiz; Assato, Aline Kawassaki; Teodoro, Walcy Rosolia; Rodrigues, Silvia; Lima, Mariana; Castellano, Maria Vera; Coletta, Ester; Parra, Edwin Roger; Capelozzi, Vera Luiza

2018-05-01

This study analyzed the type 1 and type 2T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-β. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-β might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas. Copyright © 2018 Elsevier Inc. All rights reserved.

Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

PubMed

Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter A; Christman, Gregory M; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Schlaff, William; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2017-08-01

While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function. Copyright © 2017 Elsevier Inc. All rights reserved.

Myasthenia Gravis: Tests and Diagnostic Methods

MedlinePlus

... Focus on MG Newsletter MG Quarterly Test & Diagnostic methods In addition to a complete medical and neurological ... How can I help? About MGFA Test & Diagnostic methods Treatment for MG FAQ's Upcoming Events 2018 MG ...

Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

PubMed

Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine; Fink-Jensen, Anders; Nielsen, Jimmi

2016-10-01

Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients.

Nonepileptic Seizures: An Updated Review

PubMed Central

Perez, David L.; LaFrance, W. Curt

2016-01-01

Psychogenic nonepileptic seizures are a Functional Neurological Disorder/ Conversion Disorder subtype, which are neurobehavioral conditions at the interface of Neurology and Psychiatry. Significant advancements over the past decade have been made in the diagnosis, management and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions and outcome studies. Epidemiology and health care utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES and should be assessed in diagnostic evaluations, and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders. PMID:26996600

Where no guideline has gone before: retrospective analysis of resuscitation in the 24th century.

PubMed

Hörburger, David; Haslinger, Julia; Bickel, Hubert; Graf, Nikolaus; Schober, Andreas; Testori, Christoph; Weiser, Christoph; Sterz, Fritz; Haugk, Moritz

2014-12-01

Evaluation of the treatment, epidemiology and outcome of cardiac arrest in the television franchise Star Trek. Retrospective cohort study of prospective events. Screening of all episodes of Star Trek: The Next Generation, Star Trek: Deep Space Nine and Star Trek: Voyager for cardiac arrest events. Documentation was performed according to the Utstein guidelines for cardiac arrest documentation. All adult, single person cardiac arrests were included. Patients were excluded if cardiac arrest occurred during mass casualties, if the victims were annihilated by energy weapons or were murdered and nobody besides the assassin could provide first aid. Epidemiological data, treatment and outcome of cardiac arrest victims in the 24th century were studied. Ninety-six cardiac arrests were included. Twenty-three individuals were female (24%). Cardiac arrest was witnessed in 91 cases (95%), trauma was the leading cause (n = 38; 40%). Resuscitation was initiated in 17 cases (18%) and 12 patients (13%) had return of spontaneous circulation. Favorable neurological outcome and long-term survival was documented in nine patients (9%). Technically diagnosed cardiac arrest was associated with higher rates of favorable neurological outcome and long-term survival. Neurological outcome and survival did not depend on cardiac arrest location. Cardiac arrest remains a critical event in the 24th century. We observed a change of etiology from cardiac toward traumatic origin. Quick access to medical help and new prognostic tools were established to treat cardiac arrest.

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials.

PubMed

Brill, Anne-Kathrin; Horvath, Thomas; Seiler, Andrea; Camilo, Millene; Haynes, Alan G; Ott, Sebastian R; Egger, Matthias; Bassetti, Claudio L

2018-04-03

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97-5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05-3.21, p = 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263-1.0548) but with a considerable heterogeneity ( I 2 = 78.9%, p = 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs. © 2018 American Academy of Neurology.

A Bermuda Triangle of Science

ERIC Educational Resources Information Center

Winkelsas, John

2006-01-01

The Bermuda Triangle is famous for the unexplained disappearances of ships and aircraft, and for strange meteorological phenomena that allegedly have occurred within its boundaries. This article presents an activity wherein students are asked to create their own geographical triangles to research, but instead of focusing on the unexplainable,…

Discrepancy between clinical practice and standardized indications for an implantable loop recorder in patients with unexplained syncope†

PubMed Central

Vitale, Elena; Ungar, Andrea; Maggi, Roberto; Francese, Maura; Lunati, Maurizio; Colaceci, Roberto; Del Rosso, Attilio; Castro, Antonio; Santini, Massimo; Giuli, Silvia; Belgini, Lara; Casagranda, Ivo; Brignole, Michele

2010-01-01

Aim An implantable loop recorder (ILR) is indicated in patients with unexplained syncope after complete conventional work-up. Data from the literature imply that, in clinical practice, the ILR is underused. The aim of the study was to verify if there is any discrepancy between the use of ILRs in clinical practice and the potential indications based on the most potentially appropriate guideline indications. Method and results We compared the prevalence of ILRs actually implanted in patients with unexplained syncope in the Syncope Unit Project (SUP) study and the potential one using the standard given by the guidelines. In the SUP study, 28 (18%) out of 159 patients with unexplained syncope received an ILR. Appropriate criteria for implantation of ILRs according to guidelines were present in 110 (69%) patients. Moreover, 7 (25%) of ILRs actually implanted did not satisfy the guideline standards. During the follow-up, 32% of patients who had received an ILR had a diagnosis compared with 5% of those who did not (P= 0.001). Conclusions The estimated indications were four times higher than those observed. Moreover, in about one quarter of the cases, the use of ILRs proved to be potentially inappropriate according to guideline indications. Two-thirds of patients with unexplained syncope had indications potentially appropriate for ILRs. PMID:20876604

Paroxysmal non-epileptic events in infants and toddlers: A phenomenologic analysis.

PubMed

Chen, Li; Knight, Elia M Pestana; Tuxhorn, Ingrid; Shahid, Asim; Lüders, Hans O

2015-06-01

The aim of this study was to analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEE) in infants and toddlers. We studied all children aged ≤2 years who were diagnosed with PNEE based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: (i) motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing); (ii) oral/vocal (crying, vocalization, sighing); (iii) behavioral change (arrest of activity, staring); (iv) and autonomic (facial flushing, breath holding). Thirty-one of 81 (38.3%) infants and toddlers had 38 PNEE recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events, and autonomic in 8/38 events. Epileptic seizures and PNEE coexisted in four children (12.9%). Seventeen children (54.8%) had one or more risk factors suggestive of epilepsy. Twelve children (38.7%) had a normal neurologic examination, 10 (32.3%) had developmental delay, and eight (25.8%) had a family history of epilepsy or seizures. VEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that paroxysmal non-epileptic seizures may frequently coexist in young children with epilepsy. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

National Institute of Neurological Disorders and Stroke

MedlinePlus

... All News Technical Assistance Webinar for the BRAIN Initiative Diversity K99/R00 Tuesday, June 12, 2018 | Online ... View All Events Director's Corner The NIH HEAL Initiative and Pain Research Thursday, June 21, 2018 At ...

Increased pediatric functional neurological symptom disorders after the Boston marathon bombings: a case series.

PubMed

Guerriero, Réjean M; Pier, Danielle B; de Gusmão, Claudio M; Bernson-Leung, Miya E; Maski, Kiran P; Urion, David K; Waugh, Jeff L

2014-11-01

Functional neurological symptom disorders are frequently the basis for acute neurological consultation. In children, they are often precipitated by high-frequency everyday stressors. The extent to which a severe traumatic experience may also precipitate functional neurological abnormalities is unknown. For the 2-week period after the Boston Marathon bombings, we prospectively collected data on patients whose presentation suggested a functional neurological symptom disorder. We assessed clinical and demographic variables, duration of symptoms, extent of educational impact, and degree of connection to the Marathon bombing. We contacted all patients at 6 months after presentation to determine the outcome and accuracy of the diagnosis. In a parallel study, we reported a baseline of 2.6 functional neurological presentations per week in our emergency room. In the week after the Marathon bombings, this frequency tripled. Ninety-one percent of presentations were delayed by 1 week, with onset around the first school day after a city-wide lockdown. Seventy-three percent had a history of a prior psychiatric diagnosis. At the 6 months follow-up, no functional neurological symptom disorder diagnoses were overturned and no new organic diagnosis was made. Pediatric functional neurological symptom disorder may be precipitated by both casual and high-intensity stressors. The 3.4-fold increase in incidence after the Boston Marathon bombings and city-wide lockdown demonstrates the marked effect that a community-wide tragedy can have on the mental health of children. Care providers must be aware of functional neurological symptom disorders after stressful community events in vulnerable patient populations, particularly those with prior psychiatric diagnoses. Copyright © 2014 Elsevier Inc. All rights reserved.

Yellow fever: epidemiology and prevention.

PubMed

Barnett, Elizabeth D

2007-03-15

Yellow fever continues to occur in regions of Africa and South America, despite the availability of effective vaccines. Recently, some cases of severe neurologic disease and multiorgan system disease have been described in individuals who received yellow fever vaccine. These events have focused attention on the need to define criteria for judicious use of yellow fever vaccine and to describe the spectrum of adverse events that may be associated with yellow fever vaccine. Describing host factors that would increase risk of these events and identifying potential treatment modalities for yellow fever and yellow fever vaccine-associated adverse events are subjects of intense investigation.

Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases

PubMed Central

Lallana, Enrico C; Fadul, Camilo E

2011-01-01

In parallel to our better understanding of the role of the immune system in neurologic diseases, there has been an increased availability in therapeutic options for autoimmune neurologic diseases such as multiple sclerosis, myasthenia gravis, polyneuropathies, central nervous system vasculitides and neurosarcoidosis. In many cases, the purported benefits of this class of therapy are anecdotal and not the result of good controlled clinical trials. Nonetheless, their potential efficacy is better known than their adverse event profile. A rationale therapeutic decision by the clinician will depend on a comprehensive understanding of the ratio between efficacy and toxicity. In this review, we outline the most commonly used immune suppressive medications in neurologic disease: cytotoxic chemotherapy, nucleoside analogues, calcineurin inhibitors, monoclonal antibodies and miscellaneous immune suppressants. A discussion of their mechanisms of action and related toxicity is highlighted, with the goal that the reader will be able to recognize the most commonly associated toxicities and identify strategies to prevent and manage problems that are expected to arise with their use. PMID:22379461

Recurrent laughter-induced syncope.

PubMed

Gaitatzis, Athanasios; Petzold, Axel

2012-07-01

Syncope is a common presenting complaint in Neurology clinics or Emergency departments, but its causes are sometimes difficult to diagnose. Apart from vasovagal attacks, other benign, neurally mediated syncopes include "situational" syncopes, which occur after urination, coughing, swallowing, or defecation. A healthy 42-year-old male patient presented to the neurology clinic with a long history of faints triggered by spontaneous laughter, especially after funny jokes. Physical and neurological examination, and electroencephalography and magnetic resonance imaging were unremarkable. There was no evidence to suggest cardiogenic causes, epilepsy, or cataplexy and a diagnosis of laughing syncope was made. Laughter-induced syncope is usually a single event in the majority of cases, but may present as recurrent attacks as in our case. Some cases occur in association with underlying neurological conditions. Prognosis is good in the case of neurally mediated attacks. Laughter may not be recognized by physicians as a cause of syncope, which may lead to unnecessary investigations or misdiagnosis, and affect patients' quality of life.

Chapter 4: neurology in the Bible and the Talmud.

PubMed

Feinsod, Moshe

2010-01-01

The Bible, a major pillar of Western Civilization consists of Hebrew Scriptures, assembled over a millennium and accepted as of divine origin. The Talmud is a compendium of Jewish laws, covering every possible aspect of life, analyzed in depth from 200 BCE to 600 CE, becoming the foundation of Jewish existence. The all-encompassing character of the books provides numerous medical problems and observations that appear in various connotations. When in need to clarify various legal dilemmas, the Talmudic sages displayed astoundingly accurate anatomical knowledge and were pioneers in clinical-pathological correlations. The descriptions of "neurological" events in the Bible are very precise but show no evidence of neurological knowledge. Those reported in the various tractates of the Talmud are evidence of a substantial medical knowledge, marked by Hellenistic influence. Subjects such as head and spinal injuries, epilepsy, handedness neuralgias aphasia tinnitus and tremor were discussed in depth. This chapter is an updated collection of the studies, extracting observations and discussions of neurological manifestations from the ancient texts.

Neurologic features of chronic Minamata disease (organic mercury poisoning) certified at autopsy.

PubMed

Uchino, M; Okajima, T; Eto, K; Kumamoto, T; Mishima, I; Ando, M

1995-08-01

To better understand the neurologic events related to chronic Minamata disease (organic mercury poisoning), we studied data from 77 patients with Minamata disease as certified at autopsies performed from 1976 to 1994 (mean age: 72.3 years). Major neurologic findings included: sensory impairment in 80.5% of the patients which was limited to the extremities in 42.9%. Impairment of lower extremity coordination was present in 35.8% of the patients, constriction of the visual fields in 28.8%, and retrocochlear hearing loss in 15.3%. There was no correlation between the degree of cerebellar incoordination and the methylmercury concentration in the cerebellum. Compared with the classic type of Minamata disease, the incidence of major neurologic findings was markedly decreased. In light of these findings, supplemental examinations including brain computed tomography (CT), magnetic resonance imaging (MRI), short latency somatosensory evoked potential (SSEP), or tremogram may be necessary to clinically diagnose Minamata disease, especially in atypical or mild cases.

Safe use of epidural corticosteroid injections: recommendations of the WIP Benelux workgroup.

PubMed

Van Boxem, Koen; Rijsdijk, Mienke; Hans, Guy; de Jong, Jasper; Kallewaard, Jan Willem; Vissers, Kris; van Kleef, Maarten; Rathmell, James P; Van Zundert, Jan

2018-05-14

Epidural corticosteroid injections are used frequently worldwide in the treatment of radicular pain. Concerns have risen involving rare major neurologic injuries after this treatment. Recommendations to prevent these complications have been published, but local implementation is not always feasible due to local circumstances and necessitating local recommendations based on literature review. A workgroup of 4 stakeholder pain societies in Belgium, The Netherlands and Luxembourg (Benelux) has reviewed the literature involving neurological complications after epidural corticosteroid injections and possible safety measures to prevent these major neurologic injuries. Twenty-six considerations and recommendations were selected by the workgroup. These involve the use of imaging, injection equipment particulate and non-particulate corticosteroids, epidural approach and maximal volume to be injected. Raising awareness about possible neurological complications and adoption of safety measures recommended by the work group aim at reducing the risks of these devastating events. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Management of Recurrent Delayed Neurologic Deficit After Thoracoabdominal Aortic Operation.

PubMed

Boutrous, Mina L; Afifi, Rana O; Safi, Hazim J; Estrera, Anthony L

2016-01-01

Delayed neurologic deficit (DND) is a devastating adverse event after thoracoabdominal aortic aneurysm repair. Multiple adjuncts have been devised to counteract the development of DND, most notably cerebrospinal fluid (CSF) drainage. We report a case of a 63-year-old woman in whom DND developed four times during the first 10 days after her thoracoabdominal aortic operation. This necessitated lumbar drain "weaning" to allow for a slowly rising CSF pressure and preservation of lower extremity motor function. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Frida Kahlo's neurological deficits and her art.

PubMed

Budrys, Valmantas

2013-01-01

World-famous Mexican painter Frida Kahlo is an impressive example of a professional artist whose artistic subject matter was extremely influenced by her chronic, severe illness. Many of her best-known works depict her physical and mental suffering. She was one of those very uncommon artists who dared to show their nude, sick body. This chapter describes and explains the biographical events and works of Frida Kahlo that are closely related to neurology: congenital anomaly (spina bifida), poliomyelitis, spine injury, and neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

[Etiology of initially unexplained confusion of excitability in deadly nightshade poisoning with suicidal intent. Symptoms, differential diagnosis, toxicology and physostigmine therapy of anticholinergic syndrome].

PubMed

Heindl, S; Binder, C; Desel, H; Matthies, U; Lojewski, I; Bandelow, B; Kahl, G F; Chemnitius, J M

2000-11-10

After a walk in a wood a 55-year-old teacher was admitted to the emergency unit of a university hospital because of somnolence and excitability. Her rectal temperature was 37.8 degrees C, she had sinus tachycardia (rate of 130/min) but no other significant findings. With the exception of C-reactive protein (10 mg/dl), MCV (101 fl), MCH (34 pg) and arterial blood gases (pH 7.483, pCO2 35.5 mmHg, base excess 5.1 mmp/l) laboratory tests were within normal limits. Qualitative screening of serum for benzodiazepines, barbiturates and antidepressives was negative. Neurological examination, including lumbar puncture and cranial computed tomography were noncontributory. 10 hours after admission the patient developed signs of an anticholinergic syndrome with mydriasis, dry mouth, tachycardia, hot skin and an atonic bladder. Physostigmine 2 mg completely reversed the neurological and mental symptoms. After gas chromatography, mass-spectrometry of a urine sample showed an atropine molecular fragment with a molecular weight of 271. At intervals of 3 to 5 hours the recurrence of confusion and excitability required 4 further i.v. injection of physostigmine. The patient subsequently became accessible to psychiatric examination and reported that during the walk she had swallowed 8-10 berries of deadly nightshade with suicidal intent. In case of excitability and confusion as well as somnolence or coma of uncertain aetiology an anticholinergic syndrome caused by ingestion of atropine-containing plants or psychoactive drugs (phenothiazines, butyrophenones, tri- or tetracyclic antidepressants) should be included in the differential diagnosis. If there are suggestive clinical findings (tachycardia, somnolence, coma or threatened respiratory arrest, physostigmine should be given if there are no contraindications.

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide.

PubMed

Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

2018-01-01

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness.

PubMed

Lahmann, Claas; Henningsen, Peter; Brandt, Thomas; Strupp, Michael; Jahn, Klaus; Dieterich, Marianne; Eckhardt-Henn, Annegret; Feuerecker, Regina; Dinkel, Andreas; Schmid, Gabriele

2015-03-01

Vertigo and dizziness are often not fully explained by an organic illness, but instead are related to psychiatric disorders. This study aimed to evaluate psychiatric comorbidity and assess psychosocial impairment in a large sample of patients with a wide range of unselected organic and non-organic (ie, medically unexplained) vertigo/dizziness syndromes. This cross-sectional study involved a sample of 547 patients recruited from a specialised interdisciplinary treatment centre for vertigo/dizziness. Diagnostic evaluation included standardised neurological examinations, structured clinical interview for major mental disorders (SCID-I) and self-report questionnaires regarding dizziness, depression, anxiety, somatisation and quality of life. Neurological diagnostic workup revealed organic and non-organic vertigo/dizziness in 80.8% and 19.2% of patients, respectively. In 48.8% of patients, SCID-I led to the diagnosis of a current psychiatric disorder, most frequently anxiety/phobic, somatoform and affective disorders. In the organic vertigo/dizziness group, 42.5% of patients, particularly those with vestibular paroxysmia or vestibular migraine, had a current psychiatric comorbidity. Patients with psychiatric comorbidity reported more vertigo-related handicaps, more depressive, anxiety and somatisation symptoms, and lower psychological quality of life compared with patients without psychiatric comorbidity. Almost half of patients with vertigo/dizziness suffer from a psychiatric comorbidity. These patients show more severe psychosocial impairment compared with patients without psychiatric disorders. The worst combination, in terms of vertigo-related handicaps, is having non-organic vertigo/dizziness and psychiatric comorbidity. This phenomenon should be considered when diagnosing and treating vertigo/dizziness in the early stages of the disease. 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.

Brain Injury Association of America

MedlinePlus

... Only) 1-800-444-6443 Welcome to the Brain Injury Association of America (BIAA) Brain injury is not an event or an outcome. ... misunderstood, under-funded neurological disease. People who sustain brain injuries must have timely access to expert trauma ...

Neurological Disorders in Medical Use of Cannabis: An Update.

PubMed

Solimini, Renata; Rotolo, Maria Concetta; Pichini, Simona; Pacifici, Roberta

2017-01-01

Medical cannabis is increasingly used as a treatment or adjunct treatment with different levels of efficacy in several neurological disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain, epilepsy, headache), as well as in other medical conditions (e.g. nausea and vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions, asthma). Nevertheless, a number of neurological adverse effects from use of medical cannabis on the short- and on the longterm have been reported, in addition to other adverse health events. It has been noticed that the use of medical cannabis can lead to a paradoxical effects depending on the amount of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain. Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis, seizures, epilepsy, headache) may be caused or exacerbated by the same treatment supposed to cure them. The current review presents an update of the neurological adverse effects resulting from the use of cannabis for medical purposes, highlighting the need to weigh the benefits and risks, when using cannabinoidbased treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adverse neurological outcomes in Nigerian children with sickle cell disease.

PubMed

Lagunju, I A; Brown, B J

2012-12-01

Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehta, Minesh P.; Shapiro, William R.; Phan, See C.

2009-03-15

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% ofmore » the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.« less

Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2011-06-20

To identify the rate of serious adverse events attributable to yellow fever vaccination with 17D and 17DD strains reported in active and passive surveillance data. We conducted a systematic review of published literature on adverse events associated with yellow fever. We searched 9 electronic databases for peer reviewed and grey literature in all languages. There were no restrictions on date of publication. Reference lists of key studies were also reviewed to identify additional studies. We identified 66 relevant studies: 24 used active, 17 a combination of passive and active (15 of which were pharmacovigilance databases), and 25 passive surveillance. ACTIVE SURVEILLANCE: A total of 2,660,929 patients in general populations were followed for adverse events after vaccination, heavily weighted (97.7%) by one large Brazilian study. There were no observed cases of viscerotropic or neurotropic disease, one of anaphylaxis and 26 cases of urticaria (hypersensitivity). We also identified four studies of infants and children (n=2199), four studies of women (n=1334), and one study of 174 HIV+, and no serious adverse events were observed. PHARMACOVIGILANCE DATABASES: 10 of the 15 databases contributed data to this review, with 107,621,154 patients, heavily weighted (94%) by the Brazilian database. The estimates for Australia were low at 0/210,656 for "severe neurological disease" and 1/210,656 for YEL-AVD, and also low for Brazil with 9 hypersensitivity events, 0.23 anaphylactic shock events, 0.84 neurologic syndrome events and 0.19 viscerotropic events cases/million doses. The five analyses of partly overlapping periods for the US VAERS database provided an estimate of 6.6 YEL-AVD and YEL-AND cases per million, and estimates between 11.1 and 15.6 of overall "serious adverse events" per million. The estimates for the UK were higher at 34 "serious adverse events" and also for Switzerland with 14.6 "neurologic events" and 40 "serious events not neurological"/million doses. PASSIVE SURVEILLANCE: Six studies of campaigns in general populations included 94,500,528 individuals, very heavily weighted (99%) by the Brazilian data, and providing an estimate of 0.51 serious AEFIs/million doses. Five retrospective reviews of hospital or clinic records included 60,698 individuals, and no serious AEFIs were proven. The data are heavily weighted (96%) by the data from the Hospital for Tropical Diseases, London. Two studies included 35,723 children, four studies included 138 pregnant women, six studies included 191 HIV+ patients, and there was one review of patients who were HIV+, and no serious AEFIs were proven. The databases in each country used different definitions, protocols, surveillance mechanisms for the initial identification and reporting of cases, and strategies for the clinical and laboratory follow up of cases. The pharmacovigilance databases provide three sets of estimates: a low estimate from the Brazilian and Australian data, a medium estimate from the US VAERS data, and a higher estimate from the UK and Swiss data. The estimates from the active surveillance data are lower (and strongly influenced by the Brazilian data) and the estimates from the passive surveillance studies are also lower (strongly influenced by the London Hospital for Tropical Diseases data from the early 1950s). Sophisticated pathology, histopathology and tests such as PCR amplicon sequencing are needed to prove that serious adverse events were actually caused by the yellow fever vaccine, and the availability of such diagnostic capability is strongly biased towards recent reports from developed countries. Despite these variations in the estimation of serious harm, overall the 17D and 17DD yellow fever vaccine has proven to be a very safe vaccine and is highly effective against an illness with high potential mortality rates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sexual, Physical, Verbal/Emotional Abuse and Unexplained Chest Pain

ERIC Educational Resources Information Center

Eslick, Guy D.; Koloski, Natasha A.; Talley, Nicholas J.

2011-01-01

Objectives: Approximately one third of patients with non cardiac chest pain (NCCP) report a history of abuse, however no data exists on the prevalence of abuse among people with unexplained chest pain in the general population. We aimed to determine if there is a relationship between childhood sexual, physical, emotional abuse and unexplained…

Psychological Mechanisms of Medically Unexplained Symptoms: An Integrative Conceptual Model

ERIC Educational Resources Information Center

Brown, Richard J.

2004-01-01

Theories of medically unexplained illness based on the concepts of dissociation, conversion, and somatization are summarized. Evidence cited in support of these theories is described and the conceptual strengths and shortcomings of each approach are considered. It is argued that each of these approaches adds to the understanding of unexplained…

Dexamethasone in unexplained infertility.

PubMed

Moradan, Sanam; Ghorbani, Raheb

2009-08-01

To determine if dexamethasone could be a suitable option in the treatment of patients with unexplained infertility. This study was carried out in the Obstetrics Department of Amir University Hospital, Semnan, Iran, from April 2001 to May 2008. One hundred and twenty-four cases of unexplained infertility that underwent ovulation induction and intrauterine insemination (IUI) (only one cycle) were evaluated, and divided into 2 groups. Sixteen cases were excluded, as they were unresponsive to the induction ovulation regimen. Group I (n=42) received clomiphene citrate (CC) + dexamethasone, and the control group (group II, n=66) received CC alone. These groups were the same in age, duration of infertility, and body mass index. The clinical pregnancy rates were evaluated in 2 groups by using statistical tests. The clinical pregnancy rate was 21.4% in group I, and 4.5% in group II. There was a significant statistical difference between the groups (relative risk=4.71, 95% confidence interval=1.35-16.42, p=0.0085). The pregnancy rate in women with unexplained infertility that underwent ovulation induction with CC + dexamethasone + IUI was significantly higher than those who underwent ovulation induction with CC alone + IUI.

Unexplained agglutination of stored red blood cells in Alsever's solution caused by the gram-negative bacterium Serratia liquefaciens.

PubMed

Martincic, I; Mastronardi, C; Chung, A; Ramirez-Arcos, S

2008-01-01

Alsever's solution has been used for decades as a preservative solution for storage of RBCs. From October 2005 to January 2006, unexplained hemagglutination of approximately 10 to 20 percent of RBCs stored for several days in a modified version of Alsever's solution was noticed in quality control testing at the Canadian Blood Services Serology Laboratory. An investigation, including microbial testing, was initiated to determine the cause of the unexplained hemagglutination. The gram-negative bacterium Serratia liquefaciens was isolated from supernatant solutions of agglutinated RBCs. Further characterization of this strain revealed that it has the ability to form biofilms; presents high levels of resistance to chloramphenicol, neomycin, and gentamicin; and causes mannose-sensitive hemagglutination. The source of S. liquefaciens contamination in RBC supernatants was not found. However, this bacterium has not been isolated since January 2006 after enhanced cleaning practices were implemented in the serology laboratory where the RBCs are stored. This biofilm-forming, antibiotic-resistant S. liquefaciens strain could be directly linked to the unexplained hemagglutination observed in stored RBCs.

A Practical Methodology for Quantifying Random and Systematic Components of Unexplained Variance in a Wind Tunnel

NASA Technical Reports Server (NTRS)

Deloach, Richard; Obara, Clifford J.; Goodman, Wesley L.

2012-01-01

This paper documents a check standard wind tunnel test conducted in the Langley 0.3-Meter Transonic Cryogenic Tunnel (0.3M TCT) that was designed and analyzed using the Modern Design of Experiments (MDOE). The test designed to partition the unexplained variance of typical wind tunnel data samples into two constituent components, one attributable to ordinary random error, and one attributable to systematic error induced by covariate effects. Covariate effects in wind tunnel testing are discussed, with examples. The impact of systematic (non-random) unexplained variance on the statistical independence of sequential measurements is reviewed. The corresponding correlation among experimental errors is discussed, as is the impact of such correlation on experimental results generally. The specific experiment documented herein was organized as a formal test for the presence of unexplained variance in representative samples of wind tunnel data, in order to quantify the frequency with which such systematic error was detected, and its magnitude relative to ordinary random error. Levels of systematic and random error reported here are representative of those quantified in other facilities, as cited in the references.

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

PubMed

Barbero, Pierangelo; Busso, Marco; Tinivella, Marco; Artusi, Carlo Alberto; De Mercanti, Stefania; Cucci, Angele; Veltri, Andrea; Avagnina, Paolo; Calvo, Andrea; Chio', Adriano; Durelli, Luca; Clerico, Marinella

2015-12-01

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2 ± 4.4 months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p < 0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6 ± 1 months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

Clinical Applications for EPs in the ICU.

PubMed

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

Modeling patterns of coral bleaching at a remote Central Pacific atoll.

PubMed

Williams, Gareth J; Knapp, Ingrid S; Maragos, James E; Davy, Simon K

2010-09-01

A mild bleaching event (9.2% prevalence) at Palmyra Atoll occurred in response to the 2009 ENSO, when mean water temperature reached 29.8-30.1 degrees C. Prevalence among both abundant and sparse taxa varied with no clear pattern in susceptibility relating to coral morphology. Seven taxon-specific models showed that turbidity exacerbated while prior exposure to higher background temperatures alleviated bleaching, with these predictors explaining an average 16.3% and 11.5% variation in prevalence patterns, respectively. Positive associations occurred between bleaching prevalence and both immediate temperature during the bleaching event (average 8.4% variation explained) and increased sand cover (average 3.7%). Despite these associations, mean unexplained variation in prevalence equalled 59%. Lower bleaching prevalence in areas experiencing higher background temperatures suggests acclimation to temperature stress among several coral genera, while WWII modifications may still be impacting the reefs via shoreline sediment re-distribution and increased turbidity, exacerbating coral bleaching susceptibility during periods of high temperature stress. Copyright 2010 Elsevier Ltd. All rights reserved.

Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and ranavirus in Russia

USGS Publications Warehouse

Reshetnikov, Andrey N.; Chestnut, Tara E.; Brunner, Jesse L.; Charles, Kaylene M.; Nebergall, Emily E.; Olson, Deanna H.

2014-01-01

In a population of the European common toad Bufo bufo from a rural pond in the region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained mass mortality events involving larvae and metamorphs have been observed over a monitoring period of >20 yr. We tested toads from this and a nearby site for the emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus (Rv). Both pathogens were detected, and at the rural pond site, with the above-noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens. Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25 and 55%, respectively). This is the first confirmation of these pathogens in Russia. Questions remain as to the origins of these pathogens in Russia and their roles in documented mass mortality events.

Television Image of a Large Upward Electrical Discharge Above a Thunderstorm System

NASA Astrophysics Data System (ADS)

Franz, R. C.; Nemzek, R. J.; Winckler, J. R.

1990-07-01

An image of an unusual luminous electrical discharge over a thunderstorm 250 kilometers from the observing site has been obtained with a low-light-level television camera. The discharge began at the cloud tops at 14 kilometers and extended into the clear air 20 kilometers higher. The image, which had a duration of less than 30 milliseconds, resembled two jets or fountains and was probably caused by two localized electric charge concentrations at the cloud tops. Large upward discharges may create a hazard for aircraft and rocket launches and, by penetrating into the ionosphere, may initiate whistler waves and other effects on a magnetospheric scale. Such upward electrical discharges may account for unexplained photometric observations of distant lightning events that showed a low rise rate of the luminous pulse and no electromagnetic sferic pulse of the type that accompanies cloud-to-earth lightning strokes. An unusually high rate of such photometric events was recorded during the night of 22 to 23 September 1989 during a storm associated with hurricane Hugo.

Television image of a large upward electrical discharge above a thunderstorm system.

