Therapeutic Developments for Tics and Myoclonus.

PubMed

Jankovic, Joseph

2015-09-15

Tics and myoclonus are phenomenologically similar given that both are jerk-like movements, but, in contrast to myoclonus, tics are often preceded by premonitory sensations and are typically associated with a variety of behavioral comorbidities, including attention deficit and obsessive-compulsive disorder. There are many other clinical features that help differentiate these two hyperkinetic disorders. Whereas behavioral and antidopaminergic therapies are most effective in the management of tics, clonazepam, other anticonvulsants, and serotonergic drugs are often used to control myoclonic movements. Botulinum toxin may also be helpful in focal tics and in segmental forms of myoclonus. DBS plays an increasingly important role in the treatment of these disorders, particularly when they are generalized and are disabling despite optimal medical therapy. © 2015 International Parkinson and Movement Disorder Society.

Platysmal myoclonus in subclinical hyperthyroidism.

PubMed

Teoh, Hock-Luen; Lim, Erle Chuen-Hian

2005-08-01

Hyperthyroidism is associated with various movement disorders, such as chorea and tremors. We report on a young Chinese woman with an unusual presentation of myoclonus, involving both platysmal muscles, in association with subclinical hyperthyroidism. The myoclonus was preceded by symptoms of hyperthyroidism, namely weight loss, menstrual disturbances, and heat intolerance. The movements abated with clonazepam and hyperthyroidism was treated with carbimazole. The myoclonus recurred briefly when she stopped taking clonazepam, but she has since remained well and euthyroid. Copyright 2005 Movement Disorder Society

Jerky periods: myoclonus occurring solely during menses.

PubMed

Buijink, Arthur W G; Gelauff, Jeannette M; van der Salm, Sandra M A; Tijssen, Marina A J; van Rootselaar, Anne-Fleur

2013-01-01

In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus.

Familial Cortical Myoclonus with a Mutation in NOL3

PubMed Central

Russell, Jonathan F.; Steckley, Jamie L.; Coppola, Giovanni; Hahn, Angelika F.G.; Howard, MacKenzie A.; Kornberg, Zachary; Huang, Alden; Mirsattari, Seyed M.; Merriman, Barry; Klein, Eric; Choi, Murim; Lee, Hsien-Yang; Kirk, Andrew; Nelson-Williams, Carol; Gibson, Gillian; Baraban, Scott C.; Lifton, Richard P.; Geschwind, Daniel H.; Fu, Ying-Hui; Ptáček, Louis J.

2012-01-01

Objective Myoclonus is characterized by sudden, brief involuntary movements and its presence is debilitating. We identified a family suffering from adult-onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype. Methods A large, four-generation family with history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included SNP mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation. Results We identified 11 members of a Canadian Mennonite family suffering from adult-onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single co-segregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro. Interpretation We propose that Familial Cortical Myoclonus (FCM) is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders. PMID:22926851

Butorphanol pre-treatment prevents myoclonus induced by etomidate: a randomised, double-blind, controlled clinical trial.

PubMed

He, Liang; Ding, Ying; Chen, Huiyu; Qian, Yanning; Li, Zhong

2014-01-01

Myoclonic movements are common problems during induction of anaesthesia with etomidate. The myoclonus occurring after etomidate administration may represent a form of seizure. Agonistic modulation of the κ opiate receptor may reduce seizures, and butorphanol acts in such a manner. The aim of this randomised, double-blind, placebo-controlled clinical trial was to test our hypothesis that pre-treatment with butorphanol might reduce the incidence and severity of myoclonus induced by etomidate. Patients (108) with American Society of Anaesthesiologists physical status I or II were randomly assigned to one of two groups to receive either 0.015 mg/kg of butorphanol (n = 54) or saline (n = 54) intravenously. At two minutes after infusion of butorphanol or saline, 0.3 mg/kg etomidate was given. The occurrence and severity (observational score of 0-3) of myoclonus was assessed during 2 minutes after administration of etomidate. For each patient, blood pressure (BP), saturation of peripheral oxygen (SpO₂), and heart rate (HR) were measured. The incidence of myoclonus was significantly lower in Group Butorphanol than in Group Saline (13.0% vs 79.6%; RR = 0.163, 95%CI: 0.081-0.329; χ² = 48.265, p <0.0001). The severity levels of myoclonic movement were also significantly lower in Group Butorphanol than in Group Saline (p <0.0001). Throughout the procedure, changes of BP, SpO₂, and HR did not differ between the groups. There were no problems with bradycardia or hypotension. Infusion of 0.015 mg/kg butorphanol 2 minutes before etomidate administration is effective for suppressing myoclonus induced by etomidate during induction of general anaesthesia.

Piracetam in the treatment of cortical myoclonus.

PubMed

Genton, P; Guerrini, R; Remy, C

1999-03-01

This paper reviews existing publications on the use of piracetam for the treatment of cortical myoclonus of various etiologies and includes the personal experience of the authors in progressive myoclonus epilepsy. Two double-blind comparisons with placebo provided results which allow recommendations for the dosage and usage of piracetam in cortical myoclonus. Wide individual variation (7-24g daily) exists in dosage requirements but responses are dose-related so that dosage should be increased until an optimum effect is obtained. Tolerability after long-term use of piracetam in high dosage has been very good and without toxicity or serious adverse effects. Side effects have been occasional, mild and transient. The authors present their experience of 12 patients with progressive myoclonus epilepsy in whom the administration of up to 45 g piracetam daily, when added to existing anti-epileptic treatment, caused marked and sometimes spectacular improvement and was without significant adverse effects. Improvement was maintained for up to 7 years. The use of piracetam for disabling cortical myoclonus of any etiology, either as an addition to existing antimyoclonic drugs or as monotherapy, may bring about profound improvement in disability and quality of life. Piracetam should be considered a first-line drug for the treatment of cortical myoclonus.

Spinal myoclonus associated with vitamin B12 deficiency.

PubMed

Dogan, Ebru Apaydin; Yuruten, Betigul

2007-11-01

We report a 85-year-old female patient with involuntary and regular movements restricted to abdominal muscles, resembling belly dance, with additional clinical features; ataxia, impaired cognition, neuropathy and glossitis. We initially excluded the possible cortical and spinal structural abnormalities with magnetic resonance imagings and performed routine blood analysis which revealed that serum vitamin B12 (vB12) level was under normal ranges. The relation of low serum vB12 level and myoclonus is speculative and very few studies have demonstrated such patients. In this case report, serum vB12 deficiency is discussed in the context of its probable role in the generation of spinal myoclonus.

Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

PubMed

Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

2017-02-01

A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

Autosomal dominant cortical tremor, myoclonus and epilepsy.

PubMed

Striano, Pasquale; Zara, Federico

2016-09-01

The term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.

Left hemibody myoclonus due to anomalous right vertebral artery.

PubMed

Coelho, Miguel; Marti, Maria J; Valls-Solé, Josep; Pujol, Teresa; Tolosa, Eduardo

2005-01-01

A 43-year-old man presented with sporadic, sudden, brief, and involuntary jerks of his left limbs and trunk muscles. The electromyographic recordings showed short-lasting highly synchronized bursts, compatible with myoclonus limited to the left hemibody. Blink reflex, masseter silent period, cortical and spinal magnetic stimulation, somatosensory cortical evoked potentials, and electroencephalogram (EEG) were normal; the EEG back-averaging showed no spikes preceding the myoclonus. Magnetic resonance imaging and magnetic resonance angiography showed the presence of an anomalous nonectasic right vertebral artery compressing the right side of ventral medulla oblongata. We hypothesize that the aberrant right vertebral artery induced abnormal activation of descending motor tracts responsible for the myoclonus. (c) 2004 Movement Disorder Society.

Reflex reticular myoclonus: relationship to some brainstem pathophysiological mechanisms.

PubMed

Rektor, I; Kadanka, Z; Bednarik, J

1991-04-01

Two patients with reflex reticular myoclonus [RRM] were tested electrophysiologically and pharmacologically. In one of the cases the underlying disease was chronic Lyme borreliosis. In the other, the RRM attacks may have been associated with procarbazine therapy applied for Hodgkin's disease. No cortical lesion could be demonstrated either clinically or electrophysiologically [EEG, averaged EEg preceeding the jerks, SSEP]. An EMG analysis of the jerks revealed the shortest latency in the muscles innervated by the accessory nerve. The latencies became longer in a more rostral muscle [masseter], as well as in a more caudal one, the muscles innervated by the facial nerve were spared. it is presumed that the complete movement pattern of the myoclonus residues in the jerk generating structure. RRM in the described cases differs from the startle by sparing the facial nerve and from the Papio papio baboon non-epileptic myoclonus by the activating effect of physostigmine. A partial therapeutic effect was achieved with a serotonine precursor, but a GABAergic therapy proved to be the most effective.

Increased clinical anticipation with maternal transmission in benign adult familial myoclonus epilepsy in Japan.

PubMed

Hitomi, Takefumi; Kobayashi, Katsuya; Jingami, Naoto; Nakagawa, Tomokazu; Imamura, Hisaji; Matsumoto, Riki; Kondo, Takayuki; Chin, Kazuo; Takahashi, Ryosuke; Ikeda, Akio

2013-12-01

We recently reported clinical anticipation in Japanese families with benign adult familial myoclonus epilepsy (BAFME). However, it remains unknown whether clinical anticipation is predominantly associated with paternal or maternal transmission. We investigated the relationship between gender of the transmitting parent and clinical anticipation in nine BAFME families. Clinical anticipation regarding either cortical tremor or generalised seizures was observed in all 12 parent/child pairs (8 mother/child pairs and 4 father/child pairs). Moreover, a higher degree of clinical anticipation was associated with maternal transmission than with paternal transmission (p=0.03). Although a causative gene for BAFME still remains unknown, our finding suggests that BAFME and diseases with unstable expanding repeats, including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission.

Middle ear myoclonus associated with forced eyelid closure in children: diagnosis and treatment outcome.

PubMed

Lee, Guen-Ho; Bae, Seong-Cheon; Jin, Sang-Gyun; Park, Kyoung-Ho; Yeo, Sang-Won; Park, Shi-Nae

2012-09-01

Forceful eyelid closure syndrome (FECS) was first reported at the Proceedings of the Second International Tinnitus Seminar in 1983. The main symptom of this syndrome is a spontaneous muscular tinnitus related only to forced eye closure, specifically the voluntary contraction of the periorbital muscles. Although investigation of the syndrome was initiated >100 years ago, only four cases have been published in the past 20 years. We report six cases of middle ear myoclonus tinnitus diagnosed as FECS in children and discuss issues surrounding the diagnosis and treatment of this syndrome. Retrospective case series. From 2009 to 2011, six children complaining of clicking or crackling sounds in their ears presented at Seoul St. Mary's Hospital. Endoscopic examination and recording of the tympanic membrane were performed while the patients were asked to close their eyes forcefully. Audiologic studies including acoustic reflex decay and static compliance were performed for documentation of the movement of the tympanic membrane. Triggering factors of FECS in the children were carefully evaluated. Synchronous movement of the tympanic membrane in response to forced eye closure on endoscopic examination was the most reliable finding to diagnose FECS. Acoustic reflex decay and other impedance audiogram findings showed irregular perturbations during forced eye closure, which led to diagnosis of the tinnitus as middle ear myoclonus. Most of the patients had triggering factors for FECS. Reassurance and removal of the triggering or causal factors with or without medication improved clicking sounds coming from middle ear myoclonus. FECS is a rare clinical entity and can be easily missed in routine clinical examination. We suggest that patients, especially children, with clicking or crackling tinnitus should be evaluated for FECS using proper diagnostic tools. A possible mechanism of FECS in children postulated from our case review is suggested. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis.

PubMed

Ferlazzo, Edoardo; Striano, Pasquale; Italiano, Domenico; Calarese, Tiziana; Gasparini, Sara; Vanni, Nicola; Fruscione, Floriana; Genton, Pierre; Zara, Federico

2016-09-01

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans.

Symmetric corticobasal degeneration (S-CBD).

PubMed

Hassan, Anhar; Whitwell, Jennifer L; Boeve, Bradley F; Jack, Clifford R; Parisi, Joseph E; Dickson, Dennis W; Josephs, Keith A

2010-03-01

Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

PubMed

Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies.

PubMed

Hu, Lin-Yan; Shi, Xiu-Yu; Feng, Chen; Wang, Jian-Wen; Yang, Guan; Lammers, Stephen H T; Yang, Xiao Fan; Ebrahimi-Fakhari, Darius; Zou, Li-Ping

2015-03-01

To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. A combination of clinical characterization and follow-up, video EEG and laboratory investigations. We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review

PubMed Central

van den Ende, Tom; Sharifi, Sarvi; van der Salm, Sandra M. A.; van Rootselaar, Anne-Fleur

2018-01-01

Background Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings. Methods We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria. Results Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A “benign” phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity. Discussion Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes. PMID:29416935

Clinical identification of the simple sleep-related movement disorders.

PubMed

Walters, Arthur S

2007-04-01

Simple sleep-related movement disorders must be distinguished from daytime movement disorders that persist during sleep, sleep-related epilepsy, and parasomnias, which are generally characterized by activity that appears to be simultaneously complex, goal-directed, and purposeful but is outside the conscious awareness of the patient and, therefore, inappropriate. Once it is determined that the patient has a simple sleep-related movement disorder, the part of the body affected by the movement and the age of the patient give clues as to which sleep-related movement disorder is present. In some cases, all-night polysomnography with accompanying video may be necessary to make the diagnosis. Hypnic jerks (ie, sleep starts), bruxism, rhythmic movement disorder (ie, head banging/body rocking), and nocturnal leg cramps are discussed in addition to less well-appreciated disorders such as benign sleep myoclonus of infancy, excessive fragmentary myoclonus, and hypnagogic foot tremor/alternating leg muscle activation.

The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias.

PubMed

Popa, Traian; Milani, Paolo; Richard, Aliénor; Hubsch, Cécile; Brochard, Vanessa; Tranchant, Christine; Sadnicka, Anna; Rothwell, John; Vidailhet, Marie; Meunier, Sabine; Roze, Emmanuel

2014-05-01

Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown. To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias. We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale. Myoclonus-dystonia with a proven SGCE mutation. We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores. We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC. Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.

[Whole-body magnetic resonance imaging in a patient with an occult abdominal neuroblastoma and opsoclonus-myoclonus syndrome].

PubMed

Miras Azcón, F; Culiañez Casas, M; Pastor Pons, E

2014-01-01

Opsoclonus-myoclonus syndrome is a rare neurological disorder. In children, the etiology varies, although it is a paraneoplastic manifestation (mainly of neuroblastoma) in 40% to 80% of cases. Whole-body MRI promises to be a powerful tool in the search for a possible primary tumor in this condition for which the diagnostic algorithm is yet to be established. We present the case of a two-year-old boy with signs of opsoclonus-myoclonus syndrome in whom a retroperitoneal neuroblastoma was detected by whole-body MRI. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

PubMed

Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

Dancing Eye Syndrome associated with spontaneous recovery and normal neurodevelopment.

PubMed

Ki Pang, K; Lynch, Bryan J; Osborne, John P; Pike, Michael G

2010-03-01

Five patients with spontaneously recovering Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome are described. Age at presentation ranged from 4 to 19 months. Four had symptoms of fever and a coryzal illness within days to a few weeks prior to the onset. One of the 4 also had varicella zoster 4 weeks before presentation. All had opsoclonus, myoclonus/ataxia and irritability. Associated infective agents identified were Coxsackie virus and rotavirus. Spontaneous improvement of symptoms started within 9 days of presentation and total duration of illness ranged from 10 to 24 days. Developmental progress at follow-up was normal in all cases. A range of immunomodulatory therapies have been advocated for the treatment of Dancing Eye Syndrome/Opsoclonus Myoclonus Syndrome. However, in some children, early spontaneous recovery may occur, an observation which should be borne in mind when designing therapeutic trials in this condition. 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

PubMed Central

Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus.

PubMed Central

Hallett, M; Chadwick, D; Adam, J; Marsden, C D

1977-01-01

A patient with post-hypoxic myoclonus, sensitive to therapy with 5-hydroxytryptophan and clonazepam, was subjected to detailed electrophysiological investigation. Brief generalised jerks followed the critical stimulus of muscle stretch. The electroencephalogram showed generalised spikes that were associated with, but not time locked to, the myoclonus. The cranial nerve nuclei were activated upward. Analysis of the findings suggests that the mechanism of the myoclonus is hyperactivity of a reflex mediated in the reticular formation of the medulla oblongata. PMID:301926

Myoclonus

MedlinePlus

... people experience while drifting off to sleep. These simple forms of myoclonus occur in normal, healthy persons ... people experience while drifting off to sleep. These simple forms of myoclonus occur in normal, healthy persons ...

Palatal myoclonus

MedlinePlus

... Updated by: Sumana Jothi MD, specialist in laryngology, Assistant Clinical Professor, UCSF Otolaryngology, NCHCS VA, SFVA, San Francisco, CA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, ...

Transcranial magnetic stimulation in myoclonus of different aetiologies.

PubMed

Nardone, Raffaele; Versace, Viviana; Höller, Yvonne; Sebastianelli, Luca; Brigo, Francesco; Lochner, Piergiorgio; Golaszewski, Stefan; Saltuari, Leopold; Trinka, Eugen

2018-05-24

Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of myoclonus. Moreover, repetitive TMS (rTMS) can influence neural activity. In this review we performed a systematic search of all studies using TMS in order to explore cortical excitability/plasticity and rTMS for the treatment of myoclonus due to different aetiologies. We identified and reviewed 40 articles matching the inclusion criteria; 415 patients were included in these studies. The reviewed TMS studies have detected abnormalities in motor cortex excitability and sensorimotor plasticity. The most consistent finding is a decrease in intracortical inhibition. Short-interval intracortical inhibition (SICI) is reduced in myoclonic epilepsies. Unlike the juvenile and the benign myoclonus epilepsy, long-interval intracortical inhibition, interhemispheric inhibition and sensorimotor integration were altered in patients with progressive myoclonic epilepsies. In patients with myoclonus-dystonia the results are partly conflicting. Cortical membrane excitability was impaired while parameters assessing cortical synaptic activity were normal in DYT11 gene carriers. In other studies normal SICI suggests that the GABAergic cortical circuits are largely intact and that the mechanisms of myoclonus-dystonia are different from those for cortical myoclonus and other dystonic disorders. In conclusion, different TMS study protocols have provided new insights into sensorimotor plasticity and cortical excitability of the different forms of myoclonus, and have shed some light on the pathophysiology of this movement disorder. Well-defined motor cortical excitability patterns can be identified in the different disorders characterized by myoclonus, even if preliminary findings should be confirmed in future studies in larger cohorts of patients. Repetitive TMS might have therapeutic potential at least in some patients with myoclonus, similar to that reported in other neurological and psychiatric disorders. Copyright © 2018. Published by Elsevier Inc.

[Adult-onset opsoclonus-myoclonus-ataxia syndrome revealing rubella meningoencephalitis].

PubMed

Nasri, A; Mansour, M; Messelmani, M; Riahi, A; Derbali, H; Bedoui, I; Zaouali, J; Mrissa, R

2016-12-01

Opsoclonus-myoclonus-ataxia (OMS) is a rare clinical syndrome, of paraneoplastic infectious, post-infectious, post-vaccinal or idiopathic origin. We report a 24-year-old young man who presented with gait disorder preceded by a febrile rash and retroauricular lymph nodes. Three days before admission, he had headache, vertigo, nausea and vomiting followed by gait unsteadiness and movement disorders of limbs and eyes. On examination, he had OMS syndrome. Brain MRI, total body scan, MIBG scintigraphy, tumor markers and onconeural antibodies were normal. Cerebro-spinal fluid (CSF) analysis showed lymphocytic meningitis. Positive serum and CSF immunoglobulin M antibody against rubella virus was demonstrated. He received acyclovir with full recovery within two weeks. We discuss the peculiarities of this association with a literature review. This observation enlarges the spectrum of neurological manifestations of rubella as well as that of OMS etiologies. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

[Myoclonus epilepsy with ragged-red fibers: a case report and literature review].

PubMed

Zhao, Man-man; Zhang, Yao; Bao, Xin-hua

2015-12-18

To demonstrate the clinical manifestation, diagnosis and treatment of myoclonus epilepsy with ragged-red-fibers (MERRF), a case of MERRF was presented with review of the literature. A 4-year-7-month-old girl was diagnosed with MERRF. She had tremor, fatigue and developmental delay for more than 2 years. Laboratory tests showed that the serum and urine lactic acid and pyruvic acid increased significantly. Electroencephalogram showed diffuse and focal spike slow wave and slow wave in right central and parietal regions. Electromyogram showed neurological damage. Gene mutational analysis showed mtDNA 8344 A>G mutation. The mutational rate was 78%. Mitochondrial disease MERRF syndrome was diagnosed. Cocktails therapy with vitamins B1, B6, B12, L-carnitine, and coenzyme Q10 was administrated to the patient. MERRF is a rare disease. The diagnosis can be made by gene mutational analysis. Cocktail therapy may slow down the deterioration of the disease. Gene therapy is still experimental.

SGCE mutations cause psychiatric disorders: clinical and genetic characterization

PubMed Central

Peall, Kathryn J.; Smith, Daniel J.; Kurian, Manju A.; Wardle, Mark; Waite, Adrian J.; Hedderly, Tammy; Lin, Jean-Pierre; Smith, Martin; Whone, Alan; Pall, Hardev; White, Cathy; Lux, Andrew; Jardine, Philip; Bajaj, Narinder; Lynch, Bryan; Kirov, George; O’Riordan, Sean; Samuel, Michael; Lynch, Timothy; King, Mary D.; Chinnery, Patrick F.; Warner, Thomas T.; Blake, Derek J.; Owen, Michael J.; Morris, Huw R.

2014-01-01

Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive–compulsive disorder was eight times more likely (P < 0.001) in mutation positive cases, compulsivity being the predominant feature (P < 0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms. PMID:23365103

Opsoclonus Myoclonus

MedlinePlus

... Strategy Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ... Diversity Resources Jobs at NINDS Director, Division of Neuroscience Director, NIH BRAIN Initiative® Health Scientist Administrator Channels ...

[Parasomnias].

PubMed

Bassetti, C; Hess, C W

1993-10-01

Parasomnias are frequent. They usually represent either the exaggeration of a physiological phenomenon (e.g. sleep starts) or a non-disturbing, idiopathic and usually benign sleep disorder (e.g. sleep talking and bruxism), which need only counseling and improvement of sleep hygiene. However, occasionally parasomnias are of clinical relevance. They can cause insomnia or hypersomnia (e.g. 'myoclonus nocturnus'), psychosocial stress (e.g. sleep-related enuresis and sleep walking) and injuries to oneself and others (e.g. REM-parasomnia). Finally, they can be symptomatic of neurological and medical disorders (e.g. sleep paralysis and 'myoclonus nocturnus'). In these cases special investigations including video-polysomnography can establish a correct diagnosis and allow a specific treatment.

MERRF/MELAS overlap syndrome due to the m.3291T>C mutation.

PubMed

Liu, Kaiming; Zhao, Hui; Ji, Kunqian; Yan, Chuanzhu

2014-03-01

We report the case of a 19-year-old Chinese female harboring the m.3291T>C mutation in the MT-TL1 gene encoding the mitochondrial transfer RNA for leucine. She presented with a complex phenotype characterized by progressive cerebellar ataxia, frequent myoclonus seizures, recurrent stroke-like episodes, migraine-like headaches with nausea and vomiting, and elevated resting lactate blood level. It is known that the myoclonus epilepsy with ragged-red fibers (MERRF) is characterized by cerebellar ataxia and myoclonus epilepsy, while that the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by recurrent stroke-like episodes, migraine-like headaches, and elevated resting lactate blood level. So the patient's clinical manifestations suggest the presence of a MERRF/MELAS overlap syndrome. Muscle biopsy of the patient showed the presence of numerous scattered ragged-red fibers, some cytochrome c oxidase-deficient fibers, and several strongly succinate dehygrogenase-reactive vessels, suggestive of a mitochondrial disorder. Direct sequencing of the complete mitochondrial genome of the proband revealed no mutations other than the T-to-C transition at nucleotide position 3291. Restriction fragment length polymorphism analysis of the proband and her family revealed maternal inheritance of the mutation in a heteroplasmic manner. The analysis of aerobic respiration and glycolysis demonstrated that the fibroblasts from the patient had mitochondrial dysfunction. Our results suggest that the m.3291T>C is pathogenic. This study is the first to describe the m.3291T>C mutation in association with the MERRF/MELAS overlap syndrome.

More Than Ataxia: Hyperkinetic Movement Disorders in Childhood Autosomal Recessive Ataxia Syndromes.

PubMed

Pearson, Toni S

2016-01-01

The autosomal recessive ataxias are a heterogeneous group of disorders that are characterized by complex neurological features in addition to progressive ataxia. Hyperkinetic movement disorders occur in a significant proportion of patients, and may sometimes be the presenting motor symptom. Presentations with involuntary movements rather than ataxia are diagnostically challenging, and are likely under-recognized. A PubMed literature search was performed in October 2015 utilizing pairwise combinations of disease-related terms (autosomal recessive ataxia, ataxia-telangiectasia, ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia type 2 (AOA2), Friedreich ataxia, ataxia with vitamin E deficiency), and symptom-related terms (movement disorder, dystonia, chorea, choreoathetosis, myoclonus). Involuntary movements occur in the majority of patients with ataxia-telangiectasia and AOA1, and less frequently in patients with AOA2, Friedreich ataxia, and ataxia with vitamin E deficiency. Clinical presentations with an isolated hyperkinetic movement disorder in the absence of ataxia include dystonia or dystonia with myoclonus with predominant upper limb and cervical involvement (ataxia-telangiectasia, ataxia with vitamin E deficiency), and generalized chorea (ataxia with oculomotor apraxia type 1, ataxia-telangiectasia). An awareness of atypical presentations facilitates early and accurate diagnosis in these challenging cases. Recognition of involuntary movements is important not only for diagnosis, but also because of the potential for effective targeted symptomatic treatment.

Reduced striatal D2 receptor binding in myoclonus-dystonia.

PubMed

Beukers, R J; Booij, J; Weisscher, N; Zijlstra, F; van Amelsvoort, T A M J; Tijssen, M A J

2009-02-01

To study striatal dopamine D(2) receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D(2) receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

Severe pruritus and myoclonus following intrathecal morphine administration in a dog

PubMed Central

Iff, Isabelle; Valeskini, Karin; Mosing, Martina

2012-01-01

During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated. PMID:23450863

Three cases of Creutzfeldt-Jakob disease with prion protein gene codon180 mutation presenting with pathological laughing and crying.

PubMed

Iwasaki, Yasushi

2012-08-15

Although there are no reports of pathological laughing and crying being observed in patients with Creutzfeldt-Jakob disease (CJD), the author experienced three patients with CJD with prion protein gene codon180 mutation (V180I CJD) who showed this characteristic clinical finding. This finding was observed from the early disease stage in all 3 patients and continued for several months. Startle reaction was also remarkable in all patients, although myoclonus was generally mild. The dissociation between the startle reaction and myoclonus was suspected to be another feature of V180I CJD. The pathological laughing and crying co-occured with the startle reaction and stopped right before the onset of akinetic mutism, and the degree of both symptoms was almost parallel during this period. On the basis of MRI and autopsy findings, pathological laughing and crying was suspected of being induced by the widespread cerebral cortical involvement that is characteristic of V180I CJD. From the present observations, the author speculated that pathological laughing and crying may be a comparatively frequent observation in V180I CJD patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.

PubMed

Walker, Melissa A; Mohler, Kyle P; Hopkins, Kyle W; Oakley, Derek H; Sweetser, David A; Ibba, Michael; Frosch, Matthew P; Thibert, Ronald L

2016-08-01

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins. © The Author(s) 2016.

The proper effect site concentration of remifentanil for prevention of myoclonus after etomidate injection

PubMed Central

Ri, Hyun Su; Kim, Tae Kyun; Baik, Seung Wan; Yoon, Ji Uk; Byeon, Gyeong Jo

2011-01-01

Background Etomidate frequently induces myoclonus when administered intravenously with bolus injection during anesthetic induction. This can be bothersome for the anesthesiologist. The dose of remifentanil appropriate for preventing myoclonus without side effects was investigated. Methods All patients with American Society of Anesthesiologists (ASA) physical status I-III were divided into three groups (n = 33 per group) according to the pretreatment effect site concentration of remifentanil (Ultiva, Glaxo-Wellcome, München, Germany) of 0, 2 or 4 ng/ml (Group N: 0 ng/ml, Group R: 2 ng/ml, Group Q: 4 ng/ml) by a target controlled infusion (TCI) system. After a 0.3 mg/kg dose of etomidate was injected intravenously for over 1 minute for anesthetic induction, myoclonus was observed. Before the etomidate injection, the patients were pretreated with remifentanil and their side effects were monitored. Results The number of patients showing myoclonus was significantly different among the groups. The incidence of myoclonus was 81%, 12% and 0% (groups N, R, and Q, respectively, P < 0.01). Side effects including bradycardia and hypotension did not occur in either Group R or Q. Chest wall rigidity occured in 45% of patients in Group Q. Conclusions Administration with a 2 ng/ml effect site concentration of remifentanil could reduce the incidence of myoclonus caused by etomidate bolus injection without chest wall rigidity. PMID:21927682

Neuroblastoma-associated paraneoplastic syndrome with anti-Hu antineuronal antibodies presenting at the time of recurrence.

PubMed

Mpofu, C; Sztriha, L; Revesz, T

1996-01-01

A 27-month-old girl presented with chest pain. Further evaluation confirmed posterior mediastinal neuroblastoma with bone marrow infiltration, which was treated with a combination of chemotherapy and surgery. Four months after completing treatment, she presented with myoclonus and weakness of her right arm. The myoclonus eventually subsided but her right arm weakness progressed to a right hemiplegia. High titers of antineuronal nuclear antibodies identified as anti-Hu were found in both serum and cerebrospinal fluid. One month later she presented with a relapse of her original tumor, from which she died. Identification of anti-Hu antineuronal nuclear antibodies in this neuroblastoma-associated paraneoplastic syndrome supports the hypothesis that the syndrome is due to autoimmune disease.

Ultrasound as Diagnostic Tool for Diaphragmatic Myoclonus

PubMed Central

Llaneza Ramos, Vesper Fe Marie; Considine, Elaine; Karp, Barbara I.; Lungu, Codrin; Alter, Katharine; Hallett, Mark

2015-01-01

Background Diaphragmatic myoclonus is a rare disorder of repetitive diaphragmatic contractions, acknowledged to be a spectrum that includes psychogenic features. Electromyography has been the diagnostic tool most commonly used in the literature. Methods To test if we could perform a noninvasive technique to delineate the diaphragm as the source of abnormal movements and demonstrate distractibility and entrainability, we used B-mode ultrasound in a patient with diaphragmatic myoclonus. Results Ultrasound imaging clearly delineated the diaphragm as the source of her abdominal movements. We were able to demonstrate entrainability of the diaphragm to hand tapping to a prescribed rhythm set by examiner. Conclusion We recommend the use of ultrasound as a noninvasive, convenient diagnostic tool for further studies of diaphragmatic myoclonus. We agree with previous findings that diaphragmatic myoclonus may be a functional movement disorder, as evidenced by distractibility and entrainability demonstrated on real-time video with ultrasonography. PMID:27430001

A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection.

PubMed

Hwang, J-Y; Kim, J-H; Oh, A-Y; Do, S-H; Jeon, Y-T; Han, S-H

2008-01-01

Etomidate is a popular anaesthetic induction agent, but it frequently causes myoclonic movements. Although both benzodiazepines and opioids reduce myoclonus, there has been no comparative study between these agents. Thus, we conducted a prospective, randomized study to compare midazolam and remifentanil as pre-treatment agents for reducing etomidate-induced myoclonus in 90 adults undergoing surgery. Patients were pre-treated before the etomidate injection, either with saline (Group C), midazolam 0.5 mg/kg (Group M) or remifentanil 1 microg/kg (Group R). Both Groups M and R showed a significantly lower incidence of myoclonus compared with Group C (17%, 17% and 77%, respectively). The incidence of myoclonus was not significantly different between Groups M and R, but 10% (n = 10) of the patients in Group R experienced remifentanil-related side-effects. We conclude that midazolam is probably a better choice than remifentanil for reducing etomidate-induced myoclonus during anaesthesia induction.

Creutzfeldt-Jakob Disease Presenting With Dizziness and Gaze-Evoked Nystagmus: A Case Report.

PubMed

Choi, Yun-Ju; Kang, Kyung-Wook; Lee, Sae-Young; Kang, Seung-Ho; Lee, Seung-Han; Kim, Byeong C

2016-02-01

Sporadic Creutzfeldt-Jakob disease (CJD) is clinically characterized by rapidly progressive dementia combined with other cardinal symptoms, such as myoclonus, visual or cerebellar disturbances, extrapyramidal or pyramidal disturbance, and akinetic mutism. However, as an initial manifestation, focal neurologic deficits other than the aforementioned or nonspecific generalized symptoms may lead to a misdiagnosis or a delayed diagnosis. The authors report a case of 66-year-old male patient with sporadic CJD who had dizziness, gaze-evoked nystagmus (GEN), and other central eye signs (impaired smooth pursuit, saccadic dysmetria) as an initial manifestation without dementia. The central eye signs led us to perform brain magnetic resonance images, which showed abnormal cortical high-signal intensity in both the cerebral and cerebellar hemispheres including the vestibulocerebellum. We reached a presumptive diagnosis of CJD, but the findings did not meet diagnostic criteria for probable CJD at that time. Three weeks after the initial work-ups, the patient presented with typical neurological findings of CJD: rapidly progressive dementia, akinetic mutism, and myoclonus of the left arm. Cerebrospinal fluid was positive for 14-3-3 protein, and electroencephalography showed periodic sharp wave complexes. In this patient, GEN and other central eye signs provided diagnostic clues for CJD. These unusual neurological manifestations may help physicians have a thorough knowledge of early deficits of CJD.

Simultaneous recording of EEG and electromyographic polygraphy increases the diagnostic yield of video-EEG monitoring.

PubMed

Hill, Aron T; Briggs, Belinda A; Seneviratne, Udaya

2014-06-01

To investigate the usefulness of adjunctive electromyographic (EMG) polygraphy in the diagnosis of clinical events captured during long-term video-EEG monitoring. A total of 40 patients (21 women, 19 men) aged between 19 and 72 years (mean 43) investigated using video-EEG monitoring were studied. Electromyographic activity was simultaneously recorded with EEG in four patients selected on clinical grounds. In these patients, surface EMG electrodes were placed over muscles suspected to be activated during a typical clinical event. Of the 40 patients investigated, 24 (60%) were given a diagnosis, whereas 16 (40%) remained undiagnosed. All four patients receiving adjunctive EMG polygraphy obtained a diagnosis, with three of these diagnoses being exclusively reliant on the EMG recordings. Specifically, one patient was diagnosed with propriospinal myoclonus, another patient was diagnosed with facio-mandibular myoclonus, and a third patient was found to have bruxism and periodic leg movements of sleep. The information obtained from surface EMG recordings aided the diagnosis of clinical events captured during video-EEG monitoring in 7.5% of the total cohort. This study suggests that EEG-EMG polygraphy may be used as a technique of improving the diagnostic yield of video-EEG monitoring in selected cases.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

PubMed

Lee, Kyung Yeon; Yeh, Hye-Ryun

2015-02-01

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm. Georg Thieme Verlag KG Stuttgart · New York.

The Phenotypic Spectrum of DYT24 Due to ANO3 Mutations

PubMed Central

Stamelou, Maria; Charlesworth, Gavin; Cordivari, Carla; Schneider, Susanne A; Kägi, Georg; Sheerin, Una-Marie; Rubio-Agusti, Ignacio; Batla, Amit; Houlden, Henry; Wood, Nicholas W; Bhatia, Kailash P

2014-01-01

Genes causing primary dystonia are rare. Recently, pathogenic mutations in the anoctamin 3 gene (ANO3) have been identified to cause autosomal dominant craniocervical dystonia and have been assigned to the dystonia locus dystonia-24 (DYT24). Here, we expand on the phenotypic spectrum of DYT24 and provide demonstrative videos. Moreover, tremor recordings were performed, and back-averaged electroencephalography, sensory evoked potentials, and C-reflex studies were carried out in two individuals who carried two different mutations in ANO3. Ten patients from three families are described. The age at onset ranged from early childhood to the forties. Cervical dystonia was the most common site of onset followed by laryngeal dystonia. The characteristic feature in all affected individuals was the presence of tremor, which contrasts DYT24 from the typical DYT6 phenotype. Tremor was the sole initial manifestation in some individuals with ANO3 mutations, leading to misdiagnosis as essential tremor. Electrophysiology in two patients with two different mutations showed co-contraction of antagonist muscles, confirming dystonia, and a 6-Hz arm tremor at rest, which increased in amplitude during action. In one of the studied patients, clinically superimposed myoclonus was observed. The duration of the myoclonus was in the range of 250 msec at about 3 Hz, which is more consistent with subcortical myoclonus. In summary, ANO3 causes a varied phenotype of young-onset or adult-onset craniocervical dystonia with tremor and/or myoclonic jerks. Patients with familial cervical dystonia who also have myoclonus-dystonia as well as patients with prominent tremor and mild dystonia should be tested for ANO3 mutations. © 2014 The Authors. Movement Disorders published by International Parkinson and Movement Disorder Society PMID:24442708

Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis and pseudotumour cerebri

PubMed Central

Panda, Akhila Kumar; Mehta, Vachan Jayant; Maheshwari, Siddharth; Kar, Sujit Kumar

2013-01-01

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive encephalitis of childhood and young adults due to persistent measles virus infection. The usual age of onset is between 5 and 15 years. There are wide varieties of presentations of SSPE described in the literatures. Variable clinical presentations may lead to diagnostic dilemma and unnecessary investigations especially in developing countries, where the measles is quite endemic and vaccination status is not up to the mark because of poor literacy and socioeconomic status. Good clinical correlations, neuroimaging findings, EEG and cerebrospinal fluid (CSF) marker for SSPE yield the clue to diagnosis. This case illustrates a 13-year-old boy presented with short history of intellectual decline, headache, papilloedema, cranial nerve palsy, myoclonus with suggestive neuroimaging mimicking acute disseminated encephalomyelitis (ADEM) and pseudotumour cerebri. Subsequently he was diagnosed to be a case of SSPE on the basis of CSF and serum measles antibody titer. PMID:23964034

Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis and pseudotumour cerebri.

PubMed

Panda, Akhila Kumar; Mehta, Vachan Jayant; Maheshwari, Siddharth; Kar, Sujit Kumar

2013-08-20

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive encephalitis of childhood and young adults due to persistent measles virus infection. The usual age of onset is between 5 and 15 years. There are wide varieties of presentations of SSPE described in the literatures. Variable clinical presentations may lead to diagnostic dilemma and unnecessary investigations especially in developing countries, where the measles is quite endemic and vaccination status is not up to the mark because of poor literacy and socioeconomic status. Good clinical correlations, neuroimaging findings, EEG and cerebrospinal fluid (CSF) marker for SSPE yield the clue to diagnosis. This case illustrates a 13-year-old boy presented with short history of intellectual decline, headache, papilloedema, cranial nerve palsy, myoclonus with suggestive neuroimaging mimicking acute disseminated encephalomyelitis (ADEM) and pseudotumour cerebri. Subsequently he was diagnosed to be a case of SSPE on the basis of CSF and serum measles antibody titer.

Case vignettes of movement disorders.

PubMed

Yung, C Y

1983-08-01

This paper reports five movement disorders cases to serve as a basis for discussion of the problems encountered in the clinical management of these cases, and the pathophysiological mechanisms involved in these disorders as presented. Case 1 is a description of the subjective experience of a patient with acute orofacial dystonia from promethazine. Case 2 is the use of clonazepam is post-head injury tics. Case 3 is the complication from discontinuation of haloperidol and benztropine mesylate treatment. Case 4 is myoclonus in subacute sclerosing Panencephalitis, and Case 5 is rebound tremor from withdrawal of a beta-adrenergic blocker.

Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome.

PubMed

Joshi, Prathamesh; Lele, Vikram

2013-04-01

Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood, associated with occult neuroblastoma in 20%-50% of all cases. OMA is the initial presentation of neuroblastoma in 1%-3% of children. Conventional radiological imaging approaches include chest radiography and abdominal computed tomography (CT). Nuclear medicine techniques, in form of (123)I/(131)I-metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. We describe use of somatostatin receptor PET/CT with (68)Gallium- DOTA-DPhe(1), Tyr(3)-octreotate (DOTATATE) in diagnosis of neuroblastoma in two cases of OMA.

Propriospinal myoclonus

PubMed Central

van der Salm, Sandra M.A.; Erro, Roberto; Cordivari, Carla; Edwards, Mark J.; Koelman, Johannes H.T.M.; van den Ende, Tom; Bhatia, Kailash P.; van Rootselaar, Anne-Fleur; Brown, Peter

2014-01-01

Objective: Propriospinal myoclonus (PSM) is a rare disorder with repetitive, usually flexor arrhythmic brief jerks of the trunk, hips, and knees in a fixed pattern. It has a presumed generation in the spinal cord and diagnosis depends on characteristic features at polymyography. Recently, a historical paradigm shift took place as PSM has been reported to be a functional (or psychogenic) movement disorder (FMD) in most patients. This review aims to characterize the clinical features, etiology, electrophysiologic features, and treatment outcomes of PSM. Methods: Re-evaluation of all published PSM cases and systematic scoring of clinical and electrophysiologic characteristics in all published cases since 1991. Results: Of the 179 identified patients with PSM (55% male), the mean age at onset was 43 years (range 6–88 years). FMD was diagnosed in 104 (58%) cases. In 12 cases (26% of reported secondary cases, 7% of total cases), a structural spinal cord lesion was found. Clonazepam and botulinum toxin may be effective in reducing jerks. Conclusions: FMD is more frequent than previously assumed. Structural lesions reported to underlie PSM are scarce. Based on our clinical experience and the reviewed literature, we recommend polymyography to assess recruitment variability combined with a Bereitschaftspotential recording in all cases. PMID:25305154

Genetics Home Reference: myoclonus-dystonia

MedlinePlus

... Page Esapa CT, Waite A, Locke M, Benson MA, Kraus M, McIlhinney RA, Sillitoe RV, Beesley PW, ... PubMed Gerrits MC, Foncke EM, Koelman JH, Tijssen MA. Pediatric writer's cramp in myoclonus-dystonia: maternal imprinting ...

Spinal myoclonus following intrathecal administration of diatrizoate meglumine.

PubMed

Sam, M C; Gutmann, L

1996-10-01

Life-threatening myoclonus developed in a patient following inadvertent intrathecal usage of 60% diatrizoate meglumine. Rhabdomyolysis and myoglobinuria occurred. The patient was successfully treated with midazolam and vecuronium and complete recovery occurred.

Prediction of Recovery from Coma After CPR

MedlinePlus

... to pain. There is good evidence* that myoclonus status epilepticus within the first day after CPR accurately predicts poor recovery from coma. Myoclonus status epilepticus is a constant twitching of muscles, including the ...

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

PubMed

Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Genetics Home Reference: PRICKLE1-related progressive myoclonus epilepsy with ataxia

MedlinePlus

... PROGRESSIVE MYOCLONIC, 1B Sources for This Page Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, ... Jan 10. Citation on PubMed Fox MH, Bassuk AG. PRICKLE1-Related Progressive Myoclonus Epilepsy with Ataxia. 2009 ...

Myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications associated with a novel m.5513G>A mutation in the MT-TW gene.

PubMed

Cardaioli, Elena; Mignarri, Andrea; Cantisani, Teresa Anna; Malandrini, Alessandro; Nesti, Claudia; Rubegni, Anna; Funel, Niccola; Federico, Antonio; Santorelli, Filippo Maria; Dotti, Maria Teresa

2018-06-02

We sequenced the mitochondrial genome from a 40-year-old woman with myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications. Histological and biochemical features of mitochondrial respiratory chain dysfunction were present. Direct sequencing showed a novel heteroplasmic mutation at nucleotide 5513 in the MT-TW gene that encodes tRNA Trp . Restriction Fragment Length Polymorphism analysis confirmed that about 80% of muscle mtDNA harboured the mutation while it was present in minor percentages in mtDNA from other tissues. The mutation is predicted to disrupt a highly conserved base pair within the aminoacyl acceptor stem of the tRNA. This is the 17° mutation in MT-TW gene and expands the known causes of late-onset mitochondrial diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

A nationwide survey of opsoclonus-myoclonus syndrome in Japanese children.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Kajimoto, Madoka; Inoue, Hirofumi; Momonaka, Hiroshi; Oka, Momoko; Ohga, Shouchi; Ichiyama, Takashi

2015-08-01

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease characterized by opsoclonus, myoclonus, ataxia, and behavioral changes. The aim of our study was to investigate the epidemiological characteristics of OMS in Japan and to clarify the association between therapy and prognosis. We retrospectively collected the data from 626 Japanese medical institutions from 2005 to 2010, and analyzed the clinical features of pediatric patients with OMS based on the data. In this survey, there were 23 patients (10 males and 13 females). The median ages at the disease onset and the time of study were 16.5 months (range: 11-152 months) and 54 months (range: 24-160 months), respectively. The principal symptoms were opsoclonus (23 patients, 100%), myoclonus (21 patients, 91.3%), and ataxia (23 patients, 100%). The related factors were neuroblastoma (10, 43.5%), infection (9, 39.1%), and immunization (2, 8.7%). The treatments for OMS were included intravenous immunoglobulin (17, 73.9%), methylprednisolone pulse (13, 56.5%), oral prednisolone (12 patients, 52.2%), and chemotherapy and/or operation for the underlying tumors (6, 26.1%), and rituximab (2, 8.7%). Complete remissions were obtained in 35.3%, 23.1%, 33.3%, 66.7%, and 100% of these treatments, respectively. At the latest follow-up period, 8 (34.8%) and 17 patients (73.9%) showed neurological sequelae of motor and intellectual functions, respectively. Patients whose treatment was started more than 30 weeks after the disease onset suffered from the severest neurological sequelae (OMS severity 4) more frequently than those less than 30 weeks (p=0.022). The annual incidence of OMS was estimated to be 0.27-0.40 cases per million in Japanese children. More than 70% of OMS patients had neurological sequelae, especially intellectual function. Early effective treatments within 30 weeks after the onset may be required to prevent the serious neurological outcome. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Rare mtDNA variants in Leber hereditary optic neuropathy families with recurrence of myoclonus.