PubMed

Franz, R C; Nemzek, R J; Winckler, J R

1990-07-06

An image of an unusual luminous electrical discharge over a thunderstorm 250 kilometers from the observing site has been obtained with a low-light-level television camera. The discharge began at the cloud tops at 14 kilometers and extended into the clear air 20 kilometers higher. The image, which had a duration of less than 30 milliseconds,resembled two jets or fountains and was probably caused by two localizd electric charge concentrations at the cloud tops. Large upward discharges may create a hazard for aircraft and rocket launches and, by penetrating into the ionosphere, may initiate whistler waves and other effects on a magnetospheric scale. Such upward electrical discharges may account for unexplained photometric observations of distant lightning events that showed a low rise rate of the luminous pulse and no electromagnetic sferic pulse of the type that accompanies cloud-to-earth lightning strokes. An unusually high rate of such photometric events was recorded during the night of 22 to 23 September 1989 during a storm associated with hurricane Hugo.

What we are watching—five top global infectious disease threats, 2012: a perspective from CDC’s Global Disease Detection Operations Center

PubMed Central

Christian, Kira A.; Ijaz, Kashef; Dowell, Scott F.; Chow, Catherine C.; Chitale, Rohit A.; Bresee, Joseph S.; Mintz, Eric; Pallansch, Mark A.; Wassilak, Steven; McCray, Eugene; Arthur, Ray R.

2013-01-01

Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention’s (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30–40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: (1) avian influenza A (H5N1), (2) cholera, (3) wild poliovirus, (4) enterovirus-71, and (5) extensively drug-resistant tuberculosis. PMID:23827387

Unexplained apnoea and loss of consciousness during sub arachnoid block for caesarean section.

PubMed

Acharya, S P; Marhatta, M N; Amatya, R

2009-01-01

Sub arachnoid block (SAB) is often perceived safe by many anesthesiologists and other faculties but is also not completely safe choice especially in pregnant females, as the incidence of complications and local anaesthetic agent toxicity is high in these groups of patients. Here we present four such cases out of the seventeen patients over a period of six months, who developed apnea and transient loss of consciousness after spinal anesthesia for lower segment caesarean section. Typically all these patients after spinal anesthesia developed difficulty in breathing, became apnoea and had loss of consciousness for about a minute or two. The apnea was relieved with bag and mask ventilation following which the patient regained consciousness and start breathing normally. The rest of the procedure was uneventful. We presented these cases with aim of sharing similar experiences, and to aware about the possibility of such events as these events do occur frequently but case reports and literatures are unavailable.

[Relationship between unexplained palpitation in 
children and head-up tilt test].

PubMed

Gan, Tuoyu; Wu, Lijia; Zou, Runmei; Lin, Ping; Li, Fang; Yang, Hong; Liu, Ping; Gong, Xiaohui; Wang, Cheng

2018-03-28

To explore the relationship between unexplained palpitation in children and head-up tilt test (HUTT).
 Methods: A total of 142 children with the main symptom of unexplained palpitation were admitted to the Specialist Out-Patient Clinic of Children's Cardiovascular Disease from Sept. 2008 to Feb. 2017 in the Second Xiangya Hospital, Central South University. Among them, 63 cases were male, 79 cases were female, with the mean age of (10.12±2.88) years old. The detailed history, physical examinations, conventional 12 electrocardiogram, chest X-ray, echocardiography, myocardial enzymes and thyroid function were all examined. The disorders of heart disease, systemic disease and drug effect were ruled out. The HUTT inspection was then given to them.
 Results: Among the 142 palpitation cases, 79 cases were HUTT positive (55.6%) and 63 cases were HUTT negative (44.4%). The age in HUTT positive patients was older than that in HUTT negative patients (P<0.05), with no significant difference in gender (P>0.05). There were three types of hemodynamic changes in HUTT positive patients. Among them, 38 cases were postural orthostatic tachycardia syndrome (48.1%), 36 cases were the vasovagal syncope vasodepressive type (45.6%) and 5 cases were the vasovagal syncope mixed type (6.3%). There were no hemodynamic types for vasovagal syncope cardioinhibitory type, orthostatic hypotension and orthostatic hypertension.
 Conclusion: Among the clinically unexplained palpitations children, more than half are caused by unbalanced autonomic nervous function. HUTT can help clear the cause of unexplained palpitations.

Medically unexplained conditions considered by patients in general practice.

PubMed

Tschudi-Madsen, Hedda; Kjeldsberg, Mona; Natvig, Bård; Ihlebaek, Camilla; Straand, Jørund; Bruusgaard, Dag

2014-04-01

Patients frequently present with multiple and 'unexplained' symptoms, often resulting in complex consultations. To better understand these patients is a challenge to health care professionals, in general, and GPs, in particular. In our research on symptom reporting, we wanted to explore whether patients consider that they may suffer from conditions commonly regarded as unexplained, and we explored associations between these concerns and symptom load, life stressors and socio-demographic factors. Consecutive, unselected patients in general practice completed questionnaires addressing eight conditions commonly regarded as unexplained (amalgam poisoning, Candida syndrome, fibromyalgia, food intolerance, electromagnetic hypersensitivity, burnout syndrome, chronic fatigue syndrome and irritable bowel syndrome). With logistic regression, we analysed associations with symptom load, burden of life stressors with negative impact on present health and socio-demographic variables. Out of the 909 respondents (response rate = 88.8%), 863 had complete data. In total, 39.6% of patients had considered that they may suffer from one or more unexplained conditions (UCs). These concerns were strongly and positively associated with recent symptom load and number of life stressors. If we excluded burnout and food intolerance, corresponding associations were found. Patients frequently considered that they may suffer from UCs. The likelihood of such concerns strongly increased with an increasing symptom load and with the number of life stressors with negative impact on present health. Hence, the number of symptoms may be a strong indicator of whether patients consider their symptoms part of such often controversial multisymptom conditions.

Explained and unexplained tissue loss in corals from the Tropical Eastern Pacific

USGS Publications Warehouse

Rodriguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguilera, Luis Eduardo; Reyes-Bonilla, Hector; Hernández, Luis

2015-01-01

Coral reefs rival rainforest in biodiversity, but are declining in part because of disease. Tissue loss lesions, a manifestation of disease, are present in dominant Pocillopora along the Pacific coast of Mexico. We characterized tissue loss in 7 species of Pocillopora from 9 locations (44 sites) spanning southern to northern Mexico. Corals were identified to species, and tissue loss lesions were photographed and classified as those explainable by predation and those that were unexplained. A focal predation study was done concurrently at 3 locations to confirm origin of explained lesions. Of 1054 cases of tissue loss in 7 species of corals, 84% were associated with predation (fish, snails, or seastar) and the remainder were unexplained. Types of tissue loss were not related to coral density; however there was significant geographic heterogeneity in type of lesion; one site in particular (Cabo Pulmo) had the highest prevalence of predator-induced tissue loss (mainly pufferfish predation). Crown-of-thorns starfish, pufferfish, and snails were the most common predators and preferred P. verrucosa, P. meandrina, and P. capitata, respectively. Of the 9 locations, 4 had unexplained tissue loss with prevalence ranging from 1 to 3% with no species predilection. Unexplained tissue loss was similar to white syndrome (WS) in morphology, indicating additional study is necessary to clarify the cause(s) of the lesions and the potential impacts to dominant corals along the Pacific coast of Mexico.

Preovulatory uterine flushing with saline as a treatment for unexplained infertility: a randomised controlled trial protocol.

PubMed

Maheux-Lacroix, Sarah; Dodin, Sylvie; Moore, Lynne; Bujold, Emmanuel; Lefebvre, Jessica; Bergeron, Marie-Ève

2016-01-06

In vitro fertilisation (IVF) is the treatment of choice for unexplained infertility. Preovulatory uterine flushing could reduce intrauterine debris and inflammatory factors preventing pregnancy and constitute an alternative to IVF. Our objective is to assess the efficacy of preovulatory uterine flushing with physiological saline for the treatment of unexplained infertility. We will perform a randomised controlled trial based on consecutive women aged between 18 and 37 years consulting for unexplained infertility for at least 1 year. On the day of their luteinising hormone surge, 192 participants will be randomised in two equal groups to either receive 20 mL of physiological saline by an intrauterine catheter or 10 mL of saline intravaginally. We will assess relative risk of live birth (primary outcome), as well as pregnancy (secondary outcome) over one cycle of treatment. We will report the side effects, complications and acceptability of the intervention. This project was approved by the Ethics committee of the Centre Hospitatlier Universitaire de Quebec (no 2015-1146). Uterine flushing is usually well tolerated by women and would constitute a simple, affordable and minimally invasive treatment for unexplained infertility. We plan to communicate the results of the review by presenting research abstracts at conferences and by publishing the results in a peer-reviewed journal. NCT02539290; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chronic fatigue in patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome: validation of a Norwegian translation of the Fatigue Impact Scale.

PubMed

Lind, Ragna; Berstad, Arnold; Hatlebakk, Jan; Valeur, Jørgen

2013-01-01

Patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome (IBS) suffer from several health complaints, including fatigue. The aim of the present study was to validate a Norwegian translation of the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients with self-reported food hypersensitivity and IBS, as compared with healthy controls. Thirty-eight patients with unexplained self-reported food hypersensitivity and IBS, who participated in the validation of the FIS completed the following additional questionnaires: the Short Form of Nepean Dyspepsia Index for assessment of quality of life, the Subjective Health Complaint Inventory, and questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied in 43 patients with unexplained self-reported food hypersensitivity, 70% diagnosed with IBS, and 42 healthy controls. Cronbach's α for the FIS was 0.98, indicating excellent agreement between individual items. Scores on the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r = 0.50, P = 0.001), indicating good convergent validity, and were higher in patients (median 85.0, interquartile range 36.8-105.3) than in controls (median 14.0, interquartile range 3.0-29.0, P ≤ 0.0001). The Norwegian translation of the FIS performed excellently in patients with unexplained self-reported food hypersensitivity and IBS, with patients reporting significantly more impact of chronic fatigue than healthy controls.

Obesity and Subtypes of Incident Cardiovascular Disease.

PubMed

Ndumele, Chiadi E; Matsushita, Kunihiro; Lazo, Mariana; Bello, Natalie; Blumenthal, Roger S; Gerstenblith, Gary; Nambi, Vijay; Ballantyne, Christie M; Solomon, Scott D; Selvin, Elizabeth; Folsom, Aaron R; Coresh, Josef

2016-07-28

Obesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comparisons of the associations of obesity with each of these CVD subtypes, particularly regarding the extent to which they are unexplained by traditional CVD mediators. We followed 13 730 participants in the Atherosclerosis Risk in Communities (ARIC) study who had a body mass index ≥18.5 and no CVD at baseline (visit 1, 1987-1989). We compared the association of higher body mass index with incident HF, CHD, and stroke before and after adjusting for traditional CVD mediators (including systolic blood pressure, diabetes mellitus, and lipid measures). Over a median follow-up of 23 years, there were 2235 HF events, 1653 CHD events, and 986 strokes. After adjustment for demographics, smoking, physical activity, and alcohol intake, higher body mass index had the strongest association with incident HF among CVD subtypes, with hazard ratios for severe obesity (body mass index ≥35 versus normal weight) of 3.74 (95% CI 3.24-4.31) for HF, 2.00 (95% CI 1.67-2.40) for CHD, and 1.75 (95% CI 1.40-2.20) for stroke (P<0.0001 for comparisons of HF versus CHD or stroke). Further adjustment for traditional mediators fully explained the association of higher body mass index with CHD and stroke but not with HF (hazard ratio 2.27, 95% CI 1.94-2.64). The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors. Weight management is likely critical for optimal HF prevention, and nontraditional pathways linking obesity to HF need to be elucidated. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Unravelling associations between unassigned mass spectrometry peaks with frequent itemset mining techniques.

PubMed

Vu, Trung Nghia; Mrzic, Aida; Valkenborg, Dirk; Maes, Evelyne; Lemière, Filip; Goethals, Bart; Laukens, Kris

2014-01-01

Mass spectrometry-based proteomics experiments generate spectra that are rich in information. Often only a fraction of this information is used for peptide/protein identification, whereas a significant proportion of the peaks in a spectrum remain unexplained. In this paper we explore how a specific class of data mining techniques termed "frequent itemset mining" can be employed to discover patterns in the unassigned data, and how such patterns can help us interpret the origin of the unexpected/unexplained peaks. First a model is proposed that describes the origin of the observed peaks in a mass spectrum. For this purpose we use the classical correlative database search algorithm. Peaks that support a positive identification of the spectrum are termed explained peaks. Next, frequent itemset mining techniques are introduced to infer which unexplained peaks are associated in a spectrum. The method is validated on two types of experimental proteomic data. First, peptide mass fingerprint data is analyzed to explain the unassigned peaks in a full scan mass spectrum. Interestingly, a large numbers of experimental spectra reveals several highly frequent unexplained masses, and pattern mining on these frequent masses demonstrates that subsets of these peaks frequently co-occur. Further evaluation shows that several of these co-occurring peaks indeed have a known common origin, and other patterns are promising hypothesis generators for further analysis. Second, the proposed methodology is validated on tandem mass spectrometral data using a public spectral library, where associations within the mass differences of unassigned peaks and peptide modifications are explored. The investigation of the found patterns illustrates that meaningful patterns can be discovered that can be explained by features of the employed technology and found modifications. This simple approach offers opportunities to monitor accumulating unexplained mass spectrometry data for emerging new patterns, with possible applications for the development of mass exclusion lists, for the refinement of quality control strategies and for a further interpretation of unexplained spectral peaks in mass spectrometry and tandem mass spectrometry.

Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe vasospasm: preliminary results.

PubMed

Sherif, Camillo; Wambacher, Bernhard; Loyoddin, Michel; Karaic, Radenko; Krafft, Peter; Valentin, Andreas; Tscholakoff, Dimiter; Kleinpeter, Guenther

2015-01-01

Delayed vasospasm (VSP) following aneurysmal subarachnoid hemorrhage (aSAH) remains a major source of morbidity. Milrinone was recently suggested as an invasive VSP treatment option. It is a phosphodiesterase III inhibitor with vasodilating and additional positive inotrope and anti-inflammatory effects. In this preliminary series, we included patients with severe VSP and unsuccessful maximum conservative therapy. Inclusion criteria were (1) transcranial Doppler (TCD) mean >180 cm/s; (2) increase of >50 % of TCD mean values within 6 h to values >150 cm/s; and/or (3) neurological deterioration (after exclusion of hemorrhage, hydrocephalus, and other systemic reasons). Patients received endovascular therapy with nimodipine 2 mg followed by milrinone 4-8 mg. Reinterventions were indicated aggressively in cases of persistent neurological deficits or persistent high mean TCD >180 cm/s. Of 121 consecutive aSAH patients, 16 (13.2 %) received endovascular VSP therapy. Of these, 11 patients (68.5 %) received ≥ 3 interventions (median 4; maximum 9); 14 (87.5 %) showed postinterventional angiographic improvement of vessel diameters; and 11 (68.5 %) showed improvement of their neurological deficits after a mean follow-up time of 4.5 months. No cardiovascular adverse events attributed to milrinone were observed. Milrinone may be a useful supplementary substance for endovascular VSP therapy. Aggressive reintervention indications did not cause additional adverse events.

Neurologic manifestations of achondroplasia.

PubMed

Hecht, Jacqueline T; Bodensteiner, John B; Butler, Ian J

2014-01-01

Achondroplasia is the best described and most common form of the congenital short-limbed dwarfing conditions. Achondroplasia is apparent at birth and has a birth prevalence of 1 in 20000-30000 live-born infants. Achondroplasia is inherited as an autosomal dominant condition, although 80% of cases occur sporadically as new events in their families. Achondroplasia is caused, in virtually all of the cases, by a G380R mutation in fibroblast growth factor receptor 3 (FGFR3). Patients with achondroplasia should be evaluated by a multidisciplinary team of clinicians including geneticists, neurologists, and orthopedists, since there are numerous bony and neurological complications. The most severe complication results from craniocervical stenosis and medullary and upper spinal cord compression, which can have devastating and even lethal sequelae during early childhood. In subsequent decades, including adolescence, spinal cord and nerve compression are more prominent. The neurological complications of achondroplasia have been recognized in adults for more than a century and are attributed to bony defects, connective tissue structures, or both. Similar neurological complications are now appreciated in infants, young children, and teenagers with achondroplasia. Defective connective tissue elements in achondroplasia frequently lead to ligamentous laxity, which can aggravate the complications associated with bony stenosis. Bony abnormalities are known to cause neurological morbidity and lead to a shortened lifespan. Neurological complications associated with achondroplasia are reviewed, including recommendations for the evaluation and management of these clinical problems. © 2014 Elsevier B.V. All rights reserved.

Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life.

PubMed

Sharma, Alok; Gokulchandran, Nandini; Chopra, Guneet; Kulkarni, Pooja; Lohia, Mamta; Badhe, Prerna; Jacob, V C

2012-01-01

Neurological disorders such as muscular dystrophy, cerebral palsy, and injury to the brain and spine currently have no known definitive treatments or cures. A study was carried out on 71 children suffering from such incurable neurological disorders and injury. They were intrathecally and intramuscularly administered autologous bone marrow-derived mononuclear cells. Assessment after transplantation showed neurological improvements in muscle power and a shift on assessment scales such as FIM and Brooke and Vignos scale. Further, imaging and electrophysiological studies also showed significant changes in selective cases. On an average follow-up of 15 ± 1 months, overall 97% muscular dystrophy cases showed subjective and functional improvement, with 2 of them also showing changes on MRI and 3 on EMG. One hundred percent of the spinal cord injury cases showed improvement with respect to muscle strength, urine control, spasticity, etc. Eighty-five percent of cases of cerebral palsy cases showed improvements, out of which 75% reported improvement in muscle tone and 50% in speech among other symptoms. Eighty-eight percent of cases of other incurable neurological disorders such as autism, Retts Syndrome, giant axonal neuropathy, etc., also showed improvement. No significant adverse events were noted. The results show that this treatment is safe, efficacious, and also improves the quality of life of children with incurable neurological disorders and injury.

Reconstructive valve surgery within 10 days of stroke in endocarditis.

PubMed

Raman, Jai; Ballal, Apoorva; Hota, Bala; Mirza, Sara; Lai, David; Bleck, Thomas; Lateef, Omar

2016-07-01

The optimal timing of surgical treatment for infective endocarditis complicated by cerebrovascular events is controversial, largely due to the perceived risk of perioperative intracranial bleeding. Current guidelines suggest waiting 2 weeks between the diagnosis of stroke and surgery. The aim of this study was to investigate the clinical and neurological outcomes of early surgery following a stroke. This was a single-center retrospective analysis of 12 consecutive patients requiring surgery for infective endocarditis between 2011 and 2014 at Rush University Medical Center, with either ischemic (n = 6) and/or hemorrhagic (n = 6) cerebrovascular complications. All underwent computed tomographic angiography prior to early valve reconstructive surgery to identify potentially actionable neurological findings. Early valve surgery was performed for ongoing sepsis or persistent emboli. Neurologic risk and outcome were assessed pre- and postoperatively using the National Institutes of Health Stroke Scale and the Glasgow Outcome Scale, respectively. All 12 patients underwent surgical treatment within 10 days of the diagnosis of stroke. Mortality in the immediate postoperative period was 8%. Eleven of the 12 patients exhibited good neurological recovery in the immediate postoperative period, with a Glasgow Outcome Scale score ≥ 3. There was no correlation between duration of cardiopulmonary bypass and neurological outcomes. Early cardiac surgery in patients with infective endocarditis and stroke maybe lifesaving with a low neurological risk. Comprehensive neurovascular imaging may help in identifying patient-related risk factors. © The Author(s) 2016.

The response time threshold for predicting favourable neurological outcomes in patients with bystander-witnessed out-of-hospital cardiac arrest.

PubMed

Ono, Yuichi; Hayakawa, Mineji; Iijima, Hiroaki; Maekawa, Kunihiko; Kodate, Akira; Sadamoto, Yoshihiro; Mizugaki, Asumi; Murakami, Hiromoto; Katabami, Kenichi; Sawamura, Atsushi; Gando, Satoshi

2016-10-01

It is well established that the period of time between a call being made to emergency medical services (EMS) and the time at which the EMS arrive at the scene (i.e. the response time) affects survival outcomes in patients who experience out-of-hospital cardiac arrest (OHCA). However, the relationship between the response time and favourable neurological outcomes remains unclear. We therefore aimed to determine a response time threshold in patients with bystander-witnessed OHCA that is associated with positive neurological outcomes and to assess the relationship between the response time and neurological outcomes in patients with OHCA. This study was a retrospective, observational analysis of data from 204,277 episodes of bystander-witnessed OHCA between 2006 and 2012 in Japan. We used classification and regression trees (CARTs) and receiver operating characteristic (ROC) curve analyses to determine the threshold of response time associated with favourable neurological outcomes (Cerebral Performance Category 1 or 2) 1 month after cardiac arrest. Both CARTs and ROC analyses indicated that a threshold of 6.5min was associated with improved neurological outcomes in all bystander-witnessed OHCA events of cardiac origin. Furthermore, bystander cardiopulmonary resuscitation (CPR) prolonged the threshold of response time by 1min (up to 7.5min). The adjusted odds ratio for favourable neurological outcomes in patients with OHCA who received care within ≤6.5min was 1.935 (95% confidential interval: 1.834-2.041, P<0.001). A response time of ≤6.5min was closely associated with favourable neurological outcomes in all bystander-witnessed patients with OHCA. Bystander CPR prolonged the response time threshold by 1min. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Myocardial Bridge and Acute Plaque Rupture

PubMed Central

Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A.; Schnittger, Ingela

2016-01-01

A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered. PMID:28251167

New parvovirus in child with unexplained diarrhea, Tunisia.

PubMed

Phan, Tung G; Sdiri-Loulizi, Khira; Aouni, Mahjoub; Ambert-Balay, Katia; Pothier, Pierre; Deng, Xutao; Delwart, Eric

2014-11-01

A divergent parvovirus genome was the only eukaryotic viral sequence detected in feces of a Tunisian child with unexplained diarrhea. Tusavirus 1 shared 44% and 39% identity with the nonstructural protein 1 and viral protein 1, respectively, of the closest genome, Kilham rat parvovirus, indicating presence of a new human viral species in the Protoparvovirus genus.

New Parvovirus in Child with Unexplained Diarrhea, Tunisia

PubMed Central

Phan, Tung G.; Sdiri-Loulizi, Khira; Aouni, Mahjoub; Ambert-Balay, Katia; Pothier, Pierre; Deng, Xutao

2014-01-01

A divergent parvovirus genome was the only eukaryotic viral sequence detected in feces of a Tunisian child with unexplained diarrhea. Tusavirus 1 shared 44% and 39% identity with the nonstructural protein 1 and viral protein 1, respectively, of the closest genome, Kilham rat parvovirus, indicating presence of a new human viral species in the Protoparvovirus genus. PMID:25340816

Psychosoma in Crisis: An Autoethnographic Study of Medically Unexplained Symptoms and Their Diverse Contexts

ERIC Educational Resources Information Center

Hills, John; Lees, John; Freshwater, Dawn; Cahill, Jane

2018-01-01

In this study, we examine autoethnographic data from three critical incidents as experienced by the first author demonstrating the importance of context in understanding medically unexplained symptoms, their incidence and underlying patterns. We make the case for ethnographies as a crucial research strand in discerning the finer aspects of the…

Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005

PubMed Central

Wei, Kuo-Chen; Jiang, Donald Dah-Shyong; Chiu, Chan-Hsian; Chang, Shan-Chwen

2008-01-01

We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%). PMID:18826839

Safety of the yellow Fever vaccine: a retrospective study.

PubMed

Nordin, James D; Parker, Emily D; Vazquez-Benitez, Gabriela; Kharbanda, Elyse O; Naleway, Allison; Marcy, S Michael; Molitor, Beth; Kuckler, Leslie; Baggs, James

2013-01-01

Yellow fever (YF) vaccine is considered safe; however, severe illness and death following vaccination have been reported. Vaccine Safety Datalink (VSD) and US Department of Defense (DoD) data were used to identify adverse reactions following YF vaccination. Within the VSD, YF-vaccine-exposed subjects were compared to age-, site-, and gender-matched unexposed subjects. YF-vaccine-exposed DoD subjects were studied using a risk-interval design. For both cohorts, ICD-9 codes were analyzed for allergic and local reactions, mild systemic reactions, and possible visceral and neurologic adverse events (AEs). The VSD cohort received 47,159 doses from 1991 through 2006. The DoD cohort received 1.12 million doses from 1999 through 2007. Most subjects received other vaccines simultaneously. In the VSD cohort, rates of allergic, local, and mild systemic reactions were not statistically different between YF-vaccine-exposed and -unexposed subjects. In the DoD, there was an increased risk for outpatient allergic events in the period following vaccination with YF and other vaccines rate ratios [RR 3.85, 95% confidence interval (CI) 3.35-4.41] but with no increased risk for inpatient allergic reactions. In both cohorts, inpatient ICD-9 codes for visceral events were significantly less common following vaccination; inpatient codes for neurologic events were less common in the VSD YF-vaccine-exposed adult cohort, but did not differ between exposed and unexposed periods in the DoD. In the DoD, one fatal case of YF-vaccine-associated viscerotropic disease (YF-vaccine-AVD) was detected. The estimated death rate was 0.89 for 1,000,000 YF vaccine doses (95% CI 0.12-6.31/1,000,000 doses). No YF vaccine-associated deaths occurred in the VSD. In these closed cohorts we did not detect increased risk for visceral or neurologic events following YF vaccination. The death rate following YF vaccine was consistent with previous reports. These data support current recommendations for use of YF vaccine in young healthy individuals. These data are inadequate to judge safety of YF vaccines in elderly patients. © 2013 International Society of Travel Medicine.

Widespread activity of multiple lineages of Usutu virus, western Europe, 2016.

PubMed

Cadar, Daniel; Lühken, Renke; van der Jeugd, Henk; Garigliany, Mutien; Ziegler, Ute; Keller, Markus; Lahoreau, Jennifer; Lachmann, Lars; Becker, Norbert; Kik, Marja; Oude Munnink, Bas B; Bosch, Stefan; Tannich, Egbert; Linden, Annick; Schmidt, Volker; Koopmans, Marion P; Rijks, Jolianne; Desmecht, Daniel; Groschup, Martin H; Reusken, Chantal; Schmidt-Chanasit, Jonas

2017-01-26

In the summer of 2016, Belgium, France, Germany and the Netherlands reported widespread Usutu virus (USUV) activity based on live and dead bird surveillance. The causative USUV strains represented four lineages, of which two putative novel lineages were most likely recently introduced into Germany and spread to other western European countries. The spatial extent of the outbreak area corresponded with R 0 values > 1. The occurrence of the outbreak, the largest USUV epizootic registered so far in Europe, allowed us to gain insight in how a recently introduced arbovirus with potential public health implications can spread and become a resident pathogen in a naïve environment. Understanding the ecological and epidemiological factors that drive the emergence or re-emergence of USUV is critical to develop and implement timely surveillance strategies for adequate preventive and control measures. Public health authorities, blood transfusion services and clinicians in countries where USUV was detected should be aware of the risk of possible USUV infection in humans, including in patients with unexplained encephalitis or other neurological impairments, especially during late summer when mosquito densities peak. This article is copyright of The Authors, 2017.

Dissociation in hysteria and hypnosis: evidence from cognitive neuroscience.

PubMed

Bell, Vaughan; Oakley, David A; Halligan, Peter W; Deeley, Quinton

2011-03-01

Jean-Martin Charcot proposed the radical hypothesis that similar brain processes were responsible for the unexplained neurological symptoms of 'hysteria', now typically diagnosed as 'conversion disorder' or 'dissociative (conversion) disorder', and the temporary effects of hypnosis. While this idea has been largely ignored, recent cognitive neuroscience studies indicate that (i) hypnotisability traits are associated with a tendency to develop dissociative symptoms in the sensorimotor domain; (ii) dissociative symptoms can be modelled with suggestions in highly hypnotisable subjects; and (iii) hypnotic phenomena engage brain processes similar to those seen in patients with symptoms of hysteria. One clear theme to emerge from the findings is that 'symptom' presentation, whether clinically diagnosed or simulated using hypnosis, is associated with increases in prefrontal cortex activity suggesting that intervention by the executive system in both automatic and voluntary cognitive processing is common to both hysteria and hypnosis. Nevertheless, while the recent literature provides some compelling leads into the understanding of these phenomena, the field still lacks well controlled systematically designed studies to give a clear insight into the neurocognitive processes underlying dissociation in both hysteria and hypnosis. The aim of this review is to provide an agenda for future research.

Transient basilar artery occlusion monitored by transcranial color Doppler presenting with a spectacular shrinking deficit: a case report

PubMed Central

2010-01-01

Introduction We describe the case of a 79-year-old Caucasian Italian woman with a transient basilar occlusion monitored by transcranial Doppler, with subsequent recanalization and clinical shrinking deficit. This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. This case is important and needs to be reported because transient basilar occlusion may be easily diagnosed if transcranial Doppler is performed. Case presentation A 79-year-old woman affected by chronic atrial fibrillation and not treated with oral anticoagulants, cardioverted to sinus rhythm during a gastric endoscopy. She then showed a sudden-onset loss of consciousness, horizontal and vertical gaze palsy, tetraparesis and bilateral miosis and coma. Two hours later, the symptoms resolved quickly, leaving no residual neurologic deficits. Transcranial Doppler examination showed a dampened flow in the basilar artery in the emergency examination and a restored flow when the symptoms resolved. Conclusion This is the first case of transient basilar occlusive disease diagnosed and monitored by transcranial Doppler. We believe that transcranial Doppler should be performed in all cases of unexplained acute loss of consciousness, in particular, if associated with signs of brainstem dysfunctions. PMID:20205759

Numb chin syndrome as a manifestation of possible breast cancer metastasis around dental implants.

PubMed

Orhan, Kaan; Bayndr, Hakan; Aksoy, Seçil; Seker, Basak Kusakci; Berberoğlu, Atilla; Ozan, Oğuz

2011-05-01

Numb chin syndrome, sometimes called numb lip syndrome, is an uncommon but well-recognized symptom in medical oncology. It may be a metastatic neurologic manifestation of malignancy, often with no clinically visible pathologic finding. The authors report a numb chin syndrome as a manifestation possible breast cancer metastasis around dental implants in a 69-year-old woman. The patient was presented with complaint of numbness in the lower jaw. Medical anamnesis revealed a metastatic breast carcinoma (CA). Radiographic imaging with conventional panoramic radiography and cone beam computed tomographic examination, revealed a moth-eaten shape, radiolucent, and radiopaque mixed appearance around the dental implants that was related with possible metastasis of the breast cancer. Numb chin syndrome is almost unknown within the dental and oral and maxillofacial community, despite being well reported in the medical literature. General dentists, oral medicine specialists, and oral and maxillofacial surgeons must be aware of this condition to consider metastatic cancer in patients with unexplained facial hypoesthesia. Moreover, although the development of metastatic lesions around implants is an uncommon pathologic finding, the examination of peri-implant lesion should be performed carefully considering the entire pathologic situations.

Analysis of the surveillance situation for viral encephalitis and meningitis in Europe.

PubMed

Donoso Mantke, O; Vaheri, A; Ambrose, H; Koopmans, M; de Ory, F; Zeller, H; Beyrer, K; Windorfer, A; Niedrig, M

2008-01-17

Infective processes in the brain, spinal cord and meninges are considered to be the main causes of encephalitis, myelitis and meningitis. However, most cases remain unexplained. The incidence of different viral aetiologies (zoonotic and non-zoonotic) is especially poorly estimated, due to the lack of a standard case definition and of agreed diagnostic algorithms, including harmonised diagnostic methods and sample collection. It is important to clarify the incidence of viral encephalitis/meningitis and to optimise the diagnosis of infectious neurological illness, particularly to ensure early recognition of outbreaks or emerging infectious such a West Nile encephalitis. The European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) has analysed the present surveillance situation for viral encephalitis/meningitis in Europe. Here we give an overview of the existing epidemiological sources of information in European Union (EU) Member States, mapping the laboratory capacity and identifying key requirements for a possible future surveillance study at European level. The data presented will help design a harmonised/standardised Europe-wide surveillance study investigating patients with encephalitis and/or meningitis in order to obtain more information on the role of infections in these rarely analysed syndromes, both from a clinical and an epidemiological perspective.

Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications.

PubMed

Olloquequi, Jordi; Cornejo-Córdova, Elizabeth; Verdaguer, Ester; Soriano, Francesc X; Binvignat, Octavio; Auladell, Carme; Camins, Antoni

2018-03-01

Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca 2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Although there is a consensus in considering excitotoxicity as a hallmark in most neurodegenerative diseases, increasing evidence points to the relevant role of this pathological mechanism in other illnesses affecting the central nervous system. Consequently, antagonists of glutamate receptors are used in current treatments or in clinical trials in both neurological and psychiatric disorders. However, drugs modulating other aspects of the excitotoxic mechanism could be more beneficial. This review discusses how excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitotoxic insult.

The early argument for prefrontal leucotomy: the collision of frontal lobe theory and psychosurgery at the 1935 International Neurological Congress in London.

PubMed

Boettcher, Lillian B; Menacho, Sarah T

2017-09-01

The pathophysiology of mental illness and its relationship to the frontal lobe were subjects of immense interest in the latter half of the 19th century. Numerous studies emerged during this time on cortical localization and frontal lobe theory, drawing upon various ideas from neurology and psychiatry. Reflecting the intense interest in this region of the brain, the 1935 International Neurological Congress in London hosted a special session on the frontal lobe. Among other presentations, Yale physiologists John Fulton and Carlyle Jacobsen presented a study on frontal lobectomy in primates, and neurologist Richard Brickner presented a case of frontal ablation for olfactory meningioma performed by the Johns Hopkins neurosurgeon Walter Dandy. Both occurrences are said to have influenced Portuguese neurologist Egas Moniz (1874-1955) to commence performing leucotomies on patients beginning in late 1935. Here the authors review the relevant events related to frontal lobe theory leading up to the 1935 Neurological Congress as well as the extent of this meeting's role in the genesis of the modern era of psychosurgery.

Misdiagnosis of acute peripheral vestibulopathy in central nervous ischemic infarction.

PubMed

Braun, Eva Maria; Tomazic, Peter Valentin; Ropposch, Thorsten; Nemetz, Ulrike; Lackner, Andreas; Walch, Christian

2011-12-01

Vertigo is a very common symptom at otorhinolaryngology (ENT), neurological, and emergency units, but often, it is difficult to distinguish between vertigo of peripheral and central origin. We conducted a retrospective analysis of a hospital database, including all patients admitted to the ENT University Hospital Graz after neurological examination, with a diagnosis of peripheral vestibular vertigo and subsequent diagnosis of central nervous infarction as the actual cause for the vertigo. Twelve patients were included in this study. All patients with acute spinning vertigo after a thorough neurological examination and with uneventful computed tomographic scans were referred to our ENT department. Nine of them presented with horizontal nystagmus. Only 1 woman experienced additional hearing loss. The mean diagnostic delay to the definite diagnosis of a central infarction through magnetic resonance imaging was 4 days (SD, 2.3 d). A careful otologic and neurological examination, including the head impulse test and caloric testing, is mandatory. Because ischemic events cannot be diagnosed in computed tomographic scans at an early stage, we strongly recommend to perform cranial magnetic resonance imaging within 48 hours from admission if vertigo has not improved under conservative treatment.

Diagnostic value of [(18)F]-FDG PET/CT in children with fever of unknown origin or unexplained signs of inflammation.

PubMed

Jasper, Niklas; Däbritz, Jan; Frosch, Michael; Loeffler, Markus; Weckesser, Matthias; Foell, Dirk

2010-01-01

Fever of unknown origin (FUO) and unexplained signs of inflammation are challenging medical problems especially in children and predominantly caused by infections, malignancies or noninfectious inflammatory diseases. The aim of this study was to assess the diagnostic value of (18)F-FDG PET and PET/CT in the diagnostic work-up in paediatric patients. In this retrospective study, 47 FDG PET and 30 PET/CT scans from 69 children (median age 8.1 years, range 0.2-18.1 years, 36 male, 33 female) were analysed. The diagnostic value of PET investigations in paediatric patients presenting with FUO (44 scans) or unexplained signs of inflammation without fever (33 scans) was analysed. A diagnosis in paediatric patients with FUO or unexplained signs of inflammation could be established in 32 patients (54%). Of all scans, 63 (82%) were abnormal, and of the total number of 77 PET and PET/CT scans 35 (45%) were clinically helpful. In patients with a final diagnosis, scans were found to have contributed to the diagnosis in 73%. Laboratory, demographic or clinical parameters of the children did not predict the usefulness of FDG PET scans. This is the first larger study demonstrating that FDG PET and PET/CT may be valuable diagnostic tools for the evaluation of children with FUO and unexplained signs of inflammation. Depicting inflammation in the whole body, while not being traumatic, it is attractive for use especially in children. The combination of PET with CT seems to be superior, since the site of inflammation can be localized more accurately.

May Underdiagnosed Nutrition Imbalances Be Responsible for a Portion of So-Called Unexplained Infertility? From Diagnosis to Potential Treatment Options.

PubMed

Noventa, Marco; Quaranta, Michela; Vitagliano, Amerigo; Cinthya, Vescio; Valentini, Romina; Campagnaro, Tania; Marci, Roberto; Paola, Rossana Di; Alviggi, Carlo; Gangemi, Michele; Saccardi, Carlo; Nardelli, Giovanni Battista; Gizzo, Salvatore

2016-06-01

The aim of the study was to investigate whether women affected by unexplained infertility may have undiagnosed dietary imbalances which negatively affect fertility. Secondarily, we investigated whether varying degrees of nutritional abnormalities may benefit from different periconceptional dietary supplementations, evaluating the most effective intervention in improving pregnancy rate after in vitro fertilization (IVF). We conducted a survey on 2 cohorts of patients (group A: unexplained infertility and group B: healthy first trimester spontaneous pregnancies) with the scope of investigating and comparing their dietary status discriminating women without dietary abnormalities (cohort 1) from those with abnormalities exclusively in micronutrient intake (cohort 2) or combined abnormalities in both micronutrient and macronutrient intake and associated obesity (cohort 3). All women included in group A were offered the opportunity to receive a prescription for one of the 3 designated daily dietary supplementation schemes (subgroups A1, A2, and A3) which were to be implemented in the 3 months immediately prior to beginning IVF treatment. When compared with fertile women, patients having unexplained infertility showed significant abnormalities in dietary habits. These differences ranged from a minimal imbalance in micronutrient intake (potentially avoidable with dietary supplementation) to severe combined macronutrient and micronutrient imbalance frequently associated with obesity (partially amendable by inositol supplementation and frequently requiring long-term dietary reeducation before establishment of fertility). Nutritional investigation and treatment may explain and resolve a portion of cases of unexplained infertility, improving the outcome of IVF treatment and, with minimal imbalances, likely restore spontaneous fertility. © The Author(s) 2015.

[Criteria for somatization studied in an outpatient clinic for general internal medicine].

PubMed

van Hemert, A M; Speckens, A E; Rooijmans, H G; Bolk, J H

1996-06-08

To compare the evolution of bodily symptoms and the frequency of medical consultation using three different operational definitions of 'somatization'. Descriptive follow-up study. General Internal Medicine Outpatient Clinic of Leiden University Hospital, the Netherlands. Information about physical and psychic symptoms and about the somatic-medical diagnosis was collected in a group of 158 newly referred patients. The concept of 'somatization' was operationalized in three ways: a) seeking medical consultation for somatically unexplained symptoms; b) seeking medical consultation for somatically unexplained symptoms combined with an anxiety disorder or a depressive disorder according to the 'present state examination'; c) seeking medical consultation for somatically unexplained symptoms combined with a somatization disorder or hypochondria according to the Diagnostic and statistical manual of mental disorders (DSM) III R criteria. After a follow-up period of 1.2 years, information was collected from the entire study group about the evolution of the physical symptoms and the frequency of medical consultation. Patients with somatically unexplained symptoms combined with a somatization disorder or hypochondria were characterized in the follow-up by numerous physical symptoms and a high frequency of medical consultation. Compared with the other patients with unexplained symptoms, they visited the general practitioner during the follow-up period 2.5 times as often, saw specialists twice as often and were admitted to a 'somatic' hospital, 6 times as often. Using criteria of low restrictiveness for somatization, a large group of patients were identified with a relatively normal (average) illness behaviour. Using more restrictive criteria led to identification of a smaller group with more extreme illness behaviour.

INCIDENCE OF ABNORMAL POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH UNEXPLAINED CARDIOMYOPATHY AND VENTRICULAR ARRHYTHMIAS

PubMed Central

Tung, Roderick; Bauer, Brenton; Schelbert, Heinrich; Lynch, Joseph; Auerbach, Martin; Gupta, Pawan; Schiepers, Christiaan; Chan, Samantha; Ferris, Julie; Barrio, Martin; Ajijola, Olujimi; Bradfield, Jason; Shivkumar, Kalyanam

2015-01-01

Background The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VA) is unknown. Objective To report fasting PET scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. Methods 18-FDG PET/CT scans with a >16 hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (EF<55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into four groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). Results Over a 3-year period, 103 PET scan were performed with 49% (AIC+=17, AIC=33) exhibiting focal FDG uptake. The mean age was 52±12 years with an EF of 36±16%. Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, p=0.002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed non-granulomatous inflammation in 6 patients and sarcoidosis in 18 patients. 90% of patients with AIC/AIC+ were prescribed immunosuppressive therapy and 58% underwent ablation. Correlation between areas of perfusion abnormalities and FDG uptake with electro-anatomic mapping was observed in 79% patients and MRI findings matched in only 33%. Conclusions Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggests that a significant proportion of patients labeled “idiopathic” may have occult arrhythmogenic inflammatory cardiomyopathy, which may benefit from early detection and immunosuppressive medical therapy. PMID:26272522

Clinical significance of somatic mutation in unexplained blood cytopenia

PubMed Central

Gallì, Anna; Travaglino, Erica; Ambaglio, Ilaria; Rizzo, Ettore; Molteni, Elisabetta; Elena, Chiara; Ferretti, Virginia Valeria; Catricalà, Silvia; Bono, Elisa; Todisco, Gabriele; Bianchessi, Antonio; Rumi, Elisa; Zibellini, Silvia; Pietra, Daniela; Boveri, Emanuela; Camaschella, Clara; Toniolo, Daniela; Papaemmanuil, Elli; Ogawa, Seishi; Cazzola, Mario

2017-01-01

Unexplained blood cytopenias, in particular anemia, are often found in older persons. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes is currently poorly defined. We studied a prospective cohort of patients with unexplained cytopenia with the aim to estimate the predictive value of somatic mutations for identifying subjects with, or at risk of, developing a myeloid neoplasm. The study included a learning cohort of 683 consecutive patients investigated for unexplained cytopenia, and a validation cohort of 190 patients referred for suspected myeloid neoplasm. Using granulocyte DNA, we looked for somatic mutations in 40 genes that are recurrently mutated in myeloid malignancies. Overall, 435/683 patients carried a somatic mutation in at least 1 of these genes. Carrying a somatic mutation with a variant allele frequency ≥0.10, or carrying 2 or more mutations, had a positive predictive value for diagnosis of myeloid neoplasm equal to 0.86 and 0.88, respectively. Spliceosome gene mutations and comutation patterns involving TET2, DNMT3A, or ASXL1 had positive predictive values for myeloid neoplasm ranging from 0.86 to 1.0. Within subjects with inconclusive diagnostic findings, carrying 1 or more somatic mutations was associated with a high probability of developing a myeloid neoplasm during follow-up (hazard ratio = 13.9, P < .001). The predictive values of mutation analysis were confirmed in the independent validation cohort. The findings of this study indicate that mutation analysis on peripheral blood granulocytes may significantly improve the current diagnostic approach to unexplained cytopenia and more generally the diagnostic accuracy of myeloid neoplasms. PMID:28424163

Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

PubMed Central

2012-01-01

Background Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program. Methods/Design This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity. Discussion The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients. Trial Registration ISRCTN: ISRCTN70763996 PMID:22429404

Antimüllerian hormone levels and antral follicle counts are not reduced compared with community controls in patients with rigorously defined unexplained infertility.

PubMed

Greenwood, Eleni A; Cedars, Marcelle I; Santoro, Nanette; Eisenberg, Esther; Kao, Chia-Ning; Haisenleder, Daniel J; Diamond, Michael P; Huddleston, Heather G

2017-12-01

To test the hypothesis that women with unexplained infertility demonstrate evidence of diminished ovarian reserve when compared with a population of community controls. Cross-sectional study. Multicenter university-based clinical practices. Study participants included 277 healthy, normo-ovulatory female partners with rigorously defined unexplained infertility randomly selected from a multicenter trial (Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation). Controls included 226 healthy, normo-ovulatory women not seeking treatment for fertility from a community-based cohort (Ovarian Aging study). Serum antimüllerian hormone (AMH) assay at a central laboratory, FSH, fasting serum metabolic testing, transvaginal ultrasonography for antral follicle counts (AFCs), anthropometric measurements. Average AMH, AFC, and AMH/AFC were compared between infertile and control women by age. Analyses of covariance compared these outcomes while controlling for confounders, including age, race, body mass index, smoking history, and study site. In our models, AMH, AFC, and AMH/AFC ovarian reserve indices did not differ between infertile women and community-based controls, after controlling for age, race, body mass index, smoking history, and study site. Currently utilized predictors of ovarian reserve do not discriminate women with rigorously defined unexplained infertility from healthy community-based women of similar demographic characteristics. Contrary to our hypothesis, among women with FSH in the normal range (≤12 IU/L), women with unexplained infertility did not show evidence of decreased ovarian reserve as measured by AMH and AFC. Ovarian reserve markers in isolation may not serve as predictors of future fertility. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

Unexplained infertility: overall ongoing pregnancy rate and mode of conception.

PubMed

Brandes, M; Hamilton, C J C M; van der Steen, J O M; de Bruin, J P; Bots, R S G M; Nelen, W L D M; Kremer, J A M

2011-02-01

Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility. In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception. Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history. Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

Progress for Women in Academe, Yet Inequities Persist: Evidence from NSOPF:99

ERIC Educational Resources Information Center

Toutkoushian, Robert K.; Conley, Valerie Martin

2005-01-01

In this study, we use data from the 1999 National Study of Postsecondary Faculty (NSOPF:99) to measure the unexplained wage gap between men and women in academe. We pay particular attention to how these unexplained wage gaps have changed over time by comparing the results from the 1999 survey to published results from previous national surveys and…

Education, Occupation and Career Expectations: Determinants of the Gender Pay Gap for UK Graduates. CEE DP 69

ERIC Educational Resources Information Center

Chevalier, Arnaud

2006-01-01

A large proportion of the gender wage gap is usually left unexplained. In this paper, we investigate whether the unexplained component is due to misspecification. Using a sample of recent UK graduates, we introduce variables on career expectations and character traits, variables that are typically not observed. The evidence indicates that women…

A unique and unexplained ricochet leak post PCI - successfully treated with intra-coronary glue.

PubMed

Goel, Pravin K; Syal, Sanjeev K

2014-01-01

We herein describe a unique case of coronary artery perforation treated with covered stent with repeat cardiac tamponade resulting out of a fresh unexplained leak from a remote vessel (Ricochet) and successfully treated with intra-coronary injection of sterile synthetic glue, cyanoacrylate. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Amiri Jahromi, Rakhshan; Nasiri, Mahboobeh; Jahromi, Athar Rasekh

2017-01-01

This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran. 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease. These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.

A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously

PubMed Central

Tamhankar, Vidya A.; Liu, Beiyu; Yan, Junhao; Li, Tin-Chiu

2015-01-01

Objective. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility. Methods. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies). Results. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%, p < 0.001) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility. Conclusions. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause. PMID:26576157

Expectant management may reduce overtreatment in women affected by unexplained infertility confirmed by diagnostic laparoscopy.

PubMed

De Cicco, S; Tagliaferri, Valeria; Selvaggi, L; Romualdi, D; Di Florio, C; Immediata, V; Lanzone, A; Guido, M

2017-02-01

To determine whether the mini-invasive surgery still play a role in the diagnostic workup and in the management of the couples affected by unexplained infertility. 170 infertile women (age range 25-38 years) with documented normal ovarian, tubal and uterine function underwent combined hysteroscopic and laparoscopic surgery; 100 women refused surgery or ART treatment (control group) choosing expectant management. A retrospective assessment questionnaire was proposed to enrolled women to collect the rate of spontaneous or ART-induced pregnancies. The combined surgery revealed pelvic pathologies in 49.4% of patients, confirming the diagnosis of unexplained infertility only in 86 of studied patients. In this group of 86 selected women, 28 of them achieved a spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square analysis shows that the pregnancy rate was not influenced by the employment of ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous pregnancy after 18 months of expectant management. Combined laparoscopy and hysteroscopy in women with unexplained infertility may reveal previously undiagnosed pathologies that could require ART, and in those without abnormal surgical finding, ART does not improve pregnancy rate.

The correlation of sperm morphology with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis

PubMed Central

Cao, Xiaodan; Cui, Yun; Zhang, Xiaoxia; Lou, Jiangtao; Zhou, Jun; Wei, Renxiong

2017-01-01

Sperm morphology displays a potential impact on sperm function and may ultimately impact reproductive function. Current studies have investigated the correlation between sperm morphology with unexplained recurrent spontaneous abortion (RSA) but have shown inconsistent results. Hence, we systematically searched MEDLINE, EMBASE, CNKI databases, as well as the Cochrane Library for studies that examined the association between sperm morphology and unexplained RSA. Fifteen studies were identified, including 883 cases and 530 controls. Our meta-analysis results indicated that the percentage of normal sperm morphology from men with RSA partners was significantly lower than those from normal controls(SMD [95% CI]: − 0.60 [−0.81, −0.40]; P<0.00001) and the percentage of sperm morphologic alterations was significantly higher in patients with RSA compared with the control group (SMD [95% CI]: 0.92 [0.42, 1.43]; P=0.0004). The present study suggested that the percentage of normal sperm morphology may indeed decrease in men from RSA group compared with controls. However, there were some limitations in the study such as the differences in stain techniques and classification criteria. Further evidences are needed to better elucidate the relationship between sperm morphology and unexplained RSA. PMID:28903451

Do patients with unexplained physical symptoms pressurise general practitioners for somatic treatment? A qualitative study.

PubMed

Ring, Adele; Dowrick, Christopher; Humphris, Gerry; Salmon, Peter

2004-05-01

To identify the ways in which patients with medically unexplained symptoms present their problems and needs to general practitioners and to identify the forms of presentation that might lead general practitioners to feel pressurised to deliver somatic interventions. Qualitative analysis of audiorecorded consultations between patients and general practitioners. 7 general practices in Merseyside, England. 36 patients selected consecutively from 21 general practices, in whom doctors considered that patients' symptoms were medically unexplained. Inductive qualitative analysis of ways in which patients presented their symptoms to general practitioners. Although 34 patients received somatic interventions (27 received drug prescriptions, 12 underwent investigations, and four were referred), only 10 requested them. However, patients presented in other ways that had the potential to pressurise general practitioners, including: graphic and emotional language; complex patterns of symptoms that resisted explanation; description of emotional and social effects of symptoms; reference to other individuals as authority for the severity of symptoms; and biomedical explanations. Most patients with unexplained symptoms received somatic interventions from their general practitioners but had not requested them. Though such patients apparently seek to engage the general practitioner by conveying the reality of their suffering, general practitioners respond symptomatically.

Effects of environmental factors on perinatal outcome: neurological development in cases of intrauterine growth retardation and school performance of children perinatally exposed to ionizing radiation.

PubMed Central

Ikenoue, T; Ikeda, T; Ibara, S; Otake, M; Schull, W J

1993-01-01

We performed two studies to investigate environmental factors in relation to neurological development in infants. The first, a field study, examined the elementary school performance of 929 children who were born from mothers exposed to the atomic bombing of Hiroshima, Japan, August 6, 1945. The most severe mental retardation was observed in the group exposed between 8 and 15 weeks following fertilization, and the second most severely damaged group was exposed between 16 and 25 weeks. The second, a clinical investigation, examined infants in the perinatal center who survived intrauterine growth retardation (IUGR). Those who survived with abnormal neurological development had a mean growth arrest corresponding to a uterine height of 27 weeks of gestation. This was at an earlier stage than those who survived with normal neurological development and had a mean growth arrest corresponding to 29-30 weeks of gestation. A smaller head circumference at birth was closely correlated with abnormal neurological sequelae. These results indicate that the brain development of the fetuses may have been affected by neurotoxic events similar to ionizing radiation. We emphasize the importance of avoiding neurotoxic stress to pregnant women when the fetus is in the critical period of neuronal development, before 27 weeks of gestational age. PMID:8243407

Symptomatic Vasospasms as a Life-Threatening Complication After Transsphenoidal Surgery.

PubMed

Osterhage, Katharina; Czorlich, Patrick; Burkhardt, Till R; Rotermund, Roman; Grzyska, Ulrich; Flitsch, Jörg

2018-02-01

To identify symptomatic vasospasms as a rare complication after transsphenoidal surgery, with emphasis on management and outcomes. In this retrospective study, the medical records of 1997 patients who underwent microscopic transsphenoidal surgery at our hospital between 2008 and 2016 were analyzed regarding postoperative vasospasm events, clinical management, and neurologic outcomes. Four patients (0.2%) were identified who developed neurologic deficits in the postoperative phase caused by proven vasospasms due to subarachnoid hemorrhage (SAH). All 4 patients were treated according to current state-of-the-art recommendations for SAH-triggered vasospasms and, as ultima ratio, intra-arterial spasmolysis. Nonetheless, all patients developed multilocular ischemic infarctions. Three patients recovered with no or only slight neurologic deficits (2 with a Glasgow Outcome Score [GOS] of 5; 1 with a GOS of 4), and 1 patient died, at 24 days after surgery. Although a rare complication, vasospasms after transsphenoidal surgery can lead to severe and multilocular ischemic infarctions with a wide variety of neurologic impairments. This rare complication should be considered in patients with unexpected postoperative neurologic deficits. Computed tomography (CT)/magnetic resonance imaging and (contrast-enhanced) CT/magnetic resonance angiography are appropriate diagnostic tools. Treatment of vasospasms, including the option of intra-arterial spasmolysis, should not be delayed. Copyright © 2017. Published by Elsevier Inc.

Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial

PubMed Central

Li, Shanshan; Zhang, Xinjiang; Fang, Qi; Zhou, Junshan; Zhang, Meijuan; Wang, Hui; Chen, Yan; Xu, Biyun; Wu, Yanfeng; Qian, Lai

2017-01-01

Purpose To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events. Methods We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events. Results 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events. Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events. Trial registration number ChiCTR-TRC-12002688. PMID:29507779

Misdiagnosis of gastroesophageal reflux disease as epileptic seizures in children.

PubMed

Bayram, Ayşe Kaçar; Canpolat, Mehmet; Karacabey, Neslihan; Gumus, Hakan; Kumandas, Sefer; Doğanay, Selim; Arslan, Duran; Per, Hüseyin

2016-03-01

Gastroesophageal reflux disease (GERD) can mimic epileptic seizure, and may be misdiagnosed as epilepsy. On the other hand, GERD can be more commonly seen in children with neurological disorders such as cerebral palsy (CP); this co-incidence may complicate the management of patients by mimicking refractory seizures. The purpose of our study was to evaluate the clinical features, definite diagnoses and treatment approaches of the patients with clinically suspected GERD who were referred to the division of pediatric neurology with a suspected diagnosis of epileptic seizure. We also aimed to investigate the occurrence of GERD in children with epilepsy and/or CP. Fifty-seven children who had a final diagnosis of GERD but were initially suspected of having epileptic seizures were assessed prospectively. All patients were assigned to 3 groups according to definite diagnoses as follows: patients with only GERD who were misdiagnosed as having epileptic seizure (group 1: n=16; 28.1%), those with comorbidity of epilepsy and GERD (group 2: n=21; 36.8%), and those with the coexistence of GERD with epilepsy and CP (group 3: n=20; 35.1%). Five patients (8.8%) did not respond to anti-reflux treatment and laparoscopic reflux surgery was performed. The positive effect of GERD therapy on paroxysmal nonepileptic events was observed in 51/57 (89.5%) patients. GERD is one of the important causes of paroxysmal nonepileptic events. In addition, GERD must be kept in mind at the initial diagnosis and also in the long-term management of patients with neurological disorders such as epilepsy and CP. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Urinary Incontinence and Indwelling Urinary Catheters as Predictors of Death after New-Onset Stroke: A Report of the South London Stroke Register.

PubMed

John, Gregor; Primmaz, Steve; Crichton, Siobhan; Wolfe, Charles

2018-01-01

To explore the relationship between indwelling urinary catheters (IUCs), urinary incontinence (UI), and death in the poststroke period and to determine when, after the neurological event, UI has the best ability to predict 1-year mortality. In a prospective observational study, 4477 patients were followed up for 1 year after a first-ever stroke. The impact of UI or urinary catheters on time to death was adjusted in a Cox model for age, sex, Glasgow Coma Scale, prestroke and poststroke Barthel Index, swallow test, motor deficit, diabetes, and year of inclusion. The predictive values of UI assessed at the maximal deficit or 7 days after a stroke were compared using receiver-operating curves. UI at the maximal neurological deficit and urinary catheters within the first week after the stroke were present in 43.9% and 31.2% patients, respectively. They were both associated with 1-year mortality in unadjusted and adjusted analysis (hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.46-2.19, and HR, 1.84, 95% CI 1.54-2.19). Patients with UI and urinary catheters had twice the mortality rate of incontinent patients without urinary catheters (HR, 10.24; 95% CI, 8.72-12.03 versus HR, 4.70; 95% CI, 3.88-5.70; P < .001). UI assessed after 1 week performed better at predicting 1-year mortality than UI assessed at the maximal neurological deficit. IUCs in the poststroke period is associated with death, especially among incontinent patients. UI assessed at 1 week after the neurological event has the best predictive ability. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Intermittent hypoxia in patients with unexplained polycythaemia.

PubMed Central

Moore-Gillon, J C; Treacher, D F; Gaminara, E J; Pearson, T C; Cameron, I R

1986-01-01

The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly. PMID:3092936

[The relation of circadian variations of heuristic behavior and CNS radioresistance in animals].

PubMed

Ushakov, I B; Davydova, O E

1996-01-01

There has been studied the influence of g-radiation (60Co, 62.5 Gy, craniocaudal) on circadian dynamics of heuristic behaviour (the elements of rational-discriminative activity) of male white rats. There has been found equivocal nature of radiation action: mostly manifestations of some symptoms of neurologic disturbances observed in definite daily periods make difficult realizing behavioural act, but in the other cases such event is not observed (acrophases of both processes coincide). After disappearance of observed neurologic manifestations of central nervous system damage (symptoms of early transitory neurologic disturbances) during the short period of time after exposure to radiation the inversion of circadian rhythm of heuristic behaviour has not been found. The changes are expressed in significant increase of values of extremums and mesor in comparison with control groups not exposed to radiation. By 30 minute after exposure the process loses signs of rhythm, acquires smooth character and mesor response significantly decreases.

Tranexamic acid-associated seizures: Causes and treatment.

PubMed

Lecker, Irene; Wang, Dian-Shi; Whissell, Paul D; Avramescu, Sinziana; Mazer, C David; Orser, Beverley A

2016-01-01

Antifibrinolytic drugs are routinely used worldwide to reduce the bleeding that results from a wide range of hemorrhagic conditions. The most commonly used antifibrinolytic drug, tranexamic acid, is associated with an increased incidence of postoperative seizures. The reported increase in the frequency of seizures is alarming, as these events are associated with adverse neurological outcomes, longer hospital stays, and increased in-hospital mortality. However, many clinicians are unaware that tranexamic acid causes seizures. The goal of this review is to summarize the incidence, risk factors, and clinical features of these seizures. This review also highlights several clinical and preclinical studies that offer mechanistic insights into the potential causes of and treatments for tranexamic acid-associated seizures. This review will aid the medical community by increasing awareness about tranexamic acid-associated seizures and by translating scientific findings into therapeutic interventions for patients. © 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Clobazam-Treated Patients with Lennox Gastaut Syndrome Experienced Fewer Seizure-Related Injuries than Placebo Patients During Trail OV-1012

DTIC Science & Technology

2016-08-19

injuries based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms from all adverse event (AE) listings. Patients receiving...injuries For this post hoc analysis, medical review of all adverse event (AE) listings, based on Medical Dictionary for Regu- latory Activities (MedDRA...study results of clobazam in Lennox-Gastaut syndrome. Neurology 2011;77:1473–1481. 5. Medical Dictionary for Regulatory Activities. Available at: http

The necessity of recognizing all events in X-ray detection.

PubMed

Papp, T; Maxwell, J A; Papp, A T

2010-01-01

In our work in studying properties of inner shell ionization, we are troubled that the experimental data used to determine the basic parameters of X-ray physics have a large and unexplainable scatter. As we looked into the problems we found that many of them contradict simple logic, elemental arithmetic, even parity and angular momentum conservation laws. We have identified that the main source of the problems, other than the human factor, is rooted in the signal processing electronics. To overcome these problems we have developed a fully digital signal processor, which not only has excellent resolution and line shape, but also allows proper accounting of all events. This is achieved by processing all events and separating them into two or more spectra (maximum 16), where the first spectrum is the accepted or good spectrum and the second spectrum is the spectrum of all rejected events. The availability of all the events allows one to see the other part of the spectrum. To our surprise the total information explains many of the shortcomings and contradictions of the X-ray database. The data processing methodology cannot be established on the partial and fractional information offered by other approaches. Comparing Monte Carlo detector modeling results with the partial spectra is ambiguous. It suggests that the metrology of calibration by radioactive sources as well as other X-ray measurements could be improved by the availability of the proper accounting of all events. It is not enough to know that an event was rejected and increment the input counter, it is necessary to know, what was rejected and why it happened, whether it was a noise or a disturbed event, a retarded event or a true event, or any pile up combination of these events. Such information is supplied by our processor reporting the events rejected by each discriminator in separate spectra. Several industrial applications of this quality assurance capable signal processor are presented. Copyright 2009 Elsevier Ltd. All rights reserved.

Development of electrophysiological indices of neurological toxicity for organophosphate pesticides and depressant drugs.

DOT National Transportation Integrated Search

1979-05-01

Accurate control of eye movements and rapid detection of unexpected events in the periphery of the visual field are critically important in the aviation environment. We have studied the effects of certain drugs and environmental pollutants on brain m...

Bacterial vaginosis and infertility: cause or association?