PubMed

La Morgia, C; Achilli, A; Iommarini, L; Barboni, P; Pala, M; Olivieri, A; Zanna, C; Vidoni, S; Tonon, C; Lodi, R; Vetrugno, R; Mostacci, B; Liguori, R; Carroccia, R; Montagna, P; Rugolo, M; Torroni, A; Carelli, V

2008-03-04

To investigate the mechanisms underlying myoclonus in Leber hereditary optic neuropathy (LHON). Five patients and one unaffected carrier from two Italian families bearing the homoplasmic 11778/ND4 and 3460/ND1 mutations underwent a uniform investigation including neurophysiologic studies, muscle biopsy, serum lactic acid after exercise, and muscle ((31)P) and cerebral ((1)H) magnetic resonance spectroscopy (MRS). Biochemical investigations on fibroblasts and complete mitochondrial DNA (mtDNA) sequences of both families were also performed. All six individuals had myoclonus. In spite of a normal EEG background and the absence of giant SEPs and C reflex, EEG-EMG back-averaging showed a preceding jerk-locked EEG potential, consistent with a cortical generator of the myoclonus. Specific comorbidities in the 11778/ND4 family included muscular cramps and psychiatric disorders, whereas features common to both families were migraine and cardiologic abnormalities. Signs of mitochondrial proliferation were seen in muscle biopsies and lactic acid elevation was observed in four of six patients. (31)P-MRS was abnormal in five of six patients and (1)H-MRS showed ventricular accumulation of lactic acid in three of six patients. Fibroblast ATP depletion was evident at 48 hours incubation with galactose in LHON/myoclonus patients. Sequence analysis revealed haplogroup T2 (11778/ND4 family) and U4a (3460/ND1 family) mtDNAs. A functional role for the non-synonymous 4136A>G/ND1, 9139G>A/ATPase6, and 15773G>A/cyt b variants was supported by amino acid conservation analysis. Myoclonus and other comorbidities characterized our Leber hereditary optic neuropathy (LHON) families. Functional investigations disclosed a bioenergetic impairment in all individuals. Our sequence analysis suggests that the LHON plus phenotype in our cases may relate to the synergic role of mtDNA variants.

Disorders of Upper Limb Movements in Ataxia-Telangiectasia

PubMed Central

Shaikh, Aasef G.; Zee, David S.; Mandir, Allen S.; Lederman, Howard M.; Crawford, Thomas O.

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia. PMID:23826191

Disorders of Upper Limb Movements in Ataxia-Telangiectasia.

PubMed

Shaikh, Aasef G; Zee, David S; Mandir, Allen S; Lederman, Howard M; Crawford, Thomas O

2013-01-01

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia.

Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.

PubMed

Deutsch, Mariel B; Mendez, Mario F

2015-03-01

Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome

PubMed Central

Panzer, Jessica A.; Anand, Ronan; Dalmau, Josep; Lynch, David R.

2015-01-01

Opsoclonus myoclonus ataxia syndrome (OMAS) is an autoimmune disorder characterized by rapid, random, conjugate eye movements (opsoclonus), myoclonus, and ataxia. Given these symptoms, autoantibodies targeting the cerebellum or brainstem could mediate the disease or be markers of autoimmunity. In a subset of patients with OMAS, we identified such autoantibodies, which bind to non-synaptic puncta on the surface of live cultured cerebellar and brainstem neuronal dendrites. These findings implicate autoimmunity to a neuronal surface antigen in the pathophysiology of OMAS. Identification of the targeted antigen(s) could elucidate the mechanisms underlying OMAS and provide a biomarker for diagnosis and response to therapy. PMID:26298330

Loss of Function of KCNC1 is associated with intellectual disability without seizures

PubMed Central

Poirier, Karine; Viot, Géraldine; Lombardi, Laura; Jauny, Clémence; Billuart, Pierre; Bienvenu, Thierry

2017-01-01

p.(Arg320His) mutation in the KCNC1 gene in human 11p15.1 has recently been identified in patients with progressive myoclonus epilepsies, a group of rare inherited disorders manifesting with action myoclonus, myoclonic epilepsy, and ataxia. This KCNC1 variant causes a dominant-negative effect. Here we describe three patients from the same family with intellectual disability and dysmorphic features. The three affected individuals carry a c.1015C>T (p.(Arg339*)) nonsense variant in KCNC1 gene. As previously observed in the mutant mouse carrying a disrupted KCNC1 gene, these findings reveal that individuals with a KCNC1 loss-of-function variant can present intellectual disability without seizure and epilepsy. PMID:28145425

[Clinical heterogeneity of Alzheimer's disease. Different clinical profiles can predict the progression rate].

PubMed

Mangone, C A

Alzheimer's disease (AD) is a degenerative dementia that may disclose different cognitive, behavioral, psychiatric and functional symptoms since onset. These distinct cognitive profiles support the conception of clinical heterogeneity and account for AD's highly variable rate of progression. In spite of strict diagnostic criteria NINCS ADRDA's and DSM IV the clinical certainty is only about 85%. Mayeux define 4 subtypes: a). Benign: mild cognitive and functional impairment without focal signs and late onset behavioral signs, slow progression; b). Myoclonic: usually of presenile onset with severe cognitive deterioration, mutism and early onset myoclonus; c). Extrapyramidal: early onset akineto rigid signs with severe cognitive, behavioral and psychiatric involvement; d). Typical: gradual and progressive cognitive, behavioral and functional impairment. The differentiation of these subtypes will allow us to define discrete patterns of progression, to define prognostic subgroups, and to homogenize them for clinical research and drug trials. We examined 1000 charts of probable AD patients from the Santojanni Center. We found 42% extrapyramidal, 35% typical, 15% benign and 8% myoclonic. The early onset of parkinsonism and myoclonus predict a rapidly evolving cognitive impairment and a more severe rate of progression with psychiatric disorders and dependency in activities of daily living. (DADL) Patients with low level of education, low cognitive performance at entry as well as those with rapid rate of cognitive deterioration had a faster rate of progression to DADL. Delusions, low level of education, extrapyramidal signs and motor hyperactivity but not hallucinations, and anosognosia were the best non cognitive predictors of DADL.

Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study.

PubMed

Narita, Aya; Shirai, Kentarou; Itamura, Shinji; Matsuda, Atsue; Ishihara, Akiko; Matsushita, Kumi; Fukuda, Chisako; Kubota, Norika; Takayama, Rumiko; Shigematsu, Hideo; Hayashi, Anri; Kumada, Tomohiro; Yuge, Kotaro; Watanabe, Yoriko; Kosugi, Saori; Nishida, Hiroshi; Kimura, Yukiko; Endo, Yusuke; Higaki, Katsumi; Nanba, Eiji; Nishimura, Yoko; Tamasaki, Akiko; Togawa, Masami; Saito, Yoshiaki; Maegaki, Yoshihiro; Ohno, Kousaku; Suzuki, Yoshiyuki

2016-03-01

Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD. This open-label pilot study included five patients who received high-dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies. High-dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood-brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again. Pharmacological chaperone therapy with high-dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.

Comparison of clinical characteristics between familial and non-familial early onset Alzheimer's disease.

PubMed

Joshi, Aditi; Ringman, John M; Lee, Albert S; Juarez, Kevin O; Mendez, Mario F

2012-10-01

Although familial Alzheimer's disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.

Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease

PubMed Central

Ringman, John M.; Lee, Albert S.; Juarez, Kevin O.; Mendez, Mario F.

2012-01-01

Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD. PMID:22460587

Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models

PubMed Central

Yokoi, Fumiaki; Dang, Mai T.; Yang, Guang; Li, JinDong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

2011-01-01

Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ε-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally-inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ε-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ε-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally-inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ε-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ε-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. PMID:22040906

Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

PubMed

Josephs, K A; Ahlskog, J E; Klos, K J; Kumar, N; Fealey, R D; Trenerry, M R; Cowl, C T

2005-06-28

Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

PubMed

Carecchio, Miryam; Picillo, Marina; Valletta, Lorella; Elia, Antonio E; Haack, Tobias B; Cozzolino, Autilia; Vitale, Annalisa; Garavaglia, Barbara; Iuso, Arcangela; Bagella, Caterina F; Pappatà, Sabina; Barone, Paolo; Prokisch, Holger; Romito, Luigi; Tiranti, Valeria

2017-07-01

Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.

'Dancing eyes, dancing feet syndrome' in small cell lung carcinoma.

PubMed

Sharma, Chandramohan; Acharya, Mihir; Kumawat, Bansi Lal; Kochar, Abhishek

2014-04-23

A 60-year-old man presented with a 25-day history of acute onset instability of gait, tremulousness of limbs and involuntary eye movements. Examination revealed presence of opsoclonus, myoclonus and ataxia, without any loss of motor power in the limbs. Prompt investigations were directed towards identifying an underlying malignancy which is often associated with this type of clinical scenario. CT of the brain was normal and cerebrospinal fluid examination showed lymphocytic pleocytosis. A cavitatory lesion was found in the right lung base on the high-resolution CT of the chest and histopathological examination of this lung mass showed small cell lung carcinoma. The patient was managed symptomatically with levetiracetam and baclofen and referred to oncology department for resection of the lung mass.

Chorioretinitis: a potential clue to the early diagnosis of subacute sclerosing panencephalitis.

PubMed

Jeevagan, Vijayabala; Dissanayake, Athula

2017-08-01

We describe a 36-year-old man with subacute sclerosing panencephalitis (SSPE) presenting with chorioretinitis two years before onset of other neurological features. He had neither myoclonus nor the typical EEG features of SSPE. The diagnosis was confirmed in the appropriate clinical setting by detecting elevated measles antibody titres in cerebrospinal fluid and serum. Clinicians should consider SSPE among the differential diagnoses in chorioretinitis. This is particularly so if there is macular or perimacular involvement with concurrent involvement of the optic nerve in young patients, even without other characteristic neurological symptoms. © 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.

Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models.

PubMed

Yokoi, Fumiaki; Dang, Mai T; Yang, Guang; Li, Jindong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

2012-02-01

Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ɛ-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ɛ-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ɛ-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ɛ-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ɛ-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. Copyright © 2011 Elsevier B.V. All rights reserved.

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

PubMed Central

Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

1998-01-01

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.

 PMID:9527146

Delayed Diagnosis, Range of Severity, and Multiple Sleep Comorbidities: A Clinical and Polysomnographic Analysis of 100 Patients of the Innsbruck Narcolepsy Cohort

PubMed Central

Frauscher, Birgit; Ehrmann, Laura; Mitterling, Thomas; Gabelia, David; Gschliesser, Viola; Brandauer, Elisabeth; Poewe, Werner; Högl, Birgit

2013-01-01

Study Objectives: Narcolepsy is reported to affect 26-56/100,000 in the general population. We aimed to describe clinical and polysomnographic features of a large narcolepsy cohort in order to comprehensively characterize the narcoleptic spectrum. Methods: We performed a chart- and polysomnographybased review of all narcolepsy patients of the Innsbruck narcolepsy cohort. Results: A total of 100 consecutive narcolepsy patients (87 with cataplexy [NC], 13 without cataplexy [N]) were included in the analysis. All subjects had either excessive daytime sleepiness or cataplexy as their initial presenting clinical feature. Age at symptom onset was 20 (6-69) years. Diagnostic delay was 6.5 (0-39) years. The complete narcolepsy tetrad was present in 36/100 patients; 28/100 patients had three cardinal symptoms; 29/100 had two; and 7/100 had only excessive daytime sleepiness. Severity varied broadly with respect to excessive daytime sleepiness (median Epworth Sleepiness Scale score: 18, range 10-24), cataplexy (8-point Likert scale: median 4.5, range 1-8), hypnagogic hallucinations (median 4.5, range 1-7), and sleep paralysis (median 3, range 1-7). Sleep comorbidity was highly prevalent and ranged from sleeprelated movement disorders (n = 55/100), parasomnias (n = 34/100), and sleeprelated breathing disorders (n = 24/100), to insomnia (n = 28/100). REM sleep without atonia or a periodic limb movement in sleep index > 5/h were present in most patients (90/100 and 75/100). A high percentage of narcoleptic patients in the present study had high frequency leg movements (35%) and excessive fragmentary myoclonus (22%). Of the narcolepsy patients with clinical features of REM sleep behavior disorder (RBD), 76.5% had EMG evidence for RBD on the multiple sleep latency test (MSLT), based on a standard cutoff of a minimum of 18% of 3-sec miniepochs. Conclusion: This study is one of the largest monocentric polysomnographic studies to date of patients with narcolepsy and confirms the frequent comorbidity of narcolepsy with many other sleep disorders. Our study is the first to evaluate the percentage of patients with high frequency leg movements and excessive fragmentary myoclonus in narcolepsy and is the first to demonstrate EMG evidence of RBD in the MSLT. These findings add to the growing body of literature suggesting that motor instability is a key feature of narcolepsy. Citation: Frauscher B; Ehrmann L; Mitterling T; Gabelia D; Gschliesser V; Brandauer E; Poewe W; Högl B. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the Innsbruck narcolepsy cohort. J Clin Sleep Med 2013;9(8):805-812. PMID:23946711

Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

PubMed

Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

2016-05-01

Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The effects of inferior olive lesion on strychnine seizure

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

Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

1990-10-01

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable ({sup 3}H)AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding in cerebella from inferior olive-lesioned rats was observed, but no difference in ({sup 3}H)AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10 imine) were tested asmore » anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the ({sup 3}H)AMPA binding data.« less

Chess-playing epilepsy: a case report with video-EEG and back averaging.

PubMed

Mann, M W; Gueguen, B; Guillou, S; Debrand, E; Soufflet, C

2004-12-01

A patient suffering from juvenile myoclonic epilepsy experienced myoclonic jerks, fairly regularly, while playing chess. The myoclonus appeared particularly when he had to plan his strategy, to choose between two solutions or while raising the arm to move a chess figure. Video-EEG-polygraphy was performed, with back averaging of the myoclonus registered during a chess match and during neuropsychological testing with Kohs cubes. The EEG spike wave complexes were localised in the fronto-central region. [Published with video sequences].

Atypical presentation of West Nile virus in a newly diagnosed human immunodeficiency virus patient in New York City.

PubMed

Josekutty, Joby; Yeh, Richard; Mathew, Sheena; Ene, Ada; Ramessar, Nina; Trinidad, Jennilee

2013-04-01

Central nervous system manifestations of West Nile virus (WNV) infection include meningitis, encephalitis, and poliomyelitis-like syndrome. We describe a 44-year-old man with no past medical history who presented with a meningoencephalitic syndrome and spastic paralysis bilaterally in the upper and lower extremities, hyperreflexia, and myoclonus and was ultimately diagnosed as being infected with HIV and WNV.

Relative hyperperfusion by SPECT in a family with a presenilin 1 (T245P) mutation.

PubMed

Edwards-Lee, Terri; Wen, Johnny; Chung, Julia A; Vasinrapee, Panukorn; Mishkin, Frederick S

2008-01-01

Clinical characteristics of autosomal dominant Alzheimer's disease often differ clinically from sporadic disease with the onset of seizures, spasticity and myoclonus early in the disease course. Similarly imaging characteristics may also differ. We report the findings of relative hyperperfusion by Tc-99m HMPAO SPECT in the medial orbitofrontal cortex and anterior temporal lobe in four affected family members carrying a presenilin 1 mutation. SPECT of the four individuals was compared to an age-matched normal database. We speculate that the findings of relative medial orbitofrontal and anterior temporal lobe hyperperfusion may be a marker of early onset Alzheimer's disease in this family.

Cortical myoclonus during IV thrombolysis for ischemic stroke

PubMed Central

Bentes, Carla; Peralta, Rita; Viana, Pedro; Morgado, Carlos; Melo, Teresa P.; Ferro, José M.

2014-01-01

We describe a patient with an acute middle cerebral artery ischemic stroke developing subtle involuntary movements of the paretic upper limb with cortical origin during rt-PA perfusion. Despite the multiple potential pathophysiological mechanisms for the relationship between thrombolysis and epileptic activity, seizures during this procedure are scarcely reported. Our hypothesis is that subtle and transient clinical seizures, like those described in our patient, may not be detected or are misdiagnosed as nonepileptic involuntary movements. We aimed to draw attention to the recognition challenge of this paroxysmal motor behavior, highlighting this clinical and neurophysiological identification using video recording and back-average analysis of the EEG. PMID:25667903

Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat.

PubMed

Plummer, C; Spring, P J; Marotta, R; Chin, J; Taylor, G; Sharpe, D; Athanasou, N A; Thyagarajan, D; Berkovic, S F

2013-07-01

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

[Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

  The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

Electroclinical presentation and genotype-phenotype relationships in patients with Unverricht-Lundborg disease carrying compound heterozygous CSTB point and indel mutations.

PubMed

Canafoglia, Laura; Gennaro, Elena; Capovilla, Giuseppe; Gobbi, Giuseppe; Boni, Antonella; Beccaria, Francesca; Viri, Maurizio; Michelucci, Roberto; Agazzi, Pamela; Assereto, Stefania; Coviello, Domenico A; Di Stefano, Maria; Rossi Sebastiano, Davide; Franceschetti, Silvana; Zara, Federico

2012-12-01

Unverricht-Lundborg disease (EPM1A) is frequently due to an unstable expansion of a dodecamer repeat in the CSTB gene, whereas other types of mutations are rare. EPM1A due to homozygous expansion has a rather stereotyped presentation with prominent action myoclonus. We describe eight patients with five different compound heterozygous CSTB point or indel mutations in order to highlight their particular phenotypical presentations and evaluate their genotype-phenotype relationships. We screened CSTB mutations by means of Southern blotting and the sequencing of the genomic DNA of each proband. CSTB messenger RNA (mRNA) aberrations were characterized by sequencing the complementary DNA (cDNA) of lymphoblastoid cells, and assessing the protein concentrations in the lymphoblasts. The patient evaluations included the use of a simplified myoclonus severity rating scale, multiple neurophysiologic tests, and electroencephalography (EEG)-polygraphic recordings. To highlight the particular clinical features and disease time-course in compound heterozygous patients, we compared some of their characteristics with those observed in a series of 40 patients carrying the common homozygous expansion mutation observed at the C. Besta Foundation, Milan, Italy. The eight compound heterozygous patients belong to six EPM1A families (out of 52; 11.5%) diagnosed at the Laboratory of Genetics of the Galliera Hospitals in Genoa, Italy. They segregated five different heterozygous point or indel mutations in association with the common dodecamer expansion. Four patients from three families had previously reported CSTB mutations (c.67-1G>C and c.168+1_18del); one had a novel nonsense mutation at the first exon (c.133C>T) leading to a premature stop codon predicting a short peptide; the other three patients from two families had a complex novel indel mutation involving the donor splice site of intron 2 (c.168+2_169+21delinsAA) and leading to an aberrant transcript with a partially retained intron. The protein dose (cystatin B/β-actin) in our heterozygous patients was 0.24 ± 0.02, which is not different from that assessed in patients bearing the homozygous dodecamer expansion. The compound heterozygous patients had a significantly earlier disease onset (7.4 ± 1.7 years) than the homozygous patients, and their disease presentations included frequent myoclonic seizures and absences, often occurring in clusters throughout the course of the disease. The seizures were resistant to the pharmacologic treatments that usually lead to complete seizure control in homozygous patients. EEG-polygraphy allowed repeated seizures to be recorded. Action myoclonus progressively worsened and all of the heterozygous patients older than 30 years were in wheelchairs. Most of the patients showed moderate to severe cognitive impairment, and six had psychiatric symptoms. EPM1A due to compound heterozygous CSTB mutations presents with variable but often markedly severe and particular phenotypes. Most of our patients presented with the electroclinical features of severe epilepsy, which is unexpected in homozygous patients, and showed frequent seizures resistant to pharmacologic treatment. The presence of variable phenotypes (even in siblings) suggests interactions with other genetic factors influencing the final disease presentation. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre

PubMed Central

Prashanth, L K; Taly, A B; Ravi, V; Sinha, S; Arunodaya, G R

2006-01-01

Clinical and laboratory characteristics of 39 patients with adult onset subacute sclerosing panencephalitis (SSPE) are described and compared to those of juvenile onset patients regarding preceding measles, age at onset, gender, interval between onset and diagnosis, clinical profile, and course during follow up. Diagnosis was based on clinical and electroencephalographic findings and raised anti‐measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom onset was 20.9±4.9 years and mean interval from onset to diagnosis was 6.3±9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. All patients received symptomatic therapy; 19 also received disease modifying agents. Five of seven pregnant women had successful deliveries. The follow‐up period varied widely (maximum 60 months, median 9 months). The profile of adult onset SSPE did not differ from the rest of the cohort, except for a longer interval between measles infection and symptom onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A high index of suspicion and appropriate investigations are necessary for early diagnosis and counselling. PMID:16464898

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

PubMed Central

Collins, S J; Ahlskog, J E; Parisi, J E; Maraganore, D M

1995-01-01

All cases examined postmortem at the Mayo Clinic that met the classic neuropathological criteria for progressive supranuclear palsy (PSP) were identified for retrospective clinical analyses. The necropsy material was re-examined by a second neuropathologist to confirm the pathological diagnosis of PSP, yielding 12 cases. A range of clinical signs were documented in these patients, with numerous findings beyond those noted in the original descriptions of this disorder. Atypical clinical findings included absence of supranuclear gaze palsy (two cases), prominent asymmetry (two), arm dystonia (two), upper limb apraxia (two), myoclonus (two), chorea (one), eyelid opening apraxia (one), and respiratory disturbance (one). A definite clinical diagnosis of PSP had been made during life in only eight of the 12 patients. From the retrospective analysis of these 12 cases, a set of clinical criteria were developed for the premortem diagnosis of PSP emphasising differences from other akinetic-rigid disorders. PMID:7876846

[A case of MM1+2 Creutzfeldt-Jakob disease with a longitudinal study of EEG and MRI].

PubMed

Katsube, Mizuho; Shiota, Yuri; Harada, Takayuki; Shibata, Hiroshi; Nagai, Atsushi

2013-11-01

We report a case of definite MM1 + 2 sporadic Creutzfeldt-Jakob disease (sCJD). A 66-year-old woman was admitted to our hospital with memory disturbance and disorientation for three months. On admission she presented a progressive cognitive insufficiency. Electroencephalography (EEG) revealed a frontal intermittent rhythmical delta activity (FIRDA) and the brain magnetic resonance imaging (MRI) showed high signal intensities in cerebral cortex on diffusion weighted images (DWI). After four months from the onset, she reached the akinetic mutism state followed by myoclonus. Follow up examination revealed that periodic synchronous discharge (PSD) was found in EEG, and DWI revealed enlargement of high signal intensity lesions in cerebral cortex. At seven months from the onset, PSD and high signal intensities of cortex became unclear with disappearance of myoclonus, and brain white matter lesions were evident on MRI. Serial studies of EEG and MRI revealed that PSD generalized from frontal lobe dominant pattern, while high signal intensity lesions of cortex diffusely increased on DWI. At ten months from the onset patient died. Pathological examination in brain showed moderate and diffuse neuronal cell loss and gliosis in cerebral cortex corresponding with DWI changes. The genotype at codon 129 of the prion protein (PrP) was homozygous methionine (MM) and the type of protease-resistant PrP (PrPres) was the mixed type of 1 and 2 in Western blot analysis. It has been rare to analyze the changes of EEG and MRI in the entire stage and to investigate pathological finding in the case of sCJD-MM1 + 2. A longitudinal examination of EEG and MRI is useful for early diagnosis of CJD. Also we could correlate these findings with clinical and histopathological phenotype.

A Case Report on Dyskinesia Following Rivastigmine Patch 13.3 mg/24 hours for Alzheimer's Disease

PubMed Central

Diaz, Maria Cristina B.; Rosales, Raymond L.

2015-01-01

Abstract Current reports on movement disorder adverse effects of acetylcholinesterase inhibitors only include extrapyramidal symptoms and myoclonus. Here is a case of an 81-year-old female Filipino with dementia who presented with first-onset generalized choreiform movements. The etiology of the clinical finding of dyskinesia was investigated through laboratories, neuroimaging, and electroencephalogram, all of which yielded negative results. Review of her medications included the rivastigmine (Exelon) patch, which had just been increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes excluded, a trial discontinuation of rivastigmine, showed decreased frequency of the dyskinesia 48 hours after, with complete resolution after 6 days, and no recurrence since then. This case thus presents a probable association or causality between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch because of clear temporal proximity, lack of alternative explanations, and a reversal of the dyskinesia upon medicament discontinuation. PMID:26313774

The effect of piracetam on ataxia: clinical observations in a group of autosomal dominant cerebellar ataxia patients.

PubMed

Ince Gunal, D; Agan, K; Afsar, N; Borucu, D; Us, O

2008-04-01

Autosomal dominant cerebellar ataxias are clinically and genetically heterogeneous neurodegenerative disorders. There is no known treatment to prevent neuronal cell death in these disorders. Current treatment is purely symptomatic; ataxia is one of the most disabling symptoms and represents the main therapeutic challenge. A previous case report suggesting benefit from administration of high dose piracetam inspired the present study of the efficacy of this agent in patients with cerebellar ataxia. Piracetam is a low molecular weight derivative of gamma-aminobutyric acid. Although little is known of its mode of action, its efficacy has been documented in a wide range of clinical indications, such as cognitive disorders, dementia, vertigo and dyslexia, as well as cortical myoclonus. The present report investigated the role of high dose piracetam in patients with cerebellar ataxia. Eight patients with autosomal dominant cerebellar ataxia were given intravenous piracetam 60 g/day by a structured protocol for 14 days. The baseline and end-of-the study evaluations were based on the International Cooperative Ataxia Rating Scale. Statistical analysis demonstrated a significant improvement in the patients' total score (P = 0.018) and a subscale analysis showed statistical significance for only the posture and gait disturbances item (P = 0.018). This study is providing good clinical observation in favour of high dose piracetam infusion to reduce the disability of the patients by improving their gait ataxia.

Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1)

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

Lalioti, M.D.; Mirotsou, M.; Rossier, C.

1997-02-01

Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G{r_arrow}C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modelingmore » predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G{r_arrow}T and 2575A{r_arrow}G, probably represent polymorphic variants. In addition, a tandem repeat in the 5{prime} UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene. 23 refs., 5 figs., 3 tabs.« less

Speech–Language Pathology Evaluation and Management of Hyperkinetic Disorders Affecting Speech and Swallowing Function

PubMed Central

Barkmeier-Kraemer, Julie M.; Clark, Heather M.

2017-01-01

Background Hyperkinetic dysarthria is characterized by abnormal involuntary movements affecting respiratory, phonatory, and articulatory structures impacting speech and deglutition. Speech–language pathologists (SLPs) play an important role in the evaluation and management of dysarthria and dysphagia. This review describes the standard clinical evaluation and treatment approaches by SLPs for addressing impaired speech and deglutition in specific hyperkinetic dysarthria populations. Methods A literature review was conducted using the data sources of PubMed, Cochrane Library, and Google Scholar. Search terms included 1) hyperkinetic dysarthria, essential voice tremor, voice tremor, vocal tremor, spasmodic dysphonia, spastic dysphonia, oromandibular dystonia, Meige syndrome, orofacial, cervical dystonia, dystonia, dyskinesia, chorea, Huntington’s Disease, myoclonus; and evaluation/treatment terms: 2) Speech–Language Pathology, Speech Pathology, Evaluation, Assessment, Dysphagia, Swallowing, Treatment, Management, and diagnosis. Results The standard SLP clinical speech and swallowing evaluation of chorea/Huntington’s disease, myoclonus, focal and segmental dystonia, and essential vocal tremor typically includes 1) case history; 2) examination of the tone, symmetry, and sensorimotor function of the speech structures during non-speech, speech and swallowing relevant activities (i.e., cranial nerve assessment); 3) evaluation of speech characteristics; and 4) patient self-report of the impact of their disorder on activities of daily living. SLP management of individuals with hyperkinetic dysarthria includes behavioral and compensatory strategies for addressing compromised speech and intelligibility. Swallowing disorders are managed based on individual symptoms and the underlying pathophysiology determined during evaluation. Discussion SLPs play an important role in contributing to the differential diagnosis and management of impaired speech and deglutition associated with hyperkinetic disorders. PMID:28983422

Opsoclonus myoclonus ataxia associated with West Nile virus infection: A dramatic presentation with benign prognosis?

PubMed

Zaltzman, Roy; Klein, Colin; Gordon, Carlos R

2017-05-15

Opsoclonus myoclonus and ataxia is a combination of severe neurological signs associated with several pathologic agents and conditions. Only few cases of opsoclonus have been related to West Nile virus infection. We report on a 61-year-old woman and on a 55-year-old man who had history of recent fever, who were hospitalized because of acute severe truncal ataxia, opsoclonus and tremor with minimal myoclonic jerks. A through work-up revealed the presence of both IgM and IgG antibodies against West Nile virus both in the serum and Cerebrospinal Fluid and excluded other causes known to be associated with this combination of neurological signs. The first case was treated with corticosteroids, followed by significant improvement, and the second recovered spontaneously. The acute combination of opsoclonus, severe truncal ataxia and tremor with a history of recent fever requires, during the relevant season and in the relevant geographic area, a search for a recent infection with West Nile virus. Though initially suffering from a devastating sickness, our patients eventually recovered. Copyright © 2017 Elsevier B.V. All rights reserved.

Opsoclonus: clinical and immunological features.

PubMed

Jen, Joanna C; Lopez, Ivan; Baloh, Robert W

2012-09-15

Opsoclonus is felt to be a saccadic oscillation disorder but the neuroanatomical substrate for generating the abnormal eye movements is poorly understood. We recorded eye movements and studied serum samples from 7 patients who presented with opsoclonus and with either myoclonus or generalized tremor. Anti neuronal antibodies were detected by immunohistochemestry using rat and human cerebellar sections. In all patients but one the opsoclonus resolved within 2weeks (after immunosuppression in 4, resection of the underlying neoplasm in 1 and spontaneously in 1). Opsoclonus was arrhythmic and multidirectional with a wide frequency range (4-10Hz). No known paraneoplastic antibodies were found in the initial commercial screen. Three patients had antiPurkinje cell antibodies with a characteristic punctate staining in the molecular layer. The clinical and immunological findings are consistent with the hypothesis, that in some patients, opsoclonus results from antibodies directed at the parallel fiber-Purkinje cell synapse. The antibodies block parallel fiber input to Purkinje cells allowing spontaneous oscillating activity generated in the inferior olives to be passed on to the oculomotor nuclei via the flocculus. Copyright © 2012 Elsevier B.V. All rights reserved.

Sleep-related movement disorders.

PubMed

Merlino, Giovanni; Gigli, Gian Luigi

2012-06-01

Several movement disorders may occur during nocturnal rest disrupting sleep. A part of these complaints is characterized by relatively simple, non-purposeful and usually stereotyped movements. The last version of the International Classification of Sleep Disorders includes these clinical conditions (i.e. restless legs syndrome, periodic limb movement disorder, sleep-related leg cramps, sleep-related bruxism and sleep-related rhythmic movement disorder) under the category entitled sleep-related movement disorders. Moreover, apparently physiological movements (e.g. alternating leg muscle activation and excessive hypnic fragmentary myoclonus) can show a high frequency and severity impairing sleep quality. Clinical and, in specific cases, neurophysiological assessments are required to detect the presence of nocturnal movement complaints. Patients reporting poor sleep due to these abnormal movements should undergo non-pharmacological or pharmacological treatments.

Cortical tremor: a variant of cortical reflex myoclonus.

PubMed

Ikeda, A; Kakigi, R; Funai, N; Neshige, R; Kuroda, Y; Shibasaki, H

1990-10-01

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

[Effects of piracetam therapy in a case of Lance-Adams syndrome].

PubMed

Hoshino, Ai; Kumada, Satoko; Yokochi, Fusako; Hachiya, Yasuo; Hanafusa, Yukiko; Tomita, Sunao; Okiyama, Ryoich; Kurihara, Eiji

2009-09-01

We report a 17-year-old female patient with Lance-Adams syndrome caused by anoxic encephalopathy during a severe attack of bronchial asthma. She had difficulty in writing because of action myoclonus in her arms. She also exhibited freezing gait and was unable to walk without cane. Although her gait disturbance resembled those seen in patients with parkinsonism secondary to anoxic encephalopathy, surface electromyography revealed that it was caused by action myoclonus in her legs. The presence of giant somatosensory evoked potentials and enhanced cortical reflexes in response to the electrical stimulation to her posterior tibial nerves supported our diagnosis. A combined therapy with valproate sodium, clonazepam and piracetam (15 g/day) was not effective. However, her freezing gait remarkably improved and she was able to walk without help, after the treatment with sufficient dose of piracetam (21 g/day). Cortical hyperexcitability as revealed by electrophysiological examination also improved. We concluded that the combined therapy with antiepileptic drugs and piracetam was effective in the treatment for action myoclonus. However, because the effects seemed dose-related, the dosage of piracetam needed to be increased until the optimum effects were obtained.

Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course.

PubMed

Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Nokura, Kazuya; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

2014-01-01

We describe an autopsied case of a Japanese woman with Gerstmann-Straeussler-Scheinker disease (GSS) presenting with a rapidly progressive clinical course. Disease onset occurred at the age of 54 with dementia and gait disturbance. Her clinical course progressively deteriorated until she reached a bedridden state with myoclonus 9 months after onset. Two months later, she reached the akinetic mutism state. Nasal tube feeding was introduced at this point and continued for several years. Electroencephalograms showed diffuse slowing without periodic sharp-wave complexes. Diffusion-weighted magnetic resonance imaging (MRI) showed widespread cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed a Pro to Leu point mutation at codon 102 with methionine homozygosity at codon 129. The patient died of respiratory failure after a total disease duration of 62 months. Neuropathologic examination revealed widespread spongiform change with numerous eosinophilic amyloid plaques (Kuru plaques) in the cerebral and cerebellar cortices by H & E staining. Diffuse myelin pallor with axon loss of the cerebral white matter, suggestive of panencephalopathic-type pathology was observed. Numerous PrP immunopositive plaques and diffuse synaptic-type PrP deposition were extensively observed, particularly in the cerebral and cerebellar cortices. Western blot analysis of proteinase Kresistant PrP showed a characteristic band pattern with a small molecular band of 6 kDa. The reason for the similarity in clinicopathologic findings between the present case and Creutzfeldt-Jakob disease is uncertain; however, the existence of an unknown disease-modifying factor is suspected.

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

PubMed

Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017 Elsevier Inc. All rights reserved.

ADCY5-related dyskinesia

PubMed Central

Chen, Dong-Hui; Méneret, Aurélie; Friedman, Jennifer R.; Korvatska, Olena; Gad, Alona; Bonkowski, Emily S.; Stessman, Holly A.; Doummar, Diane; Mignot, Cyril; Anheim, Mathieu; Bernes, Saunder; Davis, Marie Y.; Damon-Perrière, Nathalie; Degos, Bertrand; Grabli, David; Gras, Domitille; Hisama, Fuki M.; Mackenzie, Katherine M.; Swanson, Phillip D.; Tranchant, Christine; Vidailhet, Marie; Winesett, Steven; Trouillard, Oriane; Amendola, Laura M.; Dorschner, Michael O.; Weiss, Michael; Eichler, Evan E.; Torkamani, Ali; Roze, Emmanuel

2015-01-01

Objective: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)–related dyskinesia and genotype–phenotype relationship. Methods: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. Results: We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. Conclusions: ADCY5-related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis. PMID:26537056

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

PubMed

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

2017-11-01

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

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

PubMed

Chen, Dong-Hui; Méneret, Aurélie; Friedman, Jennifer R; Korvatska, Olena; Gad, Alona; Bonkowski, Emily S; Stessman, Holly A; Doummar, Diane; Mignot, Cyril; Anheim, Mathieu; Bernes, Saunder; Davis, Marie Y; Damon-Perrière, Nathalie; Degos, Bertrand; Grabli, David; Gras, Domitille; Hisama, Fuki M; Mackenzie, Katherine M; Swanson, Phillip D; Tranchant, Christine; Vidailhet, Marie; Winesett, Steven; Trouillard, Oriane; Amendola, Laura M; Dorschner, Michael O; Weiss, Michael; Eichler, Evan E; Torkamani, Ali; Roze, Emmanuel; Bird, Thomas D; Raskind, Wendy H

2015-12-08

To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship. We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. ADCY5-related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis. © 2015 American Academy of Neurology.

Dystonia: an update on phenomenology, classification, pathogenesis and treatment.

PubMed

Balint, Bettina; Bhatia, Kailash P

2014-08-01

This article will highlight recent advances in dystonia with focus on clinical aspects such as the new classification, syndromic approach, new gene discoveries and genotype-phenotype correlations. Broadening of phenotype of some of the previously described hereditary dystonias and environmental risk factors and trends in treatment will be covered. Based on phenomenology, a new consensus update on the definition, phenomenology and classification of dystonia and a syndromic approach to guide diagnosis have been proposed. Terminology has changed and 'isolated dystonia' is used wherein dystonia is the only motor feature apart from tremor, and the previously called heredodegenerative dystonias and dystonia plus syndromes are now subsumed under 'combined dystonia'. The recently discovered genes ANO3, GNAL and CIZ1 appear not to be a common cause of adult-onset cervical dystonia. Clinical and genetic heterogeneity underlie myoclonus-dystonia, dopa-responsive dystonia and deafness-dystonia syndrome. ALS2 gene mutations are a newly recognized cause for combined dystonia. The phenotypic and genotypic spectra of ATP1A3 mutations have considerably broadened. Two new genome-wide association studies identified new candidate genes. A retrospective analysis suggested complicated vaginal delivery as a modifying risk factor in DYT1. Recent studies confirm lasting therapeutic effects of deep brain stimulation in isolated dystonia, good treatment response in myoclonus-dystonia, and suggest that early treatment correlates with a better outcome. Phenotypic classification continues to be important to recognize particular forms of dystonia and this includes syndromic associations. There are a number of genes underlying isolated or combined dystonia and there will be further new discoveries with the advances in genetic technologies such as exome and whole-genome sequencing. The identification of new genes will facilitate better elucidation of pathogenetic mechanisms and possible corrective therapies.

[Clinical and electrophysiologic studies on epileptic negative myoclonus in atypical benign partial epilepsy of childhood].

PubMed

Yang, Zhi-xian; Liu, Xiao-yan; Qin, Jiong; Zhang, Yue-hua; Bao, Xin-hua; Chang, Xing-zhi; Wu, Ye; Xiong, Hui

2008-12-01

To investigate the clinical, neurophysiologic characteristics and therapeutic considerations of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy of childhood (ABPE). Video-EEG monitoring with outstretched arm tests were carried out in 17 patients, and 9 of them were examined with simultaneous electromyography (EMG). The ENM manifestations, electrophysiologic features and responses to antiepileptic drugs (AED) were analyzed. Seventeen patients were diagnosed as having benign childhood epilepsy with centrotemporal spikes (BECT) during the early course of the disease and were treated with AED. During the course of the disease, hand trembling, objects dropping, head nodding and instability during standing might be clues for ENM occurrence. ENM had been confirmed in our patients by outstretched arm tests during video-EEG recording. The ictal EEG showed that high-amplitude spikes followed by a slow wave over the contralateral motor areas. This was further confirmed by time-locked silent EMG in 9 patients. During ENM occurrence or recurrence, the habitual seizures and interictal discharges were exaggerated. Atypical absence seizures also occurred in 6 patients. The alteration of therapeutic options of AED relating to ENM appearance in some patients included the add-on therapy with carbamazepine (CBZ), oxcarbazepine, phenobarbital, or withdrawal of valproate (VPA). ENM was controlled in most cases by using VPA, clonazepam (CZP) and corticosteroid with different combination. ENM could occur during the course of ABPE. Outstretching arm tests during video-EEG monitoring in combination with EMG was essential to confirm ENM. The ENM occurrence was always associated with the frequency increasing of habitual seizures and the aggravation of interictal discharges. Some AED such as CBZ might induce ENM. VPA, benzodiazepines and corticosteroid with different combination were relatively effective in treatment of ENM.

Unmasking of myoclonus by lacosamide in generalized epilepsy.

PubMed

Birnbaum, Daniel; Koubeissi, Mohamad

2017-01-01

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, in some individuals with genetic generalized epilepsy (GGE).

Acute Opioid-Induced Myoclonic Reaction after Use of Fentanyl as an Anesthetic Drug for an Emergency Cesarean Section.

PubMed

Almedallah, Dana Khaled; Alshamlan, Dana Yousef; Shariff, Erum Mubbashir

2018-01-01

Myoclonus is an abnormal involuntary movement that has been previously reported with administration of high doses of opioids for prolonged periods of time. In this case, however, we report an acute myoclonic reaction and review the literature on the possible causative pathophysiology. We report the case of a 24-year-old woman who was admitted for postdated cesarean section. She started to have abnormal involuntary movements after administration of an epidural anesthesia containing 700 μg of fentanyl with 115 mL (0.5) bupivacaine and 40 mL (2%) lidocaine. Upon examination, the patient was conscious, alert, and oriented. Her vital signs were stable. Her movements can be described as generalized, sudden, involuntary, jerking movements, involving the upper limbs, head, torso as well as the lower limbs. The frequency of these jerks was about every 1-2 min lasting for 10 s. There was no change in level of consciousness during these abnormal movements. The rest of the neurological examination was normal. Laboratory values showed normoglycemia and normal serum biochemistry. A routine electroencephalogram showed no epileptiform activity. Brain imaging was normal. Based on history, examination, and laboratory findings, we made the diagnosis of drug-induced myoclonus, which in this clinical scenario was secondary to fentanyl. We discontinued fentanyl and, gradually, the intensity and frequency of the abnormal movements decreased and disappeared after a few hours. A clear definitive explanation of the acute effect of opioids is still to be reached. It involves an interaction of complex neuroanatomical pathways and neurophysiological receptors. Nonetheless, a unanimous effort is needed to raise awareness about the role of opioids in the development of abnormal movements and their clinical management, to insure that they do not go unnoticed in the clinical scenarios, and to further add more scientific content that could help in reaching an explanatory theory.

Expression of CXCR3 and its ligands CXCL9, -10 and -11 in paediatric opsoclonus–myoclonus syndrome

PubMed Central

Pranzatelli, M R; Tate, E D; McGee, N R; Travelstead, A L; Verhulst, S J; Ransohoff, R M

2013-01-01

Opsoclonus–myoclonus syndrome (OMS) is a neuroinflammatory disorder associated with remote cancer. To understand more clearly the role of inflammatory mediators, the concentration of CXCR3 ligands CXCL10, CXCL9 and CXCL11 was measured in 245 children with OMS and 81 paediatric controls using enzyme-linked immunosorbent assay (ELISA), and CXCR3 expression on CD4+ T cells was measured by flow cytometry. Mean cerebrospinal fluid (CSF) CXCL10 was 2·7-fold higher in untreated OMS than controls. Intrathecal production was demonstrated by significantly different CXCL10 CSF : serum ratios. The dichotomized ‘high’ CSF CXCL10 group had higher CSF leucocyte count (P = 0·0007) and B cell activating factor (BAFF) and CXCL13 concentrations (P < 0·0001). CSF CXCL10 did not correlate with clinical severity or relapse using grouped data, although it did in some patients. Among seven types of immunotherapy, including rituximab or chemotherapy, only adrenocorticotrophic hormone (ACTH) monotherapy showed reduced CSF CXCL10, but prospective longitudinal studies of ACTH combination therapies indicated no reduction in CXCL10 despite clinical improvement (P < 0·0001). CXCL10 concentrations were 11-fold higher in CSF and twofold higher in serum by multiplexed fluorescent bead-based immunoassay than enzyme-linked immunosorbent assay, but the two correlated (r = 0·7 and 0·83). In serum, no group differences for CXCL9 or CXCL11 were found. CXCR3 expression on CD4+ T cells was fivefold higher in those from CSF than blood, but was not increased in OMS or altered by conventional immunotherapy. These data suggest alternative roles for CXCL10 in OMS. Over-expression of CXCL10 was not reduced by clinical immunotherapies as a whole, indicating the need for better therapeutic approaches. PMID:23600831

Epilepsy in children with subacute sclerosing panencephalitis.

PubMed

Jović, Nebojša J

2013-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

Movement - uncontrollable

MedlinePlus

... movements; Body movements - uncontrollable; Dyskinesia; Athetosis; Myoclonus; Ballismus Images Central nervous system and peripheral nervous system References Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease ...

A Case Report on Dyskinesia Following Rivastigmine Patch 13.3 mg/24 hours for Alzheimer's Disease: Perspective in the Movement Disorders Spectrum Following Use of Cholinesterase Inhibitors.

PubMed

Diaz, Maria Cristina B; Rosales, Raymond L

2015-08-01

Current reports on movement disorder adverse effects of acetylcholinesterase inhibitors only include extrapyramidal symptoms and myoclonus.Here is a case of an 81-year-old female Filipino with dementia who presented with first-onset generalized choreiform movements.The etiology of the clinical finding of dyskinesia was investigated through laboratories, neuroimaging, and electroencephalogram, all of which yielded negative results. Review of her medications included the rivastigmine (Exelon) patch, which had just been increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes excluded, a trial discontinuation of rivastigmine, showed decreased frequency of the dyskinesia 48 hours after, with complete resolution after 6 days, and no recurrence since then.This case thus presents a probable association or causality between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch because of clear temporal proximity, lack of alternative explanations, and a reversal of the dyskinesia upon medicament discontinuation.

Clinical aspects of juvenile myoclonic epilepsy.

PubMed

Genton, Pierre; Thomas, Pierre; Kasteleijn-Nolst Trenité, Dorothee G A; Medina, Marco Tulio; Salas-Puig, Javier

2013-07-01

Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise. Copyright © 2013. Published by Elsevier Inc.

Neurosyphilis as a great imitator: a case report.

PubMed

Sabre, Liis; Braschinsky, Mark; Taba, Pille

2016-07-28

Neurosyphilis is defined as any involvement of the central nervous system by the bacterium Treponema pallidum. Movement disorders as manifestations of syphilis have been reported quite rarely. We report a case of a 42-year-old Russian man living in Estonia with rapidly progressive dementia and movement disorders manifesting as myoclonus, cerebellar ataxia and parkinsonism. The mini mental state examination score was 12/30. After excluding different neurodegenerative causes, further diagnostic testing was consistent with neurosyphilis. Treatment with penicillin was started and 6 months later his mini mental state examination score was 25/30 and he had no myoclonus, parkinsonism or cerebellar dysfunction. Since syphilis is easily diagnosed and treatable, it should be considered and tested in patients with cognitive impairment and movement disorders.

Neurological Manifestations of Autosomal Dominant Alzheimer’s Disease from the DIAN cohort and a meta-analysis

PubMed Central

Tang, Mengxuan; Ryman, Davis C.; McDade, Eric; Jasielec, Mateusz S.; Buckles, Virginia D.; Cairns, Nigel J.; Fagan, Anne M.; Goate, Alison; Marcus, Daniel S.; Xiong, Chengjie; Allegri, Ricardo F.; Chhatwal, Jasmeer P.; Danek, Adrian; Farlow, Martin R.; Fox, Nick; Ghetti, Bernardino; Graff-Radford, Neill R.; Laske, Christopher; Martins, Ralph N.; Masters, Colin L.; Mayeux, Richard P.; Ringman, John M.; Rossor, Martin N.; Salloway, Stephen P.; Schofield, Peter R.; Morris, John C.; Bateman, Randall J.