PubMed

Salah, Rasheed M; Allam, Abdelmonem M; Magdy, Amin M; Mohamed, Abeer Sh

2013-03-01

To estimate the prevalence of bacterial vaginosis (BV) in infertile women and evaluate the effect of treatment of BV on the pregnancy rate in patients with polycystic ovarian disease (PCOD) and unexplained infertility. Cohort study conducted at the Department of Obstetrics and Gynecology in collaboration with the Microbiology Department of Sohag University Hospital, Egypt. All eligible women with female factor infertility (n=874) were enrolled and all asymptomatic fertile women (n=382) attending the family planning clinic of the study hospital were recruited as a control group. The study was in two phases: the first included screening all participants for BV after Gram-staining of the vaginal discharge. The second phase was concerned with evaluating the effect of treatment of BV on the cumulative pregnancy rate (CPP) in patients with PCOD (group I; n=278) and unexplained infertility (group II; n=170). Each group was divided into three sub-groups: groups Ia (n=129) and IIa (n=73) were BV positive and treated for BV; groups Ib (n=61) and IIb (n=49) were BV positive and did not receive treatment for BV, and groups Ic (n=88) and IIc (n=48) were BV negative. The prevalence of BV was compared using the Chi-square. The long rank test of Kaplan-Meier life table analysis was used to compare the CPR. A multivariate regression model was designed to define the most significant variable which affected the pregnancy rate in patients with PCOD. The prevalence of BV was significantly higher in infertile than fertile women (45.5% vs 15.4%). The highest prevalence was found in patients with PCOD (60.1%) and unexplained infertility (37.4%). The CPR in both patients with PCOD and unexplained infertility were significantly higher in the patients who were treated for BV. Regression model showed that BV was one of the significant factors interfering with pregnancy. BV is strongly implicated in female infertility and is probably an underestimated cause of unexplained infertility. Screening and treatment of BV in patients with PCOD and unexplained infertility improved the pregnancy rate considerably. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Small-scale deflagration cylinder test with velocimetry wall-motion diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooks, Daniel E; Hill, Larry G; Pierce, Timothy H

Predicting the likelihood and effects of outcomes resultant from thermal initiation of explosives remains a significant challenge. For certain explosive formulations, the general outcome can be broadly predicted given knowledge of certain conditions. However, there remain unexplained violent events, and increased statistical understanding of outcomes as a function of many variables, or 'violence categorization,' is needed. Additionally, the development of an equation of state equivalent for deflagration would be very useful in predicting possible detailed event consequences using traditional hydrodynamic detonation moders. For violence categorization, it is desirable that testing be efficient, such that it is possible to statistically definemore » outcomes reliant on the processes of initiation of deflagration, steady state deflagration, and deflagration to detonation transitions. If the test simultaneously acquires information to inform models of violent deflagration events, overall predictive capabilities for event likelihood and consequence might improve remarkably. In this paper we describe an economical scaled deflagration cylinder test. The cyclotetramethylene tetranitramine (HMX) based explosive formu1lation PBX 9501 was tested using different temperature profiles in a thick-walled copper cylindrical confiner. This test is a scaled version of a recently demonstrated deflagration cylinder test, and is similar to several other thermal explosion tests. The primary difference is the passive velocimetry diagnostic, which enables measurement of confinement vessel wall velocities at failure, regardless of the timing and location of ignition.« less

Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features.

PubMed

Battaglia, Agatino; Doccini, Viola; Bernardini, Laura; Novelli, Antonio; Loddo, Sara; Capalbo, Anna; Filippi, Tiziana; Carey, John C

2013-11-01

Submicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients. We studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases. 91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID. Our study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Arterial Cannulation and Cerebral Perfusion Strategies for Aortic Arch Operations.

PubMed

Foley, Lisa S; Yamanaka, Katsuhiro; Reece, T Brett

2016-12-01

Neurologic injuries following aortic arch operations can be devastating, with stroke occurring in up to 12% of elective operations and significant cerebral dysfunction occurring in up to 25% of cases. The primary challenge unique to aortic arch operations involves interruption of direct perfusion of the brachiocephalic vessels during arch reconstruction. For this reason, neuroprotection is paramount. The 2 main modes of protection are (1) reducing metabolic demand through hypothermia and (2) limiting, or even eliminating, the ischemic period. Preoperative selection of the cerebral perfusion plan for each operation is imperative to maintain maximal diffuse cerebral protection and prevent focal neurologic events. © The Author(s) 2016.

Attachment, Symptom Severity, and Depression in Medically Unexplained Musculoskeletal Pain and Osteoarthritis: A Cross-Sectional Study

PubMed Central

Schroeter, Corinna; Ehrenthal, Johannes C.; Giulini, Martina; Neubauer, Eva; Gantz, Simone; Amelung, Dorothee; Balke, Doreen; Schiltenwolf, Marcus

2015-01-01

Background Attachment insecurity relates to the onset and course of chronic pain via dysfunctional reactions to pain. However, few studies have investigated the proportion of insecure attachment styles in different pain conditions, and results regarding associations between attachment, pain severity, and disability in chronic pain are inconsistent. This study aims to clarify the relationships between insecure attachment and occurrence or severity of chronic pain with and without clearly defined organic cause. To detect potential differences in the importance of global and romantic attachment representations, we included both concepts in our study. Methods 85 patients with medically unexplained musculoskeletal pain (UMP) and 89 patients with joint pain from osteoarthritis (OA) completed self-report measures of global and romantic attachment, pain intensity, physical functioning, and depression. Results Patients reporting global insecure attachment representations were more likely to suffer from medically unexplained musculoskeletal pain (OR 3.4), compared to securely attached patients. Romantic attachment did not differ between pain conditions. Pain intensity was associated with romantic attachment anxiety, and this relationship was more pronounced in the OA group compared to the UMP group. Both global and romantic attachment anxiety predicted depression, accounting for 15% and 17% of the variance, respectively. Disability was independent from attachment patterns. Conclusions Our results indicate that global insecure attachment is associated with the experience of medically unexplained musculoskeletal pain, but not with osteoarthritis. In contrast, insecure attachment patterns seem to be linked to pain intensity and pain-related depression in unexplained musculoskeletal pain and in osteoarthritis. These findings suggest that relationship-informed focused treatment strategies may alleviate pain severity and psychological distress in chronic pain independent of underlying pathology. PMID:25807172

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

PubMed

Arya, Sushila; Kupesic-Plavsic, Sanja; Mulla, Zuber D; Dwivedi, Alok K; Crisp, Zeni; Jose, Jisha; Noble, Luis S

2017-11-01

To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation. Published by Elsevier B.V.

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

PubMed Central

Waldmann, Victor; Bougouin, Wulfran; Karam, Nicole; Dumas, Florence; Sharifzadehgan, Ardalan; Gandjbakhch, Estelle; Algalarrondo, Vincent; Narayanan, Kumar; Zhao, Alexandre; Amet, Denis; Jost, Daniel; Geri, Guillaume; Lamhaut, Lionel; Beganton, Frankie; Ludes, Bertrand; Bruneval, Patrick; Plu, Isabelle; Hidden-Lucet, Françoise; Albuisson, Juliette; Lavergne, Thomas; Piot, Olivier; Alonso, Christine; Leenhardt, Antoine; Lellouche, Nicolas; Extramiana, Fabrice; Cariou, Alain; Jouven, Xavier; Marijon, Eloi

2018-01-01

Abstract Aims Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Methods and results Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80–22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12–12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Conclusion Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed. PMID:29566157

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation.

PubMed

Waldmann, Victor; Bougouin, Wulfran; Karam, Nicole; Dumas, Florence; Sharifzadehgan, Ardalan; Gandjbakhch, Estelle; Algalarrondo, Vincent; Narayanan, Kumar; Zhao, Alexandre; Amet, Denis; Jost, Daniel; Geri, Guillaume; Lamhaut, Lionel; Beganton, Frankie; Ludes, Bertrand; Bruneval, Patrick; Plu, Isabelle; Hidden-Lucet, Françoise; Albuisson, Juliette; Lavergne, Thomas; Piot, Olivier; Alonso, Christine; Leenhardt, Antoine; Lellouche, Nicolas; Extramiana, Fabrice; Cariou, Alain; Jouven, Xavier; Marijon, Eloi

2018-06-01

Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Results of the VAMPIRE trial.

PubMed

Koch, Hèlen; van Bokhoven, Marloes A; ter Riet, Gerben; van Alphen-Jager, Jm Tineke; van der Weijden, Trudy; Dinant, Geert-Jan; Bindels, Patrick J E

2009-04-01

Unexplained fatigue is frequently encountered in general practice. Because of the low prior probability of underlying somatic pathology, the positive predictive value of abnormal (blood) test results is limited in such patients. The study objectives were to investigate the relationship between established diagnoses and the occurrence of abnormal blood test results among patients with unexplained fatigue; to survey the effects of the postponement of test ordering on this relationship; and to explore consultation-related determinants of abnormal test results. Cluster randomised trial. General practices of 91 GPs in the Netherlands. GPs were randomised to immediate or postponed blood-test ordering. Patients with new unexplained fatigue were included. Limited and expanded sets of blood tests were ordered either immediately or after 4 weeks. Diagnoses during the 1-year follow-up period were extracted from medical records. Two-by-two tables were generated. To establish independent determinants of abnormal test results, a multivariate logistic regression model was used. Data of 325 patients were analysed (71% women; mean age 41 years). Eight per cent of patients had a somatic illness that was detectable by blood-test ordering. The number of false-positive test results increased in particular in the expanded test set. Patients rarely re-consulted after 4 weeks. Test postponement did not affect the distribution of patients over the two-by-two tables. No independent consultation-related determinants of abnormal test results were found. Results support restricting the number of tests ordered because of the increased risk of false-positive test results from expanded test sets. Although the number of re-consulting patients was small, the data do not refute the advice to postpone blood-test ordering for medical reasons in patients with unexplained fatigue in general practice.

A Randomized Double-Blind Controlled Trial Comparing Davanloo Intensive Short-Term Dynamic Psychotherapy as Internet-Delivered Vs Treatment as Usual for Medically Unexplained Pain: A 6-Month Pilot Study.

PubMed

Chavooshi, Behzad; Mohammadkhani, Parvaneh; Dolatshahi, Behrouz

2016-01-01

Research has shown that Intensive Short-Term Dynamic Psychotherapy (ISTDP) can effectively decrease pain intensity and improve quality of life in patients with medically unexplained pain. Understanding that not all patients with medically unexplained pain have access to in-person ISTDP, this study aims to investigate the efficacy of an Internet-delivered ISTDP for individuals with medically unexplained pain using Skype in comparison with treatment as usual. In this randomized controlled trial, 100 patients were randomly allocated into Internet-delivered ISTDP (n = 50) and treatment-as- usual (n = 50) groups. Treatment intervention consisted of 16 weekly, hour-long therapy sessions. The primary outcome was perceived pain assessed using the Numeric Pain Rating Scale. The secondary outcome included Depression Anxiety Stress Scale-21, Emotion Regulation Questionnaire, Mindful Attention Awareness Scale, and Quality-of-Life Inventory. Blind assessments were conducted at the baseline, posttreatment, and at a 6-month follow-up. In the intention-to-treat analysis, pain symptoms in the intervention group were significantly reduced (p < 0.001), whereas a reduction was not observed in the treatment as usual group (p = 0.651). Moreover, there were significant decreases in depression, anxiety, and stress, as well as a greater increase in emotion regulation functioning, mindfulness, and quality of life observed in the intervention group 6 months after the treatment compared with the treatment as usual condition. The results of this pilot trial demonstrate that 16 weeks of ISTDP delivered by Skype can significantly improve pain intensity and clinical symptoms of medically unexplained pain. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Unexplained lower abdominal pain associated with sacroiliac joint dysfunction: report of 2 cases.

PubMed

Morimoto, Daijiro; Isu, Toyohiko; Kim, Kyongsong; Matsumoto, Ryoji; Isobe, Masanori

2011-01-01

A 25-year-old woman and a 31-year-old man presented with chronic lower back pain and unexplained lower abdominal pain. Both patients had groin tenderness at the medial border of the anterior superior iliac spine. The results of radiographical and physical examinations suggested sacroiliac joint dysfunction. Sacroiliac joint injection relieved their symptoms, including groin tenderness. In our experience, groin tenderness is highly specific for sacroiliac joint dysfunction. We speculate that spasm of the iliac muscle can cause groin pain and tenderness. Groin pain and a history of unexplained abdominal pain, with lower back pain, are symptoms that suggest sacroiliac joint dysfunction. Additionally, compression of the iliac muscle is a simple and useful maneuver; therefore, it can be used as a screening test for sacroiliac joint dysfunction, alongside other provocation tests.

Adverse Event Rates Associated with Transforaminal and Interlaminar Epidural Steroid Injections: A Multi-Institutional Study.

PubMed

El-Yahchouchi, Christine A; Plastaras, Christopher T; Maus, Timothy P; Carr, Carrie M; McCormick, Zachary L; Geske, Jennifer R; Smuck, Matthew; Pingree, Matthew J; Kennedy, David J

2016-02-01

Transforaminal epidural steroid injections (TFESI) have demonstrated efficacy and effectiveness in treatment of radicular pain. Despite little evidence of efficacy/effectiveness, interlaminar epidural steroid injections (ILESI) are advocated by some as primary therapy for radicular pain due to purported greater safety. To assess immediate and delayed adverse event rates of TFESI and ILESI injections at three academic medical centers utilizing International Spine Intervention Society practice guidelines. Quality assurance databases from a Radiology and two physical medicine and rehabilitation (PM&R) practices were interrogated. Medical records were reviewed, verifying immediate and delayed adverse events. There were no immediate major adverse events of neurologic injury or hemorrhage in 16,638 consecutive procedures in all spine segments (14,956 TFESI; 1,682 ILESI). Vasovagal reactions occurred in 1.2% of procedures, more frequently (P = 0.004) in TFESI (1.3%) than ILESI (0.5%). Dural punctures occurred in 0.06% of procedures, more commonly after ILESI (0.2% vs 0.04%, P = 0.006). Delayed follow up on PM&R patients (92.5% and 78.5, next business day) and radiology patients (63.1%, 2 weeks) identified no major adverse events of neurologic injury, hemorrhage, or infection. There were no significant differences in delayed minor adverse event rates. Central steroid response (sleeplessness, flushing, nonpositional headache) was seen in 2.6% of both TFESI and ILESI patients. 2.1% of TFESI and 1.8% of ILESI patients reported increased pain. No long-term sequelae were seen from any immediate or delayed minor adverse event. Both transforaminal and ILESI are safely performed with low immediate and delayed adverse event rates when informed by evidence-based procedural guidelines. By demonstrating comparable safety, this study suggests that the choice between ILESI and TFESIs can be based on documented efficacy and effectiveness and not driven by safety concerns.

Solving medical mysteries: hidden stresses and unexplained symptoms.

PubMed

Clarke, David D

2016-09-01

Medically unexplained symptoms and chronic functional syndromes are common but few healthcare professionals have had formal training about their connection to psychosocial issues. A systematic approach to diagnosis and treatment based on experience with over 7000 of these patients is described. Outcomes improve with assessment for and treatment of current life stresses, the prolonged impact of adversity in childhood and somatic presentations of depression, post-traumatic stress, and anxiety disorders.

[The diagnostic value of medical thoracoscopy for unexplained pleural effusion].

PubMed

Jiang, Shu-juan; Mu, Xiao-yan; Zhang, Song; Su, Li-li; Ma, Wei-xia

2013-05-01

To explore the endoscopic features of patients with unexplained pleural effusion, and to evaluate the diagnostic value of medical thoracoscopy. A retrospective analysis of 2380 patients with unexplained pleural effusion (1320 males and 1060 females; age 15-94 years) in Shandong Provincial Hospital from 1992 to 2011 were performed .The diagnosis was confirmed by medical thoracoscopy. The endoscopic findings of malignant pleural effusion mostly showed nodules of varying sizes. The nodules could be grape-like, cauliflower-like, fused into masses, or diffused small nodules . The appearance of cancerous nodules was more diversified compared to tuberculous nodules. Tuberculous pleurisy was manifested as diffuse pleural congestion and miliary changes, multiple small gray-white nodules, fibrin deposition and adhesion in the pleural cavity, pleural thickening and loculation . The pathological diagnosis was as follows: pleural metastases in 899 (37.8%), primary pleural mesothelioma in 439 (18.4%), tuberculous pleurisy in 514 (21.6%), non-specific inflammation in 226 (9.5%), empyema in 190 (8.0%), hepatic pleural effusion in 36 (1.5%) and pleural effusion of unknown causes in 76 (3.2%) cases. The diagnostic positive rate of medical thoracoscopy was 96.8%. No serious complications were observed. Medical thoracoscopy is a relatively safe procedure and has an important application value in the diagnosis of unexplained pleural effusion.

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage

PubMed Central

Molazadeh, Morteza; Karimzadeh, Hadi; Azizi, Mohammad R

2014-01-01

Background: Antinuclear antibodies (ANAs) in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. Objective: In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. Materials and Methods: 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. Results: ANAs were detected in 74 of 560 (13.21%) patient with recurrent miscarriage, and in only 5 of 560 (0.9%) controls (p<0.001). ANA positivity was generally found with low-positive results (1.40-1.80) in about 38% of positive cases, whereas moderate titres (1.160-1.320) and high titres (>1.640) were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Conclusion: Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients. PMID:24799884

A research coding method to evaluate medical clinicians conduct of behavioral health care in patients with unexplained symptoms.

PubMed

Grayson-Sneed, Katelyn A; Smith, Robert C

2018-04-01

Develop a reliable coding method of a Behavioral Health Treatment Model for patients with Medically Unexplained Symptoms (BHTM-MUS). Two undergraduates trained for 30h coded videotaped interviews from 161 resident-simulated patient (SP) interactions. Trained on 45 videotapes, coders coded 33 (20%) of 161 study set tapes for the BHTM-MUS. Guetzkow's U, Cohen's Kappa, and percent of agreement were used to measure coders' reliability in unitizing and coding residents' skills for eliciting: education and informing (4 yes/no items), motivating (2), treatment statements (5), commitment and goals (2), negotiates plan (8), non-emotion patient-centered skills (4), and patient-centered emotional skills (8). 60 items were dichotomized a priori from analysis of the BHTM-MUS and were reduced to 33 during training. Guetzkow's U ranged from .00 to .082. Kappa ranged from 0.76 to 0.97 for the 7 variables and 33 individual items. The overall kappa was 0.87, and percent of agreement was 95.7%. Percent of agreement by item ranged from 85 to 100%. A highly reliable coding method is recommended to evaluate medical clinicians' behavioral care skills in patients with unexplained symptoms. A way to rate behavioral care in patients with unexplained symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Trends in the earnings gender gap among dentists, physicians, and lawyers.

PubMed

Nguyen Le, Thanh An; Lo Sasso, Anthony T; Vujicic, Marko

2017-04-01

The authors examined the factors associated with sex differences in earnings for 3 professional occupations. The authors used a multivariate Blinder-Oaxaca method to decompose the differences in mean earnings across sex. Although mean differences in earnings between men and women narrowed over time, there remained large, unaccountable earnings differences between men and women among all professions after multivariate adjustments. For dentists, the unexplained difference in earnings for women was approximately constant at 62% to 66%. For physicians, the unexplained difference in earnings for women ranged from 52% to 57%. For lawyers, the unexplained difference in earnings for women was the smallest of the 3 professions but also exhibited the most growth, increasing from 34% in 1990 to 45% in 2010. The reduction in the earnings gap is driven largely by a general convergence between men and women in some, but not all, observable characteristics over time. Nevertheless, large unexplained gender gaps in earnings remain for all 3 professions. Policy makers must use care in efforts to alleviate earnings differences for men and women because measures could make matters worse without a clear understanding of the nature of the factors driving the differences. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Investigation of fatigue by Australian general practice registrars: a cross-sectional study.

PubMed

Morgan, Simon; Henderson, Kim M; Tapley, Amanda; Thomson, Allison; Wilson, Jessica; Scott, John; Spike, Neil A; McArthur, Lawrie; van Driel, Mieke L; Magin, Parker J

2015-06-01

Fatigue is the most common undifferentiated problem presenting in general practice. Previous studies have shown that this presentation leads to multiple investigations. There is no published literature describing the management of patients with fatigue by general practice (GP) registrars. To document the investigation-ordering behaviour of GP registrars in managing patients with a new diagnosis of unexplained fatigue. This was a cross-sectional analysis of data from Registrar Clinical Encounters in Training (ReCEnT), an ongoing cohort study of GP registrars' consultations. We established the prevalence of new diagnoses of unexplained fatigue and associations with that diagnosis, the rate of test ordering and the number and types of investigations ordered. 644 registrars contributed data from 68 986 encounters. In 0.78% of patient encounters, a new diagnosis of unexplained fatigue was made. Pathology was ordered in 78.4% of these problems (versus 18.1% in non-fatigue problems), at a rate of 488 tests per 100 new fatigue problems. Our study suggests that unexplained fatigue elicits a non-rational approach to test ordering by registrars. These findings contribute to the understanding of GP registrar management of fatigue, and undifferentiated presentations more broadly, and suggest educational approaches to improve practice, including dealing with uncertainty.

High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease.

PubMed

Merchante, Nicolás; Parra-Sánchez, Manuel; Rivero-Juárez, Antonio; Cifuentes, Celia; Camacho, Ángela; Macías, Juan; Martínez-Dueñas, Loreto; Pérez-Navarro, Elisabet; Rivero, Antonio; Pineda, Juan A

2015-10-01

To look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS). Case-control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection. Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (p=.3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis. HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet.

PubMed

Ehsani-Ardakani, M J; Fallahian, M; Rostami, K; Rostami-Nejad, M; Lotfi, S; Mohaghegh-Shalmani, H; Dabiri, R; Norouzinia, M; Azizpour-Shoobi, F; Zali, M R

2014-01-01

The aim of this study was to investigate the relation between Celiac disease (CD) and unexplained dysfunctional uterine bleeding (DUB) in celiac women. The celiac patients were selected from women who were referred to celiac department. Controls were selected from those women without any signs of celiac disease and matched with age. Meanwhile, a trained physician was ready to explain the study, and then in case of their allowance, a questionnaire was completed by the physician. 24 % of celiac women reported a past history of at least one menstrual cycle disorder vs 10 % of controls reported these problems (p=0.038) and higher percentage of unexplained DUB has been observed in celiac women. All celiac patients were undertaking gluten free diet for at least 3 months and the celiac patients who reported the history of DUB were again interviewed for any signs of unexplained DUB. From 12 celiac women with DUB, 10 patients reported no more unexplained DUB after getting gluten-free diet (83.3 %). The occurrence of a significant correlation between CD and DUB suggests the possibility of considering CD as one of the potential causes of abnormal uterine bleeding. Therefore, celiac disease must be seriously considered in the screening of patients with reproductive disorders (Tab. 2,Ref. 23).

Low molecular weight heparin use in unexplained recurrent miscarriage

PubMed Central

Yuksel, Halide; Kayatas, Semra; Boza, Aysen Telce; Api, Murat; Ertekin, A. Aktug; Cam, Cetin

2014-01-01

Objective: The aim of the study was to investigate whether the use of low molecular weight heparin (LMWH) improve live birth rates when compared with control group in patients with unexplained recurrent miscarriages (URM). Methods: In this prospective observational study 150 women with a history of two or more previous unexplained first trimester pregnancy loss who received LMWH; either enoxaparin (n=50), tinzaparin (n=50) or nothing (n=50) were followed for the pregnancy outcome measures. Only the patients who have used standardized dosage of LMWH (4000 IU/day enoxaparin or 3500 IU/day tinzaparin ) were included to the study. The primary end point was the live birth rate and secondary end points were the side effects, late pregnancy complications and neonatal outcome in the study cohorts. Results: Live birth was achieved 85% of the LMWH group and 66% of the control group (p=0.007). According to the subgroup analysis; live birth rates did not differ significantly between the enoxaparin and tinzaparin group (84% and 86%, respectively). Maternal and neonatal side effects were not statistically significant among the study participants. Conclusion: Thromboprophylaxis with LMWH resulted in a improved live-birth rate in patient with 2 or more consecutive unexplained recurrent pregnancy loss. Nevertheless these findings need to be confirmed in larger randomized trials. PMID:25674114

Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

PubMed

Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

2017-05-01

Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

Post-mortem genetic testing in a family with long-QT syndrome and hypertrophic cardiomyopathy.

PubMed

Kane, David A; Triedman, John

2014-01-01

Pediatric sudden unexplained deaths are rare and tragic events that should be evaluated with all the tools available to the medical community. The current state of genetic testing is an excellent resource that improves our ability to diagnose cardiovascular disorders that can lead to sudden cardiac arrest. Post-mortem genetic testing is not typically a covered benefit of health insurance and may not be offered to families in the setting of a negative autopsy. This unusual case includes two separate cardiovascular disorders that highlight the use of genetic testing and its role in diagnosis, screening, and risk stratification. The insurance company's decision to cover post-mortem testing demonstrated both compassion as well as an understanding of the long-term cost effectiveness. Copyright © 2014 Elsevier Inc. All rights reserved.

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions.

PubMed

Pattee, Gary L; Wymer, James P; Lomen-Hoerth, Catherine; Appel, Stanley H; Formella, Andrea E; Pope, Laura E

2014-11-01

Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient's emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. #NCT00056524. A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions.

[Trans fatty acids in the nutrition of children with neurological disorders].

PubMed

Cortés, E; Aguilar, M J; Rizo, M M; Hidalgo, M J

2013-01-01

Trans-fatty acids are present in various foods, being the only source of the same in humans. Its presence in high concentrations is a risk factor for health, being involved in a series of events, cardiovascular, inflammatory, etc. Therefore, steps have been taken for its decrease in the diet. The aim is to determine serum and phospholipids of membranes in healthy children and neurological alterations. It has analyzed the fatty acids trans in 34 healthy children and 374 with various neurological pathologies. Serum and blood cells, making the lipid extraction, samples have been separation of the phospholipids of cells membranes, methylation of fatty acids, separation by gas chromatography and quantification using mass detector. The data have been processed statistically. The distribution of trans fatty acids and their sum is not normally distributed, so its nonparemetric tests were used. The values are higher than in serum phospholipids and membrane with a weak but significant correlation. The tC18: 1 is in a double proportion in children with neurological disorders in healthy children, both in serum and membrane phospholipids, with significant differences. The highest proportion of trans-fatty acids in the group of children with neurological disorders is caused no doubt by an increase in intake, due to less adequate food. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

A review of the emerging potential therapy for neurological disorders: human embryonic stem cell therapy

PubMed Central

Shroff, Geeta; Dhanda Titus, Jyoti; Shroff, Rhea

2017-01-01

The first human embryonic stem cell (hESC) line was developed in the late nineties. hESCs are capable of proliferating indefinitely and differentiate into all the three embryonic germ layers. Further, the differentiation of hESC lines into neural precursor cells and neurons, astrocytes and oligodendrocytes showed their potential in treating several incurable neurological disorders such as spinal cord injury (SCI), cerebral palsy (CP), Parkinson’s disease (PD). In this review, we will discuss the global scenario of research and therapeutic use of hESCs in the treatment of neurological disorders. Following this, we will discuss the development of a unique hESC line, how it differs from the other available hESC lines and its use in the treatment of neurological disorders. hESCs were isolated from mixture of neuronal and non-neuronal progenitor cells in their pre progenitor state in a Good Laboratory Practices, Good Tissue Practices and Good Manufacturing Practices compliant laboratory. Blastomere cells have served as a source to derive the hESCs and the xeno-free culture was demonstrated to be more safe and effective in clinical therapeutic application of hESCs. All the patients showed a remarkable improvement in their conditions and no serious adverse events were reported. This study concluded that hESC lines could be scalable and used in the treatment of various neurological disorders such as SCI, CP, and PD. PMID:28533935

Batrachochytrium salamandrivorans sp. nov. causes lethal chytridiomycosis in amphibians

PubMed Central

Martel, An; Spitzen-van der Sluijs, Annemarieke; Blooi, Mark; Bert, Wim; Ducatelle, Richard; Fisher, Matthew C.; Woeltjes, Antonius; Bosman, Wilbert; Chiers, Koen; Bossuyt, Franky; Pasmans, Frank

2013-01-01

The current biodiversity crisis encompasses a sixth mass extinction event affecting the entire class of amphibians. The infectious disease chytridiomycosis is considered one of the major drivers of global amphibian population decline and extinction and is thought to be caused by a single species of aquatic fungus, Batrachochytrium dendrobatidis. However, several amphibian population declines remain unexplained, among them a steep decrease in fire salamander populations (Salamandra salamandra) that has brought this species to the edge of local extinction. Here we isolated and characterized a unique chytrid fungus, Batrachochytrium salamandrivorans sp. nov., from this salamander population. This chytrid causes erosive skin disease and rapid mortality in experimentally infected fire salamanders and was present in skin lesions of salamanders found dead during the decline event. Together with the closely related B. dendrobatidis, this taxon forms a well-supported chytridiomycete clade, adapted to vertebrate hosts and highly pathogenic to amphibians. However, the lower thermal growth preference of B. salamandrivorans, compared with B. dendrobatidis, and resistance of midwife toads (Alytes obstetricans) to experimental infection with B. salamandrivorans suggest differential niche occupation of the two chytrid fungi. PMID:24003137

Batrachochytrium salamandrivorans sp. nov. causes lethal chytridiomycosis in amphibians.

PubMed

Martel, An; Spitzen-van der Sluijs, Annemarieke; Blooi, Mark; Bert, Wim; Ducatelle, Richard; Fisher, Matthew C; Woeltjes, Antonius; Bosman, Wilbert; Chiers, Koen; Bossuyt, Franky; Pasmans, Frank

2013-09-17

The current biodiversity crisis encompasses a sixth mass extinction event affecting the entire class of amphibians. The infectious disease chytridiomycosis is considered one of the major drivers of global amphibian population decline and extinction and is thought to be caused by a single species of aquatic fungus, Batrachochytrium dendrobatidis. However, several amphibian population declines remain unexplained, among them a steep decrease in fire salamander populations (Salamandra salamandra) that has brought this species to the edge of local extinction. Here we isolated and characterized a unique chytrid fungus, Batrachochytrium salamandrivorans sp. nov., from this salamander population. This chytrid causes erosive skin disease and rapid mortality in experimentally infected fire salamanders and was present in skin lesions of salamanders found dead during the decline event. Together with the closely related B. dendrobatidis, this taxon forms a well-supported chytridiomycete clade, adapted to vertebrate hosts and highly pathogenic to amphibians. However, the lower thermal growth preference of B. salamandrivorans, compared with B. dendrobatidis, and resistance of midwife toads (Alytes obstetricans) to experimental infection with B. salamandrivorans suggest differential niche occupation of the two chytrid fungi.

Cockayne syndrome and xeroderma pigmentosum

PubMed Central

Rapin, I.; Lindenbaum, Y.; Dickson, D.W.; Kraemer, K.H.; Robbins, J.H.

2015-01-01

Objectives To review genetic variants of Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive disorders of DNA repair that affect the nervous system, and to illustrate them by the first case of xeroderma pigmentosum–Cockayne syndrome (XP-CS) complex to undergo neuropathologic examination. Methods Published reports of clinical, pathologic, and molecular studies of CS, XP neurologic disease, and the XP-CS complex were reviewed, and a ninth case of XP-CS is summarized. Results CS is a multisystem disorder that causes both profound growth failure of the soma and brain and progressive cachexia, retinal, cochlear, and neurologic degeneration, with a leukodystrophy and demyelinating neuropathy without an increase in cancer. XP presents as extreme photosensitivity of the skin and eyes with a 1000-fold increased frequency of cutaneous basal and squamous cell carcinomas and melanomas and a small increase in nervous system neoplasms. Some 20% of patients with XP incur progressive degeneration of previously normally developed neurons resulting in cortical, basal ganglia, cerebellar, and spinal atrophy, cochlear degeneration, and a mixed distal axonal neuropathy. Cultured cells from patients with CS or XP are hypersensitive to killing by ultraviolet (UV) radiation. Both CS and most XP cells have defective DNA nucleotide excision repair of actively transcribing genes; in addition, XP cells have defective repair of the global genome. There are two complementation groups in CS and seven in XP. Patients with the XP-CS complex fall into three XP complementation groups. Despite their XP genotype, six of nine individuals with the XP-CS complex, including the boy we followed up to his death at age 6, had the typical clinically and pathologically severe CS phenotype. Cultured skin and blood cells had extreme sensitivity to killing by UV radiation, DNA repair was severely deficient, post-UV unscheduled DNA synthesis was reduced to less than 5%, and post-UV plasmid mutation frequency was increased. Conclusions The paradoxical lack of parallelism of phenotype to genotype is unexplained in these disorders. Perhaps diverse mutations responsible for UV sensitivity and deficient DNA repair may also produce profound failure of brain and somatic growth, progressive cachexia and premature aging, and tissue-selective neurologic deterioration by their roles in regulation of transcription and repair of endogenous oxidative DNA damage. PMID:11185579

[Cerebral ischemia in Rendu-Osler-Weber disease].