2016-01-01

Background To evaluate the prevalence rates of non-amnestic neurological symptoms of autosomal dominant Alzheimer’s disease (ADAD) in the DIAN Observational Study (DIAN–OBS) and the published literature. Analyses were conducted to clarify the prevalence of neurological manifestations of ADAD mutation carriers as a group. Methods Using the DIAN-OBS study database and 189 peer-reviewed publications on ADAD families, we extracted individual-level data on age of symptom onset, disease course from onset to death, and the presence of fourteen neurological findings that have been reported in association with ADAD and included symptomatic subjects only. The primary outcomes were the rates of various neurological symptoms and the contribution of age and specific mutations on the prevalence of the neurological symptoms. Analyses were done using descriptive statistics, comparisons of means and frequencies and multivariable linear regression. Findings Our meta-analysis dataset includes 1228 affected individuals, with detailed clinical descriptions of 753. The DIAN–OBS dataset included 107 individuals with detailed clinical data. The most prevalent non-amnestic cognitive manifestations in DIAN were those typical of mild-moderate Alzheimer’s disease, including visual agnosia (95% CI 45·7%–64·6%), aphasia (43·8%–62·7%), and behavioral changes (51·5%–70·0%). The prevalence of non-amnestic cognitive manifestations from the published literature were (95% CI 3·9%–7·2%) for visual agnosia, (20%–26%) for aphasia, and (28·4%–35·1%) for behavioral changes. Prevalence of non-cognitive neurological manifestations in DIAN was low, including myoclonus and spasticity (3·8%–15·0%), seizures (0·5%–9·1%) and moderate for parkinsonism (5·3%–17·1%). Whereas, in the published literature the prevalence was (95% CI 16·6%–22·2% and 12·5%–17·6%) for myoclonus and spasticity, (10·1%–15·0%) for parkinsonism, and (17·4%–23·2%) for seizures. Age of onset appears to influence the prevalence of several non-cognitive manifestations in both groups, stroke being more prevalent at older ages of onset with motor symptoms being more prevalent at younger age of onset and at an older age of onset. Further, symptoms were overall more common in later clinical stages of disease. Interpretation Comparing the prevalence of non-amnestic and non-cognitive clinical features in DIAN with the published literature indicates that previous reports of non-cognitive features are likely overestimated whereas DIAN identifies higher non-amnestic cognitive symptoms in addition to memory impairment. The non-cognitive clinical manifestations of AD appear to be in a minor fraction of mild-moderate ADAD and is likely influenced by disease severity, environmental and genetic factors in addition to genetic status. The results of this work clarify the clinical presentations of ADAD including the effects of age and disease stage. Attention to these neurologic symptoms and screening for ADAD mutations are warranted if present. Future work is needed to determine the factors which cause these neurologic symptoms. PMID:27777020

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1.

PubMed

Tiedt, Hannes O; Benjamin, Beate; Niedeggen, Michael; Lueschow, Andreas

2018-02-22

In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age. © 2018 S. Karger AG, Basel.

Redefining progressive encephalomyelitis with rigidity and myoclonus after the discovery of antibodies to glycine receptors.

PubMed

Crisp, Sarah J; Balint, Bettina; Vincent, Angela

2017-06-01

This review highlights the recent discovery of antibodies to glycine receptor (GlyR-Ab) and discusses the relationship between these antibodies and neurological disorders. Since the initial description in 2008 of antibodies to glycine receptors (GlyR-Abs) in a patient with progressive encephalomyelitis with rigidity and myoclonus (PERM), these antibodies have been found in PERM and in some patients with a variety of stiff person spectrum (SPS) or related disorders. Patients with GlyR-Abs often improve with aggressive immunotherapy, and antibody titres correlate with disease severity. Around 25% of patients have another autoimmune condition and 10-20% have an underlying malignancy. GlyR-Abs bind to extracellular determinants, are mainly Immunoglobulin G1 subclass and induce GlyR internalization in Human embryonic kidney 293 cells, suggesting pathogenicity. The spectrum of neurological disease associated with GlyR-Abs has not been fully characterized, and lower titres may not be syndrome specific, but GlyR-Abs, like antibodies to other neuronal cell-surface antigens, define immunotherapy-responsive disease and are likely to be pathogenic. This distinguishes them from the glutamic acid decarboxylase antibodies that can also be found at high titres in patients with classical stiff person syndrome which is more often chronic and relatively resistant to immunological treatments. Irrespective of the clinical features, GlyR-Abs are helpful in the diagnosis of patients who very often have a subacute, progressive and life-threatening disorder which shows a favourable response to immunotherapy.

Myoclonus

MedlinePlus

... injury, stroke, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, or other ... example, is in the brain stem close to structures that are responsible for the startle response, an ...

A 405-kb cosmid contig and HindIII restriction map of the progressive myoclonus epilepsy type 1 (EPM1) candidate region in 21q22.3

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

Lafreniere, R.G.; Rouleau, G.A.; De Jong, P.J.

1995-09-01

As a step toward identifying the molecular defect in patients afflicted with progressive myoclonus epilepsy type 1 (EPM1), we have assembled a cosmid contig of the candidate EPM1 region in 21q22.3. The contig constitutes a collection of 87 different cosmids spanning 405 kb based on a derived HindIII restriction map. Potential CpG-rich islands have been identified based on the restriction map generated from eight different rare-cutting enzymes. This contig contains the genetic material required for the isolation of expressed sequences and the identification of the gene defective in EPM1 and possibly other disorders mapping to this region. 15 refs., 1more » fig.« less

Altered functional brain connectivity in children and young people with opsoclonus-myoclonus syndrome.

PubMed

Chekroud, Adam M; Anand, Geetha; Yong, Jean; Pike, Michael; Bridge, Holly

2017-01-01

Opsoclonus-myoclonus syndrome (OMS) is a rare, poorly understood condition that can result in long-term cognitive, behavioural, and motor sequelae. Several studies have investigated structural brain changes associated with this condition, but little is known about changes in function. This study aimed to investigate changes in brain functional connectivity in patients with OMS. Seven patients with OMS and 10 age-matched comparison participants underwent 3T magnetic resonance imaging (MRI) to acquire resting-state functional MRI data (whole-brain echo-planar images; 2mm isotropic voxels; multiband factor ×2) for a cross-sectional study. A seed-based analysis identified brain regions in which signal changes over time correlated with the cerebellum. Model-free analysis was used to determine brain networks showing altered connectivity. In patients with OMS, the motor cortex showed significantly reduced connectivity, and the occipito-parietal region significantly increased connectivity with the cerebellum relative to the comparison group. A model-free analysis also showed extensive connectivity within a visual network, including the cerebellum and basal ganglia, not present in the comparison group. No other networks showed any differences between groups. Patients with OMS showed reduced connectivity between the cerebellum and motor cortex, but increased connectivity with occipito-parietal regions. This pattern of change supports widespread brain involvement in OMS. © 2016 Mac Keith Press.

Does corticobasal degeneration exist? A clinicopathological re-evaluation.

PubMed

Ling, Helen; O'Sullivan, Sean S; Holton, Janice L; Revesz, Tamas; Massey, Luke A; Williams, David R; Paviour, Dominic C; Lees, Andrew J

2010-07-01

The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed.

Voltage-Gated Potassium Channel Autoimmunity Mimicking Creutzfeldt-Jakob Disease

PubMed Central

Geschwind, Michael D.; Tan, K. Meng; Lennon, Vanda A.; Barajas, Ramon F.; Haman, Aissa; Klein, Christopher J.; Josephson, S. Andrew; Pittock, Sean J.

2009-01-01

Background Rapidly progressive dementia has a variety of causes, including Creutzfeldt-Jakob disease (CJD) and neuronal voltage-gated potassium channel (VGKC) autoantibody–associated encephalopathy. Objective To describe patients thought initially to have CJD but found subsequently to have immunotherapy-responsive VGKC autoimmunity. Design Observational, prospective case series. Setting Department of Neurology, Mayo Clinic, and the Memory and Aging Center, University of California, San Francisco. Patients A clinical serologic cohort of 15 patients referred for paraneoplastic autoantibody evaluation. Seven patients were evaluated clinically by at least one of us. Clinical information for the remaining patients was obtained by physician interview or medical record review. Main Outcome Measures Clinical features, magnetic resonance imaging abnormalities, electroencephalographic patterns, cerebrospinal fluid analyses, and responses to immunomodulatory therapy. Results All the patients presented subacutely with neurologic manifestations, including rapidly progressive dementia, myoclonus, extrapyramidal dysfunction, visual hallucinations, psychiatric disturbance, and seizures; most (60%) satisfied World Health Organization diagnostic criteria for CJD. Magnetic resonance imaging abnormalities included cerebral cortical diffusion-weighted imaging hyperintensities. Electroencephalographic abnormalities included diffuse slowing, frontal intermittent rhythmic delta activity, and focal epileptogenic activity but not periodic sharp wave complexes. Cerebrospinal fluid 14-3-3 protein or neuron-specific enolase levels were elevated in 5 of 8 patients. Hyponatremia was common (60%). Neoplasia was confirmed histologically in 5 patients (33%) and was suspected in another 5. Most patients’ conditions (92%) improved after immunomodulatory therapy. Conclusions Clinical, radiologic, electrophysiologic, and laboratory findings in VGKC autoantibody–associated encephalopathy may be confused with those of CJD. Serologic evaluation for markers of neurologic autoimmunity, including VGKC autoantibodies, may be warranted in suspected CJD cases. PMID:18852349

Vision loss due to coincident ocular and central causes in a patient with Heidenhain variant Creutzfeldt-Jakob disease.

PubMed

Foundas, Maria; Donaldson, Mark D; McAllister, Ian L; Bridges, Leslie R

2008-03-01

Creutzfeldt-Jakob disease (CJD) is a degenerative disease of the brain associated with a rapidly progressive spongiform encephalopathy. Visual symptoms and neuro-ophthalmological signs are not infrequent, and presentation to an ophthalmologist may result. A case is reported of an 89-years-old gentleman who presented with a short history of isolated deterioration in vision. He underwent ocular intervention but subsequently developed progressive dementia, asterixis, myoclonus, cerebellar and extrapyramidal signs, and cortical blindness. An electroencephalogram was consistent with CJD. The patient progressively deteriorated and died 9 weeks after symptom onset. Limited post-mortem examination confirmed CJD.

Conservative management of severe serotonin syndrome with coma, myoclonus, and crossed-extensor reflex complicated by hepatic encephalopathy.

PubMed

Ramachandran, Vignesh; Ding, Belicia; George, Rollin; Novakovic, Matthew

2018-01-01

Serotonin syndrome (SS) is an underrecognized and potentially fatal disorder that occurs secondary to combinational use or overdose of a single serotonergic medication. The presentation may be complicated by hepatic encephalopathy in cirrhotic patients, which may also affect metabolism of these serotonergic agents. The authors report a rare case of severe SS complicated by hepatic encephalopathy secondary to cirrhosis in a 52-year-old woman after an increase in her home dosage of fluoxetine and addition of other psychiatric medications.

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

PubMed Central

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

2016-01-01

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

Genetics Home Reference: ataxia with oculomotor apraxia

MedlinePlus

... muscle twitches (myoclonus), and disturbances in nerve function (neuropathy). In type 1, ataxia beings around age 4; ... all individuals with ataxia with oculomotor apraxia develop neuropathy, which leads to absent reflexes and weakness. Neuropathy ...

Progressive myoclonus epilepsy EPM1 locus maps to a 175-kb interval in distal 21q

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

Virtaneva, K.; Miao, J.; Traeskelin, A.L.

1996-06-01

The EPM1 locus responsible for progressive myoclonus epilepsy of Unverricht-Lundborg type (MIM 254800) maps to a region in distal chromosome 21q where positional cloning has been hampered by the lack of physical and genetic mapping resolution. We here report the use of a recently constituted contig of cosmid, BAC, and P1 clones that allowed new polymorphic markers to be positioned. These were typed in 53 unrelated disease families from an isolated Finnish population in which a putative single ancestral EPM1 mutation has segregated for an estimated 100 generations. By thus exploiting historical recombinations in haplotype analysis, EPM1 could be assignedmore » to the {approximately}175-kb interval between the markers D21S2040 and D21S1259. 26 refs., 2 figs., 4 tabs.« less

Array-Based Gene Discovery with Three Unrelated Subjects Shows SCARB2/LIMP-2 Deficiency Causes Myoclonus Epilepsy and Glomerulosclerosis

PubMed Central

Berkovic, Samuel F.; Dibbens, Leanne M.; Oshlack, Alicia; Silver, Jeremy D.; Katerelos, Marina; Vears, Danya F.; Lüllmann-Rauch, Renate; Blanz, Judith; Zhang, Ke Wei; Stankovich, Jim; Kalnins, Renate M.; Dowling, John P.; Andermann, Eva; Andermann, Frederick; Faldini, Enrico; D'Hooge, Rudi; Vadlamudi, Lata; Macdonell, Richard A.; Hodgson, Bree L.; Bayly, Marta A.; Savige, Judy; Mulley, John C.; Smyth, Gordon K.; Power, David A.; Saftig, Paul; Bahlo, Melanie

2008-01-01

Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies. PMID:18308289

Cortical-basal ganglionic degeneration.

PubMed

Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

1990-08-01

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

Genetics Home Reference: action myoclonus-renal failure syndrome

MedlinePlus

... Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

A large early-onset Alzheimer`s disease pedigree linked to chromosome 14q24.3

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

Hannequin, D.; Campion, D.; Brice, A.

1994-09-01

A large French pedigree including 34 subjects with early-onset progressive dementia was identified. In patients, the mean age-at-onset was 46 {plus_minus} 3.5 (SD) years and the mean age at death 52.6 {plus_minus} 5.7 (SD) years. No evidence for anticipation or genetic imprinting was found. Twelve patients were clinically diagnosed as probable Alzheimer`s disease (AD) according to the NINCDS-ADRDA criteria. Myoclonus and extrapyramidal signs were common and seizures were found in all affected subjects. At autopsy, neuropathological changes typical of AD were present in two brains. A significant lod score of 5.38 was observed at a recombination fraction of {theta} =more » 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. Furthermore, no obligate recombinant was observed with markers D14S77 and D14S71. Typing other genetic markers in this region will allow us to localize more precisely the pathological gene.« less

Clinical features of dog- and bat-acquired rabies in humans.

PubMed

Udow, Sean J; Marrie, Ruth Ann; Jackson, Alan C

2013-09-01

Clinical differences in rabies due to canine and bat rabies virus variants have been noted, but no detailed studies have been reported to support these observations. Using the Morbidity and Mortality Weekly Report and PubMed, we identified 142 case reports of rabies from North America, South America, Europe, Africa, and Asia. We systematically abstracted 126 selected data elements and compared clinical features and investigation results in dog- and bat-acquired cases of rabies. Survivors and cases acquired from aerosolized viral exposure or tissue/organ transplant were excluded (n = 20). Of 122 cases, 49 (40.2%) were dog-acquired and 54 (44.3%) were bat-acquired. Bat-acquired cases of rabies were more often misdiagnosed and lacked a bite history. Encephalopathy, hydrophobia, and aerophobia were more common in dog-acquired rabies. Abnormal cranial nerve, motor, and sensory examinations, tremor, myoclonus, local sensory symptoms, symptoms at the exposure site, and local symptoms in the absence of a bite or scratch were more common in patients with bat-acquired rabies, as was increased cerebrospinal fluid protein (P = .031). Patients with paralytic rabies had longer survival times than those with encephalitic rabies, and also had shorter incubation periods if they had received postexposure prophylaxis. Clinical differences in dog- and bat-acquired rabies may reflect differences in the route of viral spread of rabies virus variants in the nervous system, although certain variants could cause more severe dysfunction in neuronal subpopulations. Recognition that bat-acquired rabies may present with different clinical manifestations than dog-acquired rabies may help improve the early diagnosis of rabies.

Clinical features of movement disorders.

PubMed

Yung, C Y

1983-08-01

The descriptive aspects of all types of movement disorders and their related syndromes and terminologies used in the literature are reviewed and described. This comprises the features of (a) movement disorders secondary to neurological diseases affecting the extrapyramidal motor system, such as: athetosis, chorea, dystonia, hemiballismus, myoclonus, tremor, tics and spasm, (b) drug induced movement disorders, such as: akathisia, akinesia, hyperkinesia, dyskinesias, extrapyramidal syndrome, and tardive dyskinesia, and (c) abnormal movements in psychiatric disorders, such as: mannerism, stereotyped behaviour and psychomotor retardation. It is intended to bring about a more comprehensive overview of these movement disorders from a phenomenological perspective, so that clinicians can familiarize with these features for diagnosis. Some general statements are made in regard to some of the characteristics of movement disorders.

Genetics Home Reference: Lafora progressive myoclonus epilepsy

MedlinePlus

... following the discovery of the EPM2A and NHLRC1 genes. Hum Mutat. 2009 May;30(5):715-23. doi: 10.1002/humu.20954. Review. ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Beyond cervical lipomas: myoclonus, gait disorder and multisystem involvement leading to mitochondrial disease.

PubMed

López-Blanco, Roberto; Rojo-Sebastián, Ana; Torregrosa-Martínez, Maria Henedina; Blazquez, Alberto

2017-06-19

Madelung's disease (benign symmetric lipomatosis) is a rare syndrome in which there are multiple lipomas around the neck, upper limbs and trunk in the context of chronic alcoholism. We report on a female patient with lipomas and slightly progressive myoclonus, neuropathy, myopathy, ataxia and respiratory systemic involvement (labelled in the past as Madelung's disease). Multisystem involvement and family history of lipomas led to the development of mitochondrial genetic tests, which can assess two concurrent mitochondrial mutations: the m.8344A>G mutation in MT-TK gene, related MERRF (myoclonic epilepsy with ragged-red fibre) phenotype and m.14484T>C mutation in the MT-ND6 gene responsible for Leber hereditary optic neuropathy phenotype. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

PubMed

Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Motor Events during Healthy Sleep: A Quantitative Polysomnographic Study

PubMed Central

Frauscher, Birgit; Gabelia, David; Mitterling, Thomas; Biermayr, Marlene; Bregler, Deborah; Ehrmann, Laura; Ulmer, Hanno; Högl, Birgit

2014-01-01

Study Objectives: Many sleep disorders are characterized by increased motor activity during sleep. In contrast, studies on motor activity during physiological sleep are largely lacking. We quantitatively investigated a large range of motor phenomena during polysomnography in physiological sleep. Design: Prospective polysomnographic investigation. Setting: Academic referral sleep laboratory. Participants: One hundred healthy sleepers age 19-77 y were strictly selected from a representative population sample by a two-step screening procedure. Interventions: N/A. Measurements and Results: Polysomnography according to American Academy of Sleep Medicine (AASM) standards was performed, and quantitative normative values were established for periodic limb movements in sleep (PLMS), high frequency leg movements (HFLM), fragmentary myoclonus (FM), neck myoclonus (NM), and rapid eye movement (REM)-related electromyographic (EMG) activity. Thirty-six subjects had a PLMS index > 5/h, 18 had a PLMS index > 15/h (90th percentile: 24.8/h). Thirty-three subjects had HFLM (90th percentile: four sequences/night). All subjects had FM (90th percentile 143.7/h sleep). Nine subjects fulfilled AASM criteria for excessive FM. Thirty-five subjects had NM (90th percentile: 8.8/h REM sleep). For REM sleep, different EMG activity measures for the mentalis and flexor digitorum superficialis muscles were calculated: the 90th percentile for phasic mentalis EMG activity for 30-sec epochs according to AASM recommendation was 15.6%, and for tonic mentalis EMG activity 2.6%. Twenty-five subjects exceeded the recently proposed phasic mentalis cutoff of 11%. None of the subjects exceeded the tonic mentalis cutoff of 9.6%. Conclusion: Quantification of motor phenomena is a basic prerequisite to develop normative values, and is a first step toward a more precise description of the various motor phenomena present during sleep. Because rates of motor events were unexpectedly high even in physiological sleep, the future use of normative values for both research and clinical routine is essential. Citation: Frauscher B; Gabelia D; Mitterling T; Biermayr M; Bregler D; Ehrmann L; Ulmer H; Högl B. Motor events during healthy sleep: a quantitative polysomnographic study. SLEEP 2014;37(4):763-773. PMID:24744455

Genetics Home Reference: hereditary cerebral amyloid angiopathy

MedlinePlus

... uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus). Two types of hereditary cerebral amyloid angiopathy , known as familial ...

Intoxications of the new psychoactive substance 5-(2-aminopropyl)indole (5-IT): a case series from the Swedish STRIDA project.

PubMed

Bäckberg, M; Beck, O; Hultén, P; Rosengren-Holmberg, J; Helander, A

2014-07-01

5-(2-aminopropyl)indole (5-IT) is a new psychoactive substance (NPS; "legal high" or "research chemical") structurally related to indoleamines and substituted phenethylamines and implicated in several fatalities. We describe the clinical characteristics and results of laboratory investigations of 14 analytically confirmed nonfatal cases of 5-IT intoxication within the Swedish STRIDA project. Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden in 2012. Blood and/or urine samples were collected from intoxicated patients presenting to emergency departments and intensive care units over the country. Analysis of NPS was performed using an LC-MS/MS multi-component method. Clinical data were collected when caregivers consulted the Poisons Information Centre and also retrieved from medical records. The severity of poisoning was graded retrospectively using the Poisoning Severity Score (PSS). Eleven male and three female patients (age: 21-53 years, median: 27) tested positive for 5-IT in 2012, all cases appearing in April-July. The 5-IT concentration in serum ranged between 0.015 and 0.59 μg/mL (median: 0.22; n = 8) and in urine between 0.005 and 24.7 μg/mL (median: 5.95; n = 12). Five intoxications were indicated to be caused by 5-IT alone, whereas additional psychoactive substances were detected in the other nine cases. Six (43%) of fourteen cases were graded as severe (PSS 3), five (36%) as moderate (PSS 2), and three (21%) as minor (PSS 1) poisonings. In the severe cases, agitation, hallucinations, dilated pupils without light reaction, tachycardia, hypertension, hyperthermia, myoclonus, muscle rigidity, arrhythmias, seizures, rhabdomyolysis, and/or renal failure were noted. The results demonstrated that severe clinical toxicity was commonly present in patients with analytically confirmed 5-IT exposure. The clinical features are consistent with a sympathomimetic toxidrome, and some patients also displayed symptoms associated with serotonin toxicity.

Understanding the pathophysiology of reflex epilepsy using simultaneous EEG-fMRI.

PubMed

Sandhya, Manglore; Bharath, Rose Dawn; Panda, Rajanikant; Chandra, S R; Kumar, Naveen; George, Lija; Thamodharan, A; Gupta, Arun Kumar; Satishchandra, P

2014-03-01

Measuring neuro-haemodynamic correlates in the brain of epilepsy patients using EEG-fMRI has opened new avenues in clinical neuroscience, as these are two complementary methods for understanding brain function. In this study, we investigated three patients with drug-resistant reflex epilepsy using EEG-fMRI. Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. The analysis of EEG-fMRI data was based on the visual identification of interictal epileptiform discharges on scalp EEG. The convolution of onset time and duration of these epilepsy spikes was estimated, and using these condition-specific effects in a general linear model approach, we evaluated activation of fMRI. Patients with startle myoclonus epilepsy experienced epilepsy in response to sudden sound or touch, in association with increased delta and theta activity with a spike-and-slow-wave pattern of interictal epileptiform discharges on EEG and fronto-parietal network activation pattern on SPECT and EEG-fMRI. Eating epilepsy was triggered by sight or smell of food and fronto-temporal discharges were noted on video-EEG (VEEG). Similarly, fronto-temporo-parietal involvement was noted on SPECT and EEG-fMRI. Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement. SPECT and EEG fMRI revealed a similar fronto-parietal-occipital involvement. From these results, we conclude that continuous EEG recording can improve the modelling of BOLD changes related to interictal epileptic activity and this can thus be used to understand the neuro-haemodynamic substrates involved in reflex epilepsy.

A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood.

PubMed

Yang, Zhixian; Liu, Xiaoyan; Qin, Jiong; Zhang, Yuehua; Bao, Xinhua; Chang, Xingzhi; Wang, Shuang; Wu, Ye; Xiong, Hui

2009-04-01

To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient's arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient's arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.

Canine (Pet Dog) Tumor Microsurgery and Intratumoral Concentration and Safety of Metronomic Chlorambucil for Spontaneous Glioma: A Phase I Clinical Trial.

PubMed

Bentley, R Timothy; Thomovsky, Stephanie A; Miller, Margaret A; Knapp, Deborah W; Cohen-Gadol, Aaron A

2018-06-04

Metronomic (daily low-dose) chlorambucil requires further study before use in human patients with glioma. The aim of this study was to investigate distribution and safety of metronomic chlorambucil in naturally occurring canine glioma. Eight client-owned (pet) dogs with newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil was administered preoperatively at 4 mg/m 2 every 24 hours for ≥3 days and continued postoperatively until death or dose-limiting adverse events. Chlorambucil concentrations in the surgical glioma specimen, cerebrospinal fluid, and serum were analyzed. Dogs additionally received lomustine postoperatively. Dogs were monitored for seizures, myoclonus, cytopenias, and tumor recurrence. Complete microsurgical resection was achieved in 7 oligodendrogliomas and 1 astrocytoma (6 high grade, 2 low grade). Median surgical glioma specimen chlorambucil concentration was 0.52 ng/g (range, 0-2.62 ng/g), or 37% (range, 0%-178%) of serum concentration. Median cerebrospinal fluid concentration was 0.1 ng/mL (range, 0-0.3 ng/mL). Chlorambucil was not associated with increase in seizure activity. Six dogs displayed prolonged seizure-free intervals. There was no myoclonus. Three dogs developed asymptomatic thrombocytopenia after 8-12 months of chlorambucil. Median progression-free survival was 253 days (range, 63-860 days). Median overall survival was 257 days (range, 64-860 days). The presence of intratumoral chlorambucil indicated an altered blood-brain barrier that varied from case to case. Despite sporadic previous reports of neurotoxicity, prolonged seizure-free intervals supported a high safety margin at this dose in this species. Metronomic chlorambucil was well tolerated. Spontaneous canine glioma offers a robust preclinical model. Copyright © 2018 Elsevier Inc. All rights reserved.

[A family with progressive myoclonus epilepsy (author's transl)].

PubMed

Ammann, F; Schweingruber, R; Paro, M

1978-01-01

To begin, a survey of the literature concerning the group of progressive myoclonic epilepsies is presented, from the initial descriptions of Unverricht (1891) and Lundborg (1903) to the present. Recently several subforms of this nosologic entity have been delineated according to the mode of inheritance, time of manifestation, severity of course, and biochemical characteristics (i.e, eventual demonstration of mucopolysaccharide storage in Lafora bodies or diffuse in the central nervous system and other organs). The most useful classification stems from Diebold (1972): early (I) and late (II) forms of the Lafora type having autosomal recessive inheritance; an autosomal recessive early form (III) and an autosomal dominant late form (IV) with degenerative changes in the central nervous system without biochemical disturbances. The authors describe 3 young siblings from Southern Tyrol, who clinically manifested the cardinal symptoms of the disease in addition to extrapyramidal cerebellar disturbances. In spite of extensive bioptic and biochemical examinations, neither Lafora bodies nor diffuse deposits or excretion of mucopolysaccharides could be demonstrated. The distant blood relationship between the parents of these patients supports the assumption of an autosomal recessive mode of transmission. The relatively early manifestation of the disease and the demonstration of degenerative changes within the central nervous system suggest assignment of these patients to Diebold's subgroup III of the progressive myoclonic epilepsy.

Cerebral lactic acidosis correlates with neurological impairment in MELAS.

PubMed

Kaufmann, P; Shungu, D C; Sano, M C; Jhung, S; Engelstad, K; Mitsis, E; Mao, X; Shanske, S; Hirano, M; DiMauro, S; De Vivo, D C

2004-04-27

To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.

Differential diagnosis of epileptic seizures in infancy including the neonatal period.

PubMed

Cross, J Helen

2013-08-01

It is important to accurately diagnose epileptic seizures in early life to optimise management and prognosis. Conversely, however, many different movements and behaviours may manifest in the neonatal period and infancy that may not have at their root cause a change in electrical activity of the brain. It is important to distinguish them from epileptic seizures to avoid over- and inappropriate treatment. Some are physiological in the normal infant, such as neonatal tremor, benign neonatal sleep myoclonus, and shuddering attacks, whereas others may herald alternative rare neurological diagnoses with differing prognoses such as hyperekplexia, paroxysmal extreme pain disorder and alternating hemiplegia of childhood. Here are highlighted the key clinical features that distinguish some of these disorders, their management and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy.

PubMed

Coppola, Antonietta; Caccavale, Carmela; Santulli, Lia; Balestrini, Simona; Cagnetti, Claudia; Licchetta, Laura; Esposito, Marcello; Bisulli, Francesca; Tinuper, Paolo; Provinciali, Leandro; Minetti, Carlo; Zara, Federico; Striano, Pasquale; Striano, Salvatore

2016-03-01

The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME). Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls. There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms. Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them. Copyright © 2016 Elsevier Inc. All rights reserved.

The α2B adrenergic receptor is mutant in cortical myoclonus and epilepsy

PubMed Central

De Fusco, Maurizio; Vago, Riccardo; Striano, Pasquale; Di Bonaventura, Carlo; Zara, Federico; Mei, Davide; Kim, Min Seuk; Muallem, Shmuel; Chen, Yunjia; Wang, Qin; Guerrini, Renzo; Casari, Giorgio

2013-01-01

Objective Autosomal dominant cortical myoclonus and epilepsy (ADCME) is characterized by distal, fairly rhythmic myoclonus and epilepsy with variable severity. We have previously mapped the disease locus on chromosome 2p11.1-q12.2 by genome-wide linkage analysis. Additional pedigrees affected by similar forms of epilepsy have been associated to chromosome 8q, 5p and 3q, but none of the causing genes has been identified. We aim at identifying the mutant gene responsible for this epileptic form. Methods Genes included in the ADCME critical region were prioritized and directly sequenced. Co-immunoprecipitation, immunofluorescence and electrophysiology approaches on transfected human cells have been utilized for testing the functional significance of the identified mutation. Results Here we show that mutation in the α2-adrenergic receptor subtype B (α2B-AR) associates to ADCME by identifying a novel in-frame insertion/deletion in two Italian families. The mutation alters several conserved residues of the third intracellular (3i) loop, neither hampering the α2B-AR plasma membrane localization nor the arrestin-mediated internalization capacity, but altering the binding with the scaffolding protein spinophilin upon neurotransmitter activation. Spinophilin, in turn, regulates interaction of GPCRs with Regulators of G proteins Signaling proteins. Accordingly, the mutant α2B-AR increases the epinephrine-stimulated calcium signaling. Interpretation The identified mutation is responsible for ADCME, as the loss of α2B-AR/spinophilin interaction causes a gain of function effect. This work implicates for the first time the α-adrenergic system in human epilepsy and opens new ways for understanding the molecular pathway of epileptogenesis, widening the spectrum of possible therapeutic targets. PMID:24114805

Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).

PubMed

Tang, Mengxuan; Ryman, Davis C; McDade, Eric; Jasielec, Mateusz S; Buckles, Virginia D; Cairns, Nigel J; Fagan, Anne M; Goate, Alison; Marcus, Daniel S; Xiong, Chengjie; Allegri, Ricardo F; Chhatwal, Jasmeer P; Danek, Adrian; Farlow, Martin R; Fox, Nick C; Ghetti, Bernardino; Graff-Radford, Neill R; Laske, Christopher; Martins, Ralph N; Masters, Colin L; Mayeux, Richard P; Ringman, John M; Rossor, Martin N; Salloway, Stephen P; Schofield, Peter R; Morris, John C; Bateman, Randall J

2016-12-01

Autosomal dominant familial Alzheimer's disease (ADAD) is a rare disorder with non-amnestic neurological symptoms in some clinical presentations. We aimed to compile and compare data from symptomatic participants in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) with those reported in the literature to estimate the prevalences of non-amnestic neurological symptoms in participants with ADAD. We prospectively collected data from the DIAN-OBS database, which recruited participants from study centres in the USA, Europe, and Australia, between Feb 29, 2008, and July 1, 2014. We also did a systematic review of publications to extract individual-level clinical data for symptomatic participants with ADAD. We used data for age of onset (from first report of cognitive decline), disease course from onset to death, and the presence of 13 neurological findings that have been reported in association with ADAD. Using multivariable linear regression, we investigated the prevalences of various non-amnestic neurological symptoms and the contributions of age of onset and specific mutation type on symptoms. The DIAN-OBS dataset included 107 individuals with detailed clinical data (forming the DIAN-OBS cohort). Our systematic review yielded 188 publications reporting on 1228 symptomatic individuals, with detailed neurological examination descriptions available for 753 individuals (forming the published data cohort). The most prevalent non-amnestic cognitive manifestations in participants in the DIAN-OBS cohort were those typical of mild to moderate Alzheimer's disease, including visual agnosia (55·1%, 95% CI 45·7-64·6), aphasia (57·9%, 48·6-67·3), and behavioural changes (61·7%, 51·5-70·0). Non-amnestic cognitive manifestations were less prevalent in the published data cohort (eg, visual agnosia [5·6%, 3·9-7·2], aphasia [23·0%, 20·0-26·0], and behavioural changes [31·7%, 28·4-35·1]). Prevalence of non-cognitive neurological manifestations in the DIAN-OBS cohort was low, including myoclonus and spasticity (9·3%, 95% CI 3·8-15·0), and seizures (2·8%, 0·5-5·9) and moderate for parkinsonism (11·2%, 5·3-17·1). By constrast, prevalence was higher in the published data cohort for myoclonus and spasticity (19·4%, 16·6-22·2 and 15·0%, 12·5-17·6, respectively), parkinsonism (12·5%, 10·1-15·0), and seizures (20·3%, 17·4-23·2). In an analysis of the published data cohort, ischaemic stroke was more prevalent at older ages of onset of symptoms of ADAD (odds ratio 1·09 per 1 year increase in age of onset, 95% CI 1·04-1·14, p=0·0003); and motor symptoms were more common at younger age of onset (myoclonus 0·93, 0·90-0·97, p=0·0007; seizures 0·95, 0·92-0·98, p=0·0018; corticobulbar deficits 0·91, 0·86-0·96, p=0·0012; and cerebellar ataxia 0·82, 0·74-0·91, p=0·0002). In the DIAN-OBS cohort, non-cognitive symptoms were more common at more severe stages of disease. The non-cognitive clinical manifestations of Alzheimer's disease seem to affect a small proportion of participants with mild to moderate ADAD, and are probably influenced by disease severity, environmental, and genetic factors. When evaluating patients with potential ADAD, clinicians should note that cognitive symptoms typical of sporadic Alzheimer's disease are the most consistent finding, with some patients manifesting non-cognitive neurological symptoms. Future work is needed to determine the environmental and genetic factors that cause these neurological symptoms. National Institutes of Health and German Center for Neurodegenerative Diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy.

PubMed

Vilchez, David; Ros, Susana; Cifuentes, Daniel; Pujadas, Lluís; Vallès, Jordi; García-Fojeda, Belén; Criado-García, Olga; Fernández-Sánchez, Elena; Medraño-Fernández, Iria; Domínguez, Jorge; García-Rocha, Mar; Soriano, Eduardo; Rodríguez de Córdoba, Santiago; Guinovart, Joan J

2007-11-01

Glycogen synthesis is normally absent in neurons. However, inclusion bodies resembling abnormal glycogen accumulate in several neurological diseases, particularly in progressive myoclonus epilepsy or Lafora disease. We show here that mouse neurons have the enzymatic machinery for synthesizing glycogen, but that it is suppressed by retention of muscle glycogen synthase (MGS) in the phosphorylated, inactive state. This suppression was further ensured by a complex of laforin and malin, which are the two proteins whose mutations cause Lafora disease. The laforin-malin complex caused proteasome-dependent degradation both of the adaptor protein targeting to glycogen, PTG, which brings protein phosphatase 1 to MGS for activation, and of MGS itself. Enforced expression of PTG led to glycogen deposition in neurons and caused apoptosis. Therefore, the malin-laforin complex ensures a blockade of neuronal glycogen synthesis even under intense glycogenic conditions. Here we explain the formation of polyglucosan inclusions in Lafora disease by demonstrating a crucial role for laforin and malin in glycogen synthesis.

Indication of peripheral nerve hyperexcitability in adult-onset subacute sclerosing panencephalitis (SSPE).

PubMed

Schreurs, Annabel; Stålberg, Erik V; Punga, Anna Rostedt

2008-04-01

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune-resistant measles virus. Diagnostic hallmarks include widespread cortical dysfunction on EEG, myoclonus, white matter abnormalities on neuroradiological examination and the presence of IgG anti-measles antibodies in the cerebrospinal fluid. We present the first case of SSPE with signs of peripheral nerve hyperexcitability, observed as extra discharges following the compound motor action potential at motor nerve stimulation. In addition we demonstrate the importance of SSPE in the differential diagnosis of adult patients with psychiatric and neurological symptoms.

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

Andermann, F.; Andermann, E.; Carpenter, S.

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantlymore » inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.« less

Progressive myoclonic epilepsies

PubMed Central

Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

2014-01-01

Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized. PMID:24384641

Progressive myoclonic epilepsies: definitive and still undetermined causes.

PubMed

Franceschetti, Silvana; Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

2014-02-04

To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.

[Scans without Evidence of Dopamine Deficit (SWEDDs)].

PubMed

Mukai, Yohei; Murata, Miho

2016-01-01

Dopamine transporter (DaT) single-photon emission computed tomography (SPECT) and [18F]fluoro-L-DOPA ([18F]DOPA) positron emission tomography (PET) facilitate the investigation of dopaminergic hypofunction in neurodegenerative diseases. DaT SPECT and [18F]DOPA PET have been adopted as survey tools in clinical trials. In a large study on Parkinson's disease, 4-15% of subjects clinically diagnosed with early-stage Parkinson's disease had normal dopaminergic functional imaging scans. These are called Scans without Evidence of Dopamine Deficit (SWEDDs), and are considered to represent a state different from Parkinson's disease. Neurological diseases that exhibit parkinsonism and have normal dopaminergic cells in the nigrostriatal system (e.g., essential tremor, psychogenic parkinsonism, DOPA-responsive dystonia, vascular parkinsonism, drug-induced parkinsonism, manganism, brain tumor, myoclonus-dystonia (DYT11), and fragile X syndrome) might be diagnosed with SWEDDs. True bradykinesia with fatigue or decrement may be useful for distinguishing between Parkinson's disease and SWEDDs. However, because SWEDDs encompass many diseases, their properties may not be uniform. In this review, we discuss DaT SPECT, the concept of SWEDDs, and differential diagnosis.

Vaccination-induced distemper in kinkajous.

PubMed

Kazacos, K R; Thacker, H L; Shivaprasad, H L; Burger, P P

1981-12-01

Following vaccination for distemper, using a modified live-virus vaccine developed for dogs, 2 young kinkajous (Potos flavus) developed diarrhea, then central nervous system disease. Clinical signs included myoclonus, head trembling, loss of muscular coordination, and convulsions. One kinkajou gradually recovered; the other seemed to recover, then relapsed and was euthanatized. Microscopic lesions included those of interstitial pneumonia and enteritis and multifocal lymphocytic inflammation, gliosis, spongiosis, and swollen and degenerating axons in the cerebral, cerebellar, and brain stem white matter. Similar lesions were found at all caudally, as exemplified by complete destruction of the dorsal funiculi and dorsal horns of the gray matter of the upper sacral cord segments. Eosinophilic intranuclear inclusions were seen histologically in the glia in the spinal cord, midbrain, and cerebellum, and were confirmed as canine distemper viral inclusions by the fluorescent antibody method. It was concluded that modified live canine distemper virus vaccines should be used with caution or not at all in kinkajous.

Late-onset Leigh syndrome with myoclonic epilepsy with ragged-red fibers.

PubMed

Monden, Yukifumi; Mori, Masato; Kuwajima, Mari; Goto, Tamako; Yamagata, Takanori; Momoi, Mariko Y

2013-06-01

We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2 years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes

PubMed Central

Carvajal-González, Alexander; Leite, M. Isabel; Waters, Patrick; Woodhall, Mark; Coutinho, Ester; Balint, Bettina; Lang, Bethan; Pettingill, Philippa; Carr, Aisling; Sheerin, Una-Marie; Press, Raomand; Lunn, Michael P.; Lim, Ming; Maddison, Paul; Meinck, H.-M.; Vandenberghe, Wim

2014-01-01

The clinical associations of glycine receptor antibodies have not yet been described fully. We identified prospectively 52 antibody-positive patients and collated their clinical features, investigations and immunotherapy responses. Serum glycine receptor antibody endpoint titres ranged from 1:20 to 1:60 000. In 11 paired samples, serum levels were higher than (n = 10) or equal to (n = 1) cerebrospinal fluid levels; there was intrathecal synthesis of glycine receptor antibodies in each of the six pairs available for detailed study. Four patients also had high glutamic acid decarboxylase antibodies (>1000 U/ml), and one had high voltage-gated potassium channel-complex antibody (2442 pM). Seven patients with very low titres (<1:50) and unknown or alternative diagnoses were excluded from further study. Three of the remaining 45 patients had newly-identified thymomas and one had a lymphoma. Thirty-three patients were classified as progressive encephalomyelitis with rigidity and myoclonus, and two as stiff person syndrome; five had a limbic encephalitis or epileptic encephalopathy, two had brainstem features mainly, two had demyelinating optic neuropathies and one had an unclear diagnosis. Four patients (9%) died during the acute disease, but most showed marked improvement with immunotherapies. At most recent follow-up, (2–7 years, median 3 years, since first antibody detection), the median modified Rankin scale scores (excluding the four deaths) decreased from 5 at maximal severity to 1 (P < 0.0001), but relapses have occurred in five patients and a proportion are on reducing steroids or other maintenance immunotherapies as well as symptomatic treatments. The glycine receptor antibodies activated complement on glycine receptor-transfected human embryonic kidney cells at room temperature, and caused internalization and lysosomal degradation of the glycine receptors at 37°C. Immunoglobulin G antibodies bound to rodent spinal cord and brainstem co-localizing with monoclonal antibodies to glycine receptor-α1. Ten glycine receptor antibody positive samples were also identified in a retrospective cohort of 56 patients with stiff person syndrome and related syndromes. Glycine receptor antibodies are strongly associated with spinal and brainstem disorders, and the majority of patients have progressive encephalomyelitis with rigidity and myoclonus. The antibodies demonstrate in vitro evidence of pathogenicity and the patients respond well to immunotherapies, contrasting with earlier studies of this syndrome, which indicated a poor prognosis. The presence of glycine receptor antibodies should help to identify a disease that responds to immunotherapies, but these treatments may need to be sustained, relapses can occur and maintenance immunosuppression may be required. PMID:24951641

[Paraesthesia in the legs].

PubMed

Eisensehr, Ilonka

2007-10-18

Paraesthesia in the legs can have numerous causes. In addition to the restless legs syndrome, other primary causes include venous insufficiency in the leg, propriospinal myoclonus, nocturnal leg cramps, peripheral polyneuropathy that affects mostly the legs or neuroleptic drug-induced akathisia. Through detailed questioning of the patient, restless legs syndrome can be specifically distinguished from the other named differential diagnoses.

A follow-up ¹⁸F-FDG brain PET study in a case of Hashimoto's encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis.

PubMed

Pari, Elisa; Rinaldi, Fabrizio; Premi, Enrico; Codella, Maria; Rao, Renata; Paghera, Barbara; Panarotto, Maria Beatrice; De Maria, Giovanni; Padovani, Alessandro

2014-04-01

Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with antithyroid antibodies. It may have an acute onset (episodes of cerebral ischemia, seizure, and psychosis) or it may present as an indolent form (depression, cognitive decline, myoclonus, tremors, and fluctuations in level of consciousness). We here describe a case of encephalopathy presenting as non-convulsive status epilepticus associated with Hashimoto's thyroiditis (HT), unresponsive to corticosteroid therapy, with improvement after plasma exchange treatment. A previously healthy 19-year-old woman, presented generalized tonic-clonic seizures. About a month later, she manifested a speech disorder characterized by difficulties in the production and comprehension of language. Within a few days she also developed confusion and difficulties in recognizing familiar places, with gradual worsening over time. EEG revealed a non-convulsive status epilepticus (NCSE). CSF examination showed slightly elevated cell count and four oligoclonal bands. MRI was unremarkable, and (18)F-FDG brain PET showed widespread hypometabolism, mostly in posterior regions bilaterally. Laboratory and ultrasound findings showed signs of HT. Treatment with steroid was introduced without any improvement. After five sessions of plasma exchange there was a decrease of antithyroid antibodies, as well as EEG and clinical improvement. Three months after discharge (18)F-FDG brain PET showed a complete normalization of the picture, and the patient was asymptomatic. This report emphasizes the successful treatment of HE with plasma exchange in a patient who presented with NCSE. Based on the actual evidence, the term "Encephalopathy associated with Hashimoto's thyroiditis" may be the most proper. Furthermore, to our knowledge, this is the first case of an adult patient studied twice with an (18)F-FDG brain PET: prior to treatment with plasma exchange, and at 3 months follow-up when the patient was clinically completely asymptomatic. Studies in more patients are needed to clarify the relevance of (18)F-FDG brain PET as a possible diagnostic tool for HE.

Paraneoplastic autoimmune movement disorders.

PubMed

Lim, Thien Thien

2017-11-01

To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes.

PubMed

Liu, Min; Concha, Luis; Beaulieu, Christian; Gross, Donald W

2011-12-01

By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel-based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE-GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross-sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

A case of Cefepime encephalopathy, being difficult to distinguish from non-convulsive status epilepticus during the treatment of bacterial meningitis.

PubMed

Toda, Yusuke; Yamazaki, Mineo; Ota, Tomohiro; Fujisawa, Yosuke; Kimura, Kazumi

2016-10-28

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

Multivariate and multiorgan analysis of cardiorespiratory variability signals: the CAP sleep case.