PubMed

Delgado Reyes, S; García de la Rocha, M L; Fernández-Armayor Ajo, V; Sierra Sierra, I; Martín Araguz, A; Moreno Martínez, J M

2000-02-01

Neurologic manifestations occur in 8-12% of the patients with Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT), principally infectious and hemorrhagic and, less frequently, ischemic ones. More than a half of these neurologic complications are associated with pulmonary arterio-venous malformations (PAVM). The diagnosis of HHT is based on the presence of telangiectases, hemorrhagic events and a family history with an autosomal dominant pattern. We report a case of a patient diagnosed as having HHT with transient ischemic attacks and a PAVM, which was occluded by the use of embolotherapy. Cerebral ischemia in HHT is related to the existence of a PAVM and results from three mechanisms: 1) secondary poliglobulia and hyperviscosity because of the hypoxemia due to a right-left shunt; 2) communication between the airway and the pulmonary circulation during cough access, which produces gas embolism and hemoptysis; 3) and, finally, paradoxical embolism trough the PAVM, the same mechanism proposed to the infectious neurologic manifestations of the disease. When the diagnosis of HHT is suspected, early search and treatment of PAVM, with embolotherapy or surgery, are necessary in order to avoid respiratory problems (hemoptysis, exertional dyspnea, cianosis, clubbing) and neurologic complications.

Conversion disorder: current problems and potential solutions for DSM-5.

PubMed

Stone, Jon; LaFrance, W Curt; Brown, Richard; Spiegel, David; Levenson, James L; Sharpe, Michael

2011-12-01

Conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) describes neurological symptoms, including weakness, numbness and events resembling epilepsy or syncope, which can be positively identified as not being due to recognised neurological disease. This review combines perspectives from psychiatry, psychology and neurology to identify and discuss key problems with the current diagnostic DSM-IV criteria for conversion disorder and to make the following proposals for DSM-5: (a) abandoning the label "conversion disorder" and replacing it with an alternative term that is both theoretically neutral and potentially more acceptable to patients and practitioners; (b) relegating the requirements for "association of psychological factors" and the "exclusion of feigning" to the accompanying text; (c) adding a criterion requiring clinical findings of internal inconsistency or incongruity with recognised neurological or medical disease and altering the current 'disease exclusion' criteria to one in which the symptom must not be 'better explained' by a disease if present, (d) adding a 'cognitive symptoms' subtype. We also discuss whether conversion symptoms are better classified with other somatic symptom disorders or with dissociative disorders and how we might address the potential heterogeneity of conversion symptoms in classification. 2011 Elsevier Inc. All rights reserved.

The explanatory structure of unexplainable events: Causal constraints on magical reasoning.

PubMed

Shtulman, Andrew; Morgan, Caitlin

2017-10-01

A common intuition, often captured in fiction, is that some impossible events (e.g., levitating a stone) are "more impossible" than others (e.g., levitating a feather). We investigated the source of this intuition, hypothesizing that graded notions of impossibility arise from explanatory considerations logically precluded by the violation at hand but still taken into account. Studies 1-4 involved college undergraduates (n = 357), and Study 5 involved preschool-aged children (n = 32). In Studies 1 and 2, participants saw pairs of magical spells that violated one of 18 causal principles-six physical, six biological, and six psychological-and were asked to indicate which spell would be more difficult to learn. Both spells violated the same causal principle but differed in their relation to a subsidiary principle. Participants' judgments of spell difficulty honored the subsidiary principle, even when participants were given the option of judging the two spells equally difficult. Study 3 replicated those effects with Likert-type ratings; Study 4 replicated them in an open-ended version of the task in which participants generated their own causal violations; and Study 5 replicated them with children. Taken together, these findings suggest that events that defy causal explanation are interpreted in terms of explanatory considerations that hold in the absence of such violations.

Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials.

PubMed

Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi

2009-01-01

Patients with neurological diseases such as Alzheimer's disease, stroke and Parkinson's disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of menatetrenone (vitamin K(2)) against non-vertebral and hip fractures in patients with neurological diseases. A literature search was conducted on PubMed from January 1995 to July 2008 to identify randomized controlled trials (RCTs) of use of menatetrenone against non-vertebral and hip fractures in patients with neurological diseases. A meta-analysis of all RCTs meeting these criteria was then performed. Three RCTs of patients with Alzheimer's disease (n = 178, mean age 78 years), stroke (n = 99, mean age 66 years) and Parkinson's disease (n = 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported with menatetrenone treatment. The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases. Further larger placebo-controlled trials are needed to confirm the results of the present study.

Analysis of obstetrics and gynecology professional liability claims in Catalonia, Spain (1986-2010).

PubMed

Gómez-Durán, Esperanza L; Mulà-Rosías, Joan Antoni; Lailla-Vicens, Josep Maria; Benet-Travé, Josep; Arimany-Manso, Josep

2013-07-01

To identify relevant factors involved in obstetrics and gynecology (OG) professional liability claims to help archive better management of risks. Analysis of 885 OG claims opened between 1986 and 2010, with the identification of the most common events leading to a claim, the economical and juridical characteristics of the claims, as well as the relevant trends over the study period. Most claims related to obstetrics. Labor, delivery and its complications accounted for 33.1% of the claims; 12.77% related specifically to cesarean. Oncological diseases, fetus death during labor and delivery, neurologically impaired infant and histerectomy-related problems were the most frequently claimed events. Most cases ended up without an indemnity payment and 37.7% of closed files were solved by an out-of-court procedure. Average payment was higher for the obstetric procedures than for those concerning gynecology cases. The proportion of claims relating to obstetrics increased during the study period, as well as the average payment. OG is at high-risk for malpractice claims, but compensation awards are not frequent. However, particular events, such as retained foreign objects, tubal ligation, ultrasound diagnosis or neurologically impaired newborns, deserve special attention regarding medico-legal issues. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

"Unexplainable" medical histories and childhood sexual abuse. New doctoral thesis tells you how to investigate the links.

PubMed

Getz, L

1999-06-01

This is a brief summary and a personal reflection on Anne Luise Kirkengen's PhD thesis "Embodiment of sexual boundary violations in childhood". It is written to encourage other clinicians to familiarise themselves with this original and important study. It has high relevance for every clinician who is ever confronted with patients that present medical histories that are "diffuse" or unexplainable according to traditional medical knowledge.

Educational Gradients and Pathways of Disability Onset Among Older Mexicans.

PubMed

Saenz, Joseph L; Wong, Rebeca

2016-04-01

Educational disparities research is less common in developing countries. We evaluate whether educational gradients of disability onset exist in Mexico across groups (birth cohort and sex) and whether the association is unexplained or indirect via health (health behaviors, chronic conditions, and self-rated health) or economic (income, wealth, and health insurance) pathways. Data come from the Mexican Health & Aging study. Activities of daily living are reported in 2001, 2003, and 2012 by respondents and spouses aged 50+ (N = 9,560). Groups are analyzed using logistic regression to test education-disability onset associations. Significant education-ADL onset associations were observed across groups, and much of these associations were direct (unexplained by pathways). Indirect effects operated primarily through the health pathway. Those with less education were disadvantaged in terms of disability across birth cohorts and sex. Unexplained effects of education may suggest unobserved mediators or differential returns to resources by educational level. © The Author(s) 2016.

Blame, shame and hopelessness: medically unexplained symptoms and the 'heartsink' experience.

PubMed

Stone, Louise

2014-04-01

'Heartsink' patients present a moral dilemma. We recognise their suffering, but at the same time struggle with the feelings they trigger in us. Patients also experience negative feelings. Without a diagnosis they lack a narrative or vocabulary to make sense of their own suffering. This article explores some of the challenges faced and strategies utilised when managing patients with medically unexplained symptoms. Doctors and patients often experience frustration and helplessness in consultations around medically unexplained symptoms. Without a diagnosis, patients lack social legitimacy as 'sick' people with 'real' illnesses. They often describe feeling blamed for their own distress. Because of this, they can experience deep feelings of worthlessness and shame. Patients with a history of abuse can be particularly vulnerable. Management includes validating their suffering, helping them construct appropriate explanations for their distress and providing empathic interpersonal care, while minimising the risk of iatrogenic harm.

Increased Prevalence of Celiac Disease in Patients with Unexplained Infertility in the United States: A Prospective Study

PubMed Central

Lebwohl, Benjamin; Wang, Jeffrey; Lee, Susie K.; Murray, Joseph A.; Sauer, Mark V.; Green, Peter H. R.

2011-01-01

Celiac disease is an autoimmune disorder which can present with a variety of non-gastrointestinal manifestations. In women, it may manifest with an assortment of gynecologic or obstetric disorders. Some reports have linked female infertility with undiagnosed celiac disease. Though there are a number of studies from Europe and the Middle East, only two prior American studies have examined the prevalence of “silent” celiac disease in a female infertility population. We prospectively performed serologic screening for celiac disease in 188 infertile women (ages 25–39). While we did not demonstrate an increased prevalence of celiac disease in our overall infertile female population, we were able to detect a significantly increased prevalence (5.9%) of undiagnosed celiac disease among women presenting with unexplained infertility (n=51). Our findings suggest the importance of screening infertile female patients, particularly those with unexplained infertility, for celiac disease. PMID:21682114

Educational Gradients and Pathways of Disability Onset Among Older Mexicans

PubMed Central

Saenz, Joseph L.; Wong, Rebeca

2016-01-01

Introduction Educational disparities research is less common in developing countries. We evaluate whether educational gradients of disability onset exist in Mexico across groups (birth cohort and sex) and whether the association is unexplained or indirect via health (health behaviors, chronic conditions, and self-rated health) or economic (income, wealth, and health insurance) pathways. Method Data come from the Mexican Health & Aging study. Activities of daily living are reported in 2001, 2003, and 2012 by respondents and spouses aged 50+ (N = 9,560). Groups are analyzed using logistic regression to test education–disability onset associations. Results Significant education–ADL onset associations were observed across groups, and much of these associations were direct (unexplained by pathways). Indirect effects operated primarily through the health pathway. Discussion Those with less education were disadvantaged in terms of disability across birth cohorts and sex. Unexplained effects of education may suggest unobserved mediators or differential returns to resources by educational level. PMID:26966253

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments.

PubMed

Nardelli, Silvia; Ridola, Lorenzo; Gioia, Stefania; Riggio, Oliviero

2018-06-01

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both. The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment. Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed. In a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed. In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.

Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes

PubMed Central

Wolfe, Heather; Zebuhr, Carleen; Topjian, Alexis A.; Nishisaki, Akira; Niles, Dana E.; Meaney, Peter A.; Boyle, Lori; Giordano, Rita T.; Davis, Daniela; Priestley, Margaret; Apkon, Michael; Berg, Robert A.; Nadkarni, Vinay M.; Sutton, Robert M.

2014-01-01

Objective In-hospital cardiac arrest is an important public health problem. High-quality resuscitation improves survival but is difficult to achieve. Our objective is to evaluate the effectiveness of a novel, interdisciplinary, postevent quantitative debriefing program to improve survival outcomes after in-hospital pediatric chest compression events. Design, Setting, and Patients Single-center prospective interventional study of children who received chest compressions between December 2008 and June 2012 in the ICU. Interventions Structured, quantitative, audiovisual, interdisciplinary debriefing of chest compression events with front-line providers. Measurements and Main Results Primary outcome was survival to hospital discharge. Secondary outcomes included survival of event (return of spontaneous circulation for ≥ 20 min) and favorable neurologic outcome. Primary resuscitation quality outcome was a composite variable, termed “excellent cardiopulmonary resuscitation,” prospectively defined as a chest compression depth ≥ 38 mm, rate ≥ 100/min, ≤ 10% of chest compressions with leaning, and a chest compression fraction > 90% during a given 30-second epoch. Quantitative data were available only for patients who are 8 years old or older. There were 119 chest compression events (60 control and 59 interventional). The intervention was associated with a trend toward improved survival to hospital discharge on both univariate analysis (52% vs 33%, p = 0.054) and after controlling for confounders (adjusted odds ratio, 2.5; 95% CI, 0.91–6.8; p = 0.075), and it significantly increased survival with favorable neurologic outcome on both univariate (50% vs 29%, p = 0.036) and multivariable analyses (adjusted odds ratio, 2.75; 95% CI, 1.01–7.5; p = 0.047). Cardiopulmonary resuscitation epochs for patients who are 8 years old or older during the debriefing period were 5.6 times more likely to meet targets of excellent cardiopulmonary resuscitation (95% CI, 2.9–10.6; p < 0.01). Conclusion Implementation of an interdisciplinary, postevent quantitative debriefing program was significantly associated with improved cardiopulmonary resuscitation quality and survival with favorable neurologic outcome. (Crit Care Med 2014; XX:00–00) PMID:24717462

Interprofessional simulation to improve safety in the epilepsy monitoring unit.

PubMed

Dworetzky, Barbara A; Peyre, Sarah; Bubrick, Ellen J; Milligan, Tracey A; Yule, Steven J; Doucette, Heidi; Pozner, Charles N

2015-04-01

Patient safety is critical for epilepsy monitoring units (EMUs). Effective training is important for educating all personnel, including residents and nurses who frequently cover these units. We performed a needs assessment and developed a simulation-based team training curriculum employing actual EMU sentinel events to train neurology resident-nurse interprofessional teams to maximize effective responses to high-acuity events. A mixed-methods design was used. This included the development of a safe-practice checklist to assess team response to acute events in the EMU using expert review with consensus (a modified Delphi process). All nineteen incoming first-year neurology residents and 2 nurses completed a questionnaire assessing baseline knowledge and attitudes regarding seizure management prior to and following a team training program employing simulation and postscenario debriefing. Four resident-nurse teams were recorded while participating in two simulated scenarios. Employing retrospective video review, four trained raters used the newly developed safe-practice checklist to assess team performance. We calculated the interobserver reliability of the checklist for consistency among the raters. We attempted to ascertain whether the training led to improvement in performance in the actual EMU by comparing 10 videos of resident-nurse team responses to seizures 4-8months into the academic year preceding the curricular training to 10 that included those who received the training within 4-8months of the captured video. Knowledge in seizure management was significantly improved following the program, but confidence in seizure management was not. Interrater agreement was moderate to high for consistency of raters for the majority of individual checklist items. We were unable to demonstrate that the training led to sustainable improvement in performance in the actual EMU by the method we used. A simulated team training curriculum using a safe-practice checklist to improve the management of acute events in an EMU may be an effective method of training neurology residents. However, translating the results into sustainable benefits and confidence in management in the EMU requires further study. Copyright © 2015 Elsevier Inc. All rights reserved.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

PubMed

Koch, H; van Bokhoven, M A; Bindels, P J E; van der Weijden, T; Dinant, G J; ter Riet, G

2009-12-01

Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low QoL.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

PubMed

Gregson, C L; Steel, S A; O'Rourke, K P; Allan, K; Ayuk, J; Bhalla, A; Clunie, G; Crabtree, N; Fogelman, I; Goodby, A; Langman, C M; Linton, S; Marriott, E; McCloskey, E; Moss, K E; Palferman, T; Panthakalam, S; Poole, K E S; Stone, M D; Turton, J; Wallis, D; Warburton, S; Wass, J; Duncan, E L; Brown, M A; Davey-Smith, G; Tobias, J H

2012-02-01

High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Comparison of microbubble presence in the right heart during mechanochemical and radiofrequency ablation for varicose veins.

PubMed

Moon, K H; Dharmarajah, B; Bootun, R; Lim, C S; Lane, Tra; Moore, H M; Sritharan, K; Davies, A H

2017-07-01

Objective Mechanochemical ablation is a novel technique for ablation of varicose veins utilising a rotating catheter and liquid sclerosant. Mechanochemical ablation and radiofrequency ablation have no reported neurological side-effect but the rotating mechanism of mechanochemical ablation may produce microbubbles. Air emboli have been implicated as a cause of cerebrovascular events during ultrasound-guided foam sclerotherapy and microbubbles in the heart during ultrasound-guided foam sclerotherapy have been demonstrated. This study investigated the presence of microbubbles in the right heart during varicose vein ablation by mechanochemical abaltion and radiofrequency abaltion. Methods Patients undergoing great saphenous vein ablation by mechanochemical abaltion or radiofrequency ablation were recruited. During the ablative procedure, the presence of microbubbles was assessed using transthoracic echocardiogram. Offline blinded image quantification was performed using International Consensus Criteria grading guidelines. Results From 32 recruited patients, 28 data sets were analysed. Eleven underwent mechanochemical abaltion and 17 underwent radiofrequency abaltion. There were no neurological complications. In total, 39% (11/28) of patients had grade 1 or 2 microbubbles detected. Thirty-six percent (4/11) of mechanochemical abaltion patients and 29% (5/17) of radiofrequency ablation patients had microbubbles with no significant difference between the groups ( p=0.8065). Conclusion A comparable prevalence of microbubbles between mechanochemical abaltion and radiofrequency ablation both of which are lower than that previously reported for ultrasound-guided foam sclerotherapy suggests that mechanochemical abaltion may not confer the same risk of neurological events as ultrasound-guided foam sclerotherapy for treatment of varicose veins.

The self-imagination effect: benefits of a self-referential encoding strategy on cued recall in memory-impaired individuals with neurological damage.

PubMed

Grilli, Matthew D; Glisky, Elizabeth L

2011-09-01

Knowledge of oneself is preserved in many memory-impaired individuals with neurological damage. Therefore, cognitive strategies that capitalize on mechanisms related to the self may be particularly effective at enhancing memory in this population. The present study investigated the effect of "self-imagining," imagining an event from a personal perspective, on short and long delayed cued recall in memory-impaired individuals with neurological damage. Sixteen patients intentionally encoded word pairs under four separate conditions: visual imagery, semantic elaboration, other person imagining, and self-imagining. The results revealed that self-imagining led to better performance than other-imagining, semantic elaboration, and visual imagery. Furthermore, the "self-imagination effect" (SIE) was preserved after a 30-min delay and was independent of memory functioning. These findings indicate that self-imagining provides a mnemonic advantage in brain-injured individuals, even those with relatively poor memory functioning, and suggest that self-imagining may tap into mnemonic mechanisms related to the self.

The addicted brain: imaging neurological complications of recreational drug abuse.

PubMed

Montoya-Filardi, A; Mazón, M

Recreational drug abuse represents a serious public health problem. Neuroimaging traditionally played a secondary role in this scenario, where it was limited to detecting acute vascular events. However, thanks to advances in knowledge about disease and in morphological and functional imaging techniques, radiologists have now become very important in the diagnosis of acute and chronic neurological complications of recreational drug abuse. The main complications are neurovascular disease, infection, toxicometabolic disorders, and brain atrophy. The nonspecific symptoms and denial of abuse make the radiologist's involvement fundamental in the management of these patients. Neuroimaging makes it possible to detect early changes and to suggest an etiological diagnosis in cases with specific patterns of involvement. We aim to describe the pattern of abuse and the pathophysiological mechanisms of the drugs with the greatest neurological repercussions as well as to illustrate the depiction of the acute and chronic cerebral complications on conventional and functional imaging techniques. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Development of Bell's Palsy After Treatment With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report.

PubMed

Zecchini, Julia M; Kim, Sara; Yum, Kendra; Friedlander, Philip

2018-01-01

Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face. We report a case of Bell's palsy in a 45-year-old male patient who received 1 dose of both ipilimumab and nivolumab for the treatment of metastatic melanoma. After the resolution of symptoms, ipilimumab was permanently discontinued and single-agent nivolumab administered. The patient has remained free of neurological symptoms. This case suggests that Bell's palsy is an irAE induced by ipilimumab.

Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

PubMed Central

Renner, Caroline I. E.

2015-01-01

Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed. PMID:26402710

Medically unexplained dyspnoea and panic.

PubMed

Hauzer, Rose; Verheul, Willeke; Griez, Eric; Wesseling, Geertjan; van Duinen, Marlies

2015-07-01

Medically unexplained dyspnoea in the pulmonary setting is often accompanied by considerable levels of anxiety, suggestive of psychopathology, in particular panic disorder (PD). This pilot study investigates the value of the Multidimensional Dyspnea Profile as a tool to facilitate identification of a specific dyspnoea profile suggestive of comorbid PD. The verbal descriptors, feeling depressed, air hunger and concentrating on breathing, significantly differentiated between the two groups of patients with pulmonary disease with and without PD. © 2015 Asian Pacific Society of Respirology.

Medically unexplained physical symptoms, misunderstood and wrongly treated? A semiotic perspective on chronic pain.

PubMed

Busvold, Kari Irene H; Bondevik, Hilde

2018-06-01

Medically unexplained physical symptoms (MUPS) are a significant and increasing health issue in the western world. Chronic pain constitutes a considerable element of these symptoms, and the lack of a biomedical explanation of their cause challenges the clinical encounter. The limitations of biomedicine become evident in these encounters and expose the need for an expanded understanding of body and symptom. Semiotics, as an anti-dualistic meta-theory, closes the gap between natural science and the humanities and views the human body in an evolutionary and existential perspective. By focusing on interpretation and communication of signs as ongoing processes at all levels of life, biology and experience, the subjective and the measurable will be integrated. A special type of sign, the self-referential, is part of the body's internal communication. These signs may be viewed as the body's warnings to itself, for instance when the individual's consciousness, thought and action run counter to the organism's physiological and psychological needs. In a semiotic perspective, existential conditions may also activate the body's defense systems. In this context, the unexplained pain may be understood as a functional warning sign. The enhanced understanding of body and symptom that a semiotic approach calls for is relevant for the work of physiotherapists and may lead to more constructive clinical encounters with patients with unexplained chronic pain.

Ongoing pregnancies in patients with unexplained recurrent pregnancy loss: adverse obstetric outcomes.

PubMed

Cozzolino, Mauro; Rizzello, Francesca; Riviello, Chiara; Romanelli, Chiara; Coccia Elisabetta, Maria

2018-05-25

To investigate the incidence of adverse pregnancy outcomes in couples with an unexplained Recurrent Pregnancy Loss (RPL) history, a retrospective cohort study was conducted between 2014 and 2015. The study group (A) included couples with an unexplained RPL, and the control group (B) was composed of couples who attended the Low-Risk Antenatal Unit during the same period. On the other hand, 53 couples were included in the study group (A) and on the other hand, 65 in the control group (B). Women with previous unexplained recurrent pregnancies loss had a significantly increased risk of gestational diabetes with 12 cases (22.6%) in the study group and 3 cases (4.6%) in the control (OR: 6.048; 95% CI: 1.607-22.762; p = 0.007). A slight increase in the risk of preterm delivery and hepatic cholestasis was observed in the study group (6 cases, 11.3%, in study group and 1 case, 1.5% in the controls (OR: 8.170; 95% CI: 0.951-70.158; p = 0.0555). Women with a history of RPL delivered more frequently by caesarean section (OR: 3.252; 95% CI: 1.460-7.241; p = 0.0039). Women with a history of RPL were at an increased risk for adverse pregnancy outcomes, mainly gestational diabetes. Therefore, a closer surveillance during the antenatal period is recommended in this group of patients.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Intermittent Astrophysical Radiation Sources and Terrestrial Life

NASA Astrophysics Data System (ADS)

Melott, Adrian

2013-04-01

Terrestrial life is exposed to a variety of radiation sources. Astrophysical observations suggest that strong excursions in cosmic ray flux and spectral hardness are expected. Gamma-ray bursts and supernovae are expected to irradiate the atmosphere with keV to GeV photons at irregular intervals. Supernovae will produce large cosmic ray excursions, with time development varying with distance from the event. Large fluxes of keV to MeV protons from the Sun pose a strong threat to electromagnetic technology. The terrestrial record shows cosmogenic isotope excursions which are consistent with major solar proton events, and there are observations of G-stars suggesting that the rate of such events may be much higher than previously assumed. In addition there are unknown and unexplained astronomical transients which may indicate new classes of events. The Sun, supernovae, and gamma-ray bursts are all capable of producing lethal fluences, and some are expected on intervals of 10^8 years or so. The history of life on Earth is filled with mass extinctions at a variety of levels of intensity. Most are not understood. Astrophysical radiation may play a role, particularly from large increases in muon irradiation on the ground, and changes in atmospheric chemistry which deplete ozone, admitting increased solar UVB. UVB is strongly absorbed by DNA and proteins, and breaks the chemical bonds---it is a known carcinogen. High muon fluxes will also be damaging to such molecules, but experiments are needed to pin down the rate. Solar proton events which are not directly dangerous for the biota may nevertheless pose a major threat to modern electromagnetic technology through direct impact on satellites and magnetic induction of large currents in power grids, disabling transformers. We will look at the kind of events that are expected on timescales from human to geological, and their likely consequences.

Serial brain MRI and ultrasound findings: relation to gestational age, bilirubin level, neonatal neurologic status and neurodevelopmental outcome in infants at risk of kernicterus.

PubMed

Gkoltsiou, Konstantina; Tzoufi, Meropi; Counsell, Serena; Rutherford, Mary; Cowan, Frances

2008-12-01

To describe cranial ultrasound (cUS) and magnetic resonance imaging (MRI) findings in neonates at risk of kernicterus, in relation to gestational age (GA), total serum bilirubin (TSB), age at imaging and neurodevelopmental outcome. Neonates with peak TSB > 400 micromol/L and/or signs of bilirubin encephalopathy. Review of neonatal data, cUS, preterm, term and later MRI scans and neurodevelopmental outcome. 11 infants were studied, two < 31, four 34-36 and five 37-40 weeks GA. TSB levels: 235-583 micromol/L (preterms); 423-720 micromol/L (terms). Neonatal neurological examination was abnormal in 8/10. cUS showed increased basal ganglia (BG) in 4/9 infants and white matter (WM) echogenicity, lenticulostriate vasculopathy (LSV) and caudothalamic hyperechogencity/cysts (GLCs) in 5/9 infants. MRI showed abnormal signal intensity (SI) in the globus pallidum (GP) in 1/2 preterm, 8/9 term and 9/11 later scans. Abnormal WM SI occurred in 2 preterm, 7 term and 10/11 later scans. Seven infants developed athetoid/dystonic cerebral palsy (CP) and 6 hearing loss (HL). Adverse outcome was associated with abnormal BG on cUS (3/4 CP, 4/4 HL), with high SI in GP (7/9 CP, 6/9 HL) on late T2-weighted MRI (all GA) and on T1/T2-weighted term MRI, mainly in term-born infants. WM abnormalities, GLCs and LSV did not correlate with outcome. Severe CP occurred with relatively low TSB levels in preterms but only at high levels in full-terms; HL was difficult to predict. Early scans did not reliably predict motor deficits whilst all children with CP had abnormal central grey matter on later scans. Abnormal WM was seen early suggesting primary involvement rather than change secondary to grey matter damage. Why characteristic central grey matter MRI features of kernicterus are not seen early remains unexplained.

A mouse model of DEPDC5-related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility.

PubMed

Yuskaitis, Christopher J; Jones, Brandon M; Wolfson, Rachel L; Super, Chloe E; Dhamne, Sameer C; Rotenberg, Alexander; Sabatini, David M; Sahin, Mustafa; Poduri, Annapurna

2018-03-01

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5 flox/flox -Syn1 Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

PubMed Central

Woo, Hye In; Joo, Eun Yeon; Lee, Kyung Wha

2012-01-01

Background Narcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles. Methods The study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT). Results The 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci. Conclusions The clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy. PMID:22259780

Inherited epilepsy in dogs.

PubMed

Ekenstedt, Kari J; Oberbauer, Anita M

2013-05-01

Epilepsy is the most common neurologic disease in dogs and many forms are considered to have a genetic basis. In contrast, some seizure disorders are also heritable, but are not technically defined as epilepsy. Investigation of true canine epilepsies has uncovered genetic associations in some cases, however, many remain unexplained. Gene mutations have been described for 2 forms of canine epilepsy: primary epilepsy (PE) and progressive myoclonic epilepsies. To date, 9 genes have been described to underlie progressive myoclonic epilepsies in several dog breeds. Investigations into genetic PE have been less successful, with only 1 causative gene described. Genetic testing as an aid to diagnosis, prognosis, and breeding decisions is available for these 10 forms. Additional studies utilizing genome-wide tools have identified PE loci of interest; however, specific genetic tests are not yet developed. Many studies of dog breeds with PE have failed to identify genes or loci of interest, suggesting that, similar to what is seen in many human genetic epilepsies, inheritance is likely complex, involving several or many genes, and reflective of environmental interactions. An individual dog's response to therapeutic intervention for epilepsy may also be genetically complex. Although the field of inherited epilepsy has faced challenges, particularly with PE, newer technologies contribute to further advances. © 2013 Elsevier Inc. All rights reserved.

A Tale of Treatable Infantile Neuroregression and Diagnostic Dilemma with Glutaric Aciduria Type I

PubMed Central

Yoganathan, Sangeetha; Varman, Mugil; Oommen, Samuel Philip; Thomas, Maya

2017-01-01

Nutritional deficiencies related neurological manifestations are not uncommon in infants and children. Here, we describe an infant with Vitamin B12 deficiency due to depleted maternal Vitamin B12 status presenting with progressive encephalopathy and extrapyramidal signs. Diagnosis of infantile tremor syndrome was established in our patient based on the clinical and biochemical parameters. Magnetic resonance imaging had shown frontotemporal atrophy with widened Sylvian fissures and prominent cerebrospinal fluid spaces. Clinical and imaging findings might create a diagnostic dilemma with glutaric aciduria type I. Knowledge and identification of infantile tremor syndrome are essential, as it is a potentially treatable disorder. Our patient had significant developmental gains with Vitamin B12 treatment and infant stimulation program. Vitamin B12 deficiency must be looked for as a cause of neuroregression in children hailing from low socioeconomic status, infants of vegetarian mother, and infants with delayed or improper weaning. Screening for Vitamin B12 deficiency is essential in all infants and children with unexplained neuroregression, as this disorder is potentially treatable. More population-based studies in India are needed to explore the prevalence of Vitamin B12 deficiency in pregnant and lactating women and also to assess the need for Vitamin B12 supplementation during pregnancy and lactation. PMID:29675077

A Tale of Treatable Infantile Neuroregression and Diagnostic Dilemma with Glutaric Aciduria Type I.

PubMed

Yoganathan, Sangeetha; Varman, Mugil; Oommen, Samuel Philip; Thomas, Maya

2017-01-01

Nutritional deficiencies related neurological manifestations are not uncommon in infants and children. Here, we describe an infant with Vitamin B12 deficiency due to depleted maternal Vitamin B12 status presenting with progressive encephalopathy and extrapyramidal signs. Diagnosis of infantile tremor syndrome was established in our patient based on the clinical and biochemical parameters. Magnetic resonance imaging had shown frontotemporal atrophy with widened Sylvian fissures and prominent cerebrospinal fluid spaces. Clinical and imaging findings might create a diagnostic dilemma with glutaric aciduria type I. Knowledge and identification of infantile tremor syndrome are essential, as it is a potentially treatable disorder. Our patient had significant developmental gains with Vitamin B12 treatment and infant stimulation program. Vitamin B12 deficiency must be looked for as a cause of neuroregression in children hailing from low socioeconomic status, infants of vegetarian mother, and infants with delayed or improper weaning. Screening for Vitamin B12 deficiency is essential in all infants and children with unexplained neuroregression, as this disorder is potentially treatable. More population-based studies in India are needed to explore the prevalence of Vitamin B12 deficiency in pregnant and lactating women and also to assess the need for Vitamin B12 supplementation during pregnancy and lactation.

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

PubMed

Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Stroke mimic diagnoses presenting to a hyperacute stroke unit.

PubMed

Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

2016-10-01

Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

Guided versus Independent Play: Which Better Sustains Attention among Infants and Toddlers?

ERIC Educational Resources Information Center

Gardner-Neblett, Nicole; Holochwost, Steven J.; Gallagher, Kathleen Cranley; Iruka, Iheoma U.; Odom, Samuel L.; Pungello, Elizabeth P.

2016-01-01

Rapid development of sustained attention occurs during infancy and toddlerhood, as neurological maturation allows children to increasingly attend to objects and events in the environment (Ruff & Rothbart, 1996). Play experiences during this period can serve as a context during which children's ability to attend can provide an opportunity for…

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM).

PubMed

Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Selbaek, Geir; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

2018-01-01

Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Of the 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group ( p <0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95-182, p =0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45-235, p =0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p =0.005) and decreased by 12.9% during the first week ( p =0.053). Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.

Intracranial and visceral arterial embolization of a cardiac myxoma that was treated with endovascular stent-retriever therapy

PubMed Central

Thibodeau, Cheryl; McGowan, Amelia

2016-01-01

We report a case of a ruptured left atrial myxoma with multiple synchronous sites of embolization, including the intracranial cerebral (left middle cerebral artery (MCA) and basilar), visceral (renal, superior mesenteric artery (SMA)) and peripheral circulatory beds (aorta and lower extremities). This synchronous embolization resulted in a catastrophic neurologic and systemic event. An intracranial stent retriever was used to restore cerebral circulation in the symptomatic left MCA distribution, which resulted in resolution of the acute neurologic deficits. Endovascular and open surgical interventions were later performed to address the residual cardiac mass and other embolic sites. The patient survived the event with the loss of her right leg below the knee and a transient dialysis requirement. The purpose of this case report is to document the successful utilization of a stent-retriever device in removing an embolized myxoma from the cerebral circulation, to review the unique pathology of this source of embolic stroke and to reiterate the importance of considering embolic and non-thrombotic etiologies of acute ischemic stroke, especially in atypical patient populations and patient presentations. PMID:27306523

Dissociation between morality and disgust: an event-related potential study.

PubMed

Yang, Qun; Li, An; Xiao, Xiao; Zhang, Ye; Tian, Xuehong

2014-10-01

This study explored the neural correlates of morality and disgust, particularly, how the mechanisms that mediate our avoidance of physically disgusting and morally abhorrent behaviors are neurologically dissociated during the time-course of processing. Twelve participants were asked to judge the acceptability of different types of behaviors, which varied in their level of moral wrongness and physical disgust, while event-related potentials (ERPs) were recorded. The main results showed that the two morally wrong conditions elicited greater amplitudes of P300-400 at frontal sites than the neutral condition and the physically disgusting, but not morally wrong, condition. The physically disgusting conditions (with and without moral content) elicited significantly more positive deflections in the 500-600 ms timeframe than the neutral condition at central-posterior sites. These findings indicate that our aversion to harmful substances in the physical environment and offensive behaviors in the social environment may be neurologically dissociable in the temporal dimension. Furthermore, the detection of moral violations may be processed earlier in time than that of physical disgust. Copyright © 2014 Elsevier B.V. All rights reserved.

The effectiveness, safety, and economic evaluation of Korean medicine for unexplained infertile women: A multi-center, prospective, observational study protocol.

PubMed

Kim, Su-Hyun; Jo, Junyoung; Kim, Dong-Il

2017-12-01

Infertility is a condition in which a woman has not been pregnant despite having had normal intercourse for 1 year. The number of unexplained infertile females is increasing because of late marriage customs, as well as environmental and lifestyle habits. In Korea, infertile females have been treated with Korean medicine (KM). However, these effects have not been objectively confirmed through clinical trials. Therefore, this study was conducted to demonstrate the effectiveness of herbal medicine treatment in infertile patients and to demonstrate the economic feasibility through economical evaluation with assisted reproductive technology.This study is designed as a multicenter, single-arm clinical trial. All participants included will be from 3 Korean Medicine hospitals in Korea and will voluntarily sign an informed consent agreement. All recruited patients will conduct related surveys and tests, and be provided with treatment according to their menstrual cycle. Patients will take herbal medicines for 4 menstruation cycles and receive acupuncture and moxibustion treatment at 3 times (menstrual cycle day 3, 8, 14) during 4 menstruation cycles. They will also undergo an approximately 4 menstrual cycle treatment period, and 3 menstrual cycle observation period. If pregnant during the study, participants will take the herbal medicine for implantation for about 15 days. In this study, the primary outcome will be the clinical pregnancy rate, whereas the secondary outcome will include the implantation rate, ongoing pregnancy rate, and live birth rate.Ultimately, this study will provide clinical data regarding the effectiveness and safety of KM treatment for females with unexplained infertility and important evidence for establishing standard KM treatments for unexplained infertility. Moreover, we will identify the most cost-effective way to treat unexplained infertility. Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002235. Date: February 21, 2017 (retrospectively registered). Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained primary infertility: a prospective analysis of 88 cases.

PubMed

Shokeir, Tarek; Abdelshaheed, Mahmoud; El-Shafie, Mohamed; Sherif, Lotfy; Badawy, Ahmed

2011-03-01

To evaluate prospectively the effect of hysteroscopic septoplasty as therapy for unexplained primary infertility in women with uterine septum as a sole cause for reproductive failure and to define the factors influencing reproductive success. In a prospective comparative study, we enrolled 103 infertile women with uterine septum as a sole cause for reproductive failure. They had had unexplained primary infertility >2 years and a follow-up >12 months. Uterine anomalies were diagnosed by means of hysterosalpingography (HSG) and 2D-transvaginal sonography (TVS) with intrauterine saline infusion. Hysteroscopic septoplasty was performed in the early follicular phase. Pregnancy rates (PR) according to patient and septum characteristics (septum size) were the main outcome measures. Follow-up was complete for 88 patients. The mean (±SD) age of the patients was 36.1±2.1 years. Forty-two patients became pregnant (40.7%). The mean (±SD) delay in conception was 7.5±2.6 months. Nearly 80% of the pregnant women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. The PR was significantly higher in women <35 years of age or with <3 years of unexplained primary infertility. Moreover, in women with a septum size larger than one-half of their uterine length the PR was significantly higher than those with septum size <1/2 of their uterus (P=.12). Fertility and pregnancy after hysteroscopic septoplasty in women with unexplained primary infertility and uterine septum as a sole cause for reproductive failure seems to depend on patient age, duration of infertility before septoplasty, and septum size. Women with a septum size larger than one-half of their uterine length have a higher chance of successful pregnancy after hysteroscopic septoplasty. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Kisspeptin: A Potential Factor for Unexplained Infertility and Impaired Embryo Implantation

PubMed Central

Mumtaz, Aaida; Khalid, Aqsa; Jamil, Zehra; Fatima, Syeda Sadia; Arif, Sara; Rehman, Rehana

2017-01-01

Background Kisspeptin (KP) is a neuropeptide that causes the release of the gonadotropin releasing hormone, which controls hypothalamo pituitary ovarian axis and exerts a number of peripheral effects on reproductive organs. The primary objective of this study was to compare baseline KP levels in females with different types of infertility and identify possible correlations with risk of failure to conceive, preclinical abortion and pregnancy after intracytoplasmic sperm injection (ICSI). Materials and Methods A longitudinal cohort study was carried out from August 2014 until May 2015 by recruiting 124 female patients undergoing ICSI, after obtaining ethical approval from the Australian Concept Infertility Medical Center. Cause of infertility due to male, female and unexplained factors was at a frequency of 32 (24%), 33 (31%) and 59 (45%) among the individuals respectively. KP levels were measured by ELISA assay before the initiation of the ICSI treatment protocol. Outcome of ICSI was categorized into three groups of non-pregnant with beta-human chorionic gonadotropin (β-hCG)<5-25 mIU/ml, preclinical abortion with β-hCG>25 mIU/ml and no cardiac activity, and clinical pregnancy declared upon confirmation of cardiac activity. Results based on cause of infertility and outcome groups were analyzed by one-way ANOVA. Results Females with unexplained infertility had significantly lower levels of KP when compared with those with male factor infertility (176.69 ± 5.03 vs. 397.6 ± 58.2, P=0.001). Clinical pregnancy was observed in 28 (23%) females of which 17 (71%) had a female cause of infertility. In the non-pregnant group of 66 (53%) females, common cause of infertility was unexplained 56(85%). A weak positive correlation of KP levels with fertilized oocytes and endometrial thickness was observed (P=0.04 and 0.01 respectively). Conclusion Deficiency of KP in females with unexplained infertility was associated with reduced chances of implantation after ICSI. PMID:28670427

[Outcomes of open endovascular operations on the internal carotid artery in acute stage of ischaemic stroke].

PubMed

Khripun, A I; Priamikov, A D; Mironkov, A B; Tiurin, I N; Asratian, S A; Suriakhin, V S; Simonov, O V; Sazhina, O A; Mikhaĭlenko, V P

The authors share their experience in diagnosis and treatment of patients with acute ischaemic stroke. The study included a total of 33 patients. Of these, 20 patients (Study Group) were operated on at terms ranging from 2 to 7 days after onset of acute cerebral circulatory impairment. The Control Group was composed of 13 patients with ischaemic stroke, having refused surgical prevention of recurrent stroke. Both groups were matched by age, gender, level of neurological deficiency and size of cerebral ischaemic foci. Surgical management in the Study Group consisted in either carotid endarterectomy (n=15) or stenting of the internal carotid artery (n=5). Depending on the severity of coronary artery lesion and the presence of accompanying therapeutic pathology, options of operative treatment with various anaesthesiological support were offered. At discharge, neurological deficit in the Study Group patients was lower - 1.2 points by the NIH Stroke Scale versus 2.7 points in the Control Group, however, this difference was not statistically significant (p=0.45). In the Study Group there were two complications: haematoma of the postoperative injury requiring its revision and a transient ischaemic attack during stenting of the internal carotid artery, having disappeared on the operation table after the distal cerebral protection device was removed. Significantly better results were obtained by the following parameters: in the Study Group the number of patients discharged with no neurological deficit (scoring 0 by the NIHSS scale) was significantly higher compared with the Control Group; 50% vs 7.7% (p<0.001). There were no lethal outcomes in either group. One patient (7.7%) from the Study Group developed recurrent ischaemic stroke, whereas neither intra- nor postoperative stroke was registered in the Control Group patients (p<0.001). In carefully selected patients with ischaemic stroke (neurological deficit not exceeding 3 points by the Rankin scale and not more than 11 points by the NIHSS, with the size of the ischaemic focus not exceeding 4 cm), surgical prevention of recurrent stroke within 7 days after the onset of an ischaemic event may be performed effectively and safely. Early operation effectively prevents relapsing ischaemic events at the in-hospital stage. Besides, reconstruction of brachiocephalic arteries during an acute stage of stroke in operated patients improves the neurological status in the postoperative period, decreases the degree of motor and sensory disorders and makes it possible in half of patients to completely eliminate neurological deficit present at admission.

[The influence of locomotor treatment using robotic body-weight-supported treadmill training on rehabilitation outcome of patients suffering from neurological disorders].

PubMed

Schwartz, Isabella; Meiner, Zeev

2013-03-01

Regaining one's ability to walk is of great importance for neurological patients and is a major goal of all rehabilitation programs. Treating neurological patients in the acute phase after the event is technically difficult because of their motor weakness and balance disturbances. Based on studies in spinalized animals, a novel locomotor training that incorporates high repetitions of task-oriented practice by the use of body weight-supported treadmill training (BWSTT) was developed to overcome these obstacles. The use of BWSTT enables early initiation of gait training, integration of weightbearing activities, stepping and balance by the use of a task-specific approach, and a symmetrical gait pattern. However, despite the theoretical potential of BWSTT to become an invaluable therapeutic tool, its effect on walking outcomes was disappointing when compared with conventional training of the same duration. To facilitate the deLivery of BWSTT, a motorized robotic driven gait orthosis (RBWSTT) was recently developed. It has many advantages over the conventional method, including less effort for the physiotherapists, longer session duration, more physiological and reproducible gait patterns, and the possibility of measuring a patient's performances. Several studies have been conducted using RBWSTT in patients after stroke, spinal cord injury, multiple sclerosis and other neurological diseases. Although some of the results were encouraging, there is still uncertainty regarding proper patient selection, timing and protocol for RBWTT treatment following neurological diseases. More large randomized controlled studies are needed in order to answer these questions.

Neurological deterioration during intubation in cervical spine disorders

PubMed Central

Durga, Padmaja; Sahu, Barada Prasad

2014-01-01

Anaesthesiologists are often involved in the management of patients with cervical spine disorders. Airway management is often implicated in the deterioration of spinal cord function. Most evidence on neurological deterioration resulting from intubation is from case reports which suggest only association, but not causation. Most anaesthesiologists and surgeons probably believe that the risk of spinal cord injury (SCI) during intubation is largely due to mechanical compression produced by movement of the cervical spine. But it is questionable that the small and brief deformations produced during intubation can produce SCI. Difficult intubation, more frequently encountered in patients with cervical spine disorders, is likely to produce greater movement of spine. Several alternative intubation techniques are shown to improve ease and success, and reduce cervical spine movement but their role in limiting SCI is not studied. The current opinion is that most neurological injuries during anaesthesia are the result of prolonged deformation, impaired perfusion of the cord, or both. To prevent further neurological injury to the spinal cord and preserve spinal cord function, minimizing movement during intubation and positioning for surgery are essential. The features that diagnose laryngoscopy induced SCI are myelopathy present on recovery, short period of unconsciousness, autonomic disturbances following laryngoscopy, cranio-cervical junction disease or gross instability below C3. It is difficult to accept or refute the claim that neurological deterioration was induced by intubation. Hence, a record of adequate care at laryngoscopy and also perioperative period are important in the event of later medico-legal proceedings. PMID:25624530

Medium-term neurological complications after off-pump coronary artery bypass grafting with and without aortic manipulation.

PubMed

Matsuura, Kaoru; Mogi, Kenji; Sakurai, Manabu; Kawamura, Tomonori; Takahara, Yoshiharu

2013-09-01

This study aimed to assess the impact of aortic manipulation during off-pump coronary artery bypass (OPCAB) on neurological complications. Of 336 isolated OPCAB surgeries, the aorta was untouched in 264 cases (group A), whereas it was manipulated by a side-biting clamp in 72 (group B). The average follow-up was 2.9±2.5 years. One patient in each group developed postoperative stroke (P=0.38). The prevalence of triple-vessel disease (group A 40.9% vs. group B 61.1%; P=0.0003) and left main trunk disease (group A 30.7% vs. group B 47.2%; P=0.1) was lower in group A than in group B. The number of bypass grafts (group A 2.18±0.97 vs. group B 3.00±0.97; P=0.0001) was lower in group A than in group B. The prevalence of preoperative atrial fibrillation and the incidence of new-onset postoperative atrial fibrillation were not different between groups (P=0.74 and 0.86, respectively). Survival rate and freedom from major adverse cardiac events were not different between groups (P=0.87 and 0.51, respectively). However, freedom from neurological complications was significantly lower in group A (P=0.0006). The Cox hazard model showed that aortic manipulation (P=0.004; odds ratio, 6.18; 95% confidence interval, 1.8-21.6) and preoperative atrial fibrillation (P=0.001; odds ratio, 14.0; 95% confidence interval, 2.7-72.5) were risk factors for neurological complications. Although there was no difference in the incidence of immediate postoperative neurological complications, there were fewer medium-term neurological complications in OPCAB cases without aortic manipulation.

Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing.

PubMed

Tran, Sheri; Deacon, Naomi; Minokadeh, Anushirvan; Malhotra, Atul; Davis, Daniel P; Villanueva, Sheri; Sell, Rebecca E

2016-10-01

Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2-7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2-7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p<0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p<0.001) while arrests due to dysrhythmia had the opposite trend (p=0.014). Rates of survival to discharge (p=0.038) and favorable neurological outcomes (p=0.002) were lower with increasing hospital days while ROSC was not different among the groups (p=0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0-45.7%], p=0.002 vs HD2-7: 34.0% [95% CI, 27.5-40.4%], p<0.001 vs HD>7: 27.2% [95% CI, 21.4-33.0%], p<0.001). The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing☆,☆☆,★

PubMed Central

Tran, Sheri; Deacon, Naomi; Minokadeh, Anushirvan; Malhotra, Atul; Davis, Daniel P.; Villanueva, Sheri; Sell, Rebecca E.

2017-01-01

Objective Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. Subject and methods Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2–7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. Results A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2–7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p < 0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p < 0.001) while arrests due to dysrhythmia had the opposite trend (p = 0.014). Rates of survival to discharge (p = 0.038) and favorable neurological outcomes (p = 0.002) were lower with increasing hospital days while ROSC was not different among the groups (p = 0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0–45.7%], p = 0.002 vs HD2–7: 34.0% [95% CI, 27.5–40.4%], p < 0.001 vs HD>7: 27.2% [95% CI, 21.4–33.0%], p < 0.001). Conclusions The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication. PMID:27456394

Natural history and magnetic resonance imaging follow-up in 9 Sturge-Weber Syndrome patients and clinical correlation.

PubMed

Udani, Vrajesh; Pujar, Suresh; Munot, Pinki; Maheshwari, Shailendra; Mehta, Nirad

2007-04-01

The natural history of Sturge-Weber Syndrome is variable where some patients have refractory epilepsy and persistent neurologic deficits while others do well. Also, evolution of MRI abnormalities is largely unknown. This long-term follow-up study tries to address these two issues. This retrospective and later prospective study followed 9 children with confirmed SWS. Clinical details of seizures, stroke-like episodes, neurologic and developmental deficits were ascertained specifically. Patients were divided into those with onset below or after 6 months of age for analysis. Disease was classified as active or inactive and correlations were made with the use of aspirin. All past, as well as prospectively acquired imaging was reviewed by two independent blinded neuroradiologists and the images were analysed as ictal (temporally related to seizure/stroke-like event) or interictal. Degree and extent of leptomeningeal enhancement was specifically looked for. Four boys and five girls were followed up for a mean of 6.1 years. Disease activity subsided in 8/9. Early-onset patients had a severe early course with significant residual deficits while late-onset patients did uniformly well. In 6 patients where aspirin was used, a stable course ensued. There was a significant increase in degree/extent of leptomeningeal enhancement during an ictus which returned to the baseline in the interictal state in all 7 patients where both images were available. Focal cerebral atrophy worsened in early-onset cases. In conclusion, SWS patients with onset of seizures/stroke-like events before 6 months of age seem to do worse with a severe early course and persistent neurologic deficits. However the course stabilizes after 5 years of age in most. Late-onset SWS patients have a benign course. Aspirin use is associated with a stable course though further studies are needed. The leptomeningeal enhancement appears to increase during acute events before returning to baseline suggesting that extent of the disease is probably best judged during the interictal state.

Nonulcer dyspepsia.

PubMed Central

Thompson, W. G.

1984-01-01

One third to one half of cases of dyspepsia remain unexplained. The cause of nonulcer dyspepsia is unknown, but aerophagia, esophageal dysfunction, pyloroduodenal dysmotility and the irritable bowel syndrome may be important factors in some patients. The symptoms are often affected by diet and emotion. History-taking and endoscopy are the most discriminating diagnostic tests. Unexplained dyspepsia tends to be a lifelong disease with few, if any, sequelae. Nevertheless, reassurance and treatment with a placebo, such as an antacid or simethicone, provide effective and safe relief for many patients. PMID:6365298

Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations.

PubMed

Kuzmanic, Antonija; Sutto, Ludovico; Saladino, Giorgio; Nebreda, Angel R; Gervasio, Francesco L; Orozco, Modesto

2017-04-26

p38α is a Ser/Thr protein kinase involved in a variety of cellular processes and pathological conditions, which makes it a promising pharmacological target. Although the activity of the enzyme is highly regulated, its molecular mechanism of activation remains largely unexplained, even after decades of research. By using state-of-the-art molecular dynamics simulations, we decipher the key elements of the complex molecular mechanism refined by evolution to allow for a fine tuning of p38α kinase activity. Our study describes for the first time the molecular effects of different regulators of the enzymatic activity, and provides an integrative picture of the activation mechanism that explains the seemingly contradictory X-ray and NMR data.

Botulinum toxin injections for chronic sialorrhoea in children are effective regardless of the degree of neurological dysfunction: A single tertiary institution experience.

PubMed

Mahadevan, Murali; Gruber, Maayan; Bilish, Darin; Edwards, Kathryn; Davies-Payne, David; van der Meer, Graeme

2016-09-01

To determine the effectiveness of submandibular salivary gland Botulinum Toxin Type-A (BTX-A) injection in the treatment of drooling in children with varying degrees of neurological dysfunction. A retrospective review of pre- and post-procedure drooling frequency and severity scores of patients receiving BTX-A between January 2008 and January 2013. Stratification to different subgroups of neurological impairment was performed according to Gross Motor Function Classification System (GMFCS) score. Drooling severity was assessed using Thomas-Stonell and Greenberg symptom questionnaires administered at time of initial consultation and 3 months after treatment. 48 sets of BTX-A injections in 26 patients with an average age of 9.45 years (range 7 months-18 years) were included in the study. Marked improvement in drooling was seen in 60.4% of patients, a marginal or brief improvement was seen in 20.8% and there was no improvement in 18.8%. No adverse events were reported following any of the BTX-A injections. BTX-A was safe and effective in the eight patients with pre-existing swallowing dysfunction. Subsequent drooling surgery was performed in 15 (57.7%) of the cohort, all 15 patients responded to BTX-A injections. In patients with Cerebral Palsy, there was no correlation between the severity of the neurological dysfunction as measured by the Gross Motor Function Classification System (GMFCS) score and the response to BTX-A treatment. Injection of BTX-A to the submandibular glands of children with neurological disorders is a safe procedure and results in a reduction in drooling in the majority of patients. Children with severe neurological dysfunction respond to BTX-A injections as effectively as their less impaired peers and the degree of response does not appear to be associated with the severity of neurological disability. BTX-A injection is a good initial procedure when drooling surgery is being considered. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke.

PubMed

Aquilani, Roberto; Scocchi, Marco; Iadarola, Paolo; Franciscone, Piero; Verri, Manuela; Boschi, Federica; Pasini, Evasio; Viglio, Simona

2008-12-01

To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). Tertiary care rehabilitation in Italy. Forty-two patients (27 male and 15 female; 66.4 +/- 11 years) 16 +/-2 days after the acute event. Supplementation with a hyperproteic nutritional formula (10% protein). NIH Stroke Scale and protein intake. At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 +/- 1.5 score versus -3 +/- 1.4 of control group; P<0.01). When expressed as difference (triangle up) between baseline and 21 days, the NIH Stroke Scale correlated negatively with change in protein intake (g/day) (r=-0.50, P= 0.001) and positively with change in carbohydrate/protein ratio (r = +0.40, P=0.01) Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke.

The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2012-02-01

Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.

Intracarotid abciximab injection to abort impending ischemic stroke during carotid angioplasty.

PubMed

Ho, D S; Wang, Y; Chui, M; Wang, Y; Ho, S L; Cheung, R T

2001-01-01

Abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, prevents ischemic complications during percutaneous transluminal coronary angioplasty and was recently shown to open occluded vessels in patients with acute myocardial infarction when used alone or in combination with other thrombolytic agents. In an animal model of arterial thrombosis, abciximab was found to be safe and effective for the prevention of carotid artery thrombosis. However, the safety and efficacy of abciximab in the treatment of acute ischemic cerebrovascular events is unknown at present. We describe 3 patients who experienced ischemic cerebrovascular events with symptoms involving the middle cerebral artery territory while undergoing percutaneous angioplasty and stenting to their internal carotid arteries. Abciximab was administered to each patient within 10 min of symptom onset as a bolus (0.25 mg/kg) into the ipsilateral common carotid artery followed by continuous intravenous infusion (9 microg/min) for 12 h. All patients' symptoms resolved completely (by 25 min, 40 min and 5 h, respectively) with no further neurological complications. Our preliminary observation suggests that abciximab may improve neurological outcome following middle cerebral artery ischemic events associated with carotid angioplasty and stenting. Large prospective studies are warranted to establish the safety and efficacy of abciximab in acute ischemic stroke, either as a primary treatment modality or an adjunct to carotid angioplasty and stenting. Copyright 2001 S. Karger AG, Basel.

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

PubMed Central

Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

2014-01-01

Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose. Conclusions: DM/Q was generally well tolerated over this 52 week trial in patients with PBA associated with a wide range of neurological conditions. PMID:25062507

A protozoal-associated epizootic impacting marine wildlife: Mass-mortality of southern sea otters (Enhydra lutris nereis) due to Sarcocystis neurona infection

PubMed Central

Conrad, Patricia A.; Harris, Michael; Hatfield, Brian; Langlois, Gregg; Jessup, David A.; Magargal, Spencer L.; Packham, Andrea E.; Toy-Choutka, Sharon; Melli, Ann C.; Murray, Michael A.; Gulland, Frances M.; Grigg, Michael E.

2016-01-01

During April, 2004, 40 sick and dead southern sea otters (Enhydra lutris nereis) were recovered over 18 km of coastline near Morro Bay, California. This event represented the single largest monthly spike in mortality ever recorded during 30 years of southern sea otter stranding data collection. Because of the point-source nature of the event and clinical signs consistent with severe, acute neurological disease, exposure to a chemical or marine toxin was initially considered. However, detailed postmortem examinations revealed lesions consistent with an infectious etiology, and further investigation confirmed the protozoan parasite Sarcocystis neurona as the underlying cause. Tissues from 94% of examined otters were PCR-positive for S. neurona, based on DNA amplification and sequencing at the ITS-1 locus, and 100% of tested animals (n = 14) had elevated IgM and IgG titers to S. neurona. Evidence to support the point-source character of this event include the striking spatial and temporal clustering of cases and detection of high concentrations of anti-S. neurona IgM in serum of stranded animals. Concurrent exposure to the marine biotoxin domoic acid may have enhanced susceptibility of affected otters to S. neurona and exacerbated the neurological signs exhibited by stranded animals. Other factors that may have contributed to the severity of this epizootic include a large rainstorm that preceded the event and an abundance of razor clams near local beaches, attracting numerous otters close to shore within the affected area. This is the first report of a localized epizootic in marine wildlife caused by apicomplexan protozoa. PMID:20615616

A protozoal-associated epizootic impacting marine wildlife: mass-mortality of southern sea otters (Enhydra lutris nereis) due to Sarcocystis neurona infection.

PubMed

Miller, Melissa A; Conrad, Patricia A; Harris, Michael; Hatfield, Brian; Langlois, Gregg; Jessup, David A; Magargal, Spencer L; Packham, Andrea E; Toy-Choutka, Sharon; Melli, Ann C; Murray, Michael A; Gulland, Frances M; Grigg, Michael E

2010-09-20

During April 2004, 40 sick and dead southern sea otters (Enhydra lutris nereis) were recovered over 18km of coastline near Morro Bay, California. This event represented the single largest monthly spike in mortality ever recorded during 30 years of southern sea otter stranding data collection. Because of the point-source nature of the event and clinical signs consistent with severe, acute neurological disease, exposure to a chemical or marine toxin was initially considered. However, detailed postmortem examinations revealed lesions consistent with an infectious etiology, and further investigation confirmed the protozoan parasite Sarcocystis neurona as the underlying cause. Tissues from 94% of examined otters were PCR-positive for S. neurona, based on DNA amplification and sequencing at the ITS-1 locus, and 100% of tested animals (n=14) had elevated IgM and IgG titers to S. neurona. Evidence to support the point-source character of this event include the striking spatial and temporal clustering of cases and detection of high concentrations of anti-S. neurona IgM in serum of stranded animals. Concurrent exposure to the marine biotoxin domoic acid may have enhanced susceptibility of affected otters to S. neurona and exacerbated the neurological signs exhibited by stranded animals. Other factors that may have contributed to the severity of this epizootic include a large rainstorm that preceded the event and an abundance of razor clams near local beaches, attracting numerous otters close to shore within the affected area. This is the first report of a localized epizootic in marine wildlife caused by apicomplexan protozoa.

A prospective cohort study investigating an exposure-response relationship among vibration-exposed male workers with numbness of the hands.

PubMed

Edlund, Maria; Burström, Lage; Gerhardsson, Lars; Lundström, Ronnie; Nilsson, Tohr; Sandén, Helena; Hagberg, Mats

2014-03-01

The aim of this study was to investigate the exposure-response relationship of hand-arm vibration exposure to neurological symptoms (numbness) of the hand in a cohort of vibration-exposed workers. The baseline cohort comprised 241 office and manual workers with and without exposure to hand-arm vibration. Numbness (the symptom or event) in the hand was assessed for all subjects at baseline and follow-ups after 5, 10, and 16 years. The workers were stratified into quartiles with no exposure in the first quartile and increasing intensity of exposure in quartiles 2-4 (groups 1-3). Data analysis was performed using survival analysis (time to event). Information on cumulative exposure and years of exposure to event was collected via questionnaires. Measurements were performed in accordance with the International Organization for Standardization (ISO) 5349-1. The hazard ratio (HR) of risk of event (numbness) differed statistically significantly between the non-exposed group (group 0) and the two higher exposure groups (groups 2 and 3). There was also a significant ratio difference between the lowest exposure group (group 1) and the two higher groups. The ratio for group 1 was 1.77 [95% confidence interval (95% CI) 0.96-3.26] compared with 3.78 (95% CI 2.15-6.62) and 5.31 (95% CI 3.06-9.20) for groups 2 and 3, respectively. The results suggest a dose-response relationship between vibration exposure and numbness of the hands. This underlines the importance of keeping vibration levels low to prevent neurological injury to the hands.

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury.

PubMed

Duran, Latif; Kayhan, Servet; Kati, Celal; Akdemir, Hizir Ufuk; Balci, Kemal; Yavuz, Yucel

2014-03-01

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible.

Meta-analysis of transcatheter closure versus medical therapy for patent foramen ovale in prevention of recurrent neurological events after presumed paradoxical embolism.

PubMed

Agarwal, Shikhar; Bajaj, Navkaranbir Singh; Kumbhani, Dharam J; Tuzcu, E Murat; Kapadia, Samir R

2012-07-01

In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO). A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO. We conducted a MEDLINE search with standard search terms to determine eligible studies. Adjusted incidence rates of RNE were 0.8 (95% confidence interval [CI]: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia. Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Investigation of unexplained infant deaths in Jerusalem, Israel 1996–2003

PubMed Central

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-01-01

Background Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. Methods We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996–2003. Results Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. Conclusions : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem. PMID:17074788

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

PubMed Central

2011-01-01

Background The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI). Methods Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration. Results Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). Conclusion The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. Trial registration ClinicalTrials.gov, NCT01232075 PMID:21693030

[The usefullness of implantable loop recorders for evaluation of unexplained syncope and palpitations].

PubMed

Kristjánsdóttir, Ingibjörg; Reimarsdóttir, Guđrun; Arnar, Davíđ O

2012-09-01

Syncope is a common complaint and determining the underlying cause can be difficult despite extensive evaluation. The purpose of this study was to evaluate the usefulness of an implantable loop recorder for patients with unexplained syncope and palpitations. This was a retrospective analysis of 18 patients, five of whom still have the device implanted. All patients had undergone extensive evaluation for their symptoms before getting the loop recorder implanted and this was therefore a highly select group. Of the thirteen patients where use of the device was completed, the mean age was 65±20 years. The loop recorder was in use for a mean time of 20±13 months. Unexplained syncope, eleven of thirteen, was the most common indication. The other two received the loop recorder for unexplained palpitations. Four patients had sick sinus syndrome during monitoring, three had supraventricular tachycardia and one had ventricular tachycardia. Further three had typical symptoms but no arrhythmia was recorded and excluding that as a cause. Two patients had no symptoms the entire time they had the loop recorder. Of the five patients still with the device three had syncope as the indication for monitoring and two have the device as a means of evaluating the results of treatment for arrhythmia. This study on our initial experience with implantable loop recorders shows that these devices can be useful in the investigation of the causes of syncope and palpitations.