PubMed

Bianchi, Anna M; Ferini-Strambi, Luigi; Castronovo, Vincenza; Cerutti, Sergio

2006-10-01

Signals from different systems are analyzed during sleep on a beat-to-beat basis to provide a quantitative measure of synchronization with the heart rate variability (HRV) signal, oscillations of which reflect the action of the autonomic nervous system. Beat-to-beat variability signals synchronized to QRS occurrence on ECG signals were extracted from respiration, electroencephalogram (EEG) and electromyogram (EMG) traces. The analysis was restricted to sleep stage 2. Cyclic alternating pattern (CAP) periods were detected from EEG signals and the following conditions were identified: stage 2 non-CAP (2 NCAP), stage 2 CAP (2 CAP) and stage 2 CAP with myoclonus (2 CAP MC). The coupling relationships between pairs of variability signals were studied in both the time and frequency domains. Passing from 2 NCAP to 2 CAP, sympathetic activation is indicated by tachycardia and reduced respiratory arrhythmia in the heart rate signal. At the same time, we observed a marked link between EEG and HRV at the CAP frequency. During 2 CAP MC, the increased synchronization involved myoclonus and respiration. The underlying mechanism seems to be related to a global control system at the central level that involves the different systems.

An unusual case of acute encephalitic syndrome: Is it acute measles encephalitis or subacute sclerosing panencephalitis?

PubMed

Garg, Ravindra K; Malhotra, Hardeep S; Rizvi, Imran; Kumar, Neeraj; Jain, Amita

2017-01-01

Subacute sclerosing panencephalitis is a late complication of measles infection and develops usually 6 to 15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form wherein the disease rapidly progresses to death. A six-year old male child presented with fever, abnormal movements of the left side of body followed by weakness of the left side of the body, and involuntary abnormal movements of right upper and lower limbs. On examination, he was drowsy and was unable to communicate. He had right-sided hemiballismus. He also had left-sided hemiparesis and the left plantar reflex was extensor. Cerebrospinal fluid examination revealed elevated protein and cells. In the serum and cerebrospinal fluid, anti-measles IgG antibodies were found to be positive. No other viral marker was noted in the cerebrospinal fluid. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, the frontal region as well as subcortical structures of these regions. Electroencephalography revealed generalized slowing of waves. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced and the patient developed periodic generalized myoclonus, which was predominantly present on the right side. The patient succumbed to his illness and died after one month. Fulminant subacute sclerosing panencephalitis may have unusual clinical manifestations such as hemiballismus. In fulminant subacute sclerosing panencephalitis, neuroimaging may show extensive cortical damage.

The Therapeutic Potential of Cannabinoids for Movement Disorders

PubMed Central

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2014-01-01

Background There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and particularly for neurologic conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science, preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. Results The pharmacology of cannabis is complex with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits but more consistently suggest potential neuroprotective effects in several animal models of Parkinson’s (PD) and Huntington’s disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia or ataxia and nonexistent for myoclonus or restless legs syndrome. Conclusions Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological and therapeutic effects of this class of drugs in movement disorders. PMID:25649017

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

Hart, Y.M.; Andermann, E.; Mitchison, H.M.

The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while themore » gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.« less

Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease.

PubMed

Berthier, Arnaud; Payá, Miguel; García-Cabrero, Ana M; Ballester, Maria Inmaculada; Heredia, Miguel; Serratosa, José M; Sánchez, Marina P; Sanz, Pascual

2016-03-01

Lafora disease (LD, OMIM 254780) is a rare fatal neurodegenerative disorder that usually occurs during childhood with generalized tonic-clonic seizures, myoclonus, absences, drop attacks, or visual seizures. Unfortunately, at present, available treatments are only palliatives and no curative drugs are available yet. The hallmark of the disease is the accumulation of insoluble polyglucosan inclusions, called Lafora bodies (LBs), within the neurons but also in heart, muscle, and liver cells. Mouse models lacking functional EPM2A or EPM2B genes (the two major loci related to the disease) recapitulate the Lafora disease phenotype: they accumulate polyglucosan inclusions, show signs of neurodegeneration, and have a dysregulation of protein clearance and endoplasmic reticulum stress response. In this study, we have subjected a mouse model of LD (Epm2b-/-) to different pharmacological interventions aimed to alleviate protein clearance and endoplasmic reticulum stress. We have used two chemical chaperones, trehalose and 4-phenylbutyric acid. In addition, we have used metformin, an activator of AMP-activated protein kinase (AMPK), as it has a recognized neuroprotective role in other neurodegenerative diseases. Here, we show that treatment with 4-phenylbutyric acid or metformin decreases the accumulation of Lafora bodies and polyubiquitin protein aggregates in the brain of treated animals. 4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice. As these compounds have good safety records and are already approved for clinical uses on different neurological pathologies, we think that the translation of our results to the clinical practice could be straightforward.

[Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease : clinical features, MRI findings and follow-up study].

PubMed

Liu, Kun; Ma, Yan-xu; Zhang, Cheng-bing; Chen, Yi-ping; Ye, Xin-jian; Bai, Guang-hui; Yu, Zhi-kang; Yan, Zhi-han

2012-07-03

To explore the clinical and magnetic resonance imaging (MRI) characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. The clinical and MRI manifestations and follow-up outcomes in 35 children, at Second Affiliated Hospital, Wenzhou Medical College from August 2008 to November 2010, hospitalized with neurologic complications of enterovirus 71-infected hand-foot-mouth disease were retrospectively analyzed. Six children with aseptic meningitis presented the clinical symptoms and signs of meningitis. Five of them showed subdural effusion and ventriculomegaly, or both on MRI. At follow-ups, neurologic sequel could not be found. Among 24 cases with brainstem encephalitis, there were myoclonic jerks and tremor, ataxia, or both (grade I disease, n = 12), myoclonus and cranial-nerve involvement (grade II disease, n = 4), and cardiopulmonary failure after brain-stem infection (grade III disease, n = 8). In patients with brainstem encephalitis, lesions were predominantly located at the posterior portions of medulla and pons with hypointensity on T1WI and hyperintensity on T2WI. Cerebellar dentate nucleus, caudate nucleus and lenticular nucleus could also be involved. At follow-ups, the patients with mild symptoms had no neurologic sequel and the lesions within brain stem became small or vanished in most cases. While in the majority of serious patients, neurologic sequel could be found and the lesions located at brain stem became encephalomalacia. Fourteen cases with acute flaccid paralysis presented acute limb myasthenia with tendon reflex and muscular tension decreased. On spinal MRI, the lesions predominantly involved anterior horn regions of spinal cord with hypointensity on T1WI and hyperintensity on T2WI. Most patients improved their muscle strength and most lesions of spinal cord became smaller or vanished during follow-ups. MRI is the most effective modality of diagnosis and follow-up for neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. On MRI, the lesions mainly involve the anterior horn of spinal cord, medulla oblongata and pons. At follow-ups, most patients have no neurologic sequel and the visualized lesions will be absorbed after active treatment.

The benefits of a Neurogenetics clinic in an adult Academic Teaching Hospital.

PubMed

Olszewska, Diana A; McVeigh, Terri; Fallon, Emer M; Pastores, Gregory M; Lynch, Tim

2018-03-09

Genetics is the backbone of Neurology, where a number of disorders have a genetic aetiology and are complex, requiring a dedicated Neurogenetics clinic. Genetics in the Republic of Ireland is under-resourced, with the lowest number of consultants per million of population in Europe. In November 2014, we established the monthly adult Neurogenetics clinic in Ireland, staffed by 2 consultants and 2 registrars from each speciality. We see patients with complex rare neurological conditions that may potentially have an underlying genetic basis, in the presence or absence of a family history. We performed a retrospective cohort analysis, reviewing symptoms and work-up data. Twenty-seven patients attended a pilot clinic over 12 months. Conditions encountered included Parkin-related PD, leucodystrophy, ataxia, fronto-temporal lobar degeneration, spinocerebellar ataxia type 6 (SCA6) and ataxia-telangiectasia. Identification of pathogenic mutations directed screening, treatment and facilitated onward genetic counselling (n = 10, 33%). A number of novel mutations were identified in MAPT gene ("missing tau mutation" McCarthy et al., Brain, 2015), SLCA1 gene and GRN (progranulin). Phenotypic features not previously reported were seen; e.g. writer's cramp in SCA6; paroxysmal myoclonus in the glucose transporter protein type 1 (GLUT1) deficiency. Breast cancer screening for ATM mutations carriers and referral to international experts in two undiagnosed patients were arranged. The establishment of a Neurogenetics clinic has addressed a gap in service and allowed identification of rare and atypical diagnoses.

Bismuth Subgallate Toxicity in the Age of Online Supplement Use.

PubMed

Sampognaro, Paul; Vo, Kathy T; Richie, Megan; Blanc, Paul D; Keenan, Kevin

2017-11-01

Bismuth salts have been used to treat gastroenterological disorders and are readily available over-the-counter and via the internet. Even though generally considered safe, bismuth compounds can cause a syndrome of subacute, progressive encephalopathy when taken in large quantities. We present the case of woman who developed progressive encephalopathy, aphasia, myoclonus, and gait instability after chronically ingesting large amounts of bismuth subgallate purchased from a major online marketing website to control symptoms of irritable bowel syndrome. After extensive neurological work-up, elevated bismuth levels in her blood, urine, and cerebrospinal fluid confirmed the diagnosis of bismuth-related neurotoxicity. She improved slowly following cessation of exposure. This case highlights bismuth subgallate as a neurotoxic bismuth formulation and reminds providers of the potential for safety misconceptions of positively reviewed online supplements.

Paraneoplastic brain stem encephalitis.

PubMed

Blaes, Franz

2013-04-01

Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment. Brain stem encephalitis with anti-Ma2 often improves after immunotherapy and/or tumor therapy, whereas only a minority of anti-Ri positive patients respond to immunosuppressants or tumor treatment. The Opsoclonus-myoclonus syndrome (OMS) in children, almost exclusively associated with neuroblastoma, shows a good response to steroids, ACTH, and rituximab, some patients do respond to intravenous immunoglobulins or cyclophosphamide. In adults, OMS is mainly associated with small cell lung cancer or gynecological tumors and only a small part of the patients show improvement after immunotherapy. Earlier diagnosis and treatment seem to be one major problem to improve the prognosis of both, paraneoplastic brain stem encephalitis, and OMS.

The “Neuro” of Neuroblastoma: Neuroblastoma as a Neurodevelopmental Disorder

PubMed Central

Ratner, Nancy; Brodeur, Garrett M.; Dale, Russell C.; Schor, Nina F.

2017-01-01

Neuroblastoma is a childhood cancer derived from cells of neural crest origin. The hallmarks of its enigmatic character include its propensity for spontaneous regression under some circumstances and its association with paraneoplastic opsoclonus, myoclonus, and ataxia. The neurodevelopmental underpinnings of its origins may provide important clues for development of novel therapeutic and preventive agents for this frequently fatal malignancy and for the associated paraneoplastic syndromes. PMID:27043043

Meloquine Use and Hospitalizations Among US Service Members, 2002-2004

DTIC Science & Technology

2005-04-12

name Lariam, was approved by the Food and Drug Administration on May 2, 1989, for malaria chemoprophylaxis.6 In 1990, the Centers for Disease...2005;293(2):212-216. 6. Food and Drug Administration. Approval history, Lariam. Available at: http://www.accessdata.fda.gov/scripts/cder...163-165. 26. Jimeniz-Huete A, Gil-Nagel A, Franch O. Multifocal myoclonus associated with mefloquine prophylaxis [letter]. Clin Neuropharmacol

Drugs acting on amino acid neurotransmitters.

PubMed

Meldrum, B S

1986-01-01

The most potent agents currently available for suppressing myoclonic activity in animals and humans act to enhance GABA-mediated inhibition and/or to diminish amino acid-induced excitation. Postsynaptic GABA-mediated inhibition plays an important role at the cortical level, diminishing the effect of augmented afferent activity and preventing pathologically enhanced output. Enhancement of GABAergic inhibition, principally at the cortical level but also at lower levels, by clonazepam and by valproate appears to be a predominant element in their antimyoclonic action. Studies in various animal models, including photically induced myoclonus in the baboon, P papio, indicate the value of other approaches to enhancing GABA-mediated inhibition. Among such approaches meriting evaluation in humans are inhibition of GABA-transaminase activity by gamma-vinyl GABA and action at some of the benzodiazepine receptors to enhance the action of GABA, as by the novel anticonvulsant beta-carbolines. Excitatory transmission mediated by dicarboxylic amino acids appears to play a role in myoclonus, especially at the spinal level, but also in the brainstem, cerebellum, basal ganglia, and cortex. Among various novel agents that act at the postsynaptic receptor site to antagonize such excitation, those specifically blocking excitation induced by aspartate and/or NMDA prevent myoclonic activity in a wide range of animal models. Further research is required before such agents can be evaluated in humans.

Epilepsy with myoclonic-atonic seizures (Doose syndrome): When video-EEG polygraphy holds the key to syndrome diagnosis.

PubMed

Dragoumi, Pinelopi; Chivers, Fiona; Brady, Megan; Craft, Sheila; Mushati, David; Venkatachalam, Gopalakrishnan; Cross, Judith Helen; Das, Krishna B

2016-01-01

An electroclinical epilepsy syndrome diagnosis enables physicians to predict outcomes as well as select appropriate treatment options. We report a child who presented with reflex myoclonus at the age of 9 months and was initially diagnosed with myoclonic epilepsy in infancy. After 9 years of medically resistant myoclonic seizures, extensive investigations, and emerging learning difficulties, she was referred for video-telemetry to characterize her seizures in an attempt to make a syndromic diagnosis. A three-day video-telemetry assessment was performed to document seizures. Neck and deltoid EMG channels were applied from the onset of the recording. Frequent generalized bursts of 3- to 5-Hz spike/polyspike and slow wave discharges, associated with clinical manifestations, mostly myoclonic seizures, were noted. In addition, definite atonic components were noted on the neck EMG as well as the deltoids associated with the slow component of the ictal discharges. The EEG and polygraphy findings are suggestive of a generalized epilepsy characterized by predominantly myoclonic seizures with atonic components. This raises the possibility whether a variant of epilepsy with myoclonic-atonic seizures (Doose syndrome) may be the underlying diagnosis for this girl. A trial of the ketogenic diet would therefore be considered as an option in her future management in view of its beneficial effect in this condition.

The therapeutic potential of cannabinoids for movement disorders.

PubMed

Kluger, Benzi; Triolo, Piera; Jones, Wallace; Jankovic, Joseph

2015-03-01

There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders. © 2015 International Parkinson and Movement Disorder Society.

The Madrid School of Neurology (1885-1939).

PubMed

Giménez-Roldán, S

2015-01-01

The emergence of neurology in Madrid between 1885 and 1939 had well-defined characteristics. On foundations laid by Cajal and Río-Hortega, pioneers combined clinical practice with cutting-edge neurohistology and neuropathology research. Luis Simarro, trained in Paris, taught many talented students including Gayarre, Achúcarro and Lafora. The untimely death of Nicolás Achúcarro curtailed his promising career, but he still completed the clinicopathological study of the first American case of Alzheimer's disease. On returning to Spain, he studied glial cells, including rod cells. Rodríguez Lafora described progressive myoclonus epilepsy and completed experimental studies of corpus callosum lesions and clinical and neuropathology studies of senile dementia. He fled to Mexico at the end of the Spanish Civil War (1936-1939). Sanchís Banús, a sterling clinical neurologist, described the first cluster of Huntington's disease in Spain, and he and Río-Hortega joined efforts to determine that pallidal degeneration underlies rigidity in advanced stages of the disease. Just after the war, Alberca Llorente eruditely described inflammatory diseases of the neuraxis. Manuel Peraita studied "the neurology of hunger" with data collected during the siege of Madrid. Dionisio Nieto, like many exiled intellectuals, settled in Mexico DF, where he taught neurohistological methods and neuropsychiatry in the tradition of the Madrid School of Neurology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Are SCN1A gene mutations responsible for genetic susceptibility to subacute sclerosing panencephalitis?

PubMed

Garg, Ravindra Kumar

2012-02-01

Dravet syndrome, characterized predominantly by myoclonus, has a striking clinical resemblance to subacute sclerosing panencephalitis (SSPE). Patients with Dravet syndrome develop significant mental decline with advancing age of affected child like in SSPE. It is well established that SCN1A gene mutations are associated with Dravet syndrome. Even periodic EEG complexes have been described in Dravet syndrome. In addition to Dravet syndrome, several other types of acute and subacute encephalopathic syndromes having clinical and electroencephalographic resemblance to SSPE are associated with SCN1A gene mutations. SSPE is a devastating progressive inflammatory disorder of the central nervous system. It is caused by persistent infection of the brain by an aberrant measles virus. Only a few of a vast number of measles infected pediatric population develop SSPE. There are several reports describing presence of SSPE is close relatives and it has been described previously in sibling and twin pairs. A genetic susceptibility for development of SSPE is likely. In fact, a variety of genetic abnormalities have already been described in patients with SSPE. It can also be argued that because of striking clinical resemblance between Dravet and various epileptic and encephalopathic syndromes associated with SCN1A gene mutations and SSPE, SCN1A gene abnormalities may also be responsible for susceptibility to SSPE in measles infected children. Copyright © 2011 Elsevier Ltd. All rights reserved.

Segregation and manifestations of the mtDNA tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome

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

Larsson, N.G.; Tulinius, M.H.; Holme, E.

1992-12-01

The authors have studied the segregation and manifestations of the tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA[sup Lys] mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, andmore » mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrone had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that >92% of mtDNA with the tRNA[sup Lys] mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA[sup Lys] mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. 30 refs., 3 figs., 5 tabs.« less

Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes.

PubMed

Collins, F A; Murphy, D L; Reiss, A L; Sims, K B; Lewis, J G; Freund, L; Karoum, F; Zhu, D; Maumenee, I H; Antonarakis, S E

1992-01-01

Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.

The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

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

Lalioti, M.D.; Rossier, C.; Antonarakis, S.E.

1996-04-15

We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of differentmore » factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.« less

Epileptic negative drop attacks in atypical benign partial epilepsy: a neurophysiological study.

PubMed

Hirano, Yoshiko; Oguni, Hirokazu; Osawa, Makiko

2009-03-01

We conducted a computer-assisted polygraphic analysis of drop attacks in a child with atypical benign partial epilepsy (ABPE) to investigate neurophysiological characteristics. The patient was a six-year two-month-old girl, who had started to have focal motor seizures, later combined with daily epileptic negative myoclonus (ENM) and drop attacks, causing multiple injuries. We studied episodes of ENM and drop attacks using video-polygraphic and computer-assisted back-averaging analysis. A total of 12 ENM episodes, seven involving the left arm (ENMlt) and five involving both arms (ENMbil), and five drop attacks were captured for analysis. All episodes were time-locked to spike-and-wave complexes (SWC) arising from both centro-temporo-parietal (CTP) areas. The latency between the onset of SWC and ENMlt, ENMbil, and drop attacks reached 68 ms, 42 ms, and 8 ms, respectively. The height of the spike as well as the slow-wave component of SWC for drop attacks were significantly larger than that for both ENMlt and ENMbil (p < 0.05). Drop attacks were considered to be epileptic negative myoclonus involving not only upper proximal but also axial muscles, causing the body to fall. Thus, drop attacks in ABPE are considered to be epileptic negative drop attacks arising from bilateral CTP foci and differ from drop attacks of a generalized origin seen in Lennox-Gastaut syndrome and myoclonic-astatic epilepsy.

Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic Problems

PubMed Central

Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Sindhu, Dodmalur Malikarjuna; Pai, Anupama Ramakanth

2017-01-01

Introduction: Immune dysregulation associated encephalopathies present with significant psychiatric manifestations and only a few soft neurological and general systemic features. They are generally resistant to treatment with psychiatric medications. Generalized orthostatic myoclonus and faciobrachial dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute sclerosing panencephalitis. Patients and Methods: Forty-two patients seen during 2010–2015 and diagnosed as noninfective encephalopathy were analyzed. Those patients with infective causes and those who had significant features of systemic manifestations of vasculitis and other disorders of central nervous system were excluded from the study. They were investigated with cerebrospinal fluid imaging, electroencephalogram (EEG), and antibody profile. Results: More than 70% patients had psychiatric manifestation as presenting features and reported to psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate, voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody related, and few were due to unknown antibody. Conclusion: Serious diagnostic errors are common and early diagnosis is based on high degree suspicion in patients presenting with new-onset refractory psychosis. Soft neurological features should be looked for and EEG serves as a very sensitive tool in establishing organicity. PMID:28515556

Neurological symptoms in patients with biopsy proven celiac disease.

PubMed

Bürk, Katrin; Farecki, Marie-Louise; Lamprecht, Georg; Roth, Guenter; Decker, Patrice; Weller, Michael; Rammensee, Hans-Georg; Oertel, Wolfang

2009-12-15

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease. A total of 72 patients with biopsy proven celiac disease (CD) (mean age 51 +/- 15 years, mean disease duration 8 +/- 11 years) were recruited through advertisements. All participants adhered to a gluten-free diet. Patients were interviewed following a standard questionnaire and examined clinically for neurological symptoms. Medical history revealed neurological disorders such as migraine (28%), carpal tunnel syndrome (20%), vestibular dysfunction (8%), seizures (6%), and myelitis (3%). Interestingly, 35% of patients with CD reported of a history of psychiatric disease including depression, personality changes, or even psychosis. Physical examination yielded stance and gait problems in about one third of patients that could be attributed to afferent ataxia in 26%, vestibular dysfunction in 6%, and cerebellar ataxia in 6%. Other motor features such as basal ganglia symptoms, pyramidal tract signs, tics, and myoclonus were infrequent. 35% of patients with CD showed deep sensory loss and reduced ankle reflexes in 14%. Gait disturbances in CD do not only result from cerebellar ataxia but also from proprioceptive or vestibular impairment. Neurological problems may even develop despite strict adherence to a gluten-free diet. (c) 2009 Movement Disorder Society.

Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis.

PubMed

Patiño, Liliana Catherine; Battu, Rajani; Ortega-Recalde, Oscar; Nallathambi, Jeyabalan; Anandula, Venkata Ramana; Renukaradhya, Umashankar; Laissue, Paul

2014-01-01

The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.

Review about gabapentin misuse, interactions, contraindications and side effects

PubMed Central

Quintero, Gabriel C

2017-01-01

The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus. PMID:28223849

Motor features in posterior cortical atrophy and their imaging correlates☆

PubMed Central

Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

2014-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities

PubMed Central

Bavarsad Shahripour, Reza; Harrigan, Mark R; Alexandrov, Andrei V

2014-01-01

Background There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Aim and discussion Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Conclusion Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage. PMID:24683506

Paraneoplastic neurologic syndrome and autoimmune Addison disease in a patient with thymoma.

PubMed

Morita, Hiroyuki; Hirota, Takuo; Mune, Tomoatsu; Suwa, Tetsuya; Ishizuka, Tatsuo; Inuzuka, Takashi; Tanaka, Keiko; Ishimori, Masatoshi; Nakamura, Shigenori; Yasuda, Keigo

2005-01-01

A 48-year-old man with autoimmune Addison disease developed the following paraneoplastic neurologic syndromes (PNNS): limbic encephalitis, opsoclonus/myoclonus, and sensorimotor and autonomic neuropathies. An anterior mediastinal mass detected on a chest computed tomographic scan was found on resection to be a noninvasive lymphocytic thymoma. The PNNS went into remission 1 year after the thymectomy. This is the first case of thymoma associated with autoimmune Addison disease and PNNS to be described in the literature.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

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

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.

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.

Construct Validity and Reliability of the SARA Gait and Posture Sub-scale in Early Onset Ataxia

PubMed Central

Lawerman, Tjitske F.; Brandsma, Rick; Verbeek, Renate J.; van der Hoeven, Johannes H.; Lunsing, Roelineke J.; Kremer, Hubertus P. H.; Sival, Deborah A.

2017-01-01

Aim: In children, gait and posture assessment provides a crucial marker for the early characterization, surveillance and treatment evaluation of early onset ataxia (EOA). For reliable data entry of studies targeting at gait and posture improvement, uniform quantitative biomarkers are necessary. Until now, the pediatric test construct of gait and posture scores of the Scale for Assessment and Rating of Ataxia sub-scale (SARA) is still unclear. In the present study, we aimed to validate the construct validity and reliability of the pediatric (SARAGAIT/POSTURE) sub-scale. Methods: We included 28 EOA patients [15.5 (6–34) years; median (range)]. For inter-observer reliability, we determined the ICC on EOA SARAGAIT/POSTURE sub-scores by three independent pediatric neurologists. For convergent validity, we associated SARAGAIT/POSTURE sub-scores with: (1) Ataxic gait Severity Measurement by Klockgether (ASMK; dynamic balance), (2) Pediatric Balance Scale (PBS; static balance), (3) Gross Motor Function Classification Scale -extended and revised version (GMFCS-E&R), (4) SARA-kinetic scores (SARAKINETIC; kinetic function of the upper and lower limbs), (5) Archimedes Spiral (AS; kinetic function of the upper limbs), and (6) total SARA scores (SARATOTAL; i.e., summed SARAGAIT/POSTURE, SARAKINETIC, and SARASPEECH sub-scores). For discriminant validity, we investigated whether EOA co-morbidity factors (myopathy and myoclonus) could influence SARAGAIT/POSTURE sub-scores. Results: The inter-observer agreement (ICC) on EOA SARAGAIT/POSTURE sub-scores was high (0.97). SARAGAIT/POSTURE was strongly correlated with the other ataxia and functional scales [ASMK (rs = -0.819; p < 0.001); PBS (rs = -0.943; p < 0.001); GMFCS-E&R (rs = -0.862; p < 0.001); SARAKINETIC (rs = 0.726; p < 0.001); AS (rs = 0.609; p = 0.002); and SARATOTAL (rs = 0.935; p < 0.001)]. Comorbid myopathy influenced SARAGAIT/POSTURE scores by concurrent muscle weakness, whereas comorbid myoclonus predominantly influenced SARAKINETIC scores. Conclusion: In young EOA patients, separate SARAGAIT/POSTURE parameters reveal a good inter-observer agreement and convergent validity, implicating the reliability of the scale. In perspective of incomplete discriminant validity, it is advisable to interpret SARAGAIT/POSTURE scores for comorbid muscle weakness. PMID:29326569

Glycinergic Pathways of the Central Auditory System and Adjacent Reticular Formation of the Rat.

NASA Astrophysics Data System (ADS)

Hunter, Chyren

The development of techniques to visualize and identify specific transmitters of neuronal circuits has stimulated work on the characterization of pathways in the rat central nervous system that utilize the inhibitory amino acid glycine as its neurotransmitter. Glycine is a major inhibitory transmitter in the spinal cord and brainstem of vertebrates where it satisfies the major criteria for neurotransmitter action. Some of these characteristics are: uneven distribution in brain, high affinity reuptake mechanisms, inhibitory neurophysiological actions on certain neuronal populations, uneven receptor distribution and the specific antagonism of its actions by the convulsant alkaloid strychnine. Behaviorally, antagonism of glycinergic neurotransmission in the medullary reticular formation is linked to the development of myoclonus and seizures which may be initiated by auditory as well as other stimuli. In the present study, decreases in the concentration of glycine as well as the density of glycine receptors in the medulla with aging were found and may be responsible for the lowered threshold for strychnine seizures observed in older rats. Neuroanatomical pathways in the central auditory system and medullary and pontine reticular formation (RF) were investigated using retrograde transport of tritiated glycine to identify glycinergic pathways; immunohistochemical techniques were used to corroborate the location of glycine neurons. Within the central auditory system, retrograde transport studies using tritiated glycine demonstrated an ipsilateral glycinergic pathway linking nuclei of the ascending auditory system. This pathway has its cell bodies in the medial nucleus of the trapezoid body (MNTB) and projects to the ventrocaudal division of the ventral nucleus of the lateral lemniscus (VLL). Collaterals of this glycinergic projection terminate in the ipsilateral lateral superior olive (LSO). Other glycinergic pathways found were afferent to the VLL and have their origin in the ventral and lateral nuclei of the trapezoid body (MVPO and LVPO). Bilateral projections from the nucleus reticularis pontis oralis (RPOo), to the VLL were also identified as glycinergic. This projection may link motor output systems to ascending auditory input, generating the auditory behavioral responses seen with glycine antagonism in animal models of myoclonus and seizure.

Clinical characteristics of chronic kidney disease of non-traditional causes in women of agricultural communities in El Salvador.

PubMed

Herrera Valdés, Raúl; Orantes, Carlos M; Almaguer López, Miguel; López Marín, Laura; Arévalo, Pedro Alfonso; Smith González, Magaly J; Morales, Fabrizio E; Bacallao, Raymed; Bayarre, Héctor D; Vela Parada, Xavier F

2015-01-01

A chronic kidney disease of non-traditional causes (CKDu) has emerged in Central America and elsewhere, predominantly affecting male farmworkers. In El Salvador (2009), it was the second cause of death in men > 18 years old. Causality has not been determined. Most available research focused on men and there is scarce data on women. Describe the clinical and histopathologic characteristics of CKDu in women of agricultural communities in El Salvador. A descriptive study was carried out in 10 women with CKDu stages 2, 3a, and 3b. Researchers studied demographics, clinical examination; hematological and biochemical analyses, urine sediment, renal injury markers, and assessed renal, cardiac, and peripheral arteries, liver, pancreas, and lung anatomy and functions. Kidney biopsy was performed in all. Data was collected on the Lime Survey platform and exported to SPSS 19.0. Patient distribution by stages: 2 (70%), 3a (10%), 3b (20%). Occupation: agricultural 7; non-agricultural 3. agrochemical exposure 100%; farmworkers 70%; incidental malaria 50%, NSAIDs use 40%; hypertension 40%. nocturia 50%; dysuria 50%; arthralgia 70%; asthenia 50%; cramps 30%, profuse sweating 20%. Renal markers: albumin creatinine ratio (ACR) > 300 mg/g 90%; β microglobulin and neutrophil gelatinase- associated lipocalin (NGAL) presence in 40%. Kidney function: hypermagnesuria 100%; hyperphosphaturia 50%, hypercalciuria 40%; hypernatriuria 30%; hyponatremia 60%, hypocalcemia 50%. Doppler: tibial artery damage 40%. Neurological: reflex abnormalities 30%; Babinski and myoclonus 20%. Neurosensorial hypoacusis 70%. Histopathology: damage restricted mostly to the tubulo-interstitium, urine was essentially bland. CKDu in women is a chronic tubulointerstitial nephropathy with varied extrarenal symptoms.

Exome Sequencing Is an Efficient Tool for Variant Late-Infantile Neuronal Ceroid Lipofuscinosis Molecular Diagnosis

PubMed Central

Ortega-Recalde, Oscar; Nallathambi, Jeyabalan; Anandula, Venkata Ramana; Renukaradhya, Umashankar; Laissue, Paul

2014-01-01

The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease. PMID:25333361

Phenotype variability and allelic heterogeneity in KMT2B-Associated disease.

PubMed

Kawarai, Toshitaka; Miyamoto, Ryosuke; Nakagawa, Eiji; Koichihara, Reiko; Sakamoto, Takashi; Mure, Hideo; Morigaki, Ryoma; Koizumi, Hidetaka; Oki, Ryosuke; Montecchiani, Celeste; Caltagirone, Carlo; Orlacchio, Antonio; Hattori, Ayako; Mashimo, Hideaki; Izumi, Yuishin; Mezaki, Takahiro; Kumada, Satoko; Taniguchi, Makoto; Yokochi, Fusako; Saitoh, Shinji; Goto, Satoshi; Kaji, Ryuji

2018-04-05

Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with complex early-onset dystonia. Almost all reported KMT2B mutations occurred de novo in the paternal germline or in the early development of the patient. We describe clinico-genetic features on four Japanese patients with novel de novo mutations and demonstrate the phenotypic spectrum of KMT2B mutations. We performed genetic studies, including trio-based whole exome sequencing (WES), in a cohort of Japanese patients with a seemingly sporadic early-onset generalized combined dystonia. Potential effects by the identified nucleotide variations were evaluated biologically. Genotype-phenotype correlations were also investigated. Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC, c.3325_3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed a reduced expression of mutant transcript frame. All patients presented with motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset generalized dystonia and superimposed choreoathetosis or myoclonus. One patient cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three patients had bilateral globus pallidal deep brain stimulation (DBS) with excellent or partial response. We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevalence of Bruxism in Hemifacial-Spasm Patients.

PubMed

Ella, Bruno; Guillaud, Etienne; Langbour, Nicolas; Guehl, Dominique; Burbaud, Pierre

2017-06-01

A previous study reported an increased prevalence of bruxism (25%) in patients with cranio-cervical dystonia (CCD) compared to normal controls (13%). CCD can affect the muscles of the head and neck. Besides the CCD affecting these muscles, hemifacial spasm (HFS) is a form of peripheral myoclonus due to a neurovascular conflict affecting the muscles of the face. The fact that they affect the same muscle regions could lead to other links in clinical manifestations such as bruxism, which is more common in patients with CCD than in the normal population. The aim was to study the prevalence of bruxism in patients with HFS. Patients with HFS were enrolled in the department of clinical neurophysiology (Bordeaux University Hospital) over a 6-month period. They were paired regarding age, the absence of neurological pathology or neuroleptics intake. To be included in the study, patients needed to have had unilateral involuntary facial muscle contractions affecting one hemiface. A hetero-questionnaire and a clinicial study were performed. The diagnostic criteria of bruxism included parafunction items such as grinding and clenching and at least one of the following clinical signs: abnormal tooth wear, temporomandibular joint (TMJ) pain, TMJ clicking, muscle hypertonia (masseter or temporal muscles). Additional epidemiological data were collected including age, sex, disease duration, stress, and sleep disorders. Stress symptoms inventory included symptoms like depression, strong heartbeat, dry mouth, anger, inability to concentrate, weakness, fatigability, insomnia, headache, and excessive sweating. The sleep disorder diagnosis included at least two of the symptoms described in the ICSD-3. All these criteria were recorded as either present (scored "1") or absent (scored "0"). The prevalence of bruxism in the two groups (normal and HFS) was not significantly different (p = 0.37). The rate was not significantly different between sleep and awake bruxism (p = 0.15) in both groups. Stress influenced the occurrence of bruxism in these two groups (p < 0.001). The results of this study indicated that clenching behaviors were higher in the HFS group, and that factors such as stress affected this group. The prevalence of bruxism was not higher in this population than in the normal control. © 2015 by the American College of Prosthodontists.

A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

PubMed

Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

2012-05-01

Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Reflex epilepsy and reflex seizures of the visual system: a clinical review.

PubMed

Zifkin, B G; Kasteleijn-Nolst Trenité, D

2000-09-01

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

Motor features in posterior cortical atrophy and their imaging correlates.

PubMed

Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

2014-12-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-03-01

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

Serotonin syndrome caused by drug to drug interaction between escitalopram and dextromethorphan.

PubMed

Dy, Prudence; Arcega, Victor; Ghali, Wael; Wolfe, Winifred

2017-08-07

A 63-year-old woman with a history of long-standing depression, maintained on escitalopram, presented with altered mental status. Patient had recently been prescribed dextromethorphan-promethazine cough syrup 2 weeks prior for an upper respiratory tract infection. On admission, she was lethargic and obtunded and found to have inducible myoclonus on examination. The rest of her physical exam was unremarkable. Pertinent lab and imaging findings showed QTc prolongation on ECG, negative electroencephalogram and CT head findings, essentially normal blood tests and a negative toxicology screen. The patient was admitted to the step down unit for close observation; both escitalopram and the cough syrup were suspended and was supportively managed. Overnight the patient's mental status improved and the serial EcGs showed resolution of the prolonged QTc. Patient was discharged home without further complication. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Using hypnosis to help deaf children help themselves: report of two cases.

PubMed

Kohen, D P; Mann-Rinehart, P; Schmitz, D; Wills, L M

1998-04-01

This is a report of deaf children who demonstrated the ability to quickly learn hypnotic skills and apply them effectively to the management of their problems. The children were taught hypnosis through American Sign Language, their preferred mode of communication. As with hypnosis with hearing children, we focused upon induction with fantasy and imaginative involvement, creation in imagination of a metaphor for, or imagery of, the desired outcome, and associated sense of pride (ego-strengthening), positive expectation, and teaching self-hypnosis to emphasize the importance of repeated, daily practice. Case examples presented are an 11-year-old deaf girl who used hypnosis to eliminate multiple warts, and a 9-year-old deaf boy with mild developmental disability whose self-hypnosis skills were applied to the management of myoclonus. In the former, the clinician is also the sign language communicator and in the latter, a professional sign language interpreter and parent are both intimately involved in the communication and hypnosis process.

Iatrogenic Baclofen Neurotoxicity in ESRD: Recognition and Management

PubMed Central

Roberts, John K.; Westphal, Scott; Sparks, Matthew A.

2016-01-01

Baclofen is an oral derivative of gamma-aminobutyric acid (GABA) used to treat muscular spasticity from disorders of the central nervous system. However, it is also being used for a variety of other conditions such as musculoskeletal pain, myoclonus, and alcohol withdrawal. The elimination of baclofen is heavily dependent on intact renal function, and the contraindication for use in patients with insufficient renal function is not well recognized by healthcare providers. Here, the authors report a series of mild to severe cases of baclofen intoxication in patients with end-stage renal disease. In all cases, baclofen was initiated by either inpatient or outpatient healthcare providers and the patients generally presented with altered mentation, somnolence, and/or respiratory depression. All patients were treated with aggressive hemodialysis and made a full recovery. This paper will briefly review the literature regarding baclofen intoxication, safety of baclofen use in renal disease, and efficacy of extra-corporeal therapy in the treatment of baclofen intoxication. PMID:26096760

Iatrogenic Baclofen Neurotoxicity in ESRD: Recognition and Management.

PubMed

Roberts, John K; Westphal, Scott; Sparks, Matthew A

2015-01-01

Baclofen is an oral derivative of gamma-aminobutyric acid (GABA) used to treat muscular spasticity from disorders of the central nervous system. However, it is also being used for a variety of other conditions such as musculoskeletal pain, myoclonus, and alcohol withdrawal. The elimination of baclofen is heavily dependent on intact renal function, and the contraindication for use in patients with insufficient renal function is not well recognized by healthcare providers. Here, the authors report a series of mild to severe cases of baclofen intoxication in patients with end-stage renal disease. In all cases, baclofen was initiated by either inpatient or outpatient healthcare providers and the patients generally presented with altered mentation, somnolence, and/or respiratory depression. All patients were treated with aggressive hemodialysis and made a full recovery. This paper will briefly review the literature regarding baclofen intoxication, safety of baclofen use in renal disease, and efficacy of extracorporeal therapy in the treatment of baclofen intoxication. © 2015 Wiley Periodicals, Inc.

Quantifying Leg Movement Activity During Sleep.

PubMed

Ferri, Raffaele; Fulda, Stephany

2016-12-01

Currently, 2 sets of similar rules for recording and scoring leg movement (LM) exist, including periodic LM during sleep (PLMS) and periodic LM during wakefulness. The former were published in 2006 by a task force of the International Restless Legs Syndrome Study Group, and the second in 2007 by the American Academy of Sleep Medicine. This article reviews the basic recording methods, scoring rules, and computer-based programs for PLMS. Less frequent LM activities, such as alternating leg muscle activation, hypnagogic foot tremor, high-frequency LMs, and excessive fragmentary myoclonus are briefly described. Copyright © 2016 Elsevier Inc. All rights reserved.

Paroxysmal myoclonic dystonia with vocalisations: new entity or variant of preexisting syndromes?

PubMed Central

Feinberg, T E; Shapiro, A K; Shapiro, E

1986-01-01

From among 1377 patients with movement disorders, four patients had an unusual movement disorder characterised by paroxysmal bursts of involuntary, regular, repetitive, rhythmic, bilateral, coordinated, simultaneous, stereotypic myoclonus and vocalisations, often associated with tonic symptoms, interference with voluntary functioning, presence of hyperactivity, attention and learning disabilities, and resistance to treatment with haloperidol and other drugs. This symptom complex may represent a new disease entity, referred to here as paroxysmal myoclonic dystonia with vocalisations or a variant or combination of other movement disorders such as Gilles de la Tourette, myoclonic, or dystonic syndromes. PMID:3457101

Clinical features of limbic encephalitis with LGI1 antibody

PubMed Central

Wang, Meiling; Cao, Xiaoyu; Liu, Qingxin; Ma, Wenbin; Guo, Xiaoqian; Liu, Xuewu

2017-01-01

Objective The objective of this study was to analyze the clinical manifestation, course, evolution, image manifestation, and treatments of LGI1 limbic encephalitis (LE). Patients and methods Studies confirmed that LE with the complex antibody of voltage-gated potassium channels is LGI1 LE. Since then, LE cases have been reported. In this study, 10 typical LE cases were searched in PubMed. These cases and one additional case, which we reported herein, were retrospectively analyzed. Results All the patients suffered from recent memory deterioration. The following cases were observed: eight with faciobrachial dystonic seizures (FBDS), six with different kinds of epileptic seizures (four complex partial seizures, one myoclonus seizure, and one generalized tonic–clonic seizure), four with FBDS and different kinds of epileptic seizures at the same time, five with mental disorders (one visual hallucination, one paranoia, one depression, one anxiety, and one dysphoria), five with hyponatremia, and two with sleep disorder. The brain MRI of nine patients revealed abnormalities in the mediotemporal lobe and the hippocampus. The LGI1 antibodies in the blood and/or cerebrospinal fluid (CSF) were positive. The content of the CSF protein of two patients increased slightly. The tumor marker of all the patients was normal, but capitate myxoma was detected in the combined pancreas duct of one patient. Gamma globulin and hormone treatments were administered to nine patients. Of these patients, six received a combination of antiepileptic drugs. The clinical symptoms of all the patients improved. Conclusion LGI1 LE is an autoimmune encephalitis whose clinical manifestations are memory deterioration, FBDS, epileptic seizure, mental disorders, and hyponatremia. Brain MRI shows that this autoimmune disease mainly involves the mediotemporal lobe and the hippocampus. This condition can also be manifested with other autoimmune encephalitis cases but can be rarely associated with tumors. After patients with LGI1 LE receive gamma globulin and hormone treatments, their clinical prognosis is good. PMID:28670128

The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the disease susceptibility and the clinical features of the Chinese patients of sCJD and FFI.

PubMed

Gao, Chen; Shi, Qiang; Wei, Jing; Zhou, Wei; Xiao, Kang; Wang, Jing; Shi, Qi; Dong, Xiao-Ping

2018-01-02

Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. Besides of the pathological agent, prion, there are some elements that can influence or determine susceptibility to prion infection and the clinical phenotype of the diseases, e.g., the polymorphism in PRNP gene. Another polymorphism in ZBTB38-RASA2 has been observed to be associated with the susceptibility of sporadic Creutzfeldt-Jacob disease (sCJD) in UK. MicroRNAs are endogenous small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. In this study, two polymorphic loci in miR-146a (rs2910164 and rs57095329) and one locus in ZBTB38-RASA2 (rs295301) of 561 Chinese patients of sCJD and 31 cases of fatal familial insomnia (FFI) were screened by PCR and sequencing. Our data did not figure out any association of those three SNPs with the susceptibility of sCJD. However, a significant association of the SNP of rs57095329 in miR-146a showed the association with the susceptibility of FFI. Additionally, the SNP of rs57095329 showed statistical significances with the appearances of mutism and the positive of cerebrospinal fluid (CSF) protein 14-3-3 in sCJD patients, while the SNP of ZBTB38-RASA2 was significantly related with the appearance of myoclonus in sCJD patients. It indicates that the SNPs of ZBTB38-RASA2 and miR-146a are not associated with the susceptibility of the Chinese sCJD patients, but may influence the appearances of clinical manifestations somehow.

[Meta analysis for the anesthesia effect and adverse reactions of etomidate and propofol on 
the painless abortion surgery].

PubMed

Wang, Li; Li, Wen; Xu, Rui; Long, Lihui

2016-04-01

To evaluate the anesthesia effect of etomidate and propofol on painless abortion surgery. 
 After screening the Cochrane Library, Pubmed, China National Knowledge Infrastructure (CNKI), WANFANG, VIP database, the literatures regarding the anesthesia effect of etomidate and propofol on painless abortion surgery were collected from 1995 to 2014. The randomized controlled trials (RCTs) were selected, the quality evaluation was performed and the data was analyzed by using RevMan5.3 software.
 A total of 1 130 patients were included in 9 RCTs. The results of Meta analysis were as follows: the anesthesia induction time in the etomidate group was less than that in propofol group (MD=-0.14, 95% CI -0.24 to -0.04, P=0.004); there were more adverse reactions, such as myoclonus, nausea and vomiting, in the etomidate group compared with the propofol group (P<0.001); the incidence of pain in the etomidate group was less than that in the propofol group (P<0.001); there was no significant difference in the incidence of respiratory depression between the 2 groups (P>0.05); the surgery time, analgesia and duration from withdrawal to the wake-up was not significantly different between the 2 groups (P>0.05). 
 Etomidate had a shorter anesthesia induction time than propofol in the painless abortion surgery. The incidence of reverse reactions such as myoclonus, nausea and vomiting, was more common in application of etomidate, whereas the incidence of injection pain was more common in the use of propofol group. There was no significant difference in respiratory depression between the 2 drugs. The comprehensive efficacy of propofol is better than etomidate.

Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016

PubMed Central

Bature, Fidelia; Guinn, Barbara-ann; Pang, Dong; Pappas, Yannis

2017-01-01

Objective Late diagnosis of Alzheimer’s disease (AD) may be due to diagnostic uncertainties. We aimed to determine the sequence and timing of the appearance of established early signs and symptoms in people who are subsequently diagnosed with AD. Methods We used systematic review methodology to investigate the existing literature. Articles were reviewed in May 2016, using the following databases: MEDLINE, PsycINFO, CINAHL, British Nursing Index, PubMed central and the Cochrane library, with no language restriction. Data from the included articles were extracted independently by two authors and quality assessment was undertaken with the quality assessment and diagnostic accuracy tool-2 (QUADAS tool-2 quality assessment tool). Results We found that depression and cognitive impairment were the first symptoms to appear in 98.5% and 99.1% of individuals in a study with late-onset AD (LOAD) and 9% and 80%, respectively, in early-onset AD (EOAD). Memory loss presented early and was experienced 12 years before the clinically defined AD dementia in the LOAD. However, the rapidly progressive late-onset AD presented predominantly with 35 non-established focal symptoms and signs including myoclonus (75%), disturbed gait (66%) and rigidity. These were misdiagnosed as symptoms of Creutzfeldt-Jacob disease (CJD) in all the cases. The participant with the lowest mini-mental state examination score of 25 remained stable for 2 years, which is consistent with the score of the healthy family members. Conclusions The findings of this review suggest that neurological and depressive behaviours are an early occurrence in EOAD with depressive and cognitive symptoms in the measure of semantic memory and conceptual formation in LOAD. Misdiagnosis of rapidly progressive AD as CJD and the familial memory score can be confounding factors while establishing a diagnosis. However, the study was limited by the fact that each one of the findings was based on a single study. PMID:28851777

Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and Malin Knock-out Mouse Models.