Anxiety and depression predicted by medically unexplained symptoms in Pakistani children: a case-control study.

PubMed

Imran, Nazish; Ani, Cornelius; Mahmood, Zahid; Hassan, Khawaja Amjad; Bhatti, Muhammad Riaz

2014-02-01

To explore association between medically unexplained symptoms in children in Pakistan with emotional difficulties and functional impairments. We conducted a matched three-group case-control study of 186 children aged 8-16 years in Lahore, Pakistan. Cases were 62 children with chronic somatic symptoms for which no organic cause was identified after investigations. Two control groups of 62 children with chronic medical paediatric conditions, and 62 healthy children were identified. Cases and controls were matched for gender, age, and school class. Somatisation was measured with the Children's Somatisation Inventory (CSI-24) while anxiety and depression were measured with the Spencer Children's Anxiety Scale and the Short Mood and Feelings Questionnaire respectively. All questionnaires were translated into Urdu. Mean age was 11.7 years (SD=2.1). Cases scored significantly higher on somatisation (CSI-24), anxiety and depression than both control groups. Paediatric controls scored significantly higher than healthy controls on all three measures. Two hierarchical linear regression models were used to explore if somatisation predicted depression and anxiety while controlling for several confounders. Somatisation (higher CSI-24 scores) independently and significantly predicted higher anxiety (β=.37, p=.0001) and depression (β=.41, p=.0001) scores. This is the first study to show an association between medically unexplained symptoms and anxiety and depression in Pakistani children. This highlights the importance of screening for emotional difficulties in children presenting with unexplained somatic symptoms in this region. Copyright © 2013 Elsevier Inc. All rights reserved.

Opinion paper: the role of work in the management of medically unexplained physical symptoms.

PubMed

Tobback, Els; Mariman, An; Clauwaert, Lies; Godderis, Lode; Heytens, Stefan; Ruppol, Patrick; Spooren, Daniel; Tytgat, Rita; De Muynck, Martine; Vogelaers, Dirk

2018-05-04

Patients with medically unexplained physical symptoms suffer from chronic fatigue and/or pain in combination with a variety of other symptoms. A flexible, biopsychosocial approach is needed for diagnostic screening and global management. It is crucial to involve the direct patient environment, including family, friends, colleagues as well as health providers, evaluation, and reintegration sector. The aim of this paper is to review the importance of work in the management of medically unexplained physical symptoms. In this paper, different actors involved explain their views and handling concerning work in the management of MUPS. Symptom severity and lack of understanding from the environment can negatively impact on earning an independent income from labor for years. Work, whether or not paid, is however, an important life domain with positive effects on physical, psychological, and social well-being. Therefore, health actors are pivotal in starting the professional reintegration process as soon as possible and should discuss this item from the early stage onward. Support services can be consulted in mutual interaction as required. A case manager, acting as a central intermediator within this multidisciplinary approach, may promote effective communication and coordination between the patients and their surrounding actors. The professional reintegration process should start as soon as possible within the management of medically unexplained physical symptoms. As such, the care sector, the evaluation sector, and the professional integration sector should collaborate and effectively communicate with each other.

Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions of unexplained aetiology.

PubMed

Yamada, H; Kishida, T; Kobayashi, N; Kato, E H; Hoshi, N; Fujimoto, S

1998-09-01

The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, +16, +20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk category of first trimester abortions.

Investigation of unexplained infant deaths in Jerusalem, Israel 1996-2003.

PubMed

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-08-01

Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996-2003. Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem.

Hydrotubation in the management of female infertility: outcome in low resource settings.

PubMed

Adesiyun, A G; Cole, B; Ogwuche, P

2009-01-01

To determine the outcome of therapeutic hydrotubation (tubal flushing) in patients with tubal infertility and unexplained infertility. Prospective non-randomised observational study. Alba hospital, a five bed multidisciplinary private hospital in Kaduna city, Nigeria. Infertile women with tubal and unexplained infertility. Two hundred and fifty seven patients that had therapeutic hydrotubation over 7.5 years were analysed. The age range was 21 to 44 years with mean of 34.5 years. Secondary infertility was found in 209 (81.3%) patients and primary infertility in 166 (64.6%) patients. Of the 257 patients, 134 (52.1%) had had induced abortion. Indications for hydrotubation were bilateral perifimbrial adhesion (incomplete tubal occlusion) 47.9%, bilateral fimbrial end occlusion 24.9%, bilateral cornual blockage 16% and unexplained infertility in 11.3% of cases. One hundred and nine conceptions were recorded in this study and the overall conception rate was 42.4%. Likewise, percentage ratio of conception in these 154 patients with evidence of post-hydrotubation tubal patency was 70.8%. Pregnancy outcome of the 109 conceptions are term pregnancy 84.4%, preterm pregnancy 9.2%, miscarriage 4.6% and ectopic pregnancy in 1.8% of the conceptions. Recorded complications were pelvic pain in 177 (68.9%) patients and vaginal bleeding in 63 (24.5%) patients. With good case selection, therapeutic hydrotubation may be beneficial in resource poor countries, especially in patients with incomplete tubal occlusion (bilateral perifimbrial adhesions) and as part of treatment for unexplained infertility.

Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid hemorrhage.

PubMed

Todd, Michael M; Hindman, Bradley J; Clarke, William R; Torner, James C; Weeks, Julie B; Bayman, Emine O; Shi, Qian; Spofford, Christina M

2009-05-01

We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever. These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

PubMed

Harrison, Neil A; Johnston, Kate; Corno, Federica; Casey, Sarah J; Friedner, Kimberley; Humphreys, Kate; Jaldow, Eli J; Pitkanen, Mervi; Kopelman, Michael D

2017-09-01

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Effects of Total Motile Sperm Count on Spontaneous Pregnancy Rate and Pregnancy After IUI Treatment in Couples with Male Factor and Unexplained Infertility.

PubMed

Hajder, Mithad; Hajder, Elmira; Husic, Amela

2016-02-01

Male infertility factor is defined if the total number of motile spermatozoa (TMSC) < 20 × 10(6)/ejaculated, and unexplained infertility if spermiogram is normal with normal female factor. of this study was to determine the predictive value of TMSC for spontaneous pregnancy (ST) and pregnancy after treatment with intrauterine insemination (IUI) in couples with male factor and unexplained infertility. According to the WHO qualification system abnormal spermiogram can be diagnosed as oligozoospermia (O), asthenozoospermia (A), teratozoospermia (T) or combination (O+A+T) and azoospermia (A). Although this classification indicates the accuracy of findings its relevance for prognosis in infertile couple and the choice of treatment is questionable. The study included 98 couples with male infertility factor (bad spermiogram) and couples with normospermia and normal female factor (unexplained infertility). Testing group is randomized at: group (A) with TMSC> 3,10(6) / ejaculate and a spontaneous pregnancy, group (B) with TMSCl <3 x 10(6) / ejaculate and pregnancy after IUI, plus couples who have not achieved SP with TMSC> 3 x 10(6) / ejaculate and couples who have not achieved pregnancy. From a total of 98 pairs of men's and unexplained infertility, 42 of them (42.8%) achieved spontaneous pregnancy, while 56 (57.2%) pairs did not achieve spontaneous pregnancy. TMSC was significantly higher (42.4 ± 28.4 vs. 26.2 ± 24, p <0.05) in the group A compared to group B. Couples with TMSC 1-5 × 10(6) ejaculate had significantly lower (9.8% vs. 22.2%, p <0.0001) rate of spontaneous pregnancy in comparison to couples after IUI treatment. Couples with unexplained infertility had significantly higher (56.8% vs. 29.9%, p <0.01) spontaneous pregnancy rate compared to couples after IUI treatment. Infertile couples had significant pregnancy rate with TMSC 5-10 x 10(6) / ejaculate (OR = 1.45, 95% CI:1.26-1.78, <0.01); with TMSC 10-20 x 10(6) / ejaculate (OR = 1.36, 95% CI: 1:12 to 1:46, <0.0001) with TMSC> 20 x 10(6) / ejaculate (RR = 1.7, 95% CI: 1.56-1.82, <0.001) after treatment with IUI compared to spontaneous pregnancy. Based on these results we can conclude that couples with the TMSC> 5 x 10(6) / ejaculate are indicated for treatment with IUI. TMSC can be used as the method of choice for diagnosis and treatment of male infertility.

[Probabilities cannot be calculated retrospectively--not even in the courtroom].

PubMed

van Gijn, J

2005-12-24

Chance events are part of everyday life, but coincidence of diseases often raises suspicions about hidden causes, for example when power lines are blamed for the geographical clustering of cancer. Recently, criminal procedures in the Netherlands have revolved around the question of whether statistical 'predictions' are a valid reason to hold a hospital nurse accountable for the occurrence of excess deaths during her duty hours, or a kindergarten employee for unexplained respiratory problems in several infants. In both cases, the appeals court judges did not accept the statistical 'argument' in the absence of other evidence. In the UK, however, Sally Clark's initial life sentence for the double murder of her 2 babies was largely based on 'probabilities in retrospect', put forward by the paediatrician Sir Roy Meadow as an expert witness. 4 years later she was acquitted, whereas Meadow was struck off the medical register on a charge of professional misconduct. There is no Bayesian or other mathematical solution to the problem of chance events. Only the detection of causal factors that are plausible and supported by new evidence can help to reinterpret coincidences as relationships. Scrupulous reasoning about probabilities is required, not only of physicians but also of judges and politicians.

Etiological diagnoses of out-of-hospital cardiac arrest survivors admitted to the intensive care unit: Insights from a French registry.

PubMed

Geri, Guillaume; Passouant, Olivier; Dumas, Florence; Bougouin, Wulfran; Champigneulle, Benoit; Arnaout, Michel; Chelly, Jonathan; Chiche, Jean-Daniel; Varenne, Olivier; Guillemet, Lucie; Pène, Frederic; Waldmann, Victor; Mira, Jean-Paul; Marijon, Eloi; Cariou, Alain

2017-08-01

Respective proportions of final etiologies are disparate in cohorts of cardiac arrest patients, depending on examined population and diagnostic algorithms. In particular, prevalence and characteristics of sudden unexplained death syndrome (SUDS) are debated. We aimed at describing etiologies in a large cohort of aborted out-of-hospital cardiac arrest (OHCA) patients, in order to assess prevalence and outcome of SUDS. We analyzed data from our prospective registry of successfully resuscitated OHCA patients admitted to a cardiac arrest centre between January 2002 and December 2014. The in-ICU diagnostic strategy included early coronary angiogram, brain and chest CT scan. This was completed by an extensive diagnostic strategy, encompassing biological and toxicological tests, repeated electrocardiograms and echocardiography, MRI and pharmacologic tests. Two independent investigators reviewed each final diagnosis. Baseline characteristics were compared between subgroups of patients. Three-month mortality was compared between subgroups using univariate Kaplan-Meier curves. Over the study period, 1657 patients were admitted to our unit after an aborted OHCA. The event was attributed to a non-cardiac and a cardiac cause in 478 (32.0%) and 978 (65.5%) patients, respectively. The main cause of cardiac related OHCA was ischemic heart disease (76.7%) while primary electrical diseases accounted for only 2.5%. Sudden unexplained deaths (SUDS) were observed in 37 (2.5%) patients. We observed that ischemic heart disease was by far the most common cause of cardiac arrest, while primary electrical diseases were much less frequent. SUDS accounted for a very small proportion of patients who suffered an aborted OHCA. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnostic value of radiological imaging pre- and post-drainage of pleural effusions.

PubMed

Corcoran, John P; Acton, Louise; Ahmed, Asia; Hallifax, Robert J; Psallidas, Ioannis; Wrightson, John M; Rahman, Najib M; Gleeson, Fergus V

2016-02-01

Patients with an unexplained pleural effusion often require urgent investigation. Clinical practice varies due to uncertainty as to whether an effusion should be drained completely before diagnostic imaging. We performed a retrospective study of patients undergoing medical thoracoscopy for an unexplained effusion. In 110 patients with paired (pre- and post-drainage) chest X-rays and 32 patients with paired computed tomography scans, post-drainage imaging did not provide additional information that would have influenced the clinical decision-making process. © 2015 Asian Pacific Society of Respirology.

[Genetics of sudden unexplained death].

PubMed

Campuzano, Oscar; Allegue, Catarina; Brugada, Ramon

2014-03-20

Sudden unexplained death is defined by death without a conclusive diagnosis after autopsy and it is responsible for a large percentage of sudden deaths. The progressive interaction between genetics and forensics in post-mortem studies has identified inheritable alterations responsible for pathologies associated with arrhythmic sudden death. The genetic diagnosis of the deceased enables the undertaking of preventive measures in family members, many of them asymptomatic but at risk. The implications of this multidisciplinary translational medical approach are complex, requiring the dedication of a specialized team. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Periodic fluctuations in deep water formation due to sea ice

NASA Astrophysics Data System (ADS)

Saha, R.

2012-12-01

During the last ice age, several abrupt warming events took place, known as Dansgaard-Oeschger (D-O) events. Their effects were felt globally, although the North Atlantic experienced the largest temperature increase. The leading hypothesis to explain their occurrence postulates that the warming was caused by abrupt disruptions of the North Atlantic Current due to meltwater discharge from destabilized ice sheets (Heinrich events). However, the number of warming events outnumber the those of ice-sheet collapse. Thus, the majority of D-O events are not attributed to surface freshwater anomalies, and the underlying mechanism behind their occurrence remain unexplained. Using a simple dynamical model of sea ice and an overturning circulation, I show the existence of self-sustained relaxation oscillations in the overturning circulation. The insulating effect of sea ice is shown to paradoxically lead to a net loss of heat from the top layer of the polar ocean when sea ice retreats. Repeated heat loss results in a denser top layer and a destabilized water column, which triggers convection. The convective state pulls the system out of its preferred mode of circulation, setting up relaxation oscillations. The period of oscillations in this case is linked to the geometry of the ocean basin, if solar forcing is assumed to remain constant. If appropriate glacial freshwater forcing is applied to the model, a pattern of oscillation is produced that bears remarkable similarity to the observed fluctuations in North Atlantic climate between 50,000 and 30,000 years before present.; Comparison of NGRIP δ 18-O (proxy for near surface air temperature) between 50,000 and 30,000 years before present, showing Bond cycles (left) with the model output when forced with appropriate glacial freshwater forcing (right).

Legal challenges in neurological practice.

PubMed

Jayalakshmi, Sita; Vooturi, Sudhindra

2016-10-01

Clinical neuroscience has made tremendous advances over the last century. Neurology as a discipline is still considered challenging and at times risky due to the natural history and progressive course of few of the neurological diseases. Encouragingly, the patient and their caregivers are now increasingly willing to be actively involved in making decisions. The patients' relationship with the doctor is a reflection of the society. A society that is orienting itself toward "rating" and "feedback" has made this doctor-patient relationship, a consumer-service provider relationship. This perhaps is due to commercialization of health that usually accompanies globalization. Moreover, a rapid influx of information from potential erroneous sources such as the Internet has also made patient and caregivers not being hesitant to taking legal course in the case of adverse events during treatment or simply because of dissatisfaction. The purpose of the legal process initiated by patients with neurological ailments is more often to compensate for the income lost, physical and psychological anguish that accompanies disease and its treatment, and to fund treatment or rehabilitation requirements. However, it is not clearly established if monetary benefits acquired lead to better opportunities for recovery of the patient. The consumer protection act and commercialization of medical services may well have an adverse effect on the doctor and patient relationship. Hence, there is a great need for all medical professionals to mutually complement and update each other. This review examines legal (litigation) processes with special interest on medicolegal system in patients with neurological ailments and the challenges faced by the neurologist during day-to-day clinical practice.

Incidence and Outcomes of Cardiopulmonary Resuscitation in PICUs.

PubMed

Berg, Robert A; Nadkarni, Vinay M; Clark, Amy E; Moler, Frank; Meert, Kathleen; Harrison, Rick E; Newth, Christopher J L; Sutton, Robert M; Wessel, David L; Berger, John T; Carcillo, Joseph; Dalton, Heidi; Heidemann, Sabrina; Shanley, Thomas P; Zuppa, Athena F; Doctor, Allan; Tamburro, Robert F; Jenkins, Tammara L; Dean, J Michael; Holubkov, Richard; Pollack, Murray M

2016-04-01

To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes. Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge in the Collaborative Pediatric Critical Care Research Network December 2011 to April 2013. Among 10,078 children enrolled, 139 (1.4%) received cardiopulmonary resuscitation for more than or equal to 1 minute and/or defibrillation. Of these children, 78% attained return of circulation, 45% survived to hospital discharge, and 89% of survivors had favorable neurologic outcomes. The relative incidence of cardiopulmonary resuscitation events was higher for cardiac patients compared with non-cardiac patients (3.4% vs 0.8%, p <0.001), but survival rate to hospital discharge with favorable neurologic outcome was not statistically different (41% vs 39%, respectively). Shorter duration of cardiopulmonary resuscitation was associated with higher survival rates: 66% (29/44) survived to hospital discharge after 1-3 minutes of cardiopulmonary resuscitation versus 28% (9/32) after more than 30 minutes (p < 0.001). Among survivors, 90% (26/29) had a favorable neurologic outcome after 1-3 minutes versus 89% (8/9) after more than 30 minutes of cardiopulmonary resuscitation. These data establish that contemporary PICU cardiopulmonary resuscitation, including long durations of cardiopulmonary resuscitation, results in high rates of survival-to-hospital discharge (45%) and favorable neurologic outcomes among survivors (89%). Rates of survival with favorable neurologic outcomes were similar among cardiac and noncardiac patients. The rigorous prospective, observational study design avoided the limitations of missing data and potential selection biases inherent in registry and administrative data.

Effectiveness of music therapy as an aid to neurorestoration of children with severe neurological disorders

PubMed Central

Bringas, Maria L.; Zaldivar, Marilyn; Rojas, Pedro A.; Martinez-Montes, Karelia; Chongo, Dora M.; Ortega, Maria A.; Galvizu, Reynaldo; Perez, Alba E.; Morales, Lilia M.; Maragoto, Carlos; Vera, Hector; Galan, Lidice; Besson, Mireille; Valdes-Sosa, Pedro A.

2015-01-01

This study was a two-armed parallel group design aimed at testing real world effectiveness of a music therapy (MT) intervention for children with severe neurological disorders. The control group received only the standard neurorestoration program and the experimental group received an additional MT “Auditory Attention plus Communication protocol” just before the usual occupational and speech therapy. Multivariate Item Response Theory (MIRT) identified a neuropsychological status-latent variable manifested in all children and which exhibited highly significant changes only in the experimental group. Changes in brain plasticity also occurred in the experimental group, as evidenced using a Mismatch Event Related paradigm which revealed significant post intervention positive responses in the latency range between 308 and 400 ms in frontal regions. LORETA EEG source analysis identified prefrontal and midcingulate regions as differentially activated by the MT in the experimental group. Taken together, our results showing improved attention and communication as well as changes in brain plasticity in children with severe neurological impairments, confirm the importance of MT for the rehabilitation of patients across a wide range of dysfunctions. PMID:26582974

Magnetic Resonance Guided Focused Ultrasound Surgery: Part 2 – A Review of Current and Future Applications

PubMed Central

Medel, Ricky; Monteith, Stephen J.; Elias, W. Jeffrey; Eames, Matthew; Snell, John; Sheehan, Jason P.; Wintermark, Max; Jolesz, Ferenc A.; Kassell, Neal F.

2014-01-01

Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) represents a novel combination of technologies that is actively being realized as a non-invasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological utilization. A combined search of Pubmed and Medline was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real-time, it allows monitored provision of treatment location and energy deposition, is noninvasive, thereby limiting or eliminating disruption of normal tissue, provides focal delivery of therapeutic agents, enhances radiation delivery, and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact. PMID:22791029

Effectiveness of music therapy as an aid to neurorestoration of children with severe neurological disorders.

PubMed

Bringas, Maria L; Zaldivar, Marilyn; Rojas, Pedro A; Martinez-Montes, Karelia; Chongo, Dora M; Ortega, Maria A; Galvizu, Reynaldo; Perez, Alba E; Morales, Lilia M; Maragoto, Carlos; Vera, Hector; Galan, Lidice; Besson, Mireille; Valdes-Sosa, Pedro A

2015-01-01

This study was a two-armed parallel group design aimed at testing real world effectiveness of a music therapy (MT) intervention for children with severe neurological disorders. The control group received only the standard neurorestoration program and the experimental group received an additional MT "Auditory Attention plus Communication protocol" just before the usual occupational and speech therapy. Multivariate Item Response Theory (MIRT) identified a neuropsychological status-latent variable manifested in all children and which exhibited highly significant changes only in the experimental group. Changes in brain plasticity also occurred in the experimental group, as evidenced using a Mismatch Event Related paradigm which revealed significant post intervention positive responses in the latency range between 308 and 400 ms in frontal regions. LORETA EEG source analysis identified prefrontal and midcingulate regions as differentially activated by the MT in the experimental group. Taken together, our results showing improved attention and communication as well as changes in brain plasticity in children with severe neurological impairments, confirm the importance of MT for the rehabilitation of patients across a wide range of dysfunctions.

Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research

PubMed Central

Whitley, Elizabeth; Anantharam, Poojya; Kim, Dong‐Suk; Kanthasamy, Arthi

2016-01-01

Hydrogen sulfide (H2S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2S is known to cause brain damage, leading to neurodegeneration and long‐term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2S concentrations. This review focuses on the neuropathology of high acute H2S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2S‐induced neurodegeneration. PMID:27442775

MRI and magnetic resonance angiography findings in patients with multiple sclerosis mimicked by stroke.

PubMed

Khedr, Abdullatif Al; Canaple, Sandrine; Monet, Pauline; Godefroy, Olivier; Bugnicourt, Jean-Marc

2013-08-01

We report a 45-year-old woman who presented with a first demyelinating event with abnormalities seen on both MRI and magnetic resonance angiography that were highly suggestive of acute ischemic stroke. This report highlights the problem of differential diagnosis of acute neurological symptoms in adult subjects. Copyright © 2012 Elsevier Ltd. All rights reserved.

ADVANCES WITH NEONATAL AERODIGESTIVE SCIENCE IN THE PURSUIT OF SAFE SWALLOWING IN INFANTS: INVITED REVIEW

PubMed Central

Jadcherla, Sudarshan R.

2017-01-01

Feeding, swallowing and airway protection are three distinct entities. Feeding involves a process of sequential, neurosensory and neuromotor interactions of reflexes and behaviors facilitating ingestion. Swallowing involves anterograde bolus movement during oral-, pharyngeal- and esophageal phases of peristalsis into stomach. During these events, coordination with airway protection is vital for homeostasis in clearing any material away from airway vicinity. Neurological-airway-digestive inter-relationships are critical to the continuum of successful feeding patterns during infancy, either in health or disease. Neonatal feeding difficulties encompass a heterogeneous group of neurological, pulmonary and aerodigestive disorders that present with multiple signs posing as clinical conundrums. Significant research breakthroughs permitted understanding of vagal neural pathways and functional aerodigestive connectivity involved in regulating swallowing and aerodigestive functions either directly or indirectly by influencing the supra-nuclear regulatory centers and peripheral effector organs. These neurosensory and neuromotor pathways are influenced by pathologies during perinatal events, prematurity, inflammatory states and coexisting medical and surgical conditions. Approaches to clarify pathophysiologic mapping of aerodigestive interactions, as well as translating these discoveries into the development of personalized and simplified feeding strategies to advance child health are discussed in this review article. PMID:28044203

Advances with Neonatal Aerodigestive Science in the Pursuit of Safe Swallowing in Infants: Invited Review.

PubMed

Jadcherla, Sudarshan R

2017-02-01

Feeding, swallowing, and airway protection are three distinct entities. Feeding involves a process of sequential, neurosensory, and neuromotor interactions of reflexes and behaviors facilitating ingestion. Swallowing involves anterograde bolus movement during oral-, pharyngeal-, and esophageal phases of peristalsis into stomach. During these events, coordination with airway protection is vital for homeostasis in clearing any material away from airway vicinity. Neurological-airway-digestive inter-relationships are critical to the continuum of successful feeding patterns during infancy, either in health or disease. Neonatal feeding difficulties encompass a heterogeneous group of neurological, pulmonary, and aerodigestive disorders that present with multiple signs posing as clinical conundrums. Significant research breakthroughs permitted understanding of vagal neural pathways and functional aerodigestive connectivity involved in regulating swallowing and aerodigestive functions either directly or indirectly by influencing the supra-nuclear regulatory centers and peripheral effector organs. These neurosensory and neuromotor pathways are influenced by pathologies during perinatal events, prematurity, inflammatory states, and coexisting medical and surgical conditions. Approaches to clarify pathophysiologic mapping of aerodigestive interactions, as well as translating these discoveries into the development of personalized and simplified feeding strategies to advance child health are discussed in this review article.

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

PubMed Central

2012-01-01

Background Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services. Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. Methods/design This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. Trial registration The trial was registered with ClinicalTrials.gov, number NCT01484223 [ http://ClinicalTrials.gov]. PMID:22551252

Inducing amnesia through systemic suppression

PubMed Central

Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

2016-01-01

Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

[HIV in the lung from 1982 to 2013].

PubMed

Mayaud, C; Cadranel, J

2014-02-01

During the last 30 years pulmonary involvement has played a major role in the history of HIV infection. Initially, the unexplained occurrence of pneumocystis revealed the emergence of AIDS and the suspicion of its African origin. Before the era of triple therapy the natural history of AIDS was dominated by the occurrence of repeated lung infections and respiratory physicians were at the forefront of their diagnosis, treatment and prophylaxis. With the provision of antiretroviral therapy (ART), the natural history of AIDS has been transformed in those patients who benefit from it. In addition to paradoxical reactions observed following the introduction of ART, the pulmonologist is also facing a chronic stage of controlled HIV infection, and unexpected events, the incidence of which increases with time: pulmonary arterial hypertension and lung cancer certainly, COPD and fibrosis perhaps… but this story remains to be written. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Changes in the free-energy landscape of p38α MAP kinase through its canonical activation and binding events as studied by enhanced molecular dynamics simulations

PubMed Central

Kuzmanic, Antonija; Sutto, Ludovico; Saladino, Giorgio; Nebreda, Angel R; Gervasio, Francesco L; Orozco, Modesto

2017-01-01

p38α is a Ser/Thr protein kinase involved in a variety of cellular processes and pathological conditions, which makes it a promising pharmacological target. Although the activity of the enzyme is highly regulated, its molecular mechanism of activation remains largely unexplained, even after decades of research. By using state-of-the-art molecular dynamics simulations, we decipher the key elements of the complex molecular mechanism refined by evolution to allow for a fine tuning of p38α kinase activity. Our study describes for the first time the molecular effects of different regulators of the enzymatic activity, and provides an integrative picture of the activation mechanism that explains the seemingly contradictory X-ray and NMR data. DOI: http://dx.doi.org/10.7554/eLife.22175.001 PMID:28445123

Loss of RNA expression and allele-specific expression associated with congenital heart disease

PubMed Central

McKean, David M.; Homsy, Jason; Wakimoto, Hiroko; Patel, Neil; Gorham, Joshua; DePalma, Steven R.; Ware, James S.; Zaidi, Samir; Ma, Wenji; Patel, Nihir; Lifton, Richard P.; Chung, Wendy K.; Kim, Richard; Shen, Yufeng; Brueckner, Martina; Goldmuntz, Elizabeth; Sharp, Andrew J.; Seidman, Christine E.; Gelb, Bruce D.; Seidman, J. G.

2016-01-01

Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression. PMID:27670201

Algodystrophy: complex regional pain syndrome and incomplete forms

PubMed Central

Giannotti, Stefano; Bottai, Vanna; Dell’Osso, Giacomo; Bugelli, Giulia; Celli, Fabio; Cazzella, Niki; Guido, Giulio

2016-01-01

Summary The algodystrophy, also known as complex regional pain syndrome (CRPS), is a painful disease characterized by erythema, edema, functional impairment, sensory and vasomotor disturbance. The diagnosis of CRPS is based solely on clinical signs and symptoms, and for exclusion compared to other forms of chronic pain. There is not a specific diagnostic procedure; careful clinical evaluation and additional test should lead to an accurate diagnosis. There are similar forms of chronic pain known as bone marrow edema syndrome, in which is absent the history of trauma or triggering events and the skin dystrophic changes and vasomotor alterations. These incomplete forms are self-limited, and surgical treatment is generally not needed. It is still controversial, if these forms represent a distinct self-limiting entity or an incomplete variant of CRPS. In painful unexplained conditions such as frozen shoulder, post-operative stiff shoulder or painful knee prosthesis, the algodystrophy, especially in its incomplete forms, could represent the cause. PMID:27252736

Insertable cardiac monitors in the diagnosis of syncope and the detection of atrial fibrillation: A systematic review and meta-analysis.

PubMed

Burkowitz, Jörg; Merzenich, Carina; Grassme, Kathrin; Brüggenjürgen, Bernd

2016-08-01

Insertable or implantable cardiac monitors (ICMs) continuously monitor the heart rhythm and record irregularities over 3 years, enabling the diagnosis of infrequent rhythm abnormalities associated with syncope and stroke. The enhanced recognition capabilities of recent ICM models are able to accurately detect atrial fibrillation (AF) and have led to new applications of ICMs for the detection and monitoring of AF. Based on a systematic literature search, two indications were identified for ICMs for which considerable evidence, including randomized studies, exists: diagnosing the underlying cardiac cause of unexplained recurrent syncope and detecting AF in patients after cryptogenic stroke (CS). Three randomized controlled trials (RCTs) were identified that compared the effectiveness of ICMs in diagnosing patients with unexplained syncope (n = 556) to standard of care. A meta-analysis was conducted in order to generate an overall effect size and confidence interval of the diagnostic yield of ICMs versus conventional monitoring. In the indication CS, one RCT and five observational studies were included in order to assess the performance of ICMs in diagnosing patients with AF (n = 1129). Based on these studies, there is strong evidence that ICMs provide a higher diagnostic yield for detecting arrhythmias in patients with unexplained syncope and for detection of AF in patients after CS compared to conventional monitoring. Prolonged monitoring with ICMs is an effective tool for diagnosing the underlying cardiac cause of unexplained syncope and for detecting AF in patients with CS. In all RCTs, ICMs have a superior diagnostic yield compared to conventional monitoring. © The European Society of Cardiology 2016.

Frequency of and reasons for paroxysmal nocturnal haemoglobinuria screening in patients with unexplained anaemia.

PubMed

England, James T; Dalal, Bakul; Leitch, Heather A

2018-04-01

Referral to hematology for anemia is common. In paroxysmal nocturnal hemoglobinuria (PNH), cells deficient in the glycosylphosphatidyl inositol (GPI) anchor are lysed by complement. Eculizumab improves overall survival and quality of life while reducing hemolysis, transfusion requirements, and thrombosis. We evaluated the frequency of screening for PNH in patients with unexplained anemia. Key clinical features, laboratory data, and investigations were recorded for patients referred for anemia since 2010, without a specific cause found. PNH testing was done by flow cytometry. 540 patients had: anemia not yet diagnosed (NYD, n=318 (including unexplained iron deficiency, n=92; DAT-negative hemolysis, n=9)); anemia of chronic disease, n=173; and pancytopenia NYD, n=49. 82.4% had LDH testing done; 85.0% total bilirubin; 78.7% reticulocyte counts; and 40.6% haptoglobin level; 131 (24.2%) had possible hemolysis. PNH testing was done in 56 (10.4%). Those screened for PNH were more likely to have: younger age (P=0.04); a history of thrombosis (P<0.001); undergone a BMBx (P<0.001); received RBC transfusions (P=0.0018); or evidence of DAT-negative hemolysis (P<0.001). In summary, PNH was tested for in a minority of patients with unexplained anemia (10.4%) despite potential indicators of hemolysis in 24.2%. Increased screening could identify patients who would benefit from treatment and should be considered. © 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.