PubMed

López-González, Irene; Viana, Rosa; Sanz, Pascual; Ferrer, Isidre

2017-07-01

Lafora progressive myoclonus epilepsy (Lafora disease, LD) is a fatal rare autosomal recessive neurodegenerative disorder characterized by the accumulation of insoluble ubiquitinated polyglucosan inclusions in the cytoplasm of neurons, which is most commonly associated with mutations in two genes: EPM2A, encoding the glucan phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. The present study analyzes possible inflammatory responses in the mouse lines Epm2a -/- (laforin knock-out) and Epm2b -/- (malin knock-out) with disease progression. Increased numbers of reactive astrocytes (expressing the GFAP marker) and microglia (expressing the Iba1 marker) together with increased expression of genes encoding cytokines and mediators of the inflammatory response occur in both mouse lines although with marked genotype differences. C3ar1 and CxCl10 messenger RNAs (mRNAs) are significantly increased in Epm2a -/- mice aged 12 months when compared with age-matched controls, whereas C3ar1, C4b, Ccl4, CxCl10, Il1b, Il6, Tnfα, and Il10ra mRNAs are significantly upregulated in Epm2b -/- at the same age. This is accompanied by increased protein levels of IL1-β, IL6, TNFα, and Cox2 particularly in Epm2b -/- mice. The severity of inflammatory changes correlates with more severe clinical symptoms previously described in Epm2b -/- mice. These findings show for the first time increased innate inflammatory responses in a neurodegenerative disease with polyglucosan intraneuronal deposits which increase with disease progression, in a way similar to what is seen in neurodegenerative diseases with abnormal protein aggregates. These findings also point to the possibility of using anti-inflammatory agents to mitigate the degenerative process in LD.

CDKL5 gene-related epileptic encephalopathy: electroclinical findings in the first year of life.

PubMed

Melani, Federico; Mei, Davide; Pisano, Tiziana; Savasta, Salvatore; Franzoni, Emilio; Ferrari, Anna Rita; Marini, Carla; Guerrini, Renzo

2011-04-01

Cyclin-dependent kinase-like 5 (CDKL5) gene abnormalities cause an early-onset epileptic encephalopathy. We performed video-electroencephalography (video-EEG) monitoring early in the course of CDKL5-related epileptic encephalopathy in order to examine the early electroclinical characteristics of the condition. We used video-EEG to monitor six infants (five females, one male) with CDKL5-related epileptic encephalopathy (five mutations; one deletion), at ages 45 days to 12 months and followed them up to the ages of 14 months to 5 years (mean age 23 mo). We focused our analysis on the first year of life. The results were evaluated against those of a comparison group of nine infants (aged below 1y) with epileptic encephalography who had tested negative for CDKL5 mutations and deletions. One infant exhibited normal background activity, three exhibited moderate slowing, and two exhibited a suppression burst pattern. Two participants had epileptic spasms and four had a stereotyped complex seizure pattern, which we defined as a 'prolonged' generalized tonic-clonic event consisting of a tonic-tonic/vibratory contraction, followed by a clonic phase with series of spasms, gradually translating into repetitive distal myoclonic jerks. Seizure duration ranged from 2 to 4 minutes. The EEG correlate of each clinical phase included an initial electrodecremental event (tonic vibratory phase), irregular series of sharp waves and spike slow waves (clonic phase with series of spasms), and bilateral rhythmic sharp waves (time locked with myoclonus). Infants with CDKL5-related early epileptic encephalopathy can present in the first year of life with an unusual electroclinical pattern of 'prolonged' generalized tonic-clonic seizures. © The Authors. Journal compilation © Mac Keith Press 2011.

Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders.

PubMed

Hinson, Shannon R; Lopez-Chiriboga, A Sebastian; Bower, James H; Matsumoto, Joseph Y; Hassan, Anhar; Basal, Eati; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew

2018-03-01

Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum , but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

Etomidate evokes synaptic vesicle exocytosis without increasing miniature endplate potentials frequency at the mice neuromuscular junction.

PubMed

Valadão, Priscila Aparecida Costa; Naves, Lígia Araújo; Gomez, Renato Santiago; Guatimosim, Cristina

2013-11-01

Etomidate is an intravenous anesthetic used during anesthesia induction. This agent induces spontaneous movements, especially myoclonus after its administration suggesting a putative primary effect at the central nervous system or the periphery. Therefore, the aim of this study was to investigate the presynaptic and postsynaptic effects of etomidate at the mouse neuromuscular junction (NMJ). Diaphragm nerve muscle preparations were isolated and stained with the styryl dye FM1-43, a fluorescent tool that tracks synaptic vesicles exo-endocytosis that are key steps for neurotransmission. We observed that etomidate induced synaptic vesicle exocytosis in a dose-dependent fashion, an effect that was independent of voltage-gated Na(+) channels. By contrast, etomidate-evoked exocytosis was dependent on extracellular Ca(2+) because its effect was abolished in Ca(2+)-free medium and also inhibited by omega-Agatoxin IVA (30 and 200nM) suggesting the participation of P/Q-subtype Ca(2+) channels. Interestingly, even though etomidate induced synaptic vesicle exocytosis, we did not observe any significant difference in the frequency and amplitude of miniature end-plate potentials (MEPPs) in the presence of the anesthetic. We therefore investigated whether etomidate could act on nicotinic acetylcholine receptors labeled with α-bungarotoxin-Alexa 594 and we observed less fluorescence in preparations exposed to the anesthetic. In conclusion, our results suggest that etomidate exerts a presynaptic effect at the NMJ inducing synaptic vesicle exocytosis, likely through the activation of P-subtype voltage gated Ca(2+) channels without interfering with MEPPs frequency. The present data contribute to a better understanding about the effect of etomidate at the neuromuscular synapse and may help to explain some clinical effects of this agent. Copyright © 2013 Elsevier Ltd. All rights reserved.

Isolated and combined dystonia syndromes - an update on new genes and their phenotypes.

PubMed

Balint, B; Bhatia, K P

2015-04-01

Recent consensus on the definition, phenomenology and classification of dystonia centres around phenomenology and guides our diagnostic approach for the heterogeneous group of dystonias. Current terminology classifies conditions where dystonia is the sole motor feature (apart from tremor) as 'isolated dystonia', while 'combined dystonia' refers to dystonias with other accompanying movement disorders. This review highlights recent advances in the genetics of some isolated and combined dystonic syndromes. Some genes, such as ANO3, GNAL and CIZ1, have been discovered for isolated dystonia, but they are probably not a common cause of classic cervical dystonia. Conversely, the phenotype associated with TUBB4A mutations expanded from that of isolated dystonia to a syndrome of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). Similarly, ATP1A3 mutations cause a wide phenotypic spectrum ranging from rapid-onset dystonia-parkinsonism to alternating hemiplegia of childhood. Other entities entailing dystonia-parkinsonism include dopamine transporter deficiency syndrome (SLC63 mutations); dopa-responsive dystonias; young-onset parkinsonism (PARKIN, PINK1 and DJ-1 mutations); PRKRA mutations; and X-linked TAF1 mutations, which rarely can also manifest in women. Clinical and genetic heterogeneity also characterizes myoclonus-dystonia, which includes not only the classical phenotype associated with epsilon-sarcoglycan mutations but rarely also presentation of ANO3 gene mutations, TITF1 gene mutations typically underlying benign hereditary chorea, and some dopamine synthesis pathway conditions due to GCH1 and TH mutations. Thus, new genes are being recognized for isolated dystonia, and the phenotype of known genes is broadening and now involves different combined dystonia syndromes. © 2015 EAN.

Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy.

PubMed

Vanni, Nicola; Fruscione, Floriana; Ferlazzo, Edoardo; Striano, Pasquale; Robbiano, Angela; Traverso, Monica; Sander, Thomas; Falace, Antonio; Gazzerro, Elisabetta; Bramanti, Placido; Bielawski, Jacek; Fassio, Anna; Minetti, Carlo; Genton, Pierre; Zara, Federico

2014-08-01

Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. © 2014 American Neurological Association.

Spinal muscular atrophy associated with progressive myoclonus epilepsy.

PubMed

Topaloglu, Haluk; Melki, Judith

2016-09-01

A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as "spinal muscular atrophy associated with progressive myoclonic epilepsy" (SMA-PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA-PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA-PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA-PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.

Neurotoxicity following the Ingestion of Bilimbi Fruit (Averrhoa bilimbi) in an End-Stage Renal Disease Patient on Hemodialysis.

PubMed

Caetano, Camille Pereira; de Sá, Cinara Barros; Faleiros, Bruno Antônio Paixão; Gomes, Marcelo Fonseca Coutinho Fernandes; Pereira, Edna Regina Silva

2017-01-01

The toxic effects of the ingestion of star fruit (Averrhoa carambola) in chronic kidney disease patients are well described in the literature. Recently, the compound caramboxin has been isolated, explaining the mechanisms of its neurotoxicity. Bilimbi fruit belongs to the family Oxalidaceae, Averrhoa bilimbi species, and exhibits similar biochemical characteristics to star fruit. To report the case of a patient with chronic kidney disease who developed a seizure disorder after the ingestion of bilimbi fruit. A 69-year-old man with chronic kidney disease on hemodialysis therapy had intractable hiccups, myoclonus, and generalized tonic-clonic seizures after the consumption of a moderate amount of bilimbi fruit. The electroencephalogram showed a pattern of seizure disorder despite the use of anticonvulsant drugs. Renal replacement therapy was maintained during the whole period and prescribed according to the patient's hemodynamic status. Despite showing clinical resolution of the seizure disorder, the patient died on the 27th day of hospitalization for infectious complications. The neurologic status without any other known cause and with clear temporal association with the ingestion of the fruit suggests the diagnosis of neurotoxicity. We propose the hypothesis that the bilimbi fruit has neurotoxic effects similar to those exhibited by the star fruit.

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Neurotoxicity following the Ingestion of Bilimbi Fruit (Averrhoa bilimbi) in an End-Stage Renal Disease Patient on Hemodialysis

PubMed Central

Caetano, Camille Pereira; de Sá, Cinara Barros; Faleiros, Bruno Antônio Paixão; Gomes, Marcelo Fonseca Coutinho Fernandes; Pereira, Edna Regina Silva

2017-01-01

Introduction The toxic effects of the ingestion of star fruit (Averrhoa carambola) in chronic kidney disease patients are well described in the literature. Recently, the compound caramboxin has been isolated, explaining the mechanisms of its neurotoxicity. Bilimbi fruit belongs to the family Oxalidaceae, Averrhoa bilimbi species, and exhibits similar biochemical characteristics to star fruit. Objective To report the case of a patient with chronic kidney disease who developed a seizure disorder after the ingestion of bilimbi fruit. Case Report A 69-year-old man with chronic kidney disease on hemodialysis therapy had intractable hiccups, myoclonus, and generalized tonic-clonic seizures after the consumption of a moderate amount of bilimbi fruit. The electroencephalogram showed a pattern of seizure disorder despite the use of anticonvulsant drugs. Renal replacement therapy was maintained during the whole period and prescribed according to the patient's hemodynamic status. Despite showing clinical resolution of the seizure disorder, the patient died on the 27th day of hospitalization for infectious complications. Conclusions The neurologic status without any other known cause and with clear temporal association with the ingestion of the fruit suggests the diagnosis of neurotoxicity. We propose the hypothesis that the bilimbi fruit has neurotoxic effects similar to those exhibited by the star fruit. PMID:28203564

Electroencephalographic features of benign adult familial myoclonic epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tanaka, Akihiro; Tsuji, Sadatoshi; Uozumi, Takenori

2014-02-01

To investigate electroencephalographic (EEG) features of benign adult familial myoclonic epilepsy (BAFME). We reviewed interictal EEG features in patients with BAFME treated between April 2005 and November 2012 at a tertiary referral center. The diagnostic criteria for BAFME were the presence of infrequent generalized tonic-clonic seizures, myoclonus or myoclonic seizures, and autosomal dominant inheritance. Interictal EEG findings of epilepsy with generalized tonic-clonic seizure only (EGTCS) were reviewed for comparison. We randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for each BAFME patient and measured the duration of them. Photic stimulation and hyperventilation were performed in all. Nineteen (eight men, 11 women) patients with BAFME were included in this study. The mean frequency of GSW was 4.3±1.0Hz (mean±SD, n=14) in BAFME and 3.2±0.8Hz (n=10) in EGTCS. There was a statistically significant difference (p=0.008) between the two. Photoparoxysmal responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with EGTCS. Faster frequency of GSW, compared with that in EGTCS, accompanied by PPR may be characteristic EEG features of BAFME. These findings may lead the diagnosis of BAFME. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan.

PubMed

Sullivan, Mitchell A; Nitschke, Silvia; Steup, Martin; Minassian, Berge A; Nitschke, Felix

2017-08-11

Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen. Recent data clearly show that an abnormal glycogen chain length distribution, but neither hyperphosphorylation nor impairment of general autophagy, strictly correlates with glycogen accumulation and the presence of LBs. This review summarizes results obtained with patients, mouse models, and cell lines and consolidates apparent paradoxes in the LD literature. Based on the growing body of evidence, it proposes that LD is predominantly caused by an impairment in chain-length regulation affecting only a small proportion of the cellular glycogen. A better grasp of LD pathogenesis will further develop our understanding of glycogen metabolism and structure. It will also facilitate the development of clinical interventions that appropriately target the underlying cause of LD.

Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan

PubMed Central

Sullivan, Mitchell A.; Nitschke, Silvia; Steup, Martin; Minassian, Berge A.; Nitschke, Felix

2017-01-01

Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen. Recent data clearly show that an abnormal glycogen chain length distribution, but neither hyperphosphorylation nor impairment of general autophagy, strictly correlates with glycogen accumulation and the presence of LBs. This review summarizes results obtained with patients, mouse models, and cell lines and consolidates apparent paradoxes in the LD literature. Based on the growing body of evidence, it proposes that LD is predominantly caused by an impairment in chain-length regulation affecting only a small proportion of the cellular glycogen. A better grasp of LD pathogenesis will further develop our understanding of glycogen metabolism and structure. It will also facilitate the development of clinical interventions that appropriately target the underlying cause of LD. PMID:28800070

[Lafora and neuropathology].

PubMed

Fernández-Armayor, V; Moreno, J M; Martín, A; García, M L; Revilla, B; Moreno, J L

1997-12-01

This article wants to be a memory to the figure and neuro-pathologic work of D. Gonzalo Rodríguez-Lafora. The tediousness of its neurological work allows to divide it in its slopes neurophatologic, neurophysiologic, clinic and therapy. Also, it embraces other topics outside of the field of the neurology, centered fundamentally in the psychiatry. It is without a doubt the facet neuro-histopathologic the one that provides him bigger national and international prestige and it contributes to deepen in the histopathology of the senility, picking up in a definitive way in their work critical valuation of the discoveries histopathological in the senility (1952) their thought in this respect. Mention separated deserves its more important discovery: The inclusions amylaceous in cells ganglionars, in a certain type of epilepsy myoclonic that today takes its name. Other entities like the illness of Wernicke, the hemorrhages hipofisarias, the Parkinson (for scarce months he is not early to Levy in an important discovery), or the alterations of the malaria in the cerebral fabric plows object of their attention, of the work of Lafora highlights its anatomo-pathologics works next to figures as Kraepelin, Alzheimer, Vogt, Openheim or Brodmann. Professor Lafora's figure is known internationally as neuropathologist, recognizing its contribution, collection in the world literature, to the study of the myoclonic epilepsy: 'Lafora disease. A form of progressive myoclonus epilepsy.

The effect of a therapeutic lithium level on a stroke-related cerebellar tremor.

PubMed

Orleans, Rachel A; Dubin, Marc J; Kast, Kristopher A

2018-01-24

Lithium is a mood stabiliser used in the treatment of acute mania, bipolar disorder and as augmentation for unipolar major depression. Tremor is a common adverse effect associated with lithium at both therapeutic and toxic serum levels. We present a case of dose-dependent changes in the quality and intensity of a stroke-related, chronic cerebellar tremor with lithium treatment at serum levels within the therapeutic range. On admission, the patient in this case had a baseline fine, postural tremor, which increased in frequency and evolved to include myoclonic jerks once lithium therapy was initiated. Although the patient's serum lithium level was never in the toxic range, his tremor returned to baseline on reduction of his serum lithium level. This case highlights that a pre-existing, baseline tremor may lower the threshold for developing myoclonus. It also suggests that caution may be warranted with lithium therapy in the setting of known cerebellar disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

PubMed Central

Payan, Christine A. M.; Viallet, François; Landwehrmeyer, Bernhard G.; Bonnet, Anne-Marie; Borg, Michel; Durif, Franck; Lacomblez, Lucette; Bloch, Frédéric; Verny, Marc; Fermanian, Jacques; Agid, Yves; Ludolph, Albert C.

2011-01-01

Background The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. Methods and Findings Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α≥0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80–0.93), and moderate (Intra-class coefficient = 0.54–0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho≥0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. Conclusions The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA. Trial Registration ClinicalTrials.gov NCT00211224 PMID:21829612

Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

PubMed

Habarou, F; Bahi-Buisson, N; Lebigot, E; Pontoizeau, C; Abi-Warde, M T; Brassier, A; Le Quan Sang, K H; Broissand, C; Vuillaumier-Barrot, S; Roubertie, A; Boutron, A; Ottolenghi, C; de Lonlay, P

2018-01-01

Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2  = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO 2 production after 14 C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures: an individual participant data review.

PubMed

Nolan, Sarah J; Marson, Anthony G; Weston, Jennifer; Tudur Smith, Catrin

2016-04-28

Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that valproate is more effective for generalised onset tonic-clonic seizures (with or without other generalised seizure types). This review is one in a series of Cochrane reviews investigating pair-wise monotherapy comparisons. This is the latest updated version of the review first published in 2001 and updated in 2013. To review the time to withdrawal, remission and first seizure of phenytoin compared to valproate when used as monotherapy in people with partial onset seizures or generalised tonic-clonic seizures (with or without other generalised seizure types). We searched the Cochrane Epilepsy Group's Specialised Register (19 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 4), MEDLINE (1946 to 19 May 2015), SCOPUS (19 February 2013), ClinicalTrials.gov (19 May 2015), and WHO International Clinical Trials Registry Platform ICTRP (19 May 2015). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. Randomised controlled trials (RCTs) in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of valproate monotherapy versus phenytoin monotherapy. This was an individual participant data (IPD) review. Outcomes were time to: (a) withdrawal of allocated treatment (retention time); (b) achieve 12-month remission (seizure-free period); (c) achieve six-month remission (seizure-free period); and (d) first seizure (post-randomisation). We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), and the generic inverse variance method to obtain the overall pooled HR and 95% CI. IPD were available for 669 individuals out of 1119 eligible individuals from five out of 11 trials, 60% of the potential data. Results apply to partial onset seizures (simple, complex and secondary generalised tonic-clonic seizures), and generalised tonic-clonic seizures, but not other generalised seizure types (absence or myoclonus seizure types). For remission outcomes: HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes: HR > 1 indicates an advantage for valproate.The main overall results (pooled HR adjusted for seizure type) were time to: (a) withdrawal of allocated treatment 1.09 (95% CI 0.76 to 1.55); (b) achieve 12-month remission 0.98 (95% CI 0.78 to 1.23); (c) achieve six-month remission 0.95 (95% CI 0.78 to 1.15); and (d) first seizure 0.93 (95% CI 0.75 to 1.14). The results suggest no overall difference between the drugs for these outcomes. We did not find any statistical interaction between treatment and seizure type (partial versus generalised). We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. However misclassification of seizure type may have confounded the results of this review. Results do not apply to absence or myoclonus seizure types. No outright evidence was found to support or refute current treatment policies.

Herpes simplex encephalitis presenting as stroke-like symptoms with atypical MRI findings and lacking cerebrospinal fluid pleocytosis.

PubMed

Tsuboguchi, Shintaro; Wakasugi, Takahiro; Umeda, Yoshitaka; Umeda, Maiko; Oyake, Mutsuo; Fujita, Nobuya

2017-07-29

A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/μl, and this later increased to 17/μl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.

Substances of abuse and movement disorders: complex interactions and comorbidities

PubMed Central

Deik, Andres; Saunders-Pullman, Rachel; Luciano, Marta San

2014-01-01

The relationship between movement disorders and substance abuse which we previously reviewed are updated. We examine these relationships bidirectionally with focus on drugs of abuse which cause movement disorders, as well as primary movement disorders that are associated with use and abuse of alcohol and dopaminergic medications. First, we review the movement disorders that may develop from the acute use or withdrawal of frequent drugs of abuse, including alcohol, cocaine, heroin, amphetamine and methcathinone. We then comment on the interaction between alcoholism and alcohol-responsive movement disorders, such as essential tremor and myoclonus-dystonia. Lastly, we discuss the potential for abuse of antiparkinsonian dopaminergic agents in patients with Parkinson’s disease (PD). PMID:23030352

Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

PubMed

Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

2014-01-01

Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if required by regulators. Non-human primates represent an important model in seizure liability assessments given similarities to humans and a high translational potential. Copyright © 2014. Published by Elsevier Inc.

Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio.

PubMed

Meldrum, B S; Menini, C; Stutzmann, J M; Naquet, R

1979-07-13

The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.

Epidemiology and outcomes of acute encephalitis.

PubMed

Venkatesan, Arun

2015-06-01

This review seeks to describe recent advances in the epidemiology, outcomes, and prognostic factors in acute encephalitis. Infectious causes continue to account for the largest proportion of encephalitis cases in which a cause is identified, although autoimmune causes are increasingly recognized. Type-A gamma-aminobutyric acid (GABAa) receptor antibodies have been recently identified in encephalitis with refractory seizures, whereas the roles of antibodies to the glycine receptor and dipeptidyl peptidase-like protein 6 have been defined in progressive encephalomyelitis with rigidity and myoclonus. Recent findings in the US cases of encephalomyelitis presenting with acute flaccid paralysis raise the possibility that enterovirus D68, a common respiratory pathogen, may cause central nervous system disease. Mortality from acute encephalitis occurs in about 10% of cases, with a large proportion of survivors suffering from cognitive or physical disability. In addition to delay in institution of appropriate antiviral or immune therapy, several potentially reversible factors associated with poor prognosis have been identified, including cerebral edema, status epilepticus, and thrombocytopenia. Encephalitis imposes a significant worldwide health burden and is associated with poor outcomes. Supportive treatment and early institution of therapy may improve outcomes. Careful neurocognitive assessment of survivors of encephalitis is needed to better define long-term outcomes.

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

PubMed

Rossetti, Andrea O; Tovar Quiroga, Diego F; Juan, Elsa; Novy, Jan; White, Roger D; Ben-Hamouda, Nawfel; Britton, Jeffrey W; Oddo, Mauro; Rabinstein, Alejandro A

2017-07-01

The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. Cohort study (April 2009 to March 2016). Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%). This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

[Sleep paroxysmal events in children in video/polysomnography].

PubMed

Zajac, Anna; Skowronek-Bała, Barbara; Wesołowska, Ewa; Kaciński, Marek

2010-01-01

It is estimated that about 25% of children have sleep disorders, from short problems with falling asleep to severe including primary sleep disorders. Majority of these problems are transitory and self-limiting and usually are not recognized by first care physicians and need education. Analysis of sleep structure at the developmental age and of sleep disorders associated with different sleep phases on the basis of video/polysomnography results. Literature review and illustration of fundamental problems associated with sleep physiology and pathology, with special attention to paroxysmal disorders. Additionally 4 cases from our own experience were presented with neurophysiological and clinical aspects. Discussion on REM and NREM sleep, its phases and alternating share according to child's age was conducted. Sleep disorders were in accordance with their international classification. Parasomnias, occupying most of the space, were divided in two groups: primary and secondary. Among primary parasomnias disorders associated with falling asleep (sleep myoclonus, hypnagogic hallucinations, sleep paralysis, rhythmic movement disorder, restless legs syndrome) are important. Another disorders are parasomians associated with light NREM sleep (bruxism, periodic limb movement disorder) and with deeper NREM sleep (confusional arousals, somnabulism, night terrors), with REM sleep (nightmares, REM sleep behavior disorder) and associated with NREM and REM sleep (catathrenia, sleep enuresis, sleep talking). Obstructive sleep apnea syndrome and epileptic seizures occurring during sleep also play an important role. Frontal lobe epilepsy and Panayiotopoulos syndrome should be considered in the first place in such cases. Our 4 cases document these diagnostic difficulties, requiring video/polysomnography examination 2 of them illustrate frontal lobe epilepsy and single ones myoclonic epilepsy graphy in children is a difficult technique and requires special device, local and trained personnel. It is crucial in gathering objective data about sleep disorders. Correct diagnosis of paroxysmal disorders during sleep in children is possible thanks to video/polysomnography, and enables proper management and pharmacotherpy. It enables improvement or cure disorders during the sleep and moreover enables the obtainment of positive changes in child's every day life.

Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease.

PubMed

Grau-Rivera, Oriol; Sánchez-Valle, Raquel; Saiz, Albert; Molinuevo, José Luis; Bernabé, Reyes; Munteis, Elvira; Pujadas, Francesc; Salvador, Antoni; Saura, Júlia; Ugarte, Antonio; Titulaer, Maarten; Dalmau, Josep; Graus, Francesc

2014-01-01

Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD. Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-d-aspartate (NMDA), and glycine (GlY) receptors. Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [δ/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs. A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD.

Etomidate anaesthesia by immersion in oriental fire-bellied toads (Bombina orientalis).

PubMed

d'Ovidio, D; Spadavecchia, C; Angeli, G; Adami, C

2015-10-01

The objective of the present study was to evaluate the efficacy and the safety of etomidate anaesthesia by immersion technique in Bombina orientalis. The study comprised two phases. The first phase was carried out to identify the etomidate concentration capable of producing anaesthetic induction, as well as surgical anaesthesia, in the toads. The second phase was aimed at testing that concentration in eight additional animals. Etomidate administered via immersion at a concentration of 37.5 mg/L produced effective anaesthesia in oriental fire-bellied toads. The average duration of surgical anaesthesia was 20 min. All the toads enrolled in the study survived the anaesthesia and long-term complications did not occur. However, undesired side-effects, namely itching, myoclonus and prolonged recovery, were noticed during the perianaesthetic period. The authors concluded that etomidate anaesthesia by immersion, at a concentration of 37.5 mg/L, is suitable in oriental fire-bellied toads and produces anaesthesia of a depth and duration that is sufficient to allow the completion of various experimental procedures, without resulting in lethal complications. However, the occurrence of undesired side-effects opens a debate on the safety of this anaesthetic technique, and imposes the need for further investigation prior to proposing the latter for routine laboratory practice. © The Author(s) 2015.

Involuntary craniofacial lingual movements in intensive care-acquired quadriplegia.

PubMed

Cartagena, A M; Jog, M; Young, G B

2012-02-01

The syndrome of involuntary craniofacial lingual movements in the setting of acute intensive care-acquired quadriplegia (critical illness neuromyopathy) following sepsis-associated encephalopathy has not been previously described. We suggest a localization and treatment for this disabling condition. Three patients (2 female) from our center were quadriplegic from critical illness neuromyopathy when they developed involuntary craniofacial lingual movements following sepsis-associated encephalopathy. Extensive investigations failed to identify an etiology for the abnormal movements. Movements were of large amplitude, of moderate speed, and semi-rhythmic in the jaw, tongue, and palate, persistent and extremely bothersome to all patients. Injection with Botulinum toxin type A was very beneficial. Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia following sepsis-associated encephalopathy are consistent with focal craniofacial brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A treatment maybe helpful in treatment.

Impact of Transient Acute Hypoxia on the Developing Mouse EEG

PubMed Central

Zanelli, S.; Goodkin, H.P.; Kowalski, S.; Kapur, J.

2015-01-01

Hypoxemic events are common in sick preterm and term infants and represent the most common cause of seizures in the newborn period. Neonatal seizures often lack clinical correlates and are only recognized by electroencephalogram (EEG). The mechanisms leading from a hypoxic/ischemic insult to acute seizures in neonates remain poorly understood. Further, the effects of hypoxia on EEG at various developmental stages have not been fully characterized in neonatal animals, in part due to technical challenges. We evaluated the impact of hypoxia on neonatal mouse EEG to define periods of increased susceptibility to seizures during postnatal development. Hippocampal and cortical electrodes were implanted stereotaxically in C57BL/6 mice from postnatal age 3 (P3) to P15. Following recovery, EEG recording were obtained during baseline, acute hypoxia (4% FiO2 for 4 min) and reoxygenation. In baseline recordings, maturation of EEG was characterized by the appearance of a more continuous background pattern that replaced alternating high and low amplitude activity. Clinical seizures during hypoxia were observed more frequently in younger animals (100% P3-4, 87.5% P5-6, 93% P7-8, 83% P9-10, 33% P11-12, 17% P15, r2=0.81) and also occurred at higher FiO2 in younger animals (11.2±1.1% P3-P6 vs. 8.9±0.8% P7-12, p<0.05). Background attenuation followed the initial hypoxemic seizure; progressive return to baseline during reoxygenation was observed in survivors. Electrographic seizures without clinical manifestations were observed during reoxygenation, again more commonly in younger animals (83% P3-4, 86% P5-6, 75% P7-8, 71% P9-10, 20% P11-12, r2=0.82). All P15 animals died with this duration and degree of hypoxia. Post-ictal abnormalities included burst attenuation and post-anoxic myoclonus and were more commonly seen in older animals. In summary, neonatal mice exposed to brief and severe hypoxia followed by rapid reoxygenation reliably develop seizures and the response to hypoxia varies with postnatal age and maturation. PMID:24636798

The clinical safety of high-dose piracetam--its use in the treatment of acute stroke.

PubMed

De Reuck, J; Van Vleymen, B

1999-03-01

Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.

3D Texture Analysis Reveals Imperceptible MRI Textural Alterations in the Thalamus and Putamen in Progressive Myoclonic Epilepsy Type 1, EPM1

PubMed Central

Suoranta, Sanna; Holli-Helenius, Kirsi; Koskenkorva, Päivi; Niskanen, Eini; Könönen, Mervi; Äikiä, Marja; Eskola, Hannu; Kälviäinen, Reetta; Vanninen, Ritva

2013-01-01

Progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessively inherited neurodegenerative disorder characterized by young onset age, myoclonus and tonic-clonic epileptic seizures. At the time of diagnosis, the visual assessment of the brain MRI is usually normal, with no major changes found later. Therefore, we utilized texture analysis (TA) to characterize and classify the underlying properties of the affected brain tissue by means of 3D texture features. Sixteen genetically verified patients with EPM1 and 16 healthy controls were included in the study. TA was performed upon 3D volumes of interest that were placed bilaterally in the thalamus, amygdala, hippocampus, caudate nucleus and putamen. Compared to the healthy controls, EPM1 patients had significant textural differences especially in the thalamus and right putamen. The most significantly differing texture features included parameters that measure the complexity and heterogeneity of the tissue, such as the co-occurrence matrix-based entropy and angular second moment, and also the run-length matrix-based parameters of gray-level non-uniformity, short run emphasis and long run emphasis. This study demonstrates the usability of 3D TA for extracting additional information from MR images. Textural alterations which suggest complex, coarse and heterogeneous appearance were found bilaterally in the thalamus, supporting the previous literature on thalamic pathology in EPM1. The observed putamenal involvement is a novel finding. Our results encourage further studies on the clinical applications, feasibility, reproducibility and reliability of 3D TA. PMID:23922849

Neuroinvasive West Nile virus disease in Canada. The Saskatchewan experience.

PubMed

Téllez-Zenteno, José F; Hunter, Gary; Hernández-Ronquillo, Lizbeth; Haghir, Edrish

2013-07-01

West Nile virus (WNV) is a virus of the family Flaviviridae. The main route of human infection is through the bite of an infected mosquito. Approximately 90% of WNV infections in humans are asymptomatic, but neurologic manifestations can be severe. This study reviews the clinical profile of cases with neuroinvasive West Nile infection (NWNI) reported by the Surveillance program of the government of Saskatchewan in the Saskatoon Health Region (SHR). In 2007, 1456 cases of human West Nile cases were reported by the government of Saskatchewan in the whole province. One hundred and thirteen cases had severe symptoms of NWNI (8%), 1172 (80%) cases had mild symptoms of WNI and 171 (12%) had asymptomatic disease. Three hundred and fifty six cases were reported in the SHR, where 57 (16%) fulfilled criteria for NWNI. From the 57 cases, 39 (68%) were females. Nine (16%) patients had a history of recent camping, two (4%) reported outdoor sports and four (8%) reported outdoor activities not otherwise specified. Twenty five patients had headache (43.9%), 25 confusion (42.1%), 23 meningitis (40.4%), 17 encephalitis (29.8%), 14 encephalopathy (24.6%), 11 meningoencephalitis (19.3%), 10 tremor (17.5%), acute flaccid paralysis 10 (17.5%), myoclonus 1 (1.8%), nystagmus 2 (3.5%), diplopia 2 (3.5%), dizziness 2 (3.5%). Three patients died related with comorbidities during admission. During a year of high occurrence of WNI in Saskatchewan, 16% of cases developed NWNI. The recognition of neurological complications associated with WNI is important to improve their referral to tertiary centers.

Use of Artificial Hydration at the End of Life: A Survey of Australian and New Zealand Palliative Medicine Doctors.

PubMed

Oehme, Jacqueline; Sheehan, Caitlin

2018-05-15

Dying is ubiquitous, yet the optimal management of hydration in the terminal phase is undetermined. Palliative care (PC) doctors' practices may act as a de facto measure of the benefits and burdens of artificial hydration (AH) use. To identify PC doctors' AH prescribing practices for imminently dying patients and possible influencing factors. An online survey of doctors belonging to the Australian and New Zealand Society of Palliative Medicine. One hundred and thirty-six surveys were completed (30% response rate). AH use for patients in the prognosticated last week of life was low: 77% of respondents prescribed AH to 0-10% of patients and 3% of respondents prescribed to more than 20%. The most common reason for prescribing AH was palliation of family/patient concern rather than a physical symptom. The majority thought there was no effect of AH on survival, or on symptoms of fatigue (90%), reduced level of consciousness (88%), agitation (75%), nausea (69%), vomiting (68%), myoclonus (66%), thirst (65%), delirium (62%), cough (57%), or bowel obstruction (50%). AH was thought to worsen subcutaneous edema (94%), upper respiratory tract secretions (85%), ascites (73%), physical discomfort (72%), dyspnea (62%), and urinary symptoms (57%). PC doctors from Australia and New Zealand reported lower use of AH for dying patients compared to international counterparts. The study showed high concordance in respondents' opinions: most thought AH was unlikely to provide clinical benefit and might cause harm. Further studies are needed to determine best practice of AH use at the end of life.

Expanding spectrum of contactin-associated protein 2 (CASPR2) autoimmunity-syndrome of parkinsonism and ataxia.

PubMed

Kannoth, Sudheeran; Nambiar, Vivek; Gopinath, Siby; Anandakuttan, Anandkumar; Mathai, Annamma; Rajan, Parvathy Kanjiramana

2018-03-01

Contactin-associated protein 2 (CASPR2) antibodies are originally associated with Morvan's syndrome and peripheral nerve hyper excitability. Our objective was to study retrospectively the clinical spectrum of CASPR2 antibody-positive patients in our hospital. This is a retrospective observational study. Patients treated at the Amrita Institute of Medical Sciences from May 2013 to April 2016, who were tested positive for CASPR2 antibodies, were included. A total of 1584 samples were tested in the neuroimmunology laboratory during the study period for voltage-gated potassium channel (VGKC) complex antibodies-leucine-rich glioma-inactivated protein 1 (LGI1) and CASPR2 antibodies. Thirty-four were positive for LGI1, 13 were positive for CASPR2, and 7 were for both (total 54-3.4% positivity). Of these 54 cases, 11 were treated in our hospital. Seven were positive for LGI1, three for CASPR2, and one for both. The patient who had both CASPR2 and LGI1 antibody positive had Morvan's syndrome. One patient with CASPR2 had neuromyotonia. The other patient was admitted with status epilepticus with a syndrome of parkinsonism and ataxia. The third patient had encephalopathy and myoclonus with a syndrome of parkinsonism and ataxia. Two of them underwent siddha treatment for other ailments prior to the onset of the disease for other ailments. Our short series shows the expanding spectrum of CASPR2 autoimmunity. Syndrome of parkinsonism and ataxia is an important manifestation of CASPR2 autoimmunity where we can offer a definitive treatment.

Rapidly Progressive Quadriplegia and Encephalopathy.

PubMed

Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

2016-11-01

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

Paraneoplastic movement disorders.

PubMed

Mehta, Shyamal H; Morgan, John C; Sethi, Kapil D

2009-07-01

Neurologic paraneoplastic syndromes (NPSs) result from damage to the nervous system due to the remote effects of cancer not related to metastasis, infection, or metabolic derangements. NPSs are rare, affecting 1 in 10,000 patients with cancer. Pathogenesis is likely related to the immune mechanisms: normal neural tissue is mistakenly attacked due to the similarity in the onconeural antigens expressed by the tumor cells. Among the various "classic" and other NPSs, this review focuses on paraneoplastic movement disorders, including ataxia due to cerebellar degeneration, stiff-person syndrome, opsoclonus-myoclonus syndrome, chorea, parkinsonism, and tremor. The recently described syndrome of paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis is also included, given that these patients have complex movements such as stereotypies and dyskinesias in addition to psychiatric symptoms, altered sensorium, and other neurologic signs. Although variable, treatment and prognosis of NPSs rely heavily on treatment of the underlying malignancy and immunotherapy.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

PubMed

Phillips, Michelle A; Acquisto, Nicole M; Gorodetsky, Rachel M; Wiegand, Timothy J

2014-06-01

Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

Effects of varying subthalamic nucleus stimulation on apraxia of lid opening in Parkinson's disease.

PubMed

Tommasi, Giorgio; Krack, Paul; Fraix, Valérie; Pollak, Pierre

2012-09-01

Apraxia of lid opening (ALO) is a non-paralytic inability to open the eyes or sustain lid elevation at will. The exact pathophysiological mechanisms underlying the syndrome are still unknown. ALO has been reported in patients with Parkinson's disease (PD) after subthalamic nucleus (STN) deep brain stimulation (DBS), suggesting a possible involvement of the basal ganglia. We aimed to assess the effects of varying STN stimulation voltage on ALO in PD patients. Seven out of 14 PD patients with bilateral STN stimulation consecutively seen in our centre presented with ALO. We progressively increased voltage on each STN, using either 130 Hz (high-frequency stimulation, HFS) or 2 or 3 Hz (low-frequency stimulation, LFS). In five patients, HFS induced ALO time-locked to stimulation in 7 out of 10 STNs at a voltage higher than that used for chronic stimulation. LFS induced myoclonus in the pretarsal orbicularis oculi muscle (pOOm) with a rhythm synchronous to the frequency. In the other two patients with ALO already present at the time of the study, HFS improved ALO in 3 out of 4 STNs. ALO recurred within minutes of stimulation arrest. Our findings show that STN-DBS can have opposite effects on ALO. On the one hand, ALO is thought to be a corticobulbar side effect due to lateral current spreading from the STN, in which case it is necessary to use voltages below the ALO-inducing threshold. On the other hand, ALO may be considered a form of off-phase focal dystonia possibly improved by increasing the stimulation voltages.

The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3

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

Kapfhamer, D.; Sufalko, D.; Warren, S.

1996-08-01

Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10more » is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene. 31 refs., 2 figs.« less

Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.

PubMed

Malykh, Andrei G; Sadaie, M Reza

2010-02-12

There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various cognitive disabilities. Subgroup 2 drugs include levetiracetam, seletracetam and brivaracetam, which demonstrate antiepileptic activity, although their cognitive effects are unclear. Subgroup 3 includes piracetam derivatives with unknown clinical efficacies, and of these nefiracetam failed to improve cognition in post-stroke patients and rolipram is currently in clinical trials as an antidepressant. The remaining compounds of this subgroup are at various preclinical stages of research. The modes of action of piracetam and most of its derivatives remain an enigma. Differential effects on subtypes of glutamate receptors, but not the GABAergic actions, have been implicated. Piracetam seems to activate calcium influx into neuronal cells; however, this function is questionable in the light of findings that a persistent calcium inflow may have deleterious impact on neuronal cells. Although subgroup 2 compounds act via binding to another neuronal receptor (synaptic vesicle 2A), some of the subgroup 3 compounds, such as nefiracetam, are similar to those of subgroup 1. Based on calculations of the efficacy rates, our assessments indicate notable improvements in clinical outcomes with some of these agents.

IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients.

PubMed

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

2017-09-01

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

The Spectrum and Burden of Influenza-Associated Neurological Disease in Children: Combined Encephalitis and Influenza Sentinel Site Surveillance From Australia, 2013-2015.

PubMed

Britton, Philip N; Blyth, Christopher C; Macartney, Kristine; Dale, Russell C; Li-Kim-Moy, Jean; Khandaker, Gulam; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Booy, Robert; Cheng, Allen C; Jones, Cheryl A

2017-08-15

There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

The Spectrum and Burden of Influenza-Associated Neurological Disease in Children: Combined Encephalitis and Influenza Sentinel Site Surveillance from Australia 2013-2015.

PubMed

Britton, P N; Blyth, C C; Macartney, K; Dale, R C; Li-Kim-Moy, J; Khandaker, G; Crawford, N; Marshall, H; Clark, J; Elliott, E; Booy, R; Cheng, A C; Jones, C A

2017-04-29

There are few longitudinal studies of seasonal influenza associated neurological disease (IAND) and none from the Southern hemisphere. We extracted prospectively acquired Australian surveillance data from two studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalised influenza that is associated with IAND and IAE, and incidence of IAE. Over three influenza seasons, we identified 54 cases of IAND at two tertiary children's hospitals from Australia that accounted for 7.6% of hospitalised influenza. These included 10 cases of IAE (1.4% hospitalised influenza). The mean annual incidence of IAE amongst Australian children (aged ≤14 years) was 2.8 per 1 000 000. The spectrum of IAND was broad and included: IAE (10) including distinct acute encephalopathy syndromes, simple febrile seizures (14), other seizures (16), acute ataxia (4), and other sub-acute syndromes (transverse myelitis (1), opsoclonus myoclonus (1)). Two thirds of children with IAND were aged ≤4 years; less than half had pre-existing neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Dystonia.

PubMed

Morgante, Francesca; Klein, Christine

2013-10-01

The purpose of this review is to provide an update on the classification, phenomenology, pathophysiology, and treatment of dystonia. A revised definition based on the main phenomenologic features of dystonia has recently been developed in an expert consensus approach. Classification is based on two main axes: clinical features and etiology. Currently, genes have been reported for 14 types of monogenic isolated and combined dystonia. Isolated dystonia (with dystonic tremor) can be caused by mutations in TOR1A (DYT1), TUBB4 (DYT4), THAP1 (DYT6), PRKRA (DYT16), CIZ1 (DYT23), ANO3 (DYT24), and GNAL (DYT25). Combined dystonias (with parkinsonism or myoclonus) are further subdivided into persistent (GCHI [DYT5], SGCE [DYT11], and ATP1A3 [DYT12], with TAF1 most likely but not yet proven to be linked to DYT3) and paroxysmal (PNKD [DYT8], PRRT2 [DYT10], and SLC2A1 [DYT18]). Recent insights from neurophysiologic studies identified functional abnormalities in two networks in dystonia: the basal ganglia-sensorimotor network and, more recently, the cerebellothalamocortical pathway. Besides the well-known lack of inhibition at different CNS levels, dystonia is specifically characterized by maladaptive plasticity in the sensorimotor cortex and loss of cortical surround inhibition. The exact role (modulatory or compensatory) of the cerebellar-cortical pathways still has to be further elucidated. In addition to botulinum toxin for focal forms, deep brain stimulation of the globus pallidus internus is increasingly recognized as an effective treatment for generalized and segmental dystonia. The revised classification and identification of new genes for different forms of dystonia, including adult-onset segmental dystonia, enable an improved diagnostic approach. Recent pathophysiologic insights have fundamentally contributed to a better understanding of the disease mechanisms and impact on treatment, such as functional neurosurgery and nonpharmacologic treatment options.

Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg disease (EPM1) - A motor fMRI study.

PubMed

Könönen, Mervi; Danner, Nils; Koskenkorva, Päivi; Kälviäinen, Reetta; Hyppönen, Jelena; Mervaala, Esa; Karjalainen, Pasi; Vanninen, Ritva; Niskanen, Eini

2015-03-01

Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1. Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms. The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls. The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Principles and approaches to the treatment of immune-mediated movement disorders.

PubMed

Mohammad, Shekeeb S; Dale, Russell C

2018-03-01

Immune mediated movement disorders include movement disorders in the context of autoimmune encephalitis such as anti-NMDAR encephalitis, post-infectious autoimmune movement disorders such as Sydenham chorea, paraneoplastic autoimmune movement disorders such as opsoclonus myoclonus ataxia syndrome, and infection triggered conditions such as paediatric acute neuropsychiatric syndrome. This review focuses on the approach to treatment of immune mediated movement disorders, which requires an understanding of the immunopathogenesis, whether the disease is destructive or 'altering', and the natural history of disease. Factors that can influence outcome include the severity of disease, the delay before starting therapy, use of multimodal therapy and whether the course is monophasic or relapsing. Although the four main conditions listed above have different pathophysiological processes, there are general themes that broadly apply including: early diagnosis and treatment is better, minimise the severity of disease, escalate treatment if the patient is not responding to initial treatments, and minimise relapse. Copyright © 2017. Published by Elsevier Ltd.

Genetic Forms of Epilepsies and other Paroxysmal Disorders

PubMed Central

Olson, Heather E.; Poduri, Annapurna; Pearl, Phillip L.

2016-01-01

Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including Tuberous Sclerosis Complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of singe gene causes or susceptibility factors associated with several epilepsy syndromes, including the early onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look towards the future of epilepsy genetics. PMID:25192505

[Neuropsychiatric manifestations ushering pernicious anemia].

PubMed

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

2015-12-01

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

Abnormal metabolism of glycogen phosphate as a cause for Lafora disease.

PubMed

Tagliabracci, Vincent S; Girard, Jean Marie; Segvich, Dyann; Meyer, Catalina; Turnbull, Julie; Zhao, Xiaochu; Minassian, Berge A; Depaoli-Roach, Anna A; Roach, Peter J

2008-12-05

Lafora disease is a progressive myoclonus epilepsy with onset in the teenage years followed by neurodegeneration and death within 10 years. A characteristic is the widespread formation of poorly branched, insoluble glycogen-like polymers (polyglucosan) known as Lafora bodies, which accumulate in neurons, muscle, liver, and other tissues. Approximately half of the cases of Lafora disease result from mutations in the EPM2A gene, which encodes laforin, a member of the dual specificity protein phosphatase family that is able to release the small amount of covalent phosphate normally present in glycogen. In studies of Epm2a(-/-) mice that lack laforin, we observed a progressive change in the properties and structure of glycogen that paralleled the formation of Lafora bodies. At three months, glycogen metabolism remained essentially normal, even though the phosphorylation of glycogen has increased 4-fold and causes altered physical properties of the polysaccharide. By 9 months, the glycogen has overaccumulated by 3-fold, has become somewhat more phosphorylated, but, more notably, is now poorly branched, is insoluble in water, and has acquired an abnormal morphology visible by electron microscopy. These glycogen molecules have a tendency to aggregate and can be recovered in the pellet after low speed centrifugation of tissue extracts. The aggregation requires the phosphorylation of glycogen. The aggregrated glycogen sequesters glycogen synthase but not other glycogen metabolizing enzymes. We propose that laforin functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen.

[Scenes in movement. Movement disorders on film].

PubMed

Olivares Romero, J

2010-03-01

There are publications in which various neurological diseases are analysed on film. However, no references have been found on movement disorders in this medium. A total of 104 documents were collected and reviewed using the internet movie data base (IMDb). The majority were associated with dystonia, Parkinson's and tics, were American commercial productions, and the most common genre was drama. The cinema usually depicts old men with developed Parkinson's disease. However, motor complications only appear in 19% and non-motor symptoms in 14%. The image of dystonia is generally that of a young man, with disabling dystonia secondary to childhood cerebral palsy. Tics appear associated with Tourette's syndrome, with the excessive use of obscene expressions and with very few references to other important aspects of this syndrome, such as mood and behavioural changes. The majority of tremors portrayed on film are associated with Parkinsonism and are not pathological. Myoclonus appears anecdotically and is normally symptomatic. Parkinson's disease is the type of movement disorder that the cinema portrays with greater neurological honesty and in a more dignified manner.

Distribution and threshold expression of the tRNA[sup Lys] mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF)

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

Boulet, L.; Karpati, G.; Shoubridge, E.A.

1992-12-01

The authors investigated the distribution and expression of mutant mtDNAs carrying the A-to-G mutation at position 8344 in the tRNA[sup Lys] gene in the skeletal muscle of four patients with myoclonus epilepsy and ragged-red fibers (MERRF). The proportion of mutant genomes was greater than 80% of total mtDNAs in muscle samples of all patients and was associated with a decrease in the activity of cytochrome c oxidase (COX). The vast majority of myoblasts, cloned from the satellite-cell population in the same muscles, were homoplasmic for the mutation. The overall proportion of mutant mtDNAs in this population was similar to thatmore » in differentiated muscle, suggesting that the ratio of mutant to wild-type mtDNAs in skeletal muscle is determined either in the ovum or during early development and changes little with age. Translation of all mtDNA-encoded genes was severely depressed in homoplasmic mutant myoblast clones but not in heteroplasmic or wild-type clones. The threshold for biochemical expression of the mutation was determined in heteroplasmic myotubes formed by fusion of different proportions of mutant and wild-type myoblasts. The magnitude of the decrease in translation in myotubes containing mutant mtDNAs was protein specific. Complex I and IV subunits were more affected than complex V subunits, and there was a rough correlation with both protein size and number of lysine residues. Approximately 15% wild-type mtDNAs restored translation and COX activity to near normal levels. These results show that the A-to-G substitution in tRNA[sup Lys] is a functionally recessive mutation that can be rescued by intraorganellar complementation with a small proportion of wild-type mtDNAs and explain the steep threshold for expression of the MERRF clinical phenotype. 40 refs., 7 figs., 2 tabs.« less

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

PubMed

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

2016-11-01

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

Rating Scales for Movement Disorders With Sleep Disturbances: A Narrative Review

PubMed Central

Rodríguez-Blázquez, Carmen; Forjaz, Maria João; Kurtis, Monica M.; Balestrino, Roberta; Martinez-Martin, Pablo

2018-01-01

Introduction: In recent years, a wide variety of rating scales and questionnaires for movement disorders have been developed and published, making reviews on their contents, and attributes convenient for the potential users. Sleep disorders are frequently present in movement disorders, and some movement disorders are accompanied by specific sleep difficulties. Aim: The aim of this study is to perform a narrative review of the most frequently used rating scales for movement disorders with sleep problems, with special attention to those recommended by the International Parkinson and Movement Disorders Society. Methods: Online databases (PubMed, SCOPUS, Web of Science, Google Scholar), related references from papers and websites and personal files were searched for information on comprehensive or global rating scales which assessed sleep disturbances in the following movement disorders: akathisia, chorea, dystonia, essential tremor, myoclonus, multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and tics and Tourette syndrome. For each rating scale, its objective and characteristics, as well as a summary of its psychometric properties and recommendations of use are described. Results: From 22 rating scales identified for the selected movement disorders, only 5 included specific questions on sleep problems. Movement Disorders Society-Unified Parkinson's Disease Rating scale (MDS-UPDRS), Non-Motor Symptoms Scale and Questionnaire (NMSS and NMSQuest), Scales for Outcomes in Parkinson's Disease (SCOPA)-Autonomic and Progressive Supranuclear Palsy Rating Scale (PSPRS) were the only rating scales that included items for assessing sleep disturbances. Conclusions: Despite sleep problems are frequent in movement disorders, very few of the rating scales addresses these specific symptoms. This may contribute to an infra diagnosis and mistreatment of the sleep problems in patients with movement disorders.

Intraoperative monitoring of motor symptoms using surface electromyography during stereotactic surgery for movement disorders.

PubMed

Liu, Xuguang; Aziz, Tipu Z; Bain, Peter G

2005-06-01

The authors present practical evidence for the usefulness of intraoperative monitoring with surface electromyograms (sEMGs) from the affected muscles to assist electrode implantation and lesioning in patients with movement disorders. In 22 consecutive patients with various movement disorders, sEMGs were monitored in selected muscles during stereotactic surgery that involved either lesioning or electrode implantation. The electromyograms related to major motor symptoms such as tremor, rigidity, myoclonus, dystonia, and chorea were monitored and characterized on-line by both amplitude and frequency. Major motor symptoms were revealed by sEMGs recorded from the affected muscles. Tremor manifested as highly rhythmic bursts with a narrow frequency band; dyskinesias and chorea appeared as irregularly repeated bursts within a broad frequency range of 1 to 5 Hz; and rigidity and dystonia appeared as sustained high-frequency activity and co-contraction between antagonist muscles. The results suggest that intraoperative monitoring of sEMGs could help to functionally refine and confirm target localization. Surface EMGs could be used (1) as reference signals of the motor symptoms so that other signals, such as the oscillatory local field potentials simultaneously recorded via the implanted electrodes, could be correlated with the sEMGs and used to fine-tune or confirm the target localization; (2) to quantify the effects of acute electrical stimulation on the motor symptoms; and (3) to sensitively detect unwanted capsular responses induced by direct stimulation of the internal capsule. The authors conclude that intraoperative monitoring of sEMGs of the affected muscles of patients with movement disorders during stereotactic surgery provides sensitive and quantitative information that can contribute to improved electrode or lesion placement.

Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks

PubMed Central

Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.

2017-01-01

Abstract See Hamandi (doi:10.1093/awx049) for a scientific commentary on this article. Photosensitivity is a condition in which lights induce epileptiform activities. This abnormal electroencephalographic response has been associated with hyperexcitability of the visuo-motor system. Here, we evaluate if intrinsic dysfunction of this network is present in brain activity at rest, independently of any stimulus and of any paroxysmal electroencephalographic activity. To address this issue, we investigated the haemodynamic correlates of the spontaneous alpha rhythm, which is considered the hallmark of the brain resting state, in photosensitive patients and in people without photosensitivity. Second, we evaluated the whole-brain functional connectivity of the visual thalamic nuclei in the various populations of subjects under investigation. Forty-four patients with epilepsy and 16 healthy control subjects underwent an electroencephalography-correlated functional magnetic resonance imaging study, during an eyes-closed condition. The following patient groups were included: (i) genetic generalized epilepsy with photosensitivity, 16 subjects (mean age 25 ± 10 years); (ii) genetic generalized epilepsy without photosensitivity, 13 patients (mean age 25 ± 11 years); (iii) focal epilepsy, 15 patients (mean age 25 ± 9 years). For each subject, the posterior alpha power variations were convolved with the standard haemodynamic response function and used as a regressor. Within- and between-groups second level analyses were performed. Whole brain functional connectivity was evaluated for two thalamic regions of interest, based on the haemodynamic findings, which included the posterior thalamus (pulvinar) and the medio-dorsal thalamic nuclei. Genetic generalized epilepsy with photosensitivity demonstrated significantly greater mean alpha-power with respect to controls and other epilepsy groups. In photosensitive epilepsy, alpha-related blood oxygen level-dependent signal changes demonstrated lower decreases relative to all other groups in the occipital, sensory-motor, anterior cingulate and supplementary motor cortices. Coherently, the same brain regions demonstrated abnormal connectivity with the visual thalamus only in epilepsy patients with photosensitivity. As predicted, our findings indicate that the cortical-subcortical network generating the alpha oscillation at rest is different in people with epilepsy and visual sensitivity. This difference consists of a decreased alpha-related inhibition of the visual cortex and sensory-motor networks at rest. These findings represent the substrate of the clinical manifestations (i.e. myoclonus) of the photoparoxysmal response. Moreover, our results provide the first evidence of the existence of a functional link between the circuits that trigger the visual sensitivity phenomenon and those that generate the posterior alpha rhythm. PMID:28334965

Estrogen increases latencies to seizures and levels of 5α-pregnan-3α-ol-20-one in hippocampus of wild-type, but not 5α-reductase knockout, mice

PubMed Central

Osborne, Danielle M.; Frye, Cheryl A.

2013-01-01

Sex steroids can influence seizures. Estrogen (E2), progesterone (P4), and its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in particular, have received much attention for exerting these effects. Typically, it is thought that E2 precipitates seizures, and progestogens, such as P4 and 3α,5α-THP, attenuate seizures. However, E2 may also have antiseizure effects, perhaps in part through its enhancement of the formation of 3α,5α-THP, which has GABAA/benzodiazepine receptor agonist-like actions. To test this hypothesis, male and female, castrated or ovariectomized, wild-type and 5α-reductase knockout mice were implanted with Silastic capsules of E2 or vehicle and then administered pentylenetetrazol (85 mg/kg, ip). Wild-type, but not 5α-reductase knockout, mice administered E2 had significantly longer latencies to myoclonus and increased levels of 3α,5α-THP in the hippocampus. Thus, some of the anticonvulsive effects of E2 may involve formation of 3α,5α-THP in the hippocampus. PMID:19782646

The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and 1,4-butanediol.

PubMed

Schep, Leo J; Knudsen, Kai; Slaughter, Robin J; Vale, J Allister; Mégarbane, Bruno

2012-07-01

Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to GHB and its analogs and discuss the features and management of GHB withdrawal. OVID MEDLINE and ISI Web of Science databases were searched using the terms "GHB," "gamma-hydroxybutyrate," "gamma-hydroxybutyric acid," "4-hydroxybutanoic acid," "sodium oxybate," "gamma-butyrolactone," "GBL," "1,4-butanediol," and "1,4-BD" alone and in combination with the keywords "pharmacokinetics," "kinetics," "poisoning," "poison," "toxicity," "ingestion," "adverse effects," "overdose," and "intoxication." In addition, bibliographies of identified articles were screened for additional relevant studies including nonindexed reports. Non-peer-reviewed sources were also included: books, relevant newspaper reports, and applicable Internet resources. These searches produced 2059 nonduplicate citations of which 219 were considered relevant. There is limited information regarding statistical trends on world-wide use of GHB and its analogs. European data suggests that the use of GHB is generally low; however, there is some evidence of higher use among some sub-populations, settings, and geographical areas. In the United States of America, poison control center data have shown that enquiries regarding GHB have decreased between 2002 and 2010 suggesting a decline in use over this timeframe. GHB is an endogenous neurotransmitter synthesized from glutamate with a high affinity for GHB-receptors, present on both on pre- and postsynaptic neurons, thereby inhibiting GABA release. In overdose, GHB acts both directly as a partial GABA(b) receptor agonist and indirectly through its metabolism to form GABA. GHB is rapidly absorbed by the oral route with peak blood concentrations typically occurring within 1 hour. It has a relatively small volume of distribution and is rapidly distributed across the blood-brain barrier. GHB is metabolized primarily in the liver and is eliminated rapidly with a reported 20-60 minute half-life. The majority of a dose is eliminated completely within 4-8 hours. The related chemicals, 1,4-butanediol and gamma butyrolactone, are metabolized endogenously to GHB. CLINICAL FEATURES OF POISONING: GHB produces CNS and respiratory depression of relatively short duration. Other commonly reported features include gastrointestinal upset, bradycardia, myoclonus, and hypothermia. Fatalities have been reported. MANAGEMENT OF POISONING: Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Airway protection, intubation, and/or assisted ventilation may be indicated for severe respiratory depression. Gastrointestinal decontamination is unlikely to be beneficial. Pharmacological intervention is rarely required for bradycardia; however, atropine administration may occasionally be warranted. WITHDRAWAL SYNDROME: Abstinence after chronic use may result in a withdrawal syndrome, which may persist for days in severe cases. Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, disorientation, confusion, and aggression/combativeness. Benzodiazepine administration appears to be the treatment of choice, with barbiturates, baclofen, or propofol as second line management options. GHB poisoning can cause potentially life-threatening CNS and respiratory depression, requiring appropriate, symptom-directed supportive care to ensure complete recovery. Withdrawal from GHB may continue for up to 21 days and can be life-threatening, though treatment with benzodiazepines is usually effective.

Adding video recording increases the diagnostic yield of routine electroencephalograms in children with frequent paroxysmal events.

PubMed

Watemberg, Nathan; Tziperman, Barak; Dabby, Ron; Hasan, Mariana; Zehavi, Liora; Lerman-Sagie, Tally

2005-05-01

To report on the usefulness of adding video recording to routine EEG studies of infants and children with frequent paroxysmal events. We analyzed the efficacy of this diagnostic means during a 4-year period. The decision whether to add video recording was made by the pediatric EEG interpreter at the time of the study. Studies were planned to last between 20 and 30 min, and, if needed, were extended by the EEG interpreter. For most studies, video recording was added from the beginning of EEG recording. In a minority of cases, the addition of video was implemented during the first part of the EEG test, as clinical events became obvious. In these cases, a new study (file) was begun. The success rate was analyzed according to the indications for the EEG study: paroxysmal eye movements, tremor, suspected seizures, myoclonus, staring episodes, suspected stereotypias and tics, absence epilepsy follow-up, cyanotic episodes, and suspected psychogenic nonepileptic events. Video recording was added to 137 of 666 routine studies. Mean patient age was 4.8 years. The nature of the event was determined in 61 (45%) of the EEG studies. Twenty-eight percent were hospitalized patients. The average study duration was 26 min. This diagnostic means was particularly useful for paroxysmal eye movements, staring spells, myoclonic jerks, stereotypias, and psychogenic nonepileptic events. About 46% of 116 patients for whom cognitive data were available were mentally retarded. EEG with added video recording was successfully performed in all 116 cases and provided useful information in 29 (55%) of these 53 patients. Adding video recording to routine EEG was helpful in 45% of cases referred for frequent paroxysmal events. This technique proved useful for hospitalized children as well as for outpatients. Moreover, it was successfully applied in cognitively impaired patients. Infants and children with paroxysmal eye movements, staring spells, myoclonic jerks, stereotypias, and pseudoseizures especially benefited from this diagnostic means. Because of its low cost and the little discomfort imposed on the patient and his or her family, this technique should be considered as a first diagnostic step in children with frequent paroxysmal events.

Expression, purification and characterization of soluble red rooster laforin as a fusion protein in Escherichia coli.

PubMed

Brewer, M Kathryn; Husodo, Satrio; Dukhande, Vikas V; Johnson, Mary Beth; Gentry, Matthew S

2014-04-02

The gene that encodes laforin, a dual-specificity phosphatase with a carbohydrate-binding module, is mutated in Lafora disease (LD). LD is an autosomal recessive, fatal progressive myoclonus epilepsy characterized by the intracellular buildup of insoluble, hyperphosphorylated glycogen-like particles, called Lafora bodies. Laforin dephosphorylates glycogen and other glucans in vitro, but the structural basis of its activity remains unknown. Recombinant human laforin when expressed in and purified from E. coli is largely insoluble and prone to aggregation and precipitation. Identification of a laforin ortholog that is more soluble and stable in vitro would circumvent this issue. In this study, we cloned multiple laforin orthologs, established a purification scheme for each, and tested their solubility and stability. Gallus gallus (Gg) laforin is more stable in vitro than human laforin, Gg-laforin is largely monomeric, and it possesses carbohydrate binding and phosphatase activity similar to human laforin. Gg-laforin is more soluble and stable than human laforin in vitro, and possesses similar activity as a glucan phosphatase. Therefore, it can be used to model human laforin in structure-function studies. We have established a protocol for purifying recombinant Gg-laforin in sufficient quantity for crystallographic and other biophysical analyses, in order to better understand the function of laforin and define the molecular mechanisms of Lafora disease.

Earlier onset of motor deficits in mice with double mutations in Dyt1 and Sgce.

PubMed

Yokoi, Fumiaki; Yang, Guang; Li, Jindong; DeAndrade, Mark P; Zhou, Tong; Li, Yuqing

2010-10-01

DYT1 early-onset generalized torsion dystonia is an inherited movement disorder caused by mutations in DYT1 coding for torsinA with ∼30% penetrance. Most of the DYT1 dystonia patients exhibit symptoms during childhood and adolescence. On the other hand, DYT1 mutation carriers without symptoms during these periods mostly do not exhibit symptoms later in their life. Little is known about what controls the timing of the onset, a critical issue for DYT1 mutation carriers. DYT11 myoclonus-dystonia is caused by mutations in SGCE coding for ε-sarcoglycan. Two dystonia patients from a single family with double mutations in DYT1 and SGCE exhibited more severe symptoms. A recent study suggested that torsinA contributes to the quality control of ε-sarcoglycan. Here, we derived mice carrying mutations in both Dyt1 and Sgce and found that these double mutant mice showed earlier onset of motor deficits in beam-walking test. A novel monoclonal antibody against mouse ε-sarcoglycan was developed by using Sgce knock-out mice to avoid the immune tolerance. Western blot analysis suggested that functional deficits of torsinA and ε-sarcoglycan may independently cause motor deficits. Examining additional mutations in other dystonia genes may be beneficial to predict the onset in DYT1 mutation carriers.

Standardized assessment of seizures in patients with juvenile neuronal ceroid lipofuscinosis.

PubMed

Augustine, Erika F; Adams, Heather R; Beck, Christopher A; Vierhile, Amy; Kwon, Jennifer; Rothberg, Paul G; Marshall, Frederick; Block, Robert; Dolan, James; Mink, Jonathan W

2015-04-01

To evaluate seizure phenomenology, treatment, and course in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL). Data from an ongoing natural history study of JNCL were analyzed using cross-sectional and longitudinal methods. Seizures were evaluated with the Unified Batten Disease Rating Scale, a disease-specific quantitative assessment tool. Eighty-six children (44 males, 42 females) with JNCL were assessed at an average of three annual visits (range 1-11). Eighty-six percent (n=74) experienced at least one seizure, most commonly generalized tonic-clonic, with mean age at onset of 9 years 7 months (SD 2y 10mo). Seizures were infrequent, typically occurring less often than once every 3 months, and were managed with one to two medications for most participants. Valproate (49%, n=36) and levetiracetam (41%, n=30) were the most commonly used seizure medications. Myoclonic seizures occurred infrequently (16%, n=14). Seizure severity did not vary by sex or genotype. Seizures showed mild worsening with increasing age. The neuronal ceroid lipofuscinoses (NCLs) represent a group of disorders unified by neurodegeneration and symptoms of blindness, seizures, motor impairment, and dementia. While NCLs are considered in the differential diagnosis of progressive myoclonus epilepsy, we show that myoclonic seizures are infrequent in JNCL. This highlights the NCLs as consisting of genetically distinct disorders with differing natural history. © 2014 Mac Keith Press.

[Neurologic disorders in Whipple's disease].

PubMed

Jović, N S; Jović, J Z

1996-01-01

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is good, although the optimal antimicrobial regimen is not clearly established. Initial parenteral therapy (tetracycline, penicilline, streptomycine, chloramphenicol, ampicilline) and peroral long-term treatment with trimetoprime-sulphametoxasole, are recommended. As CNS relapse of Whipple's disease may occur after several years, long-term treatment should include antibiotics that are able to cross the blood-brain barrier. The CNS relapse, in contrast to the systemic ones, is resistant to the treatment. Appropriate therapy instituted earlier in the course of the disease is associated with a better neurological outcome. Early recognition can be critical in Whipple's disease because of irreversible neurological sequelae seen later in the course of this potentially treatable condition. In cases with high clinical suspicion in which Whipple's disease cannot be diagnosed with procedures such as jejunal biopsy, antibiotic therapy is recommended. Recovery of an established neurological deficit may rarely occur. Longterm follow-up studies would help to identify the optimal antibiotic regimen and duration of treatment.

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

ClinicalTrials.gov

2017-09-28

Rare Disorders; Undiagnosed Disorders; Disorders of Unknown Prevalence; Cornelia De Lange Syndrome; Prenatal Benign Hypophosphatasia; Perinatal Lethal Hypophosphatasia; Odontohypophosphatasia; Adult Hypophosphatasia; Childhood-onset Hypophosphatasia; Infantile Hypophosphatasia; Hypophosphatasia; Kabuki Syndrome; Bohring-Opitz Syndrome; Narcolepsy Without Cataplexy; Narcolepsy-cataplexy; Hypersomnolence Disorder; Idiopathic Hypersomnia Without Long Sleep Time; Idiopathic Hypersomnia With Long Sleep Time; Idiopathic Hypersomnia; Kleine-Levin Syndrome; Kawasaki Disease; Leiomyosarcoma; Leiomyosarcoma of the Corpus Uteri; Leiomyosarcoma of the Cervix Uteri; Leiomyosarcoma of Small Intestine; Acquired Myasthenia Gravis; Addison Disease; Hyperacusis (Hyperacousis); Juvenile Myasthenia Gravis; Transient Neonatal Myasthenia Gravis; Williams Syndrome; Lyme Disease; Myasthenia Gravis; Marinesco Sjogren Syndrome(Marinesco-Sjogren Syndrome); Isolated Klippel-Feil Syndrome; Frasier Syndrome; Denys-Drash Syndrome; Beckwith-Wiedemann Syndrome; Emanuel Syndrome; Isolated Aniridia; Beckwith-Wiedemann Syndrome Due to Paternal Uniparental Disomy of Chromosome 11; Beckwith-Wiedemann Syndrome Due to Imprinting Defect of 11p15; Beckwith-Wiedemann Syndrome Due to 11p15 Translocation/Inversion; Beckwith-Wiedemann Syndrome Due to 11p15 Microduplication; Beckwith-Wiedemann Syndrome Due to 11p15 Microdeletion; Axenfeld-Rieger Syndrome; Aniridia-intellectual Disability Syndrome; Aniridia - Renal Agenesis - Psychomotor Retardation; Aniridia - Ptosis - Intellectual Disability - Familial Obesity; Aniridia - Cerebellar Ataxia - Intellectual Disability; Aniridia - Absent Patella; Aniridia; Peters Anomaly - Cataract; Peters Anomaly; Potocki-Shaffer Syndrome; Silver-Russell Syndrome Due to Maternal Uniparental Disomy of Chromosome 11; Silver-Russell Syndrome Due to Imprinting Defect of 11p15; Silver-Russell Syndrome Due to 11p15 Microduplication; Syndromic Aniridia; WAGR Syndrome; Wolf-Hirschhorn Syndrome; 4p16.3 Microduplication Syndrome; 4p Deletion Syndrome, Non-Wolf-Hirschhorn Syndrome; Autosomal Recessive Stickler Syndrome; Stickler Syndrome Type 2; Stickler Syndrome Type 1; Stickler Syndrome; Mucolipidosis Type 4; X-linked Spinocerebellar Ataxia Type 4; X-linked Spinocerebellar Ataxia Type 3; X-linked Intellectual Disability - Ataxia - Apraxia; X-linked Progressive Cerebellar Ataxia; X-linked Non Progressive Cerebellar Ataxia; X-linked Cerebellar Ataxia; Vitamin B12 Deficiency Ataxia; Toxic Exposure Ataxia; Unclassified Autosomal Dominant Spinocerebellar Ataxia; Thyroid Antibody Ataxia; Sporadic Adult-onset Ataxia of Unknown Etiology; Spinocerebellar Ataxia With Oculomotor Anomaly; Spinocerebellar Ataxia With Epilepsy; Spinocerebellar Ataxia With Axonal Neuropathy Type 2; Spinocerebellar Ataxia Type 8; Spinocerebellar Ataxia Type 7; Spinocerebellar Ataxia Type 6; Spinocerebellar Ataxia Type 5; Spinocerebellar Ataxia Type 4; Spinocerebellar Ataxia Type 37; Spinocerebellar Ataxia Type 36; Spinocerebellar Ataxia Type 35; Spinocerebellar Ataxia Type 34; Spinocerebellar Ataxia Type 32; Spinocerebellar Ataxia Type 31; Spinocerebellar Ataxia Type 30; Spinocerebellar Ataxia Type 3; Spinocerebellar Ataxia Type 29; Spinocerebellar Ataxia Type 28; Spinocerebellar Ataxia Type 27; Spinocerebellar Ataxia Type 26; Spinocerebellar Ataxia Type 25; Spinocerebellar Ataxia Type 23; Spinocerebellar Ataxia Type 22; Spinocerebellar Ataxia Type 21; Spinocerebellar Ataxia Type 20; Spinocerebellar Ataxia Type 2; Spinocerebellar Ataxia Type 19/22; Spinocerebellar Ataxia Type 18; Spinocerebellar Ataxia Type 17; Spinocerebellar Ataxia Type 16; Spinocerebellar Ataxia Type 15/16; Spinocerebellar Ataxia Type 14; Spinocerebellar Ataxia Type 13; Spinocerebellar Ataxia Type 12; Spinocerebellar Ataxia Type 11; Spinocerebellar Ataxia Type 10; Spinocerebellar Ataxia Type 1 With Axonal Neuropathy; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia - Unknown; Spinocerebellar Ataxia - Dysmorphism; Non Progressive Epilepsy and/or Ataxia With Myoclonus as a Major Feature; Spectrin-associated Autosomal Recessive Cerebellar Ataxia; Spasticity-ataxia-gait Anomalies Syndrome; Spastic Ataxia With Congenital Miosis; Spastic Ataxia - Corneal Dystrophy; Spastic Ataxia; Rare Hereditary Ataxia; Rare Ataxia; Recessive Mitochondrial Ataxia Syndrome; Progressive Epilepsy and/or Ataxia With Myoclonus as a Major Feature; Posterior Column Ataxia - Retinitis Pigmentosa; Post-Stroke Ataxia; Post-Head Injury Ataxia; Post Vaccination Ataxia; Polyneuropathy - Hearing Loss - Ataxia - Retinitis Pigmentosa - Cataract; Muscular Atrophy - Ataxia - Retinitis Pigmentosa - Diabetes Mellitus; Non-progressive Cerebellar Ataxia With Intellectual Disability; Non-hereditary Degenerative Ataxia; Paroxysmal Dystonic Choreathetosis With Episodic Ataxia and Spasticity; Olivopontocerebellar Atrophy - Deafness; NARP Syndrome; Myoclonus - Cerebellar Ataxia - Deafness; Multiple System Atrophy, Parkinsonian Type; Multiple System Atrophy, Cerebellar Type; Multiple System Atrophy; Maternally-inherited Leigh Syndrome; Machado-Joseph Disease Type 3; Machado-Joseph Disease Type 2; Machado-Joseph Disease Type 1; Lethal Ataxia With Deafness and Optic Atrophy; Leigh Syndrome; Leukoencephalopathy With Mild Cerebellar Ataxia and White Matter Edema; Leukoencephalopathy - Ataxia - Hypodontia - Hypomyelination; Leigh Syndrome With Nephrotic Syndrome; Leigh Syndrome With Leukodystrophy; Leigh Syndrome With Cardiomyopathy; Late-onset Ataxia With Dementia; Intellectual Disability-hyperkinetic Movement-truncal Ataxia Syndrome; Infection or Post Infection Ataxia; Infantile-onset Autosomal Recessive Nonprogressive Cerebellar Ataxia; Infantile Onset Spinocerebellar Ataxia; GAD Ataxia; Hereditary Episodic Ataxia; Gliadin/Gluten Ataxia; Friedreich Ataxia; Fragile X-associated Tremor/Ataxia Syndrome; Familial Paroxysmal Ataxia; Exposure to Medications Ataxia; Episodic Ataxia With Slurred Speech; Episodic Ataxia Unknown Type; Episodic Ataxia Type 7; Episodic Ataxia Type 6; Episodic Ataxia Type 5; Episodic Ataxia Type 4; Episodic Ataxia Type 3; Episodic Ataxia Type 1; Epilepsy and/or Ataxia With Myoclonus as Major Feature; Early-onset Spastic Ataxia-neuropathy Syndrome; Early-onset Progressive Neurodegeneration - Blindness - Ataxia - Spasticity; Early-onset Cerebellar Ataxia With Retained Tendon Reflexes; Early-onset Ataxia With Dementia; Childhood-onset Autosomal Recessive Slowly Progressive Spinocerebellar Ataxia; Dilated Cardiomyopathy With Ataxia; Cataract - Ataxia - Deafness; Cerebellar Ataxia, Cayman Type; Cerebellar Ataxia With Peripheral Neuropathy; Cerebellar Ataxia - Hypogonadism; Cerebellar Ataxia - Ectodermal Dysplasia; Cerebellar Ataxia - Areflexia - Pes Cavus - Optic Atrophy - Sensorineural Hearing Loss; Brain Tumor Ataxia; Brachydactyly - Nystagmus - Cerebellar Ataxia; Benign Paroxysmal Tonic Upgaze of Childhood With Ataxia; Autosomal Recessive Syndromic Cerebellar Ataxia; Autosomal Recessive Spastic Ataxia With Leukoencephalopathy; Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay; Autosomal Recessive Spastic Ataxia - Optic Atrophy - Dysarthria; Autosomal Recessive Spastic Ataxia; Autosomal Recessive Metabolic Cerebellar Ataxia; Autosomal Dominant Spinocerebellar Ataxia Due to Repeat Expansions That do Not Encode Polyglutamine; Autosomal Recessive Ataxia, Beauce Type; Autosomal Recessive Ataxia Due to Ubiquinone Deficiency; Autosomal Recessive Ataxia Due to PEX10 Deficiency; Autosomal Recessive Degenerative and Progressive Cerebellar Ataxia; Autosomal Recessive Congenital Cerebellar Ataxia Due to MGLUR1 Deficiency; Autosomal Recessive Congenital Cerebellar Ataxia Due to GRID2 Deficiency; Autosomal Recessive Congenital Cerebellar Ataxia; Autosomal Recessive Cerebellar Ataxia-pyramidal Signs-nystagmus-oculomotor Apraxia Syndrome; Autosomal Recessive Cerebellar Ataxia-epilepsy-intellectual Disability Syndrome Due to WWOX Deficiency; Autosomal Recessive Cerebellar Ataxia-epilepsy-intellectual Disability Syndrome Due to TUD Deficiency; Autosomal Recessive Cerebellar Ataxia-epilepsy-intellectual Disability Syndrome Due to KIAA0226 Deficiency; Autosomal Recessive Cerebellar Ataxia-epilepsy-intellectual Disability Syndrome; Autosomal Recessive Cerebellar Ataxia With Late-onset Spasticity; Autosomal Recessive Cerebellar Ataxia Due to STUB1 Deficiency; Autosomal Recessive Cerebellar Ataxia Due to a DNA Repair Defect; Autosomal Recessive Cerebellar Ataxia - Saccadic Intrusion; Autosomal Recessive Cerebellar Ataxia - Psychomotor Retardation; Autosomal Recessive Cerebellar Ataxia - Blindness - Deafness; Autosomal Recessive Cerebellar Ataxia; Autosomal Dominant Spinocerebellar Ataxia Due to a Polyglutamine Anomaly; Autosomal Dominant Spinocerebellar Ataxia Due to a Point Mutation; Autosomal Dominant Spinocerebellar Ataxia Due to a Channelopathy; Autosomal Dominant Spastic Ataxia Type 1; Autosomal Dominant Spastic Ataxia; Autosomal Dominant Optic Atrophy; Ataxia-telangiectasia Variant; Ataxia-telangiectasia; Autosomal Dominant Cerebellar Ataxia, Deafness and Narcolepsy; Autosomal Dominant Cerebellar Ataxia Type 4; Autosomal Dominant Cerebellar Ataxia Type 3; Autosomal Dominant Cerebellar Ataxia Type 2; Autosomal Dominant Cerebellar Ataxia Type 1; Autosomal Dominant Cerebellar Ataxia; Ataxia-telangiectasia-like Disorder; Ataxia-intellectual Disability-oculomotor Apraxia-cerebellar Cysts Syndrome; Ataxia-deafness-intellectual Disability Syndrome; Ataxia With Vitamin E Deficiency; Ataxia With Dementia; Ataxia Neuropathy Spectrum; Ataxia - Tapetoretinal Degeneration; Ataxia - Photosensitivity - Short Stature; Ataxia - Pancytopenia; Ataxia - Oculomotor Apraxia Type 1; Ataxia - Hypogonadism - Choroidal Dystrophy; Ataxia - Other; Ataxia - Genetic Diagnosis - Unknown; Acquired Ataxia; Adult-onset Autosomal Recessive Cerebellar Ataxia; Alcohol Related Ataxia; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type II; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Multiple Endocrine Neoplasia, Type IV; Multiple Endocrine Neoplasia, Type 3; Multiple Endocrine Neoplasia (MEN) Syndrome; Multiple Endocrine Neoplasia Type 2B; Multiple Endocrine Neoplasia Type 2A; Atypical Hemolytic Uremic Syndrome; Atypical HUS; Wiedemann-Steiner Syndrome; Breast Implant-Associated Anaplastic Large Cell Lymphoma; Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA); Hemophagocytic Lymphohistiocytosis; Behcet's Disease

[Synthetic cannabinoids: spread, addiction biology & current perspective of personal health hazard].

PubMed

Bonnet, U; Mahler, H

2015-04-01

Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e. g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e. g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs. © Georg Thieme Verlag KG Stuttgart · New York.

Serotonin syndrome: a complex but easily avoidable condition.

PubMed

Dvir, Yael; Smallwood, Patrick

2008-01-01

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.

Exploring the structural insights on human laforin mutation K87A in Lafora disease--a molecular dynamics study.

PubMed

Srikumar, P S; Rohini, K

2013-10-01

Lafora disease (LD) is an autosomal recessive, progressive form of myoclonus epilepsy which affects worldwide. LD occurs mainly in countries like southern Europe, northern Africa, South India, and in the Middle East. LD occurs with its onset mainly in teenagers and leads to decline and death within 2 to 10 years. The genes EPM2A and EPM2B are commonly involved in 90 % of LD cases. EPM2A codes for protein laforin which contains an amino terminal carbohydrate binding module (CBM) belonging to the CBM20 family and a carboxy terminal dual specificity phosphatase domain. Mutations in laforin are found to abolish glycogen binding and have been reported in wet lab methods. In order to investigate on structural insights on laforin mutation K81A, we performed molecular dynamics (MD) simulation studies for native and mutant protein. MD simulation results showed loss of stability due to mutation K87A which confirmed the structural reason for conformational changes observed in laforin. The conformational change of mutant laforin was confirmed by analysis using root mean square deviation, root mean square fluctuation, solvent accessibility surface area, radius of gyration, hydrogen bond, and principle component analysis. Our results identified that the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional CBM domain, have more impact in abolishing glycogen binding that favors LD.

Zebrafish scarb2a insertional mutant reveals a novel function for the Scarb2/Limp2 receptor in notochord development.

PubMed

Diaz-Tellez, Abigail; Zampedri, Cecilia; Ramos-Balderas, Jose L; García-Hernández, Fernando; Maldonado, Ernesto

2016-04-01

Scarb2 or Limp2 belong to a subfamily of Scavenger receptors described as lysosomal transmembrane glycosylated receptors, that are mutated in the human syndrome AMRF (action myoclonus-renal failure). The zebrafish insertional mutant scarb2a(hi1463Tg) has notochord defects, the notochord is a defining feature of chordates running along the center of the longitudinal axis and it is essential for forming the spinal column in all vertebrates. There are three paralogous scarb2 genes in zebrafish; scarb2a, scarb2b, and scarb2c. Both Scarb2a and Scarb2b proteins lack the classical di-leucine motif. We found that scarb2a(hi1463Tg) homozygous zebrafish embryos have a null mutation impairing vacuole formation in the notochord and simultaneously disrupting proper formation of the basement membrane resulting in its thickening at the ventral side of the notochord, which may be the cause for the anomalous upward bending observed in the trunk. Through whole-mount in situ hybridization, we detected scarb2a mRNA expression in the notochord and in the brain early in development. However, it is puzzling that scarb2a notochord mRNA expression is short-lived in the presumptive notochord and precedes the complete differentiation of the notochord. This work describes a novel function for the Scarb2 receptor as an essential glycoprotein for notochord development. © 2016 Wiley Periodicals, Inc.

Mitochondrial Transfer from Wharton's Jelly Mesenchymal Stem Cell to MERRF Cybrid Reduces Oxidative Stress and Improves Mitochondrial Bioenergetics

PubMed Central

Liou, Chia-Wei; Chen, Shang-Der; Wang, Pei-Wen; Chuang, Jiin-Haur; Tiao, Mao-Meng; Hsu, Te-Yao

2017-01-01

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria. The MERRF cybrid cells exhibited a high mt.8344A>G mutation ratio, enhanced ROS level and oxidative damage, impaired mitochondrial bioenergetics, defected mitochondria-dependent viability, exhibited an imbalance of mitochondrial dynamics, and are susceptible to apoptotic stress. Coculture experiments revealed that mitochondria were intercellularly conducted from the WJMSC to the MERRF cybrid. Furthermore, WJMSC transferred mitochondria exclusively to cells with defective mitochondria but not to cells with normal mitochondria. MERRF cybrid following WJMSC coculture (MF+WJ) demonstrated improvement of mt.8344A>G mutation ratio, ROS level, oxidative damage, mitochondrial bioenergetics, mitochondria-dependent viability, balance of mitochondrial dynamics, and resistance against apoptotic stress. WJMSC-derived mitochondrial transfer and its therapeutic effect were noted to be blocked by F-actin depolymerizing agent cytochalasin B. Collectively, the WJMSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction. PMID:28607632

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options.

PubMed

Lamb, Ruth; Rohrer, Jonathan D; Lees, Andrew J; Morris, Huw R

2016-09-01

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, "poor" response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord. 20 Suppl 1:S83-91, 2005; Litvan et al. Neurology. 48:119-25, 1997; Armstrong et al. Neurology. 80(5):496-503, 2013). There is some evidence that intrasalivery gland botulinum toxin is useful in managing problematic sialorrhea and that intramuscular botulinum toxin and baclofen are helpful in reducing dystonia, including blepharospasm. Benzodiazepines may also be useful in managing dystonia. Myoclonus may be managed using levetiracetam and benzodiazepines. Pharmacological agents licensed for Alzheimer's disease (such as acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonists) have been used off-label in PSP, CBD, and other tauopathies with the aim of improving cognition; however, there is limited evidence that they are effective and risk of adverse effects may outweigh benefits. The use of atypical antipsychotics for behavioural symptoms is not recommended in the elderly or those with demetia associated conditions and most antipsychotics will worsen Parkinsonism. Antidepressants may be useful for behavioral symptoms and depression but are often poorly tolerated due to adverse effects. In the absence of an effective drug treatment to target the underlying cause of CBD and PSP, management should focus on optimizing quality of life, relieving symptoms and assisting patients with their activities of daily living (ADL). Patients should be managed by a multidisciplinary team consisting of neurologists, physiotherapists (PT), occupational therapists (OT), speech and language therapists (SALT), dieticians, ophthalmologists, psychologists, and palliative care specialists.

[A case of non-photosensitive, self-induced epileptic seizures with pacygyria].

PubMed

Nagai, H; Shikata, A; Sato, N; Takeuchi, Y; Sawada, T

1998-09-01

We report an 11-year-old boy with a non-photosensitive epileptic self-induced seizures, pacygyria and familial ataxia. His grandmother and aunts had dysarthria, and his mother had developed progressive ataxia and myoclonus since 40 years old. His older sister had ataxia, mental retardation and epilepsy. As for the boy, motor developmental delay with muscle hypertonicity of left extremities was recognized at the age of 5 months. Mental retardation and ataxia was recognized at the age of 3 years and slight mental regression is recognized at the age of 11 years. No special findings were detected in an examination of his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain magnetic resonance imaging revealed pachygyria of the right cerebral cortecies. At the age of two, he began to induce seizures with impairment of consciousness in himself by waving his right hand over his face which was directed toward a source of bright light. At the age of seven, he developed spontaneous seizures with impairment of consciousness. An EEG showed frequent spikes in the occipital areas, on the right and left sides occurring either independently or synchronously. Intermittent photic stimulation and pattern stimulation did not induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the seizures was the occipital lobe. Treatment with valporate and zonisamide was effective in reducing the seizures. The findings of our case imply the pathogenesis of self-induced seizures and the relationship between PME and neuronal migration disorders.

Etomidate accurately localizes the epileptic area in patients with temporal lobe epilepsy.

PubMed

Pastor, Jesús; Wix, Rybel; Meilán, María Luisa; Martínez-Chacón, José Luís; de Dios, Eva; Domínguez-Gadea, Luis; Herrera-Peco, Iván; Sola, Rafael G

2010-04-01

A variety of drugs have been used to activate and identify the epileptogenic area in patients during presurgical evaluation. We have evaluated the safety and usefulness of etomidate in identifying the epileptic zone by measuring bioelectrical brain activity and cerebral blood flow (CBF). We studied 13 men and 9 women under presurgical evaluation for temporal lobe epilepsy. We applied etomidate (0.1 mg/kg) while patients were monitored by video-electroencephalography (VEEG) with foramen ovale electrodes. In a subset of 15 patients, we also measured CBF with single photon emission computed tomography (SPECT). (1) Etomidate induced seizures in 2 of 22 patients. (2) The main side-effects observed were myoclonus (14 of 20) and moderate pain (3 of 20). (3) No changes in capillary oxygen saturation, respiration, or heart rate were observed. (4) Irritative activity specifically increased in the temporal mesial and lateral areas. No spikes were observed in other areas, aside from those observed under baseline conditions. (5) Irritative activity induced by etomidate correctly lateralized the ictal onset zone in 19 of 20 patients. In addition, the two etomidate-induced seizures appeared in the same regions as spontaneous ones. (6) The kinetics of pharmacologically induced activity was higher in the region of the ictal-onset zone. (7) Etomidate increased the CBF in the basal ganglia and especially in the posterior hippocampus of the temporal mesial region contralateral to the ictal-onset zone. Etomidate activation is a safe, specific, and quick test that can be used to identify the epileptic region in patients evaluated as candidates for temporal lobe epilepsy surgery.

Etomidate-Remifentanil is more Suitable for Monitored Anesthesia Care during Gastroscopy in Older Patients than Propofol-Remifentanil

PubMed Central

Shen, Xiao-Chun; Ao, Xing; Cao, Yan; Lan, Li; Liu, Xin-Man; Sun, Wen-Jing; Li, Ping; Lan, Chun-Hui

2015-01-01

Background This prospective and randomized study was designed to compare safety, potential complications, and patient and examiner satisfaction of 2 anesthetic combinations – etomidate-remifentanil and propofol-remifentanil – in elderly patients undergoing diagnostic gastroscopy. Material/Methods A group of 720 patients, aged 60–80 years, scheduled for diagnostic gastroscopy under sedation were prospectively randomized. After 0.4–0.6 μg kg−1 of remifentanil was infused, etomidate or propofol was administered. Patients in the etomidate group received doses of etomidate at 0.1–0.15 mg kg−1 followed by 4–6 mg. Patients in the propofol group received doses of propofol at 1–2 mg kg−1 followed by 20–40 mg. Physiological indexes were evaluated for the 715 of 720 patients that completed the treatment. The onset time, duration time, and discharge time were recorded. Physicians, anesthetists, and patients were surveyed to assess their satisfaction. Results Systolic pressure and diastolic pressure decreased significantly after the procedure in the propofol group (P<0.001). The average heart rate was significantly lower in the propofol group (P<0.05). No periods of desaturation (SpO2 <95%) were observed in either group. The onset time was earlier in the etomidate group (P=0.00). All adverse events, with the exception of myoclonus, were greater in the propofol group, and physician and patient satisfaction in both groups was similar. Conclusions Etomidate-remifentanil administration for sedation and analgesia during gastroscopy resulted in more stable hemodynamic responses and less adverse events in older patients. PMID:25553506

Systemic distribution and speciation of diphenylarsinic acid fed to rats

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

Naranmandura, Hua; Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, T6G 2G3; Suzuki, Noriyuki

Diphenylarsinic acid (DPAA) is an environmental degradation product of diphenylarsine chloride or diphenylarsine cyanide, which were chemical warfare agents produced by Japan during the World War II. DPAA is now considered a dangerous environmental pollutant in Kamisu, Japan, where it is suspected of inducing health effects that include articulation disorders (cerebellar ataxia of the extremities and trunk), involuntary movements (myoclonus and tremor), and sleep disorders. In order to elucidate the toxic mechanism of DPAA, we focused on the distribution and metabolism of DPAA in rats. Systemic distribution of DPAA was determined by administering DPAA orally to rats at a singlemore » dose of 5.0 mg As/kg body weight, followed by speciation analysis of selected organs and body fluids. Most of the total arsenic burden was recovered in the urine (23% of the dose) and feces (27%), with the distribution in most other organs/tissues being less than 1%. However, compared with the typical distribution of inorganic dietary arsenic, DPAA administration resulted in elevated levels in the brain, testes and pancreas. In contrast to urine, in which DPAA was found mostly in its unmodified form, the tissues and organs contained arsenic that was mostly bound to non-soluble and soluble high molecular weight proteins. These bound arsenic species could be converted back to DPAA after oxidation with H{sub 2}O{sub 2}, suggesting that the DPAA bound to proteins had been reduced within the body and was in a trivalent oxidation state. Furthermore, we also detected two unknown arsenic metabolites in rat urine, which were assumed to be hydroxylated arsenic metabolites.« less

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Combined MEG-EEG source localisation in patients with sub-acute sclerosing pan-encephalitis.