Projecting the potential impact of the Cap-Score™ on clinical pregnancy, live births, and medical costs in couples with unexplained infertility.

PubMed

Babigumira, Joseph B; Sharara, Fady I; Garrison, Louis P

2018-01-01

The Cap-Score™ was developed to assess the capacitation status of men, thereby enabling personalized management of unexplained infertility by choosing timed intrauterine insemination (IUI), versus immediate in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in individuals with a low Cap-Score™. The objective of this study was to estimate the differences in outcomes and costs comparing the use of the Cap-Score™ with timed IUI (CS-TI) and the standard of care (SOC), which was assumed to be three IUI cycles followed by three IVF-ICSI cycles. We developed and parameterized a decision-analytic model of management of unexplained infertility for women based on data from the published literature. We calculated the clinical pregnancy rates, live birth rates, and medical costs comparing CS-TI and SOC. We used Monte Carlo simulation to quantify uncertainty in projected estimates and performed univariate sensitivity analysis. Compared to SOC, CS-TI was projected to increase the pregnancy rate by 1-26%, marginally reduce live birth rates by 1-3% in couples with women below 40 years, increase live birth rates by 3-7% in couples with women over 40 years, reduce mean medical costs by $4000-$19,200, reduce IUI costs by $600-$1370, and reduce IVF costs by $3400-$17,800, depending on the woman's age. The Cap-Score™ is a potentially valuable clinical tool for management of unexplained infertility because it is projected to improve clinical pregnancy rates, save money, and, depending on the price of the test, increase access to treatment for infertility.

Un-explained visual loss following silicone oil removal: results of the Pan American Collaborative Retina Study (PACORES) Group.

PubMed

Roca, Jose A; Wu, Lihteh; Berrocal, Maria; Rodriguez, Francisco; Alezzandrini, Arturo; Alvira, Gustavo; Velez-Montoya, Raul; Quiroz-Mercado, Hugo; Fernando Arevalo, J; Serrano, Martín; Lima, Luiz H; Figueroa, Marta; Farah, Michel; Chico, Giovanna

2017-01-01

To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg ( p  < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months ( p  < 0.0001). An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration.

An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.

PubMed

Jalaly, Niloofar Y; Moran, Robert A; Fargahi, Farshid; Khashab, Mouen A; Kamal, Ayesha; Lennon, Anne Marie; Walsh, Christi; Makary, Martin A; Whitcomb, David C; Yadav, Dhiraj; Cebotaru, Liudmila; Singh, Vikesh K

2017-08-01

We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis. Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)<35 years of age; and (4) family history of pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants. Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis. Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

Do alterations in follicular fluid proteases contribute to human infertility?

PubMed

Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

2015-05-01

Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

Intracystic interferon-α treatment leads to neurotoxicity in craniopharyngioma: case report.

PubMed

Sharma, Julia; Bonfield, Christopher M; Singhal, Ash; Hukin, Juliette; Steinbok, Paul

2015-09-01

Craniopharyngioma is a benign, cystic suprasellar tumor that can be treated with intracystic chemotherapy. Interferon-α (IFN-α) has been gaining popularity as an intracystic treatment for craniopharyngioma because of its efficacy and supposed benign neurotoxicity profile. In this case report the authors describe a patient who, while receiving intracystic IFN-α, suffered a neurological event, which was believed to be related to drug leakage outside the cyst. This is the first report of a focal neurological deficit potentially attributable to intracystic IFN-α therapy, highlighting the fact that IFN-α may have neurotoxic effects on the central nervous system. Given this case and the results of a literature review, the authors suggest that a positive leak test is a relative contraindication to intracystic IFN-α treatment.

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury

PubMed Central

Duran, Latif; Kayhan, Servet; Kati, Celal; Akdemir, Hizir Ufuk; Balci, Kemal; Yavuz, Yucel

2014-01-01

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible. PMID:24701067

[History of scientific and popular educational films in neurology and psychiatry in Germany 1985-1929].

PubMed

Podoll, K

2000-11-01

Based on a survey of a variety of sources from medical and film history, an account is given of the history of scientific and popular educational films in neurology and psychiatry in Germany in the era of the silent film 1895-1929. A central event for the centralization of the production and distribution of medical scientific educational films was the foundation, in 1918, of the 'cultural department' of the Ufa film company which established, under the direction of the neurologist Curt Thomalla, a large medical film archive. Curt Thomalla was also the first who developed a dramatic type of popular educational film amalgamating medical and melodramatical features, thereby greatly increasing its mass impact, but also anticipating central elements of its later misuse by the Nazi film propaganda.

Utility of Continuous EEG Monitoring in Noncritically lll Hospitalized Patients.

PubMed

Billakota, Santoshi; Sinha, Saurabh R

2016-10-01

Continuous EEG (cEEG) monitoring is used in the intensive care unit (ICU) setting to detect seizures, especially nonconvulsive seizures and status epilepticus. The utility and impact of such monitoring in non-ICU patients are largely unknown. Hospitalized patients who were not in an ICU and underwent cEEG monitoring in the first half of 2011 and 2014 were identified. Reason for admission, admitting service (neurologic and nonneurologic), indication for cEEG, comorbid conditions, duration of recording, EEG findings, whether an event/seizure was recorded, and impact of EEG findings on management were reviewed. We evaluated the impact of the year of recording, admitting service, indication for cEEG, and neurologic comorbidity on the yield of recordings based on whether an event was captured and/or a change in antiepileptic drug management occurred. Two hundred forty-nine non-ICU patients had cEEG monitoring during these periods. The indication for cEEG was altered mental status (60.6%), observed seizures (26.5%), or observed spells (12.9%); 63.5% were on neuro-related services. The average duration of recording was 1.8 days. EEG findings included interictal epileptiform discharges (14.9%), periodic lateralized discharges (4%), and generalized periodic discharges (1.6%). Clinical events were recorded in 28.1% and seizures in 16.5%. The cEEG led to a change in antiepileptic drug management in 38.6% of patients. There was no impact of type of admitting service; there was no significant impact of indication for cEEG. In non-ICU patients, cEEG monitoring had a relatively high yield of event/seizures (similar to ICU) and impact on management. Temporal trends, admitting service, and indication for cEEG did not alter this.

A protozoal-associated epizootic impacting marine wildlife: Mass-mortality of southern sea otters (Enhydra lutris nereis) due to Sarcocystis neurona infection

USGS Publications Warehouse

Miller, M.A.; Conrad, P.A.; Harris, M.; Hatfield, B.; Langlois, G.; Jessup, David A.; Magargal, S.L.; Packham, A.E.; Toy-Choutka, S.; Melli, A.C.; Murray, M.A.; Gulland, F.M.; Grigg, M.E.

2010-01-01

During April 2004, 40 sick and dead southern sea otters (Enhydra lutris nereis) were recovered over 18 km of coastline near Morro Bay, California. This event represented the single largest monthly spike in mortality ever recorded during 30 years of southern sea otter stranding data collection. Because of the point-source nature of the event and clinical signs consistent with severe, acute neurological disease, exposure to a chemical or marine toxin was initially considered. However, detailed postmortem examinations revealed lesions consistent with an infectious etiology, and further investigation confirmed the protozoan parasite Sarcocystis neurona as the underlying cause. Tissues from 94% of examined otters were PCR-positive for S. neurona, based on DNA amplification and sequencing at the ITS-1 locus, and 100% of tested animals (n= 14) had elevated IgM and IgG titers to S. neurona. Evidence to support the point-source character of this event include the striking spatial and temporal clustering of cases and detection of high concentrations of anti- S. neurona IgM in serum of stranded animals. Concurrent exposure to the marine biotoxin domoic acid may have enhanced susceptibility of affected otters to S. neurona and exacerbated the neurological signs exhibited by stranded animals. Other factors that may have contributed to the severity of this epizootic include a large rainstorm that preceded the event and an abundance of razor clams near local beaches, attracting numerous otters close to shore within the affected area. This is the first report of a localized epizootic in marine wildlife caused by apicomplexan protozoa. ?? 2010 Elsevier B.V.

Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss.

PubMed

Murugappan, Gayathree; Ohno, Mika S; Lathi, Ruth B

2015-05-01

To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. Women with unexplained RPL. IVF/PGS with 24-chromosome screening and expectant management. Cost per live birth. The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Severe oligohydramnios with intact membranes: an indication for diagnostic amnioinfusion.

PubMed

Pryde, P G; Hallak, M; Lauria, M R; Littman, L; Bottoms, S F; Johnson, M P; Evans, M I

2000-01-01

To quantify the improvement in ultrasonographic fetal imaging following diagnostic amnioinfusion for the indication of unexplained midtrimester oligohydramnios. Patients referred for unexplained midtrimester oligohydramnios were retrospectively reviewed. Videotapes of those undergoing diagnostic antenatal amnioinfusion were analyzed for quality of visualization of routinely imaged structures before and after the infusion procedure. The overall rate of adequate visualization of fetal structures improved from 50.98 to 76.79% (p < 0.0001). In fetuses having preinfusion-identified obstructive uropathy, there was improvement in identification of associated anomalies from 11.8 to 31.3%. Several authors have suggested that diagnostic amnioinfusion can facilitate fetal imaging and increase diagnostic precision in the setting of unexplained severe oligohydramnios. We have quantified the improvement in the rate of optimal visualization of fetal structures which likely translates, in experienced hands, into this observed improved diagnostic precision. Of particular importance is the improvement in appreciation of associated anomalies in cases of obstructive uropathy in which such findings may determine whether or not invasive fetal therapy is indicated. Copyright 2000 S. Karger AG, Basel.

Patients' 'thingification', unexplained symptoms and response-ability in the clinical context: in response to 'Patients' substantialization of disease, the hybrid symptom and the metaphysical care', by Alexandra Parvan.

PubMed

Eriksen, Thor Eirik; Kirkengen, Anna Luise

2016-08-01

The types of diseases, or categories of suffering, referred to as medically unexplained symptoms or syndromes (MUS) are the focus for the following commentary. Such cases seem to invite reflection. The very nature of such complex patterns of disease and suffering raises a number of fundamental epistemological and ontological issues. Furthermore, such health challenges can serve as the basis for an exploration of how the suffering person as well as the medical caretaker comes to grip with disease, incapacitation or suffering. We have structured our comments into two parts: first, we will describe medically unexplained health problems as the background for an inquiry into a process wherein patients reify their suffering in order to meet their doctors on equal terms, which carries a potential for alienation. Second, we will reflect on Alexandra Parvan's text as regards patients' 'substantialization' of their disease, the resulting 'hybrid symptom' and a proposed model for care and healing. © 2015 John Wiley & Sons, Ltd.

An experiential mind-body approach to the management of medically unexplained symptoms.

PubMed

Bakal, D; Steiert, M; Coll, P; Schaefer, J

2006-01-01

This article outlines an experiential mind-body framework for understanding and treating patients with medically unexplained symptoms. The model relies on somatic awareness, a normal part of consciousness, to resolve the mind-body dualism inherent in conventional multidisciplinary approaches. Somatic awareness represents a guiding healing heuristic which allows for a linear treatment application of the biopsychosocial model. The heuristic acknowledges the validity of the patient's physical symptoms and identifies psychological and social factors needed for the healing process. Somatic awareness is used to direct changes in coping styles, illness beliefs, medication dependence and personal dynamics that are necessary to achieve symptom control. The mind-body concept is consistent with and supported by neurobiological models which draw on central nervous system mechanisms to explain medically unexplained symptoms. The concept is also supported by a recent hypothesis concerning the role peripheral connective tissue may play in influencing illness and well-being. Finally, somatic awareness is described as having potential to enhance understanding and conscious use of inner healing mechanisms at the basis of the placebo effect.

TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

PubMed

Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

2017-05-15

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety of veralipride for the treatment of vasomotor symptoms of menopause.

PubMed

Valencia, Marcelino Hernández; Arias, María de Jesús Vega; González, Cuauhtémoc Celis; Marín, Imelda Hernández; González, Juan Humberto Martín; Campos, Enrique Rafael Morcate; Rodríguez, María Antonia Basavilvazo; Álvarez, Ignacio Morales; Vargas, María Antonia Valdés; Flores, José Braulio Everardo Otero; Haro, Samuel Santoyo; Bonilla, Manuel Cortes; Escudero, Roberto Bernardo; Campero, Rosalba Alonso

2014-05-01

Veralipride is a nonhormonal option for the treatment of vasomotor symptoms of menopause. Incidence of adverse events in a Mexican population and drug compliance according to correct use were evaluated. We carried out a longitudinal, prospective, and analytical study in Mexican women who received veralipride to treat symptoms of menopause from 2011 to 2012. There were 386 treatment cycles; 272 were assigned to dosing schedule 1, which included 20 days of treatment with 10 days of suspension, and 114 were assigned to dosing schedule 2, which included 5 days of treatment and 2 days of suspension. A total of 57 adverse events were registered during the 386-month treatment. For the 20 × 10 dosing schedule, the highest incidence was observed for anxiety (2.2%), drowsiness, and weakness (1.5%); for the 5 × 2 dosing schedule, the highest incidence was observed for drowsiness (5.3%) and headache (2.6%). The Hamilton Depression Rating Scale was used to assess the presence and severity of depression; improvement was noted. The Unified Parkinson's Disease Rating Scale was used to assess neurological movement disorders; no adverse neurological events were detected. Based on the assessments of both women and physicians, the highest frequency was observed for "very satisfied" (45.5% and 52.3%, respectively), followed by "satisfied" (23.9% and 27.3%, respectively). Both dosing schedules show acceptable safety profiles for up to 6 months of use when used according to the contraindications in the current prescribing information for standard use (2012) and recent medical literature.

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

PubMed

Ye, Xiaoqin; Wei, Xu; Xie, Yanming; Zou, Yihuai; Zhao, Xingquan; Han, Jianhua; Wang, Xinzhi; Ma, Yunzhi; Bi, Qi; Xie, Qingfan; Zhao, Jianjun; Cao, Xiaolan; Chen, Hongxia; Wang, Shizhong; Yan, Rongmei; Han, Zucheng; Yi, Danhui; Wang, Yongyan

2011-10-01

To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

Prevalence of epilepsy and seizure disorders as causes of apparent life- threatening event (ALTE) in children admitted to a tertiary hospital.

PubMed

Anjos, Alessandra Marques dos; Nunes, Magda Lahorgue

2009-09-01

To determine the prevalence and describe clinical characteristics of seizure disorders and epilepsy as causes of apparent life- threatening event (ALTE) in children admitted at the emergency and followed in a tertiary hospital. Cross-sectional study with prospective data collection using specific guidelines to determine the etiology of ALTE. During the study, 30 (4.2%) children admitted to the hospital had a diagnosis of ALTE. There was a predominance of males (73%) and term infants (70%). Neonatal neurological disorders and neuropsychomotor development delay were found respectively in 13.4% and 10% of the cases. Etiological investigation revealed that 50% of the cases were idiopathic, and 13.4% were caused by epilepsy or seizure disorders. Although all patients had recurrent ALTE events, epilepsy had not been previously suspected. Epilepsy should be included in the differential diagnosis of ALTE, particularly when events are recurrent.

Cobalamin C Deficiency in an Adolescent With Altered Mental Status and Anorexia

PubMed Central

Bawcom, Amanda; Romano, Mary E.

2014-01-01

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient’s diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.1 PMID:25367534

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases.

PubMed

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-12-17

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1's actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases.

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

PubMed Central

Song, Chunzi; Sakurai, Masayuki; Shiromoto, Yusuke; Nishikura, Kazuko

2016-01-01

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases. PMID:27999332

Tick borne illness-Lyme disease.

PubMed

Bush, Larry M; Vazquez-Pertejo, Maria T

2018-05-01

Lyme disease is the most commonly reported tick-borneillness in the United States. Thecausative spirochete, Borrelia burgdorferi is transmitted by 4 species of Ixodes tick species. Over 90% of US cases occur in northeasternstates from Maine to Virginia, and in Wisconsin, Minnesota, and Michigan. Infection also takes place in northern California and Oregon. Lyme borreliosis is also diagnosed in parts of Europe, China, and Japan. The white-footed mouse is the primary animal reservoir for B. burgdorferi in the U.S. and the preferred host for nymphal and larval forms of the deer tick. Deer are hosts for the adult ticks but do not carry the spirochete. Signs and symptomsof infection occur in 3 stages; early localized, typified by erythema migrans; early disseminated with a flu-like syndrome, neurologic, and cardiac manifestations; and late, characteristically with arthritis. Although, the term 'Chronic Lyme Disease' has been assigned to many patients with a variety of unexplained symptoms, experts in the field question the validity of this diagnosis and warn against prolonged unproven antimicrobial therapies. Diagnosis relies upon clinical evaluation and is supported by serologic testing using a 2-step process which requires careful interpretation. Treatmentvaries with stage of disease, but normally includes doxycycline, amoxicillin,and ceftriaxone. Currently, no preventative vaccine is available. In some geographic areas, patients may be confected with Babesia, Ehrlichia, and Anaplasma since the same Ixodes ticks transmit these pathogens. Copyright © 2018 Mosby, Inc. All rights reserved.

AAN Epilepsy Quality Measures in clinical practice: a survey of neurologists.

PubMed

Wasade, Vibhangini S; Spanaki, Marianna; Iyengar, Revathi; Barkley, Gregory L; Schultz, Lonni

2012-08-01

Epilepsy Quality Measures (EQM) were developed by the American Academy of Neurology (AAN) to convey standardization and eliminate gaps and variations in the delivery of epilepsy care (Fountain et al., 2011 [1]). The aim of this study was to identify adherence to these measures and other emerging practice standards in epilepsy care. A 15-item survey was mailed to neurologists in Michigan, USA, inquiring about their practice patterns in relation to EQM. One hundred thirteen of the 792 surveyed Michigan Neurologists responded (14%). The majority (83% to 94%) addressed seizure type and frequency, reviewed EEG and MRI, and provided pregnancy counseling to women of childbearing potential. Our survey identified gaps in practice patterns such as counseling about antiepileptic drug (AED) side effects and knowledge about referral for surgical therapy of intractable epilepsy. Statistical significance in the responses on the AAN EQM was noted in relation to number of years in practice, number of epilepsy patients seen, and additional fellowship training in epilepsy. Practice patterns assessment in relation to other comorbidities revealed that although bone health and sudden unexplained death in epilepsy are addressed mainly in patients at risk, depression is infrequently discussed. The findings in this study indicate that additional educational efforts are needed to increase awareness and to improve quality of epilepsy care at various points of health care delivery. Copyright © 2012 Elsevier Inc. All rights reserved.

Response inhibition in motor conversion disorder.

PubMed

Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A; Hallett, Mark

2013-05-01

Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P < .001) compared with healthy volunteers, which remained significant after Bonferroni correction for multiple comparisons and after controlling for attention, sustained attention, depression, and anxiety. There were no significant differences in other cognitive measures. We highlight a specific deficit in motor response inhibition that may play a role in impaired inhibition of unwanted movement such as the excessive and aberrant movements seen in motor conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

Cobalamin C deficiency in an adolescent with altered mental status and anorexia.

PubMed

Rahmandar, Maria H; Bawcom, Amanda; Romano, Mary E; Hamid, Rizwan

2014-12-01

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient's diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.(1.) Copyright © 2014 by the American Academy of Pediatrics.

Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion combined with deep hypothermia circulatory arrest in aortic arch surgery: a meta-analysis and systematic review of 5060 patients.

PubMed

Hu, Zhipeng; Wang, Zhiwei; Ren, Zongli; Wu, Hongbing; Zhang, Min; Zhang, Hao; Hu, Xiaoping

2014-08-01

Our objective was to determine if antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP) combined with deep hypothermia circulatory arrest in aortic arch surgery results in different mortality and neurologic outcomes. The Cochrane Library, Medline, EMBASE, CINAHL, Web of Science, and the Chinese Biomedical Database were searched for studies reporting on postoperative strokes, permanent neurologic dysfunction, temporary neurologic dysfunction, and all causes mortality within 30 days postoperation in aortic arch surgery. Meta-analysis for effect size, t test, and I(2) for detecting heterogeneity and sensitivity analysis for assessing the relative influence of each study was performed. Fifteen included studies encompassed a total of 5060 patients of whom 2855 were treated with deep hypothermic circulatory arrest plus ACP and 1897 were treated with deep hypothermic circulatory arrest plus RCP. Pooled analysis showed no significant statistical difference (P > .01) of 30-day mortality, permanent neurologic dysfunction, and transient neurologic dysfunction in the 2 groups. Before sensitivity analysis, postoperative stroke incidence in the ACP group was higher than in the RCP group (7.2% vs 4.7%; P < .01). After a study that included a different percentage of patients with a history of central neurologic events in the 2 groups was ruled out, postoperative stroke incidence in the 2 groups also showed no significant statistical difference (P > .01). ACP and RCP provide similar cerebral protective effectiveness combined with deep hypothermia circulatory arrest and could be selected according to the actual condition in aortic arch surgery. A high-quality randomized controlled trial is urgently needed to confirm this conclusion, especially for stroke morbidity following ACP or RCP. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Outcomes of children admitted to intensive care after out-of-hospital cardiac arrest in Victoria, Australia.

PubMed

Forrest, Anri; Butt, Warwick W; Namachivayam, Siva P

2017-06-01

Paediatric out-of-hospital cardiac arrest (OHCA) is an uncommon event but is associated with high mortality and severe neurological sequelae among survivors. Most studies of paediatric OHCA are population-based, with very few reports on the cohort admitted to the paediatric intensive care unit (PICU). We sought to determine outcomes and predictors of neurologically intact survival in these children admitted to the PICU. Retrospective analysis of data prospectively collected from the PICU and emergency department (ED) databases and cross-checked with medical records and coronial reports for January 2005 to December 2014. Neurological outcome was assessed using the Paediatric Cerebral Performance Category scale. Survival with a favourable neurological outcome at hospital discharge. In the 10 years, 283 children presented with OHCA. After 16 study exclusions (because of cardiopulmonary resuscitation [CPR] duration < 1 min or age > 16 years), there were 121 children who died in the ED and 146 admitted to the PICU. Among the PICU cohort, hospital survival with favourable neurological outcome was 42% (60 of 143), and at 1 year after arrest it was 41% (59 of 143). The following factors were associated with the primary outcome: bystander CPR (odds ratio [OR], 4.74 [95% CI, 1.49-15.05]); cardiac aetiology (OR, 6.40 [95% CI, 1.65-24.76]); male sex (OR, 0.32 [95% CI, 0.12- 0.84]); and CPR duration: = 20 min v 0-5 min (OR, 0.05 [95% CI, 0.01-0.16]) and 6-20 min v 0-5 min (OR, 0.45 [95% CI, 0.16-1.28]). Bystander CPR and primary cardiac aetiology had strong associations with survival with a favourable neurological outcome after paediatric OHCA. Maximising CPR education for the community, and targeting people most likely to witness a paediatric OHCA may further improve outcomes.

Dielectric Spectroscopic Detection of Early Failures in 3-D Integrated Circuits.

PubMed

Obeng, Yaw; Okoro, C A; Ahn, Jung-Joon; You, Lin; Kopanski, Joseph J

The commercial introduction of three dimensional integrated circuits (3D-ICs) has been hindered by reliability challenges, such as stress related failures, resistivity changes, and unexplained early failures. In this paper, we discuss a new RF-based metrology, based on dielectric spectroscopy, for detecting and characterizing electrically active defects in fully integrated 3D devices. These defects are traceable to the chemistry of the insolation dielectrics used in the through silicon via (TSV) construction. We show that these defects may be responsible for some of the unexplained early reliability failures observed in TSV enabled 3D devices.

Implementation of Intraoperative Neurophysiological Monitoring during Endovascular Procedures in the Central Nervous System.

PubMed

Martinez Piñeiro, Alicia; Cubells, Carles; Garcia, Pablo; Castaño, Carlos; Dávalos, Antonio; Coll-Canti, Jaume

2015-03-01

Intraoperative monitoring (IOM) has been used in different surgical disciplines since the 1980s. Nonetheless, regular routine use of IOM in interventional neuroradiology units has only been reported in a few centers. The aim of this study is to report our experience, 1 year after deciding to implement standardized IOM during endovascular treatment of vascular abnormalities of the central nervous system. Basic recordings included somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs). Corticobulbar motor-evoked potentials and flash-visual-evoked potentials were also recorded depending on the topography of the lesion. Intra-arterial provocative tests (PTs) with amobarbital and lidocaine were also performed. All patients except 1 were under total intravenous anesthesia. Clinical outcome was assessed prospectively and correlated with IOM events. Twelve patients and 15 procedures were monitored during the inclusion period. Significant IOM events were detected during 3 of the 15 procedures (20%). We observed temporary MEP changes in 2 cases which resolved after interruption of the embolization or application of corrective measures, leaving no postoperative neurological deficits. In 1 case, persistent SEP and MEP deterioration was detected secondary to a frontal hematoma, resulting in mild sensory-motor deficit in the right upper extremity after the procedure. Overall, 12 PTs (4 spinal cord and 8 brain abnormalities) were performed using lidocaine and sodium amytal injections. One positive result occurred after the injection of lidocaine. No false negatives were detected. IOM may provide continuous real-time data about the functional status of eloquent areas and pathways of the central nervous system in patients under general anesthesia. It therefore allows us to detect early neurological damage in time to perform specific actions that may prevent irreversible neurological deficits.

The Perinatal Adverse events and Special Trends in Cognitive Trajectory (PLASTICITY) - pre-protocol for a prospective longitudinal follow-up cohort study

PubMed Central

Hokkanen, Laura

2013-01-01

Prospective follow-up studies on long term effects of pre- and perinatal adverse conditions in adulthood are rare. We will continue to follow the prospective cohort of initially 1196 subjects with predefined at-delivery risk factors out of 22,359 consecutive deliveries during 1971-74 at a single maternity hospital. The risk cohort and 93 controls have been followed up with a comprehensive clinical program at 5, 9, and 16 years of age and by questionnaire at the age of 30 years. Major medical events known to affect the development and growth of the brain, or cognitive functions and personality have been documented. Here we present a pre-protocol for the project, which we will call PLASTICITY, whose aim is to follow consenting subjects and controls into mid-adulthood and beyond, and to explore how the neonatal risk factors modulate neurodevelopmental and neurodegenerative processes such as learning disabilities, ADHD, aging, early onset mild cognitive impairment and even dementia. Our first focus is on the neurological and cognitive outcomes at age 40 years, using detailed neurological, neuropsychological, neuroimaging, genetic, blood chemistry and registry based methods. Results will be expected to offer information on the risk of neurological, psychiatric, metabolic and other medical consequences as well as the need for health and social services at the brink of middle age, when new degenerative phenomena are known to emerge. The evaluation at age 40 years will serve as a baseline for later aging studies. We welcome all comments and suggestions, which we will apply in finalizing details and inviting collaboration. PMID:24358867

Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies

PubMed Central

Farina, Marcelo; Rocha, João B. T.; Aschner, Michael

2011-01-01

Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle. PMID:21683713

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

PubMed

Burgess, Sarah; Abu-Laban, Riyad B; Slavik, Richard S; Vu, Erik N; Zed, Peter J

2016-04-01

To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. © The Author(s) 2016.

Survival and Neurologic Outcome After Out-of-hospital Cardiac Arrest. Results of the Andalusian Out-of-hospital Cardiopulmonary Arrest Registry.

PubMed

Rosell Ortiz, Fernando; Mellado Vergel, Francisco; López Messa, Juan Bautista; Fernández Valle, Patricia; Ruiz Montero, María M; Martínez Lara, Manuela; Vergara Pérez, Santiago; Vivar Díaz, Itziar; Caballero García, Auxiliadora; García Alcántara, Ángel; García Del Águila, Javier

2016-05-01

There is a paucity of data on prehospital cardiac arrest in Spain. Our aim was to describe the incidence, patient characteristics, and outcomes of out-of-hospital emergency care for this event. We conducted a retrospective analysis of a prospective registry of cardiopulmonary arrest handled by an out-of-hospital emergency service between January 2008 and December 2012. The registry included all patients considered to have a cardiac etiology as the cause of arrest, with a descriptive analysis performed of general patient characteristics and factors associated with good neurologic outcome at hospital discharge. A total of 4072 patients were included, with an estimated incidence of 14.6 events per 100000 inhabitants and year; 72.6% were men. The mean age was 62.0 ± 15.8 years, 58.6% of cases occurred in the home, 25% of patients had initial defibrillable rhythm, 28.8% of patients arrived with a pulse at the hospital (58.3% of the group with defibrillable rhythm), and 10.2% were discharged with good neurologic outcome. The variables associated with this recovery were: witnessed arrest (P=.04), arrest witnessed by emergency team (P=.005), previous life support (P=.04), initial defibrillable rhythm (P=.0001), and performance of a coronary interventional procedure (P=.0001). More than half the cases of sudden cardiac arrest occur at home, and the population was found to be relatively young. Although recovery was satisfactory in 1 out of every 10 patients, there is a need for improvement in the phase prior to emergency team arrival. Coronary interventional procedures had an impact on patient prognosis. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

PubMed

Halperin, John J; Kurlan, Roger; Schwalb, Jason M; Cusimano, Michael D; Gronseth, Gary; Gloss, David

2015-12-08

We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. We identified and classified relevant published studies according to 2004 and 2011 American Academy of Neurology methodology. Of 21 articles, we identified 3 Class I articles. Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI. Clinicians may choose to offer shunting for subjective iNPH symptoms and gait (Level C). Because of significant adverse event risk, risks and benefits should be carefully weighed (Level B). Clinicians should inform patients with iNPH with elevated Ro and their families that they have an increased chance of responding to shunting compared with those without such elevation (Level B). Clinicians may counsel patients with iNPH and their families that (1) positive response to external lumbar drainage or to repeated lumbar punctures increases the chance of response to shunting, and (2) increasing age does not decrease the chance of shunting being successful (both Level C). © 2015 American Academy of Neurology.

PD-1 checkpoint inhibition: Toxicities and management.

PubMed

Hahn, Andrew W; Gill, David M; Agarwal, Neeraj; Maughan, Benjamin L

2017-12-01

With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression patterns associated with neurological disease in human HIV infection

PubMed Central

Repunte-Canonigo, Vez; Masliah, Eliezer; Lefebvre, Celine

2017-01-01

The pathogenesis and nosology of HIV-associated neurological disease (HAND) remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI) in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE) and control subjects. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb). We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC), which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN), cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV infection and identify better therapeutic targets for NCI. PMID:28445538

Electrophysiological correlates of processing subject's own name.

PubMed

Li, Ran; Song, Weiqun; Du, Jubao; Huo, Su; Shan, Guixiang

2015-11-11

To understand the neurological mechanisms associated with the perception of subject's own name (SON) and provide a reference for assessing residual cognitive functions in patients with disorders of consciousness, event-related potentials were recorded in 16 healthy volunteers. Compared with event-related potentials elicited by tone stimuli, SON elicited larger MMN and P300. The amplitudes and latencies of MMN and P300 induced by subject's derived name (SDN) were similar to those induced by SON. Discriminating SON from SDN resulted in longer MMN and P300 latencies. These data showed that the SDN had similar quality as SON and might provide a useful reference for quantitatively evaluating disorders of consciousness.

Cortical localization of cognitive function by regression of performance on event-related potentials

NASA Technical Reports Server (NTRS)

Montgomery, R. W.; Montgomery, L. D.; Guisado, R.

1992-01-01

This paper demonstrates a new method of mapping cortical localization of cognitive function, using electroencephalographic data. Cross-subject regression analyses are used to identify cortical sites and post-stimulus latencies where there is a high correlation between subjects' performance and their cognitive event-related potential amplitude. The procedure was tested using a mental arithmetic task and was found to identify essentially the same cortical regions that have been associated with such tasks on the basis of research with patients suffering localized cortical lesions. Thus, it appears to offer an inexpensive, noninvasive tool for exploring the dynamics of localization in neurologically normal subjects.