PubMed

Velmurugan, J; Sinha, Sanjib; Nagappa, Madhu; Mariyappa, N; Bindu, P S; Ravi, G S; Hazra, Nandita; Thennarasu, K; Ravi, V; Taly, A B; Satishchandra, P

2016-08-01

To study the genesis and propagation patterns of periodic complexes (PCs) associated with myoclonic jerks in sub-acute sclerosing pan-encephalitis (SSPE) using magnetoencephalography (MEG) and electroencephalography (EEG). Simultaneous recording of MEG (306 channels) and EEG (64 channels) in five patients of SSPE (M:F = 3:2; age 10.8 ± 3.2 years; symptom-duration 6.2 ± 10 months) was carried out using Elekta Neuromag(®) TRIUX™ system. Qualitative analysis of 80-160 PCs per patient was performed. Ten isomorphic classical PCs with significant field topography per patient were analysed at the 'onset' and at 'earliest significant peak' of the burst using discrete and distributed source imaging methods. MEG background was asymmetrical in 2 and slow in 3 patients. Complexes were periodic (3) or quasi-periodic (2), occurring every 4-16 s and varied in morphology among patients. Mean source localization at onset of bursts using discrete and distributed source imaging in magnetic source imaging (MSI) was in thalami and or insula (50 and 50 %, respectively) and in electric source imaging (ESI) was also in thalami and or insula (38 and 46 %, respectively). Mean source localization at the earliest rising phase of peak in MSI was in peri-central gyrus (49 and 42 %) and in ESI it was in frontal cortex (52 and 56 %). Further analysis revealed that PCs were generated in thalami and or insula and thereafter propagated to anterolateral surface of the cortices (viz. sensori-motor cortex and frontal cortex) to same side as that of the onset. This novel MEG-EEG based case series of PCs provides newer insights for understanding the plausible generators of myoclonus in SSPE and patterns of their propagation.

High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

PubMed

Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

2017-07-01

The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

Cranial dural arteriovenous shunts. Part 4. Clinical presentation of the shunts with leptomeningeal venous drainage.

PubMed

Baltsavias, Gerasimos; Spiessberger, Alex; Hothorn, Torsten; Valavanis, Anton

2015-04-01

Cranial dural arteriovenous fistulae have been classified into high- and low-risk lesions mainly based on the pattern of venous drainage. Those with leptomeningeal venous drainage carry a higher risk of an aggressive clinical presentation. Recently, it has been proposed that the clinical presentation should be considered as an additional independent factor determining the clinical course of these lesions. However, dural shunts with leptomeningeal venous drainage include a very wide spectrum of inhomogeneous lesions. In the current study, we correlated the clinical presentation of 107 consecutive patients harboring cranial dural arteriovenous shunts with leptomeningeal venous drainage, with their distinct anatomic and angiographic features categorized into eight groups based on the "DES" (Directness and Exclusivity of leptomeningeal venous drainage and features of venous Strain) concept. We found that among these groups, there are significant angioarchitectural differences, which are reflected by considerable differences in clinical presentation. Leptomeningeal venous drainage of dural sinus shunts that is neither direct nor exclusive and without venous strain manifested only benign symptoms (aggressive presentation 0%). On the other end of the spectrum, the bridging vein shunts with direct and exclusive leptomeningeal venous drainage and venous strain are expected to present aggressive symptoms almost always and most likely with bleeding (aggressive presentation 91.5%). Important aspects of the above correlations are discussed. Therefore, the consideration of leptomeningeal venous drainage alone, for prediction of the clinical presentation of these shunts appears insufficient. Angiographic analysis based on the above concept, offers the possibility to distinguish the higher- from the lower-risk types of leptomeningeal venous drainage. In this context, consideration of the clinical presentation as an additional independent factor for the prediction of their clinical course seems superfluous and possibly misleading. Topography is connected to the clinical presentation of the dural shunts inasmuch as the former determines the venous anatomy and the angioarchitectural features of the lesions.

Profiling the clinical presentation of diagnostic characteristics of a sample of symptomatic TMD patients.

PubMed

Pimenta e Silva Machado, Luciana; de Macedo Nery, Marianita Batista; de Góis Nery, Cláudio; Leles, Cláudio Rodrigues

2012-08-02

Temporomandibular disorder (TMD) patients might present a number of concurrent clinical diagnoses that may be clustered according to their similarity. Profiling patients' clinical presentations can be useful for better understanding the behavior of TMD and for providing appropriate treatment planning. The aim of this study was to simultaneously classify symptomatic patients diagnosed with a variety of subtypes of TMD into homogenous groups based on their clinical presentation and occurrence of comorbidities. Clinical records of 357 consecutive TMD patients seeking treatment in a private specialized clinic were included in the study sample. Patients presenting multiple subtypes of TMD diagnosed simultaneously were categorized according to the AAOP criteria. Descriptive statistics and two-step cluster analysis were used to characterize the clinical presentation of these patients based on the primary and secondary clinical diagnoses. The most common diagnoses were localized masticatory muscle pain (n = 125) and disc displacement without reduction (n = 104). Comorbidity was identified in 288 patients. The automatic selection of an optimal number of clusters included 100% of cases, generating an initial 6-cluster solution and a final 4-cluster solution. The interpretation of within-group ranking of the importance of variables in the clustering solutions resulted in the following characterization of clusters: chronic facial pain (n = 36), acute muscle pain (n = 125), acute articular pain (n = 75) and chronic articular impairment (n = 121). Subgroups of acute and chronic TMD patients seeking treatment can be identified using clustering methods to provide a better understanding of the clinical presentation of TMD when multiple diagnosis are present. Classifying patients into identifiable symptomatic profiles would help clinicians to estimate how common a disorder is within a population of TMD patients and understand the probability of certain pattern of clinical complaints.

Impact of delay in clinical presentation on the diagnostic management and prognosis of patients with suspected pulmonary embolism.

PubMed

den Exter, Paul L; van Es, Josien; Erkens, Petra M G; van Roosmalen, Mark J G; van den Hoven, Pim; Hovens, Marcel M C; Kamphuisen, Pieter W; Klok, Frederikus A; Huisman, Menno V

2013-06-15

The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis. This study aimed to assess the impact of delay in presentation on the diagnostic management and clinical outcome of patients with suspected PE. In 4,044 consecutive patients with suspected PE, patients presenting more than 7 days from the onset of symptoms were contrasted with those presenting within 7 days as regards the safety of excluding PE on the basis of a clinical decision rule combined with D-dimer testing. Patients were followed for 3 months to assess the rates of recurrent venous thromboembolism and mortality. A delayed presentation (presentation >7 d) was present in 754 (18.6%) of the patients. The failure rate of an unlikely clinical probability and normal D-dimer test was 0.5% (95% confidence interval [CI], 0.01-2.7) for patients with and 0.5% (95% CI, 0.2-1.2) for those without diagnostic delay. D-dimer testing yielded a sensitivity of 99% (95% CI, 96-99%) and 98% (95% CI, 97-99%) in these groups, respectively. Patients with PE with diagnostic delay more frequently had centrally located PE (41% vs. 26%; P < 0.001). The cumulative rates of recurrent venous thromboembolism (4.6% vs. 2.7%; P = 0.14) and mortality (7.6% vs. 6.6%; P = 0.31) were not different for patients with and without delayed presentation. PE can be safely excluded based on a clinical decision rule and D-dimer testing in patients with a delayed clinical presentation. A delayed presentation for patients who survived acute PE was associated with a more central PE location, although this did not affect the clinical outcome at 3 months.

Psychotherapy for PTSD: An evidence-based guide to a theranostic approach to treatment.

PubMed

Goodnight, Jessica R M; Ragsdale, Katie A; Rauch, Sheila A M; Rothbaum, Barbara O

2018-05-18

Posttraumatic stress disorder (PTSD) is often a clinically complex disorder, frequently presenting with comorbid clinical conditions. Individuals with PTSD may also present with high-risk symptoms such as substance misuse and suicidal ideation. The clinical complexity of PTSD has precluded some clinicians from providing gold-standard trauma-focused treatment due to concern of iatrogenic effects. However, evidence to date suggests that trauma-focused treatments are safe and effective for PTSD even when higher-risk comorbidity presents. Occasionally, while some patients present with clinical concerns that may benefit from modifications to standard recommended treatment protocols, research suggests there are few absolute contraindications to trauma-focused treatment. The present manuscript provides a review of evidence-based assessment and treatment recommendations for PTSD. A clinical decision-making guide for PTSD across areas of clinical complexity is provided. Copyright © 2018 Elsevier Inc. All rights reserved.

[Progress in methodological characteristics of clinical practice guideline for osteoarthritis].

PubMed

Xing, D; Wang, B; Lin, J H

2017-06-01

At present, several clinical practice guidelines for the treatment of osteoarthritis have been developed by institutes or societies. The ultimate purpose of developing clinical practice guidelines is to formulate the process in the treatment of osteoarthritis effectively. However, the methodologies used in developing clinical practice guidelines may place an influence on the transformation and application of that in treating osteoarthritis. The present study summarized the methodological features of individual clinical practice guideline and presented the tools for quality evaluation of clinical practice guideline. The limitations of current osteoarthritis guidelines of China are also indicated. The review article might help relevant institutions improve the quality in developing guide and clinical transformation.

Web Tools for Distributed Clinical Case Conferencing

PubMed Central

Lober, WB; Li, H; Trigg, LJ; Stewart, BK; Chou, D

2001-01-01

We have developed an information system to support distributed clinical case conferences held via video conferencing. The system has been designed by studying physicians of several specialties presenting hematology-oncology patients at Tumor Board. However, the principles of clinical case presentation are similar across many medical specialties, and we believe our approach has general applicability for presenting image and other clinical information, and organizing it for subsequent re-use in teaching files.

Clinical and Laboratory Characteristics of a Tinea Capitis Outbreak Among Novice Buddhist Monks.

PubMed

Bunyaratavej, Sumanas; Leeyaphan, Charussri; Rujitharanawong, Chuda; Muanprasat, Chanai; Matthapan, Lalita

2017-05-01

Sixty novice Buddhist monks with tinea capitis confirmed according to clinical presentation and mycological laboratory finding were included in this study. Mixed-type clinical presentation was observed in approximately half of all cases, together with scarring alopecia (95%) and superficial fungal skin infection at locations other than the scalp (43.3%). The major isolated organism was Trichophyton violaceum, and mixed-organism infection was found in 27 cases (45%). Slow-onset presentation and an extensive area of infection were significantly associated with mixed-type clinical presentation. © 2017 Wiley Periodicals, Inc.

Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation.

PubMed

Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

2018-06-04

Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p < 0.001), and showed a longer duration from onset to DLB diagnosis (p < 0.001) than the other clusters. Patients in cluster II (neuropsychiatric-predominant, n = 22) were older at disease onset (78.1±5 versus 73.6±6.1 and 73.6±4.2 in clusters I and III, respectively, both p < 0.01), presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p < 0.001). Patients in cluster III (parkinsonism-predominant, n = 13) showed a shorter time from onset to presence of parkinsonism (p < 0.001) and dementia (0.008). Three subtypes of clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

[Clinical presentation of different severities of hemorrhagic fever with renal syndrome: how to recognise it].

PubMed

Lausević, Mirjana; Lausević, Zeljko; Stojimirović, Biljana

2012-07-01

Besides viral serotype, HLA haplotype and cytokine genes polymorphism are associated with clinical presentation of hemorrhagic fever with renal syndrome. Since these analyses are unavailable in routine clinical practice, the aim of this study was to assess clinical, laboratory and radiographic findings associated with clinical presentation of disease severity. A total of 30 patients (27 men and 3 women), average age 40 +/- 14.9 years, treated for hemorrhagic fever with renal syndrome from January 1, 1999 to December 31, 2009 in Clinical Center of Serbia, were included in the study. Nine patients (30%) had mild, 14 (46.7%) moderate and 7 (23.3%) severe form of the disease; 24 (800%) recovered, 6 (20%) died in the acute phase of the illness, and 19 patients (63.3%) required hemodialysis. The average titer of antiviral antibodies in patients infected with Belgrade serotype virus were significantly higher in those with severe clinical presentation. Hypotension, anuria, macrohaematuria, pulmonary infiltration, pleural effusion, hepatomegalia and positive meningeal signs were more frequent in the patients with severe form of the disease. Statistically significant differences between groups with mild, moderate and severe clinical picture were found in serum total protein, albumin, calcium, glutamate pyruvate and glutamate oxaloacetate transaminase on admittance; serum creatinine and phosphorus concentration on day 14 and day 21; serum sodium and calciums on day 14; hemoglobine concentration on day 21. A statistically significant correlation was found between clinical presentation of the disease severity and platelet count, white blood cell count, hemoglobine concentration, serum calcium and serum transaminases on admittance. Multivariate analysis identified variables' combinations associated with clinical presentation of the disease. Our study confirmed that we can distinguish patients who will manifest different severities of the disease on the basis of careful consideration of laboratory and clinical findings on admission.

Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

PubMed

Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

2013-04-01

Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

[Vertical fractures: apropos of 2 clinical cases].

PubMed

Félix Mañes Ferrer, J; Micò Muñoz, P; Sánchez Cortés, J L; Paricio Martín, J J; Miñana Laliga, R

1991-01-01

The aim of the study is to present a clinical review of the vertical root fractures. Two clinical cases are presented to demonstrates the criteria for obtaining a correct diagnosis of vertical root fractures.

Case formulation and management using pattern-based formulation (PBF) methodology: clinical case 1.

PubMed

Fernando, Irosh; Cohen, Martin

2014-02-01

A tool for psychiatric case formulation known as pattern-based formulation (PBF) has been recently introduced. This paper presents an application of this methodology in formulating and managing complex clinical cases. The symptomatology of the clinical presentation has been parsed into individual clinical phenomena and interpreted by selecting explanatory models. The clinical presentation demonstrates how PBF has been used as a clinical tool to guide clinicians' thinking, that takes a structured approach to manage multiple issues using a broad range of management strategies. In doing so, the paper also introduces a number of patterns related to the observed clinical phenomena that can be re-used as explanatory models when formulating other clinical cases. It is expected that this paper will assist clinicians, and particularly trainees, to better understand PBF methodology and apply it to improve their formulation skills.

Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin. Results from the AMPLIFY trial.

PubMed

Bleker, Suzanne M; Cohen, Alexander T; Büller, Harry R; Agnelli, Giancarlo; Gallus, Alexander S; Raskob, Gary E; Weitz, Jeffrey I; Curto, Madelyn; Sisson, Melanie; Middeldorp, Saskia

2016-11-30

Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using pre-designed classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5 % of apixaban versus 44.9 % of enoxaparin/warfarin related recipients (OR 0.49, 95 % confidence interval [CI] 0.14-1.78). A severe clinical course was observed in 14.3 % and in 12.2 %, respectively (OR 1.19, 95 %CI 0.21-6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25 % of apixaban recipients compared to 22.7 % in the enoxaparin/warfarin group (OR 1.13, 95 %CI 0.65-1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.

Barriers to the conduct of randomised clinical trials within all disease areas.

PubMed

Djurisic, Snezana; Rath, Ana; Gaber, Sabrina; Garattini, Silvio; Bertele, Vittorio; Ngwabyt, Sandra-Nadia; Hivert, Virginie; Neugebauer, Edmund A M; Laville, Martine; Hiesmayr, Michael; Demotes-Mainard, Jacques; Kubiak, Christine; Jakobsen, Janus C; Gluud, Christian

2017-08-01

Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential. The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.

Multimedia platform for authoring and presentation of clinical rounds in cardiology

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Allada, Vivekanand; Dahlbom, Magdalena; Lapstra, Lorelle

2003-05-01

We developed a multimedia presentation platform that allows retrieving data from any digital and analog modalities and to prepare a script of a clinical presentation in an XML format. This system was designed for cardiac multi-disciplinary conferences involving different cardiology specialists as well as cardiovascular surgeons. A typical presentation requires preparation of summary reports of data obtained from the different investigations and imaging techniques. An XML-based scripting methodology was developed to allow for preparation of clinical presentations. The image display program uses the generated script for the sequential presentation of different images that are displayed on pre-determined presentation settings. The ability to prepare and present clinical conferences electronically is more efficient and less time consuming than conventional settings using analog and digital documents, films and videotapes. The script of a given presentation can further be saved as part of the patient record for subsequent review of the documents and images that supported a given medical or therapeutic decision. This also constitutes a perfect documentation method for surgeons and physicians responsible of therapeutic procedures that were decided upon during the clinical conference. It allows them to review the relevant data that supported a given therapeutic decision.

Spontaneous Pneumomediastinum: Case Presentation to a College Student Health Clinic

ERIC Educational Resources Information Center

Spotts, P. Hunter

2017-01-01

The author describes a case of spontaneous pneumomediastinum (SPM) in a 19-year-old man presenting to a college student health clinic. The author also provides a review on SPM, including clinical manifestations, diagnostic evaluation, and management.

Cognitive Fusion Questionnaire-Body Image: Psychometric Properties and Its Incremental Power in the Prediction of Binge Eating Severity.

PubMed

Lucena-Santos, Paola; Trindade, Inês A; Oliveira, Margareth; Pinto-Gouveia, José

2017-05-19

Given the clinical usefulness of the CFQ-BI (Cognitive Fusion Questionnaire-Body Image; the only existing measure to assess the body-image-related cognitive fusion), the present study aimed to confirm its one-factor structure, to verify its measurement invariance between clinical and non-clinical samples, to analyze its internal consistency and sensitivity to detect differences between samples, as well as to explore the incremental and convergent validities of the CFQ-BI scores in Brazilian samples.  This was a cross-sectional study, which was conducted in clinical (women with overweight or obesity in treatment for weight loss) and non-clinical samples (women from the general population). The one-factor structure was confirmed showing factorial measurement invariance across clinical and non-clinical samples. The CFQ-BI scores presented an excellent internal consistency, were able to discriminate clinical and non-clinical samples, and were positively associated with binge eating severity, general cognitive fusion, and psychological inflexibility. Furthermore, body-image-related cognitive fusion scores (CFQ-BI) presented incremental validity over a general measure of cognitive fusion in the prediction of binge eating symptoms. This study demonstrated that CFQ-BI is a short scale with reliable and robust scores in Brazilian samples, presenting incremental and convergent validities, measurement invariance, and sensitivity to detect differences between clinical and non-clinical groups of women, enabling comparative studies between them.

Spectrum of complicated migraine in children: A common profile in aid to clinical diagnosis

PubMed Central

Gupta, Surya N; Gupta, Vikash S; Fields, Dawn M

2015-01-01

Complicated migraine encompasses several individual clinical syndromes of migraine. Such a syndrome in children frequently presents with various neurological symptoms in the Emergency Department. An acute presentation in the absence of headache presents a diagnostic challenge. A delay in diagnosis and treatment may have medicolegal implication. To date, there are no reports of a common clinical profile proposed in making a clinical diagnosis for the complicated migraine. In this clinical review, we propose and describe: (1) A common clinical profile in aid to clinical diagnosis for spectrum of complicated migraine; (2) How it can be used in differentiating complicated migraine from migraine without aura, migraine with aura, and seizure; (3) We discuss the status of complicated migraine in the International Headache Society classification 2013; and (4) In addition, a common treatment strategy for the spectrum of migraine has been described. To diagnose complicated migraine clinically, it is imperative to adhere with the proposed profile. This will optimize the use of investigation and will also avoid a legal implication of delay in their management. The proposed common clinical profile is incongruent with the International Headache Society 2013. Future classification should minimize the dissociation from clinically encountered syndromes and coin a single word to address collectively this subtype of migraine with an acute presentation of a common clinical profile. PMID:25664241

Angio-Architectural Features of High-Grade Intracranial Dural Arteriovenous Fistulas: Correlation With Aggressive Clinical Presentation and Hemorrhagic Risk.

PubMed

Della Pepa, Giuseppe Maria; Parente, Paolo; D'Argento, Francesco; Pedicelli, Alessandro; Sturiale, Carmelo Lucio; Sabatino, Giovanni; Albanese, Alessio; Puca, Alfredo; Fernandez, Eduardo; Olivi, Alessando; Marchese, Enrico

2017-08-01

High-grade dural arteriovenous fistulas (dAVFs) can present shunts with very different angio-architectural characteristics. Specific hemodynamic factors may affect clinical history and determine very different clinical courses. To evaluate the relationship between some venous angio-architectural features in high-grade dAVFs and clinical presentation. Specific indicators of moderate or severe venous hypertension were analyzed, such as altered configurations of the dural sinuses (by a single or a dual thrombosis), or overload of cortical vessels (restrictions of outflow, pseudophlebitic cortical vessels, and venous aneurysms). The institutional series was retrospectively reviewed (49 cases), and the pattern of venous drainage was analyzed in relationship with clinical presentation (benign/aggressive/hemorrhage). Thirty-five of 49 cases displayed cortical reflux (high-grade dAVFs). This subgroup displayed a benign presentation in 31.42% of cases, an aggressive in 31.42%, and hemorrhage in 37.14%. Our data confirm that within high-grade dAVFs, 2 distinct subpopulations exist according to severity of clinical presentation. Some indicators we examined showed correlation with aggressive nonhemorrhagic manifestations (outflow restriction and pseudophlebitic cortical vessels), while other showed a correlation with hemorrhage (dual thrombosis and venous aneurysms). Current classifications appear insufficient to identify a wide range of conditions that ultimately determine the organization of the cortical venous drainage. Intermediate degrees of venous congestion correlate better with the clinical risk than the simple definition of cortical reflux. The angiographic aspects of venous drainage presented in this study may prove useful to assess dAVF hemodynamic characteristics and identify conditions at higher clinical risk. Copyright © 2017 by the Congress of Neurological Surgeons

Using Best Practices to Extract, Organize, and Reuse Embedded Decision Support Content Knowledge Rules from Mature Clinical Systems.

PubMed

DesAutels, Spencer J; Fox, Zachary E; Giuse, Dario A; Williams, Annette M; Kou, Qing-Hua; Weitkamp, Asli; Neal R, Patel; Bettinsoli Giuse, Nunzia

2016-01-01

Clinical decision support (CDS) knowledge, embedded over time in mature medical systems, presents an interesting and complex opportunity for information organization, maintenance, and reuse. To have a holistic view of all decision support requires an in-depth understanding of each clinical system as well as expert knowledge of the latest evidence. This approach to clinical decision support presents an opportunity to unify and externalize the knowledge within rules-based decision support. Driven by an institutional need to prioritize decision support content for migration to new clinical systems, the Center for Knowledge Management and Health Information Technology teams applied their unique expertise to extract content from individual systems, organize it through a single extensible schema, and present it for discovery and reuse through a newly created Clinical Support Knowledge Acquisition and Archival Tool (CS-KAAT). CS-KAAT can build and maintain the underlying knowledge infrastructure needed by clinical systems.

Clinical Supervision of Interns: Understanding the View of Interns and the Potential of ICT to Deliver Supervision for Safer Patient Care.

PubMed

Yee, Kwang Chien; Madden, Angela; Nash, Rosie; Connolly, Michael

2017-01-01

Clinical communication and clinical supervision of junior healthcare professionals are identified as the two most common preventable factors to reduce medical errors. While multiple strategies have been implemented to improve clinical communication, clinical supervision has not attracted as much attention. This is in part due to the lack of understanding of clinical supervision. Furthermore, there is a lack of exploration of information communication technology (ICT) in assisting the delivery of clinical supervision from the perspective of users (i.e. junior clinicians). This paper presents a study to understand clinical supervision from the perspective of medical and pharmacy interns. The important elements of good clinical supervisors and good clinical supervision have been presented in this paper based on our study. More importantly, our results suggest a distinction between good supervisors and good supervisions. Both these factors impact on patient safety. Through discussion of user requirements of good supervision by users (interns), this paper then explores and presents a conceptual framework to assist in the discussion and design of ICT by healthcare organisations to improve clinical supervision of interns and therefore improve patient safety.

Developing a "clinical presentation" curriculum at the University of Calgary.

PubMed

Mandin, H; Harasym, P; Eagle, C; Watanabe, M

1995-03-01

Currently, medical curricula are structured according to disciplines, body systems, or clinical problems. Beginning in 1988, the faculty of the University of Calgary Faculty of Medicine (U of C) carefully evaluated the advantages and disadvantages of each of these models in seeking to revise their school's curriculum. However, all three models fell short of a curricular structure based on current knowledge and principles of adult learning, clinical problem solving, community demands, and curriculum management. By 1991, the U of C had formulated a strategic plan for a revised curriculum structure based on the way patients present to physicians, and implementation of this plan has begun. In creating the new curriculum, 120 clinical presentations (e.g., "loss of consciousness/syncope") were defined and each was assigned to an individual or small group of faculty for development based on faculty expertise and interest. Terminal objectives (i.e., "what to do") were defined for each presentation to describe the appropriate clinical behaviors of a graduating physician. Experts developed schemes that outlined how they differentiated one cause (i.e., disease category) from another. The underlying enabling objectives (i.e., knowledge, skills, and attitudes) for reaching the terminal objectives for each clinical presentation were assigned as departmental responsibilities. A new administrative structure evolved in which there is a partnership between a centralized multidisciplinary curriculum committee and the departments. This new competency-based, clinical presentation curriculum is expected to significantly enhance students' development of clinical problem-solving skills and affirms the premise that prudent, continuous updating is essential for improving the quality of medical education.

Catatonia as presenting clinical feature of subacute sclerosing panencephalitis

PubMed Central

Dayal, Prabhoo; Balhara, Yatan Pal Singh

2014-01-01

Catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis (SSPE), especially in the initial stages of illness. However, there is only one reported case of SSPE presenting as catatonia among children. In this report, however, there were SSPE-specific changes on EEG and the catatonia failed to respond to lorazepam. We describe a case of SSPE in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical EEG findings when assessed at first contact. He responded to lorazepam and EEG changes emerged during the course of follow-up. PMID:24891908

A Supernumerary Nipple-Like Clinical Presentation of Lymphangioma Circumscriptum.

PubMed

Taylor, Dustin; Kash, Natalie; Silapunt, Sirunya

2018-01-01

Lymphangioma circumscriptum is a superficially localized variant of lymphangioma. The characteristic clinical presentation is a "frogspawn" grouping of vesicles or papulovesicles on the proximal limb or limb girdle areas. Though most lymphangiomas develop congenitally, the lymphangioma circumscriptum subtype is known to present in adults. We report a case of lymphangioma circumscriptum on the left inframammary area of an African American female with an unusual supernumerary nipple-like clinical presentation. Our patient presented with a firm, smooth, hypopigmented papule, and the clinical diagnosis of keloid was made initially. However, she returned reporting growth of the lesion and was noted to have a firm, exophytic, lobulated, pink to skin-colored nodule. Histopathological examination demonstrated dilated lymphatic vessels, consistent with the diagnosis of lymphangioma. The presentation as a firm, hypopigmented papule and later exophytic, lobulated, skin-colored nodule in our case represents a clinical presentation of lymphangioma circumscriptum not previously described in the literature. Correct diagnosis in lymphangioma circumscriptum is vital, as recurrence following surgical resection and secondary development of lymphangiosarcoma and squamous cell carcinoma following treatment with radiation have been reported. Thus, it is important to consider lymphangioma circumscriptum in the differential of similar lesions in the future to allow appropriate diagnosis, treatment, and monitoring.

Clinical presentation of acute Q fever in lanzarote (Canary Islands): a 2-year prospective study.

PubMed

Pascual Velasco, F; Borobio Enciso, M V; González Lama, Z; Carrascosa Porras, M

1996-01-01

The clinical manifestations of acute Q fever may differ markedly from country to country. In this regard, fever and hepatitis seem to be the dominant clinical features of acute Coxiella burnetii infection in Lanzarote, Canary Islands. A possible interaction between environmental factors and some strains of C. burnetii could explain the different clinical presentations of acute Q fever.

Cerebrospinal fluid γδ T cell frequency is age-related: a case-control study of 435 children with inflammatory and non-inflammatory neurological disorders.

PubMed

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

2018-02-27

Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, due especially to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in paediatric neuroinflammation, we immunophenotyped cerebrospinal fluid (CSF) and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurological disorders (NIND), 312 with opsoclonus-myoclonus (OMS) and 23 with other inflammatory neurological disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency of 27% in infants and 3·3% in teens. Interindividual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation [human leucocyte antigen D-related (HLA-DR)], maturation (CD45RA, CD45RO) or intracellular cytokine staining [interleukin (IL)-4, interferon (IFN)-γ] failed to discriminate OMS and NIND groups. Of seven OMS immunotherapies/combinations, none altered the frequency of total CSF γδ T cells or subsets significantly. In OIND, the CSF γδ T cell frequency was < 10% for single samples of other paraneoplastic disorders [anti-neuronal nuclear antibody (ANNA)-1, PCA-1, teratoma-associated syndrome], cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis and encephalitis. This study provides new insights into CSF γδ T cells in the paediatric population. Although their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy and our age cut-off references for NIND are important findings for the design of future paediatric studies. © 2018 British Society for Immunology.

Delayed-onset progressive movement disorders after static brain lesions.

PubMed

Scott, B L; Jankovic, J

1996-01-01

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

ORAL CLINICAL LONG CASE PRESENTATION, THE NEED FOR STANDARDIZATION AND DOCUMENTATION.

PubMed

Agodirin, S O; Olatoke, S A; Rahman, G A; Agbakwuru, E A; Kolawole, O A

2015-01-01

The oral presentation of the clinical long case is commonly an implied knowledge. The challenge of the presentation is compounded by the examiners' preferences and sometimes inadequate understanding of what should be assessed. To highlight the different opinions and misconceptions of trainers as the basis for improving our understanding and assessment of oral presentation of the clinical long case. Questionnaire was administered during the West African College of Surgeons fellowship clinical examinations and at their workplaces. Eligibility criteria included being a surgeon, a trainer and responding to all questions. Of the 72 questionnaires that were returned, 36(50%) were eligible for the analysis. The 36 respondents were from 14 centers in Nigeria and Ghana. Fifty-two percent were examiners at the postgraduate medical colleges and 9(25%) were professors. Eight(22.2%) indicated they were unaware of the separate methods of oral presentation for different occasions while 21( 58.3%) respondents were aware that candidate used the "5Cs" method and the traditional compartmentalized method in long case oral presentation. Eleven(30.6%) wanted postgraduates to present differently on a much higher level than undergraduate despite not encountering same in literature and 21(58.3%) indicated it was an unwritten rule. Seventeen (47.2%) had not previously encountered the "5Cs" of history of presenting complaint in literature also 17(47.2%) teach it to medical students and their junior residents. This study has shown that examiners definitely have varying opinions on what form the oral presentation of the clinical long case at surgery fellowship/professional examination should be and it translates to their expectations of the residents or clinical students. This highlights the need for standardization and consensus of what is expected at a formal oral presentation during the clinical long case examination in order to avoid subjectivity and bias.

Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

PubMed

Koric, L; Guedj, E; Habert, M O; Semah, F; Branger, P; Payoux, P; Le Jeune, F

2016-12-01

The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

On implementing clinical decision support: achieving scalability and maintainability by combining business rules and ontologies.

PubMed

Kashyap, Vipul; Morales, Alfredo; Hongsermeier, Tonya

2006-01-01

We present an approach and architecture for implementing scalable and maintainable clinical decision support at the Partners HealthCare System. The architecture integrates a business rules engine that executes declarative if-then rules stored in a rule-base referencing objects and methods in a business object model. The rules engine executes object methods by invoking services implemented on the clinical data repository. Specialized inferences that support classification of data and instances into classes are identified and an approach to implement these inferences using an OWL based ontology engine is presented. Alternative representations of these specialized inferences as if-then rules or OWL axioms are explored and their impact on the scalability and maintenance of the system is presented. Architectural alternatives for integration of clinical decision support functionality with the invoking application and the underlying clinical data repository; and their associated trade-offs are discussed and presented.

[Application of Delphi method in traditional Chinese medicine clinical research].

PubMed

Bi, Ying-fei; Mao, Jing-yuan

2012-03-01

In recent years, Delphi method has been widely applied in traditional Chinese medicine (TCM) clinical research. This article analyzed the present application situation of Delphi method in TCM clinical research, and discussed some problems presented in the choice of evaluation method, classification of observation indexes and selection of survey items. On the basis of present application of Delphi method, the author analyzed the method on questionnaire making, selection of experts, evaluation of observation indexes and selection of survey items. Furthermore, the author summarized the steps of application of Delphi method in TCM clinical research.

Dental, dermatological and radiographic findings in a case of Gorlin-Goltz Syndrome: report and review.

PubMed

Nilesh, Kumar; Tewary, Shivsagar; Zope, Sameer; Patel, Jinesh; Vande, Aaditee

2017-01-01

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. Thus a multidisciplinary approach is required for its prompt clinical diagnosis and management of this condition. This paper highlights a case of GGS presenting in a young male patient with cranial, facial, dermatological, dental and skeletal involvement. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. A review of the diagnostic criteria is also presented.

Dental, dermatological and radiographic findings in a case of Gorlin-Goltz Syndrome: report and review

PubMed Central

Nilesh, Kumar; Tewary, Shivsagar; Zope, Sameer; Patel, Jinesh; Vande, Aaditee

2017-01-01

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. Thus a multidisciplinary approach is required for its prompt clinical diagnosis and management of this condition. This paper highlights a case of GGS presenting in a young male patient with cranial, facial, dermatological, dental and skeletal involvement. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. A review of the diagnostic criteria is also presented. PMID:28819517

Conceptual Models and Guidelines for Clinical Assessment of Financial Capacity

PubMed Central

Marson, Daniel

2016-01-01

The ability to manage financial affairs is a life skill of critical importance, and neuropsychologists are increasingly asked to assess financial capacity across a variety of settings. Sound clinical assessment of financial capacity requires knowledge and appreciation of applicable clinical conceptual models and principles. However, the literature has presented relatively little conceptual guidance for clinicians concerning financial capacity and its assessment. This article seeks to address this gap. The article presents six clinical models of financial capacity : (1) the early gerontological IADL model of Lawton, (2) the clinical skills model and (3) related cognitive psychological model developed by Marson and colleagues, (4) a financial decision-making model adapting earlier decisional capacity work of Appelbaum and Grisso, (5) a person-centered model of financial decision-making developed by Lichtenberg and colleagues, and (6) a recent model of financial capacity in the real world developed through the Institute of Medicine. Accompanying presentation of the models is discussion of conceptual and practical perspectives they represent for clinician assessment. Based on the models, the article concludes by presenting a series of conceptually oriented guidelines for clinical assessment of financial capacity. In summary, sound assessment of financial capacity requires knowledge and appreciation of clinical conceptual models and principles. Awareness of such models, principles and guidelines will strengthen and advance clinical assessment of financial capacity. PMID:27506235

Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies.

PubMed

Petit-Pedrol, Mar; Armangue, Thaís; Peng, Xiaoyu; Bataller, Luis; Cellucci, Tania; Davis, Rebecca; McCracken, Lindsey; Martinez-Hernandez, Eugenia; Mason, Warren P; Kruer, Michael C; Ritacco, David G; Grisold, Wolfgang; Meaney, Brandon F; Alcalá, Carmen; Sillevis-Smitt, Peter; Titulaer, Maarten J; Balice-Gordon, Rita; Graus, Francesc; Dalmau, Josep

2014-03-01

Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients' antibodies on neuronal cultures. In this observational study, we selected serum and CSF samples for antigen characterisation from 140 patients with encephalitis, seizures or status epilepticus, and antibodies to unknown neuropil antigens. The samples were obtained from worldwide referrals of patients with disorders suspected to be autoimmune between April 28, 2006, and April 25, 2013. We used samples from 75 healthy individuals and 416 patients with a range of neurological diseases as controls. We assessed the samples using immunoprecipitation, mass spectrometry, cell-based assay, and analysis of antibody effects in cultured rat hippocampal neurons with confocal microscopy. Neuronal cell-membrane immunoprecipitation with serum of two index patients revealed GABAA receptor sequences. Cell-based assay with HEK293 expressing α1/β3 subunits of the GABAA receptor showed high titre serum antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3-63 years, median 22 years; five male patients) developed refractory status epilepticus or epilepsia partialis continua along with extensive cortical-subcortical MRI abnormalities; four patients needed pharmacologically induced coma. 12 of 416 control patients with other diseases, but none of the healthy controls, had low-titre GABAA receptor antibodies detectable in only serum samples, five of them also had GAD-65 antibodies. These 12 patients (age 2-74 years, median 26.5 years; seven male patients) developed a broader spectrum of symptoms probably indicative of coexisting autoimmune disorders: six had encephalitis with seizures (one with status epilepticus needing pharmacologically induced coma; one with epilepsia partialis continua), four had stiff-person syndrome (one with seizures and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABAA receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABAA receptor). High titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundació la Marató de TV3, the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch Epilepsy Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products: Results From the Acute Liver Failure Study Group.

PubMed

Serper, Marina; Wolf, Michael S; Parikh, Nikhil A; Tillman, Holly; Lee, William M; Ganger, Daniel R

2016-01-01

Acetaminophen (APAP) is the most common cause of acute liver failure (ALF) in the west. It is unknown if APAP overdose in combination with diphenhydramine or opioids confers a different clinical presentation or prognosis. Study objectives were to compare (1) baseline patient characteristics; (2) initial clinical presentation; and (3) clinical outcomes among patients with ALF due to APAP alone or in combination with diphenhydramine or opioids. We analyzed 666 cases of APAP-related liver failure using the Acute Liver Failure Study Group database from 1998 to 2012. The database contains detailed demographic, laboratory, and clinical outcome data, including hemodialysis, transplantation, and death and in-hospital complications such as arrhythmia and infection. The final sample included 666 patients with APAP liver injury. A total 30.3% of patients were overdosed with APAP alone, 14.1% with APAP/diphenhydramine, and 56.6% with APAP/opioids. Patients taking APAP with opioids were older, had more comorbidities, and were more likely to have unintentional overdose (all P<0.0001). On presentation, 58% in the APAP/opioid group had advanced encephalopathy as compared with 43% with APAP alone (P=0.001) The APAP/diphenhydramine group presented with the highest serum aminotransferase levels, no differences in laboratory values were noted at 3 days postenrollment. No significant differences were observed in clinical outcomes among the groups. Most patients with APAP-induced ALF were taking APAP combination products. There were significant differences in patient characteristics and clinical presentation based on the type of product ingested, however, there were no differences noted in delayed hepatotoxicity or clinical outcomes.

Thyrotoxic crisis presenting with jaundice.

PubMed

Wickramasinghe, R D S S; Luke, W A N V; Sebastiampillai, B S; Gunathilake, M P M L; Premaratna, R

2016-06-23

Thyrotoxic crisis is a medical emergency requiring early diagnosis and urgent management, which can be challenging due to its diverse clinical presentations. While common presentations include fever, sweating, palpitations, tremors and confusion, presence of jaundice is rare. We report a 35-year-old male who presented with jaundice due to cholestasis along with other features of thyrotoxic crisis due to Graves' disease. He had a good clinical recovery with resolution of cholestasis following treatment for thyrotoxic crisis. Jaundice can be a rare manifestation of thyrotoxic crisis, and should be considered in the differential diagnosis when other clinical features of thyrotoxic crisis are present. However secondary causes of jaundice should be looked into and excluded.

Using Best Practices to Extract, Organize, and Reuse Embedded Decision Support Content Knowledge Rules from Mature Clinical Systems

PubMed Central

DesAutels, Spencer J.; Fox, Zachary E.; Giuse, Dario A.; Williams, Annette M.; Kou, Qing-hua; Weitkamp, Asli; Neal R, Patel; Bettinsoli Giuse, Nunzia

2016-01-01

Clinical decision support (CDS) knowledge, embedded over time in mature medical systems, presents an interesting and complex opportunity for information organization, maintenance, and reuse. To have a holistic view of all decision support requires an in-depth understanding of each clinical system as well as expert knowledge of the latest evidence. This approach to clinical decision support presents an opportunity to unify and externalize the knowledge within rules-based decision support. Driven by an institutional need to prioritize decision support content for migration to new clinical systems, the Center for Knowledge Management and Health Information Technology teams applied their unique expertise to extract content from individual systems, organize it through a single extensible schema, and present it for discovery and reuse through a newly created Clinical Support Knowledge Acquisition and Archival Tool (CS-KAAT). CS-KAAT can build and maintain the underlying knowledge infrastructure needed by clinical systems. PMID:28269846

Leiomyoma of the anal canal: report of two cases.

PubMed

Witz, M; Bernheim, J; Griffel, B; Dinbar, A

1986-10-01

Leiomyoma of the rectum and anal canal is an unusual clinical entity. Generally, it does not produce any clinical signs and in most cases it is discovered incidentally in the course of routine rectal examination. The clinical presentation, diagnosis, and surgical treatment are described in two presented cases of anal canal leiomyoma.

Changes observed in the thymus and lymph nodes 14 days after exposure to BVDV field strains of enhanced or typical virulence in neonatal calves

USDA-ARS?s Scientific Manuscript database

Clinical presentation following uncomplicated acute infection with bovine viral diarrhea viruses (BVDV) ranges from clinically unapparent to severe (including hemorrhagic disease and death) depending on the strain virulence. Regardless of clinical presentation, BVDV infection of cattle results in i...

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

Infectious Risk Assessment of Unsafe Handling Practices and Management of Clinical Solid Waste

PubMed Central

Hossain, Md. Sohrab; Rahman, Nik Norulaini Nik Ab; Balakrishnan, Venugopal; Puvanesuaran, Vignesh R.; Sarker, Md. Zaidul Islam; Kadir, Mohd Omar Ab

2013-01-01

The present study was undertaken to determine the bacterial agents present in various clinical solid wastes, general waste and clinical sharp waste. The waste was collected from different wards/units in a healthcare facility in Penang Island, Malaysia. The presence of bacterial agents in clinical and general waste was determined using the conventional bacteria identification methods. Several pathogenic bacteria including opportunistic bacterial agent such as Pseudomonas aeruginosa, Salmonella spp., Klebsiella pneumoniae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes were detected in clinical solid wastes. The presence of specific pathogenic bacterial strains in clinical sharp waste was determined using 16s rDNA analysis. In this study, several nosocomial pathogenic bacteria strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Lysinibacillus sphaericus, Serratia marcescens, and Staphylococcus aureus were detected in clinical sharp waste. The present study suggests that waste generated from healthcare facilities should be sterilized at the point of generation in order to eliminate nosocomial infections from the general waste or either of the clinical wastes. PMID:23435587

Piperacillin-tazobactam-induced linear IgA bullous dermatosis presenting clinically as Stevens-Johnson syndrome/toxic epidermal necrolysis overlap.

PubMed

Adler, N R; McLean, C A; Aung, A K; Goh, M S Y

2017-04-01

Linear IgA bullous dermatosis (LABD) is a subepidermal autoimmune bullous disease characterized by linear IgA deposition at the basement membrane zone, which is visualized by direct immunofluorescence. Patients with LABD typically present with widespread vesicles and bullae; however, this is not necessarily the case, as the clinical presentation of this disease is heterogeneous. LABD clinically presenting as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is an infrequent, yet well-described phenomenon. Most cases of LABD are idiopathic, but some cases are drug-induced. Multiple drugs have been implicated in the development of LABD. We report a case of piperacillin-tazobactam-induced LABD presenting clinically as SJS/TEN overlap. This is the first reported case of a strong causal association between piperacillin-tazobactam and the development of LABD. © 2017 British Association of Dermatologists.

XML-based scripting of multimodality image presentations in multidisciplinary clinical conferences

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Allada, Vivekanand; Dahlbom, Magdalena; Marcus, Phillip; Fine, Ian; Lapstra, Lorelle

2002-05-01

We developed a multi-modality image presentation software for display and analysis of images and related data from different imaging modalities. The software is part of a cardiac image review and presentation platform that supports integration of digital images and data from digital and analog media such as videotapes, analog x-ray films and 35 mm cine films. The software supports standard DICOM image files as well as AVI and PDF data formats. The system is integrated in a digital conferencing room that includes projections of digital and analog sources, remote videoconferencing capabilities, and an electronic whiteboard. The goal of this pilot project is to: 1) develop a new paradigm for image and data management for presentation in a clinically meaningful sequence adapted to case-specific scenarios, 2) design and implement a multi-modality review and conferencing workstation using component technology and customizable 'plug-in' architecture to support complex review and diagnostic tasks applicable to all cardiac imaging modalities and 3) develop an XML-based scripting model of image and data presentation for clinical review and decision making during routine clinical tasks and multidisciplinary clinical conferences.

Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.

PubMed

King, Jill; Pana, Zoi-Dorothea; Lehrnbecher, Thomas; Steinbach, William J; Warris, Adilia

2017-09-01

Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.

The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

PubMed

Hershberg, Julie A; Rose, Dorian K; Tilson, Julie K; Brutsch, Bettina; Correa, Anita; Gallichio, Joann; McLeod, Molly; Moore, Craig; Wu, Sam; Duncan, Pamela W; Behrman, Andrea L

2017-01-01

Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).

Unpacking the Clinical and Participatory Dimensions of the Trump Math-Teacher-Residency-Program

ERIC Educational Resources Information Center

Imanuel-Noy, Dalia; Wagner, Tili

2016-01-01

The research presents a Residency Math teacher education program that has been developed in Israel in search of transforming initial teacher preparation on the Clinical-Participatory continuum. It is a "multi-phase" mixed-method research aiming to present the clinical and participatory dimensions of the TMR: the way in which they are…

Massive ovarian oedema: a misleading clinical entity.

PubMed

Machairiotis, Nikolaos; Stylianaki, Aikaterini; Kouroutou, Paraskevi; Sarli, Polixeni; Alexiou, Nikolaos Konstantinos; Efthymiou, Elias; Maras, Athanasios; Alexiou, Nikolaos Georgios; Nikolaou, Spyridon Evaggelos; Courcoutsakis, Nikolaos; Papakonstantinou, Eleni; Zarogoulidis, Paul; Barbetakis, Nikolaos; Paliouras, Dimitrios; Gogakos, Apostolos; Machairiotis, Christodoulos

2016-02-03

Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

Emergency Department Referrals for Adolescent Urgent Psychiatric Consultation: Comparison of Clinical Characteristics of Repeat-presentations and Single-presentation.

PubMed

Roberts, Nasreen; Nesdole, Robert; Hu, Tina

2018-01-01

a) to examine the demographic and clinical characteristics of repeat-presentations to an adolescent urgent psychiatric clinic, and b) to compare them with single-time presentation. This 18-month retrospective study compared repeat-presenters to age and gender matched single-time presenters. Demographic variables included age gender and ethnicity. Clinical variables included reason for referral, family history, diagnosis, recommendations and compliance. Data were analyzed using descriptive statistics, McNemar's Chi-square tests for matched pairs, and conditional logistic regression. Of 624 assessments 24% (N=151) were repeat-presentations. Compared with single-presentation, repeat-presentation group had a higher proportion of Aboriginal youth (X2 (1) = 108.28 p < 0.01), a higher proportion in special educational placement (X2 (1) = 6.82, p < 0.01), a higher proportion with a family history of anxiety disorders (X2 (1) = 10.62, p = 0.01) and substance use disorder (X2 (1) = 18.99, p < 0.01). Conditional logistic regression results suggested that repeat-presentation group had higher odds of past hospital admission (OR: 3.50, p < 0.01) higher odds of family history of mood disorders (OR: 4.86, p < 0.01) and of antisocial disorders (OR: 4.97, p = 0.02), and lower odds of recommendation compliance (OR: 0.10, p < 0.01). Repeat-presentations for urgent psychiatric consultation constitute a quarter of referrals to the urgent psychiatric clinic. Identifying and addressing factors that contribute to repeat-presentations may, assist in improving treatment compliance by ensuring focused interventions and service delivery for these youth. In turn, this will improve access to the limited urgent services for other youth.

The variable clinical presentation of tuberculosis otitis media and the importance of early detection.

PubMed

Abes, Generoso T; Abes, Franco Louie L B; Jamir, Joselito C

2011-06-01

Tuberculosis (TB) is a rare cause of otitis media. This study aims to increase awareness on the clinical presentation of TB otitis media and illustrate how early detection affects treatment outcome. Chart review of 12 patients (13 ears) from a tertiary hospital in Manila, Philippines, seen from 2004 to 2009. Clinical predictors of the disease were summarized. Clinical, radiologic, and audiometric outcomes after treatment were compared between treatment groups. The 5 otoscopic presentations were multiple perforations, single perforation with refractory otorrhea and exuberant granulation tissue formation, single perforation with minimal otorrhea and no granulation tissue formation, intact tympanic membrane with middle ear effusion, and intact tympanic membrane with tumorlike tissue in the middle ear. Clinical predictors of the disease were history of pulmonary TB, work-related contamination of the infection, positive purified protein derivative test, positive chest radiographic finding and intraoperative granulation tissue with cheesy material, and temporal bone computed tomographic scan findings. Patients who had no middle ear surgery showed significantly better clinical, radiologic, and audiometric outcomes than those who were diagnosed late and had more complicated surgical procedure. The clinical presentation of TB otitis media is variable. Early detection of the early forms entail less surgical intervention and favors better treatment results.

Exploring the structure and organization of information within nursing clinical handovers.

PubMed

Johnson, Maree; Jefferies, Diana; Nicholls, Daniel

2012-10-01

Clinical handover is the primary source of patient information for nurses; however, inadequate information transfer compromises patient safety. We investigated the content and organization of information conveyed at 81 handovers. A structure that captures and presents the information transferred at handover emerged: identification of the patient and clinical risks, clinical history/presentation, clinical status, care plan and outcomes/goals of care (ICCCO). This approach covers essential information while allowing for prioritization of information when required. Further research into the impact of ICCCO on patient safety is in progress. © 2012 Wiley Publishing Asia Pty Ltd.

Neuropathological Assessment as an Endpoint in Clinical Trial Design.

PubMed

Gentleman, Steve; Liu, Alan King Lun

2018-01-01

Different neurodegenerative conditions can have complex, overlapping clinical presentations that make accurate diagnosis during life very challenging. For this reason, confirmation of the clinical diagnosis still requires postmortem verification. This is particularly relevant for clinical trials of novel therapeutics where it is important to ascertain what disease and/or pathology modifying effects the therapeutics have had. Furthermore, it is important to confirm that patients in the trial actually had the correct clinical diagnosis as this will have a major bearing on the interpretation of trial results. Here we present a simple protocol for pathological assessment of neurodegenerative changes.

Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis.

PubMed

Sweetser, Lisel J; Douglas, James A; Riha, Renata L; Bell, Scott C

2005-03-01

In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

"Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

ERIC Educational Resources Information Center

Peterson, Lisa S.

2008-01-01

Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

PubMed Central

Yang, Jason; Ciacci, Joseph D.

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. PMID:29112137

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

PubMed

Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

2017-11-07

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

A problem solving and decision making toolbox for approaching clinical problems and decisions.

PubMed

Margolis, C; Jotkowitz, A; Sitter, H

2004-08-01

In this paper, we begin by presenting three real patients and then review all the practical conceptual tools that have been suggested for systematically analyzing clinical problems. Each of these conceptual tools (e.g. Evidence-Based Medicine, Clinical Practice Guidelines, Decision Analysis) deals mainly with a different type or aspect of clinical problems. We suggest that all of these conceptual tools can be thought of as belonging in the clinician's toolbox for solving clinical problems and making clinical decisions. A heuristic for guiding the clinician in using the tools is proposed. The heuristic is then used to analyze management of the three patients presented at the outset. Copyright 2004 Birkhäuser Verlag, Basel

Chorea as a rare manifestation of hyperglycaemia.

PubMed

Patil, Rajesh; Sangoi, Parin; Wasekar, Nilesh; Vishwanathan, Deepti; Jadhav, S G; Joglekar, V K

2013-09-01

We present a case of chorea presenting as a clinical manifestation of hyperglycaemia.The purpose of presenting this case is to highlight the fact that movement disorder may be the clinical presentation of hyperglycaemia and it reverts on treatment of hyperglycaemia. A 66-year-old female known case of type 2 diabetes mellitus and on oral hypoglycaemic drugs presented with abnormal and involuntary movements of the whole body and face since 7 days and high plasma glucose (446 mg/dl) and without ketosis. On controlling the blood sugar, there has been significant decrease in choreiform movements within 48 hrs and complete resolution of involuntary movements found at discharge at 1 week. Movement disorder like chorea may be the clinical presentation of the hyperglycaemia which could completely recover on rapid detection and correction of hyperglycaemia.

[Choledocal cyst: analysis of 29 cases and review or the literature].

PubMed

Vila-Carbó, J J; Ayuso, L; Hernández, E; Lluna, J; Ibáñez, V

2006-01-01

The aim of the present study has been to systematize the clinical presentation of the entity named choledochal cyst, in relation with its probable etiopathology and the intraoperative findings as well as its evolution after surgery, based on the revision of the literature and of our experience in 29 cases. 29 cases of cystic dilatation of the biliar duct extra and/or intrahepatic are analyzed. In 4 cases the diagnosis was prenatal and two were excluded of the study after it has been confirmed they suffered biliary atresia type I. In the left 27 cases, 19 variables are analyzed retrospectively, like age, sex, weight, symptoms, ultrasonographic images, etc. Subsequently, intra-operative cholangiographic findings were correlated with the clinic presentation and the evolution of the patients after surgery. Of the 27 cases analyzed 16 (59,25%) were cystic dilatations from which 14 had a neonatal or early clinic presentation (before 2 years), however the fusiform dilatations were presented later on. From the analyzed symptoms, in relation with the age only the pain and the jaundice showed significant differences, being the pain most frequent in later presentation ande the jaundice in the early form. The two cases of type 3 of Todani or choledochocele were of later presentation. An anomaly in the bilionpacreatric junction was detected in 15 patients; the majority had a later presentation, associated to pancreatitis in 4 cases. Primary cyst excision and biliary Roux-en-Y reconstruction was the treatment of election in the majority of cases. In 3 cases we used the appendix to replace the choledocus, but all three cases were reconverted two years later because of permanent elevation of ALT and GGT. In favour of the literature and of our experience nowadays it would be possible to systematize this malformation and make a division in two groups, depending on the cholangiographic findings and clinical presentation: 1. Cystic dilatations with a clinical neonatal presentation or beneath 2 years. 2. Fusiform dilatations with a later clinical predominance and associated frequently to pancreatitis and anomalous pancreatobiliary junction. Choledochocele is an entity that must be considered not only for its etiology but for its clinical presentation and treatment. Primary cyst excision and biliary Roux-en-Y reconstruction is the treatment of election. Regular long-term review of these patients is mandatory in the surveillance of sub-clinic cholangitis and the risk of possible long-term malignance of this entity.

A prospective cohort study of the clinical presentation of non-traumatic osteonecrosis of the femoral head: spine and knee symptoms as clinical presentation of hip osteonecrosis.

PubMed

Hauzeur, Jean-Philippe; Malaise, Michel; de Maertelaer, Viviane

2016-07-01

To study the clinical presentation of femoral head osteonecrosis (ONFH). Publications dedicated to this aspect of ONFH are rare. Our aim was to systematically collect and describe the clinical data. A prospective survey was conducted in a cohort of ONFH recruited from a dedicated clinic for osteonecrosis. The history of symptoms, medical management, and physical findings were obtained from 88 patients suffering from 125 ONFH. Subgroups were formed: bilateral versus unilateral ONFH, radiological stages 1-2 (pre-fractured) versus fractured stage 3 versus stage 4. ONFH was bilateral in 63 %, especially in corticosteroid users and in sickle-cell cases. These patients were younger but had similar BMIs compared to the unilateral cases. The pain was mechanical in 79 % of hips and inflammatory in 21 %. Acute pain at the onset was present in 55 % of hips. The localization of this pain was variable, including in the groin, the buttocks, or diffused in the lower limbs. A limp was present in 50 % of the patients, only when one hip was painful. The physical examination of the hip was normal in 31 %, especially in stages 1-2 (55 %). The diagnosis delay was 12 months, with inadequate medical management in 51 % of patients. In ONFH cases, no typical clinical pattern was found. The clinical presentation was very variable, sometimes having spine or knee symptoms with a normal physical examination of the hip. ONFH should be systematically suspected in cases of onset of pain in the pelvis, buttocks, groin, and lower limbs.

Retrospective study of clinical and hematological aspects associated with dogs naturally infected by Hepatozoon canis in Ludhiana, Punjab, India

PubMed Central

Chhabra, Sushma; Uppal, Sanjeev Kumar; Singla, Lachhman Das

2013-01-01

Objective To evaluate clinical and hematological aspects of dogs naturally infected with Hepatozoon canis (H. canis) presented at the Small Animal Clinics of Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana. Methods Blood films of 34 naturally infected dogs were examined for haematological alterations and parasitaemia. Signalment and clinical signs were recorded from the animals. Clinical histories were filled out during the consultation. Results Of the 34 positive dogs by Giemsa stained peripheral blood films, 88.23% presented parasitaemia by H. canis only, while 11.77% had the combination of H. canis, Babesia sp. and Ehrlichia sp. Young male dogs less than one-year-old, of non-descript breed, were the most commonly affected. And 26.47% were presented with anorexia/inappetence as the only clinical symptom. Other clinical symptoms were mild to moderate fever, pale mucosae and lethargy; a few were also showing the signs of vomiting and diarrhoea. Haematological alterations showed mainly normochromic-normocytic anaemia, leukocytosis and neutrophilia. Conclusions The findings of this study substantiate that H. canis caused clinical and haematological alterations of the varied intensity in dogs, even with low parasitaemia, should be taken into consideration. PMID:23730562

Retrospective study of clinical and hematological aspects associated with dogs naturally infected by Hepatozoon canis in Ludhiana, Punjab, India.

PubMed

Chhabra, Sushma; Uppal, Sanjeev Kumar; Singla, Lachhman Das

2013-06-01

To evaluate clinical and hematological aspects of dogs naturally infected with Hepatozoon canis (H. canis) presented at the Small Animal Clinics of Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana. Blood films of 34 naturally infected dogs were examined for haematological alterations and parasitaemia. Signalment and clinical signs were recorded from the animals. Clinical histories were filled out during the consultation. Of the 34 positive dogs by Giemsa stained peripheral blood films, 88.23% presented parasitaemia by H. canis only, while 11.77% had the combination of H. canis, Babesia sp. and Ehrlichia sp. Young male dogs less than one-year-old, of non-descript breed, were the most commonly affected. And 26.47% were presented with anorexia/inappetence as the only clinical symptom. Other clinical symptoms were mild to moderate fever, pale mucosae and lethargy; a few were also showing the signs of vomiting and diarrhoea. Haematological alterations showed mainly normochromic-normocytic anaemia, leukocytosis and neutrophilia. The findings of this study substantiate that H. canis caused clinical and haematological alterations of the varied intensity in dogs, even with low parasitaemia, should be taken into consideration.

Clinical pictures of unknown origin in neurology: past, present and future usefulness of artificial intelligence.

PubMed

Conti, Andrea A; Conti, Antonio; Masoni, Marco; Gensini, Gian Franco

2005-01-01

Although, in the course of the last 50 years, the achievements in the medical field have been astonishing, at the beginning of the third millennium a number of clinical pictures are still left without a precise nosographic origin. In the past, the delay in scientific communication was the main explanation presented for the lack of understanding of clinical pictures of unknown nosographic origin. The history of medicine provides excellent examples of this dispersion of human capital, even if the history of clinical neurology presents "exceptions" (the pictures that we now call de la Tourette's syndrome and Parkinson's disease) that indicate that major clinical syndromes could be clearly detected and relatively rapidly diffused even in the 19th century. Contrary to the past, the delay in scientific communication no longer seems an obstacle to the sharing of medical knowledge. Nevertheless, the problem of the in-depth comprehension of clinical pictures of unknown nosographic origin still remains dominant, mainly because of the limited spread of ample and flexible online accessible databases of unknown nosographic origin clinical syndromes. The need for interactive electronic archives and other artificial intelligence resources in order to promote progress in clinical knowledge is discussed in this paper.

Isolated lower brachial plexus (Klumpke) palsy with compound arm presentation: case report.

PubMed

Buchanan, Edward P; Richardson, Randal; Tse, Raymond

2013-08-01

Klumpke palsy has yet to be clearly documented in the newborn, because previous reports lack any description of the obstetrical history, clinical progression, or outcome. Based on a high incidence of breach presentation in the few clinical series that report Klumpke palsy, hyperabduction with arm overhead during delivery has been the presumed mechanism. We report a child with isolated lower brachial plexus palsy and Horner syndrome who presented at birth with a vertex compound arm presentation. Recognition of this condition and details of the clinical progression and outcome are important, because guidelines for management are currently not available. Copyright © 2013. Published by Elsevier Inc.

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

PubMed

Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter defibrillator in non-ischemic cardiomyopathy), and electrophysiology (cryoballoon vs radiofrequency ablation). This paper presents a summary of key clinical cardiology trials during the past year and should be of practical value to both clinicians and cardiology researchers.

Clinical diagnosis of syphilis: a ten-year retrospective analysis in a South Australian urban sexual health clinic.

PubMed

Forrest, C E; Ward, A

2016-12-01

National notifications for infectious syphilis in Australia have increased in recent years. Outside of sexual health clinics, junior clinicians seldom encounter this disease in its infectious stage (primary, secondary and early latent). With such a variable clinical presentation, textbook teaching is no substitute for real-life experience. The importance of accurate classification and staging of disease is relevant to the risk of transmission and determines treatment duration. In this article, the authors review the clinical presentation of syphilis over ten years in an urban sexual health clinic with a focus on the clinical presentation and diagnosis of infectious syphilis, in particular secondary syphilis, compared with that outlined in the Australian National Notifiable Diseases Surveillance System guidelines. This retrospective review of all patients diagnosed with syphilis at an urban sexual health clinic showed that between 2005 and 2015, 226 cases of syphilis were diagnosed. Documentation of impression of clinical staging of disease was present in 46% of the cases. Seventeen of these cases were recorded as secondary syphilis. The criteria used by clinicians to diagnose the secondary syphilis cases were consistent with criteria defined by the Australian National Notifiable Diseases Surveillance System. All cases of secondary syphilis had at least one cutaneous manifestation of disease. The demographic of the cohort of syphilis cases was consistent with that recorded in the literature. This review showed that the clinician's diagnosis of secondary syphilis in this service is consistent with the National Notifiable Diseases Surveillance System guidelines. Continuing education of junior medical staff is important to facilitate diagnosis and improve documentation of clinical staging, minimise disease transmission and ensure appropriate treatment. © The Author(s) 2016.

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

PubMed

Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe; Aquino, Melissa; Stone, Gregg W; Sartori, Samantha; Steg, Philippe Gabriel; Wijns, William; Smits, Pieter C; Jeger, Raban V; Leon, Martin B; Windecker, Stephan; Serruys, Patrick W; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Kandzari, David; Dangas, George D; Mastoris, Ioannis; Von Birgelen, Clemens; Galatius, Soren; Kimura, Takeshi; Mikhail, Ghada; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Valgimigli, Marco; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

2015-09-15

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women. Published by Elsevier Inc.

Excess of non-verbal cases of autism spectrum disorders presenting to orthodox clinical practice in Africa – a trend possibly resulting from late diagnosis and intervention

PubMed Central

Bakare, Muideen O; Munir, Kerim M

2012-01-01

Objectives Characteristics of children with autism spectrum disorders (ASDs) in Africa are not known because of unavailability of large-scale epidemiological studies in this region. This review explored the age at first presentation to orthodox clinical practice of African children with ASDs and their expressive language ability at presentation. Methods A literature search of case series and case reports of ASDs from Africa was done through PubMed/MEDLINE, Google Scholar, African Journals Online (AJOL), and archives of the Nigerian Journal of Psychiatry. Six articles included content relating to age of the child at first presentation to orthodox clinical practice and symptoms at presentation related to expressive language ability and therefore fulfilled the inclusion criteria. Suggestions are made to explain the observations emanating from the review. Results An excess of non-verbal over verbal cases of ASDs have been presenting to orthodox clinical practice and there is a common denominator of late presentation/diagnosis and in turn late intervention, with most cases presenting for the first time well above 8 years of age. Attempts to explain these observations included low levels of knowledge and awareness about ASDs in Africa; problems with help-seeking behaviour; and lack of mental healthcare facilities and trained personnel. Conclusions Enhancement of processes directed at ensuring early diagnosis and interventions, especially interventions aimed at improving speech and language development well and sufficiently early, may bring about a shift in the trend of excess non-verbal cases of ASDs over verbal cases presenting to orthodox clinical practice. PMID:22229024

Clinical presentation of retinoblastoma in Alexandria: A step toward earlier diagnosis.

PubMed

Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad

2017-01-01

To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.

Graphical Presentation of Patient-Treatment Interaction Elucidated by Continuous Biomarkers. Current Practice and Scope for Improvement.

PubMed

Shen, Yu-Ming; Le, Lien D; Wilson, Rory; Mansmann, Ulrich

2017-01-09

Biomarkers providing evidence for patient-treatment interaction are key in the development and practice of personalized medicine. Knowledge that a patient with a specific feature - as demonstrated through a biomarker - would have an advantage under a given treatment vs. a competing treatment can aid immensely in medical decision-making. Statistical strategies to establish evidence of continuous biomarkers are complex and their formal results are thus not easy to communicate. Good graphical representations would help to translate such findings for use in the clinical community. Although general guidelines on how to present figures in clinical reports are available, there remains little guidance for figures elucidating the role of continuous biomarkers in patient-treatment interaction (CBPTI). To combat the current lack of comprehensive reviews or adequate guides on graphical presentation within this topic, our study proposes presentation principles for CBPTI plots. In order to understand current practice, we review the development of CBPTI methodology and how CBPTI plots are currently used in clinical research. The quality of a CBPTI plot is determined by how well the presentation provides key information for clinical decision-making. Several criteria for a good CBPTI plot are proposed, including general principles of visual display, use of units presenting absolute outcome measures, appropriate quantification of statistical uncertainty, correct display of benchmarks, and informative content for answering clinical questions especially on the quantitative advantage for an individual patient with regard to a specific treatment. We examined the development of CBPTI methodology from the years 2000 - 2014, and reviewed how CBPTI plots were currently used in clinical research in six major clinical journals from 2013 - 2014 using the principle of theoretical saturation. Each CBPTI plot found was assessed for appropriateness of its presentation and clinical utility. In our review, a total of seven methodological papers and five clinical reports used CBPTI plots which we categorized into four types: those that distinguish the outcome effect for each treatment group; those that show the outcome differences between treatment groups (by either partitioning all individuals into subpopulations or modelling the functional form of the interaction); those that evaluate the proportion of population impact of the biomarker; and those that show the classification accuracy of the biomarker. The current practice of utilizing CBPTI plots in clinical reports suffers from methodological shortcomings: the lack of presentation of statistical uncertainty, the outcome measure scaled by relative unit instead of absolute unit, incorrect use of benchmarks, and being non-informative in answering clinical questions. There is considerable scope for improvement in the graphical representation of CBPTI in clinical reports. The current challenge is to develop instruments for high-quality graphical plots which not only convey quantitative concepts to readers with limited statistical knowledge, but also facilitate medical decision-making.

Visualizing Subject Access for 21st Century Information Resources. Papers Presented at the Clinic on Library Applications of Data Processing (34th, Urbana, Illinois, March 2-4, 1997).

ERIC Educational Resources Information Center

Cochrane, Pauline Atherton, Ed.; Johnson, Eric H., Ed.

This proceedings represents and documents in part the 16 presentations made at the 34th Annual Clinic on Library Applications of Data Processing. World Wide Web URLs that provide insight into each presentation are included. Presentations include: (1) "Hypostatizing Data Collections, Especially Bibliographic: Abstractions, Representations,…

Bronchogenic cyst presenting as a symptomatic neck mass in an adult: case report and review of the literature.

PubMed

Al-kasspooles, Mazin F; Alberico, Ronald A; Douglas, Wade G; Litwin, Alan M; Wiseman, Sam M; Rigual, Nestor R; Loree, Thom R; Hicks, Wesley L

2004-12-01

We report the unusual clinical manifestation and subsequent management of a symptomatic congenital bronchogenic cyst that connected to the trachea and presented in the neck of an adult. The embryology, clinical presentation, diagnostic evaluation, and management options of this rare aberration are discussed.

Diagnoses and Presenting Symptoms in an Infant Psychiatry Clinic: Comparison of Two Diagnostic Systems.

ERIC Educational Resources Information Center

Frankel, Karen A.; Boyum, Lisa A.; Harmon, Robert J.

2004-01-01

Objective: To present data from a general infant psychiatry clinic, including range and frequency of presenting symptoms, relationship between symptoms and diagnoses, and comparison of two diagnostic systems, DSM-IV and Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0-3). Method: A…

A Learner-Centered Technique and Clinical Reasoning, Reflection, and Case Presentation Attributes in Athletic Training Students

PubMed Central

Heinerichs, Scott; Vela, Luzita I.; Drouin, Joshua M.

2013-01-01

Context: Providing opportunities to develop clinical decision-making skills, including clinical reasoning, is an important aspect of clinical education. The learner-centered technique of summarizing the history and findings, narrowing the differential, analyzing the differential, probing the instructor about uncertainties, plan management, and selecting an issue for self-directed study (SNAPPS) is used in medicine to express clinical reasoning. Objective: To investigate the effects of SNAPPS on the clinical reasoning, reflection, and 4 case presentation attributes (length, conciseness, case summary, and expression of clinical reasoning) in athletic training students. Design: Randomized controlled clinical trial. Setting: Three undergraduate programs accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants: We randomly assigned 38 athletic training students (17 men, 21 women; age = 21.53 ± 1.18 years, grade point average = 3.25 ± 0.31) who had completed at least 1 year of clinical education and all orthopaedic evaluation coursework to the SNAPPS group or the usual and customary group using a stratification scheme. Intervention(s): The SNAPPS group completed four 45-minute clinical reasoning and case presentation learning modules led by an investigator to learn the SNAPPS technique, whereas the usual and customary group received no formal instruction. Both groups audio recorded all injury evaluations performed over a 2-week period. Main Outcome Measures: Participants completed the Diagnostic Thinking Inventory and Reflection in Learning Scale twice. Case presentations were analyzed for 4 attributes: length, conciseness, case summary, and expression of clinical reasoning. Results: Case presentations were longer (t18.806 = −5.862, P < .001) but were more concise (t32 = 11.297, P < .001) for the SNAPPS group than for the usual and customary group. The SNAPPS group performed better on both the case summary subscale (t32 = 2.857, P = .007) and the clinical reasoning subscale (t25.773 = −14.162, P < .001) than the other group. We found a time effect for Diagnostic Thinking Inventory scores (F1,34 = 6.230, P = .02) but observed no group effects (F1,34 = 0.698, P = .41) or time-by-group interaction (F1,34 = 1.050, P = .31). The Reflection in Learning Scale scores analysis revealed no group-by-time interaction (F1,34 = 1.470, P = .23) and no group (F1,34 = 3.751, P = .06) or time (F1,34 = 0.835, P = .37) effects. Conclusions: The SNAPPS is an effective and feasible clinical education technique for case presentations. This learner-centered technique provides the opportunity for the expression of clinical reasoning skills. PMID:23675796

Beyond human subjects: risk, ethics, and clinical development of nanomedicines.

PubMed

Kimmelman, Jonathan

2012-01-01

Clinical testing of nanomedicines presents two challenges to prevailing, human subject-centered frameworks governing research ethics. First, some nanomedical applications may present risk to persons other than research subjects. Second, pressures encountered in testing nanomedicines may present threats to the kinds of collaborations and collective activities needed for supporting clinical translation and redeeming research risk. In this article, I describe how similar challenges were encountered and addressed in gene transfer, and sketch policy options that might be explored in the nanomedicine translation arena. © 2012 American Society of Law, Medicine & Ethics, Inc.

Conceptual Models and Guidelines for Clinical Assessment of Financial Capacity.

PubMed

Marson, Daniel

2016-09-01

The ability to manage financial affairs is a life skill of critical importance, and neuropsychologists are increasingly asked to assess financial capacity across a variety of settings. Sound clinical assessment of financial capacity requires knowledge and appreciation of applicable clinical conceptual models and principles. However, the literature has presented relatively little conceptual guidance for clinicians concerning financial capacity and its assessment. This article seeks to address this gap. The article presents six clinical models of financial capacity : (1) the early gerontological IADL model of Lawton, (2) the clinical skills model and (3) related cognitive psychological model developed by Marson and colleagues, (4) a financial decision-making model adapting earlier decisional capacity work of Appelbaum and Grisso, (5) a person-centered model of financial decision-making developed by Lichtenberg and colleagues, and (6) a recent model of financial capacity in the real world developed through the Institute of Medicine. Accompanying presentation of the models is discussion of conceptual and practical perspectives they represent for clinician assessment. Based on the models, the article concludes by presenting a series of conceptually oriented guidelines for clinical assessment of financial capacity. In summary, sound assessment of financial capacity requires knowledge and appreciation of clinical conceptual models and principles. Awareness of such models, principles and guidelines will strengthen and advance clinical assessment of financial capacity. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Is diabetes a risk factor for a severe clinical presentation of dengue?--review and meta-analysis.

PubMed

Htun, Nan Shwe Nwe; Odermatt, Peter; Eze, Ikenna C; Boillat-Blanco, Noémie; D'Acremont, Valérie; Probst-Hensch, Nicole

2015-04-01

The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08-2.84, p = 0.022). Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue.

Research progress in muscle-derived stem cells: Literature retrieval results based on international database.

PubMed

Zhang, Li; Wang, Wei

2012-04-05

To identify global research trends of muscle-derived stem cells (MDSCs) using a bibliometric analysis of the Web of Science, Research Portfolio Online Reporting Tools of the National Institutes of Health (NIH), and the Clinical Trials registry database (ClinicalTrials.gov). We performed a bibliometric analysis of data retrievals for MDSCs from 2002 to 2011 using the Web of Science, NIH, and ClinicalTrials.gov. (1) Web of Science: (a) peer-reviewed articles on MDSCs that were published and indexed in the Web of Science. (b) Type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items. (c) Year of publication: 2002-2011. (d) Citation databases: Science Citation Index-Expanded (SCI-E), 1899-present; Conference Proceedings Citation Index-Science (CPCI-S), 1991-present; Book Citation Index-Science (BKCI-S), 2005-present. (2) NIH: (a) Projects on MDSCs supported by the NIH. (b) Fiscal year: 1988-present. (3) ClinicalTrials.gov: All clinical trials relating to MDSCs were searched in this database. (1) Web of Science: (a) Articles that required manual searching or telephone access. (b) We excluded documents that were not published in the public domain. (c) We excluded a number of corrected papers from the total number of articles. (d) We excluded articles from the following databases: Social Sciences Citation Index (SSCI), 1898-present; Arts & Humanities Citation Index (A&HCI), 1975-present; Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), 1991-present; Book Citation Index - Social Sciences & Humanities (BKCI-SSH), 2005-present; Current Chemical Reactions (CCR-EXPANDED), 1985-present; Index Chemicus (IC), 1993-present. (2) NIH: (a) We excluded publications related to MDSCs that were supported by the NIH. (b) We limited the keyword search to studies that included MDSCs within the title or abstract. (3) ClinicalTrials.gov: (a) We excluded clinical trials that were not in the ClinicalTrials.gov database. (b) We excluded clinical trials that dealt with stem cells other than MDSCs in the ClinicalTrials.gov database. (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) top cited authors over the last 10 years; (7) projects financially supported by the NIH; and (8) clinical trials registered. (1) In all, 802 studies on MDSCs appeared in the Web of Science from 2002 to 2011, almost half of which derived from American authors and institutes. The number of studies on MDSCs has gradually increased over the past 10 years. Most papers on MDSCs appeared in journals with a particular focus on cell biology research, such as Experimental Cell Research, Journal of Cell Science, and PLoS One. (2) Eight MDSC research projects have received over US$6 billion in funding from the NIH. The current project led by Dr. Johnny Huard of the University of Pittsburgh-"Muscle-Based Tissue Engineering to Improve Bone Healing"-is supported by the NIH. Dr. Huard has been the most productive and top-cited author in the field of gene therapy and adult stem cell research in the Web of Science over last 10 years. (3) On ClinicalTrials.gov, "Muscle Derived Cell Therapy for Bladder Exstrophy Epispadias Induced Incontinence" Phase 1 is registered and sponsored by Johns Hopkins University and has been led by Dr. John P. Gearhart since November 2009. From our analysis of the literature and research trends, we found that MDSCs may offer further benefits in regenerative medicine.

Nutritional Needs of the Child with a Handicap or Chronic Illness. Manual II: Clinical Nutrition. Presentations from a National Interdisciplinary Symposium.

ERIC Educational Resources Information Center

Ekvall, Shirley M.; Wheby, Elizabeth A.

The following papers were presented at a symposium on clinical nutrition for the child who is chronically ill or handicapped: (1) "Food Allergy"; (2) "Anemia and the Chronically Ill or Handicapped Child"; (3) "Nutrition and Neurotransmitters--Clinical Implications"; (4) "The Importance of Lipid Type in the Diet after Burn Injury"; (5) "Advances of…

[Ulcus-molle epidemic in Turkey].

PubMed

Murat, A; Oke, N; Baransü, O

1978-11-01

240 patients with soft chancre who have been observed within a year dating from March 1976 at the University Dermatological Clinic of Istanbul are presented. The clinical findings encountered in our cases are presented and the therapeutic results are discussed.

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

PubMed

Kararizou, E; Markou, I; Zalonis, I; Gkiatas, K; Triantafyllou, N; Kararizos, G; Likomanos, D; Zambelis, T; Vassilopoulos, D

2005-11-01

To describe a case of limbic encephalitis which initially presented as viral limbic encephalitis and during the clinical evaluation a renal carcinoma was diagnosed. Patient with history of peripheral paresis of right facial nerve, 1 month after symptoms appearance and treatment, developed fever, vomiting, grand mal seizure, decreased level of consciousness, confusion, hallucinations and agitation. The patient initially presented a clinical picture of viral LE. which confirmed by CSF. MRI brain showed areas with pathological intensity signal in the region of limbic system unilateral. During the clinical evaluation a renal carcinoma was discovered and a nephrectomy has been performed. Although PLE typically presents as a chronic or subacute disease, it may be fulminant and clinically indistinguishable from an acute HSVE. This association pose the problem of a possible relation between this two syndromes and the correct diagnosis is very important, because there are effective treatments.

Extracutaneous atypical syphilis in HIV-infected patients.

PubMed

Prieto, Paula; Imaz, Arkaitz; Calatayud, Laura; García, Olga; Saumoy, María; Podzamczer, Daniel

2017-12-07

We describe a series of cases of syphilis with atypical extracutaneous clinical presentation diagnosed in HIV-infected patients. Retrospective observational study. All cases of syphilis diagnosed in HIV-infected patients during the period between June 2013 and June 2016 in a tertiary hospital of the Barcelona metropolitan area were analysed. A total of 71 cases of syphilis were diagnosed, 32 of them presenting with clinical signs or symptoms. Seven of these cases (9.8% of the total and 21.8% of the symptomatic cases) had atypical presentations with extracutaneous involvement: ocular (4), gastric (1), multiple hepatic abscesses (1) and generalised adenopathies (1). Patients were treated with intramuscular or intravenous penicillin and the clinical and serological evolution was good in all of them. Extracutaneous atypical clinical presentations were observed in 21.8% of symptomatic cases of syphilis in HIV+ patients with ocular involvement being the most freqent. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The varied clinical presentations of major depressive disorder.

PubMed

Rush, A John

2007-01-01

DSM-IV major depressive disorder (MDD) is a clinical syndrome notable for heterogeneity of its clinical presentation, genetics, neurobiology, clinical course, and treatment responsiveness. In an attempt to make sense of this heterogeneity, clinicians and researchers have proposed a number of MDD "subtypes" based on differences in characteristic symptoms (e.g., atypical, melancholic, psychotic), onset (e.g., early vs. late, post-partum, seasonal), course of illness (e.g., single vs. recurrent, chronic, double), and severity. This article provides a brief review of the status of several of the most common subtypes in terms of their clinical features, biological correlates, course of illness, and treatment implications.

Reflections on the present and future of upper limb prostheses.

PubMed

Farina, Dario; Amsüss, Sebastian

2016-01-01

Despite progress in research and media attention on active upper limb prostheses, presently the most common commercial upper limb prosthetic devices are not fundamentally different from solutions offered almost one century ago. Limited information transfer for both control and sensory-motor integration and challenges in socket technology have been major obstacles. By analysing the present state-of-the-art and academic achievements, we provide our opinion on the future of upper limb prostheses. We believe that surgical procedures for muscle reinnervation and osseointegration will become increasingly clinically relevant; muscle electrical signals will remain the main clinical means for prosthetic control; and chronic electrode implants, first in muscles (control), then in nerves (sensory feedback), will become viable clinical solutions. After decades of suspended clinically relevant progress, it is foreseeable that a new generation of upper limb prostheses will enter the market in the near future based on such advances, thereby offering substantial clinical benefit for patients.

Clinical simulation as a boundary object in design of health IT-systems.

PubMed

Rasmussen, Stine Loft; Jensen, Sanne; Lyng, Karen Marie

2013-01-01

Healthcare organizations are very complex, holding numerous stakeholders with various approaches and goals towards the design of health IT-systems. Some of these differences may be approached by applying the concept of boundary objects in a participatory IT-design process. Traditionally clinical simulation provides the opportunity to evaluate the design and the usage of clinical IT-systems without endangering the patients and interrupting clinical work. In this paper we present how clinical simulation additionally holds the potential to function as a boundary object in the design process. The case points out that clinical simulation provides an opportunity for discussions and mutual learning among the various stakeholders involved in design of standardized electronic clinical documentation templates. The paper presents and discusses the use of clinical simulation in the translation, transfer and transformation of knowledge between various stakeholders in a large healthcare organization.

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

PubMed Central

Garcia Torres, Rafael; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Micheletti, Adilha Rua; Ribeiro, Barbara de Melo; Silva, Leonardo Eurípedes Andrade; Mora, Delio Jose; Paim, Kennio Ferreira; Silva-Vergara, Mario León

2016-01-01

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training. PMID:27458037

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics.

PubMed

Li, Zhaoyang; Easton, Rachael

2018-01-01

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

PubMed Central

Easton, Rachael

2018-01-01

ABSTRACT The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field. PMID:29035675

The clinics of acute coronary syndrome

PubMed Central

Rastelli, Gianni

2016-01-01

Risk stratification and management of patients with chest pain continues to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The throutful evaluation necessitates that the physicians have a high index of suspicion for acute coronary syndrome (ACS) and always keep in mind the myriad of often subtle and atypical presentations of ischemic heart disease, especially in certain patient populations such as the elderly ones. In this article we aim to review and discuss the available evidence on the value of clinical presentation in patients with a suspected ACS, with special emphasis on history, characteristics of chest pain, associated symptoms, atypical presentations, precipitating and relieving factors, drugs, clinical rules and significance of clinical Gestalt. PMID:27294087

Coagulopathy in liver disease: Lack of an assessment tool.

PubMed

Blasi, Annabel

2015-09-21

There is a discrepancy between the information from clotting tests which have routinely been used in clinical practice and evidence regarding thrombotic and bleeding events in patients with liver disease. This discrepancy leads us to rely on other variables which have been shown to be involved in haemostasis in these patients and/or to extrapolate the behaviour of these patients to other settings in order to decide the best clinical approach. The aims of the present review are as follows: (1) to present the information provided by clotting tests in cirrhotic patients; (2) to present the factors that may influence clotting in these patients; (3) to review the clinical evidence; and (4) to put forward a clinical approach based on the first 3 points.

Coagulopathy in liver disease: Lack of an assessment tool

PubMed Central

Blasi, Annabel

2015-01-01

There is a discrepancy between the information from clotting tests which have routinely been used in clinical practice and evidence regarding thrombotic and bleeding events in patients with liver disease. This discrepancy leads us to rely on other variables which have been shown to be involved in haemostasis in these patients and/or to extrapolate the behaviour of these patients to other settings in order to decide the best clinical approach. The aims of the present review are as follows: (1) to present the information provided by clotting tests in cirrhotic patients; (2) to present the factors that may influence clotting in these patients; (3) to review the clinical evidence; and (4) to put forward a clinical approach based on the first 3 points. PMID:26401071

Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence.

PubMed

Bourget, Dominique; Whitehurst, Laurie

2004-11-01

Acts of violence have been frequently reported in cases of Capgras syndrome (CS), a misidentification syndrome characterized by the delusional belief that imposters have replaced people familiar to the individual. CS has been observed in many neuropsychiatric and organic disorders, and neuroimaging studies indicate an association between CS and right hemisphere abnormalities. However, CS has received limited attention from a forensic psychiatric perspective. We propose that elucidating demographic and clinical features noted in cases of violence secondary to CS may highlight important factors in the progression of CS to violence. We review the neurophysiological correlates and clinical factors observed in CS and present characteristics of a series of cases that demonstrate the potential of CS patients for severe physical violence toward the misidentified person. For patients with CS involving assault, we present and discuss commonly reported demographic and clinical features that may contribute to an increased risk for violence. An understanding of the presenting clinical features of CS resulting in aggressive acts may assist clinicians to assess the potential for violence in these patients.

Magnetic Resonance Angiography Using Fresh Blood Imaging in Oral and Maxillofacial Regions

PubMed Central

Oda, Masafumi; Tanaka, Tatsurou; Kito, Shinji; Habu, Manabu; Kodama, Masaaki; Kokuryo, Shinya; Miyamoto, Ikuya; Yoshiga, Daigo; Yamauchi, Kensuke; Nogami, Shinnosuke; Wakasugi-Sato, Nao; Matsumoto-Takeda, Shinobu; Ishikawa, Ayataka; Nishida, Ikuko; Saeki, Katsura; Morikawa, Kazumasa; Matsuo, Kou; Seta, Yuji; Yamashita, Yoshihiro; Maki, Kenshi; Tominaga, Kazuhiro; Morimoto, Yasuhiro

2012-01-01

The present paper provides general dentists with an introduction to the clinical applications and significance of magnetic resonance angiography (MRA) in the oral and maxillofacial regions. Specifically, the method and characteristics of MRA are first explained using the relevant MR sequences. Next, clinical applications to the oral and maxillofacial regions, such as identification of hemangiomas and surrounding vessels by MRA, are discussed. Moreover, the clinical significance of MRA for other regions is presented to elucidate future clinical applications of MRA in the oral and maxillofacial regions. PMID:23118751

[The quality management in clinical diagnostic laboratory in conditions of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary)].

PubMed

Nikolaev, N S; Nazarova, V V; Dobrovol'skaia, N Iu; Orlova, A V; Pchelova, N N

2014-10-01

The article presents experience of clinical diagnostic laboratory of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary) in the area of quality management of medical laboratory services on the basis of evaluation of efficacy and effectiveness of processes. The factors effecting quality of functioning of clinical diagnostic laboratory are indicated. The criteria and indicators of efficacy of work of employees of clinical diagnostic laboratory are presented.

Emerging souvenirs-clinical presentation of the returning traveller with imported arbovirus infections in Europe.

PubMed

Eckerle, I; Briciu, V T; Ergönül, Ö; Lupşe, M; Papa, A; Radulescu, A; Tsiodras, S; Tsitou, C; Drosten, C; Nussenblatt, V R; Reusken, C B; Sigfrid, L A; Beeching, N J

2018-03-01

Arboviruses are an emerging group of viruses that are causing increasing health concerns globally, including in Europe. Clinical presentation usually consists of a nonspecific febrile illness that may be accompanied by rash, arthralgia and arthritis, with or without neurological or haemorrhagic syndromes. The range of differential diagnoses of other infectious and noninfectious aetiologies is broad, presenting a challenge for physicians. While knowledge of the geographical distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the nonspecific and variable clinical presentation can delay final diagnosis. This narrative review aims to summarize the main clinical and laboratory-based findings of the three most common imported arboviruses in Europe. Evidence is extracted from published literature and clinical expertise of European arbovirus experts. We present three cases that highlight similarities and differences between some of the most common travel-related arboviruses imported to Europe. These include a patient with chikungunya virus infection presenting in Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus infection in Romania. Early diagnosis of travel-imported cases is important to reduce the risk of localized outbreaks of tropical arboviruses such as dengue and chikungunya and the risk of local transmission from body fluids or vertical transmission. Given the global relevance of arboviruses and the continuous risk of (re)emerging arbovirus events, clinicians should be aware of the clinical syndromes of arbovirus fevers and the potential pitfalls in diagnosis. Copyright © 2018. Published by Elsevier Ltd.

Gynecologic issues of adolescents with Down syndrome, autism, and cerebral palsy.

PubMed

Burke, Lori M; Kalpakjian, Claire Z; Smith, Yolanda R; Quint, Elisabeth H

2010-02-01

The gynecologic issues of adolescents with disabilities are understudied. The purpose of this study was to identify and compare the presenting complaints, treatments, and follow-up of adolescent girls with Down syndrome (DS), autism, and cerebral palsy (CP) presenting to a specialized gynecologic clinic for women with developmental disabilities. Outpatient gynecology clinic. Forty four adolescents (<21 y); 13 with DS, 14 with autism, and 17 with CP who presented to the clinic from 1999 to 2006. None. A retrospective review of the electronic medical records to collect data on age at presentation to clinic, ethnicity, menstrual history, chief complaint, treatment, and follow-up. Mean age at presentation to clinic was 15+/-3.5 years, and age of menarche was 12.5+/-2 years; age at menarche did not significantly differ between groups. The most frequent complaints were irregular bleeding (n=10) and mood/behavioral changes (n=6). Girls with autism were significantly (chi(2)=8.89, P=.012) more likely to present with behavioral issues than the other 2 groups. Initial management for the behavior issues in the autism group included nonsteroidal anti-inflammatory drugs (NSAID), oral contraceptives, and education. The most common gynecologic complaints of adolescent girls with DS, autism, and CP centered on menstruation and mood disorders. Patients with autism were more likely to present with behavioral issues related to the onset of periods. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Troubleshooting the diagnostic conundrums

USDA-ARS?s Scientific Manuscript database

Because so many different clinical presentations can be associated with infection with BVDV, diagnosis based on history, clinical presentation, and postmortem of affected animals is presumptive at best. Accurate and definitive detection of infection with BVDV depends on laboratory diagnosis. While t...

Ethical or Unethical Persuasion? The Rhetoric of Offers to Participate in Clinical Trials

ERIC Educational Resources Information Center

Barton, Ellen; Eggly, Susan

2009-01-01

Based on a sample of 22 oncology encounters, this article presents a discourse analysis of positive, neutral, or negative valence in the presentation of three elements of informed consent--purpose, benefits, and risks--in offers to participate in clinical trials. It is found that physicians regularly present these key elements of consent with a…

EMRs and Clinical IS Implementation in Hospitals: A Statewide Survey

ERIC Educational Resources Information Center

Jaana, Mirou; Ward, Marcia M.; Bahensky, James A.

2012-01-01

Purpose: Present an overview of clinical information systems (IS) in hospitals and analyze the level of electronic medical records (EMR) implementation in relation to clinical IS capabilities and organizational characteristics. Methods: We developed a survey instrument measuring clinical IS implementation and classified clinical IS across 5 EMR…

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

PubMed

Falup-Pecurariu, Oana G; Diez-Domingo, Javier; Esposito, Susanna; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Usonis, Vytautas; Greenberg, David

2018-07-01

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm 3 ) and ANC (11.5 ± 7.5 cells/mm 3 ) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm 3 , ANC 9.2 ± 5.1 cells/mm 3 ) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.

PubMed

Derksen, V F A M; Ajeganova, S; Trouw, L A; van der Helm-van Mil, A H M; Hafström, I; Huizinga, T W J; Toes, R E M; Svensson, B; van der Woude, D

2017-04-01

In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype. 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/.

Results from an audit feedback strategy for chronic obstructive pulmonary disease in-hospital care: a joint analysis from the AUDIPOC and European COPD audit studies.

PubMed

Lopez-Campos, Jose Luis; Asensio-Cruz, M Isabel; Castro-Acosta, Ady; Calero, Carmen; Pozo-Rodriguez, Francisco

2014-01-01

Clinical audits have emerged as a potential tool to summarize the clinical performance of healthcare over a specified period of time. However, the effectiveness of audit and feedback has shown inconsistent results and the impact of audit and feedback on clinical performance has not been evaluated for COPD exacerbations. In the present study, we analyzed the results of two consecutive nationwide clinical audits performed in Spain to evaluate both the in-hospital clinical care provided and the feedback strategy. The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation. The first audit was performed from November-December 2008. The feedback strategy consisted of personalized reports for each participant center, the presentation and discussion of the results at regional, national and international meetings and the creation of health-care quality standards for COPD. The second audit was part of a European study during January and February 2011. The impact of the feedback strategy was evaluated in term of clinical care provided and in-hospital survival. A total of 94 centers participated in the two audits, recruiting 8,143 admissions (audit 1∶3,493 and audit 2∶4,650). The initially provided clinical care was reasonably acceptable even though there was considerable variability. Several diagnostic and therapeutic procedures improved in the second audit. Although the differences were significant, the degree of improvement was small to moderate. We found no impact on in-hospital mortality. The present study describes COPD hospital care in Spanish hospitals and evaluates the impact of peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations. It describes small to moderate improvements in the clinical care provided to COPD patients with no impact on in-hospital mortality.

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

[Classification of results of studying blood plasma with laser correlation spectroscopy based on semiotics of preclinical and clinical states].

PubMed

Ternovoĭ, K S; Kryzhanovskiĭ, G N; Musiĭchuk, Iu I; Noskin, L A; Klopov, N V; Noskin, V A; Starodub, N F

1998-01-01

The usage of laser correlation spectroscopy for verification of preclinical and clinical states is substantiated. Developed "semiotic" classifier for solving the problems of preclinical and clinical states is presented. The substantiation of biological algorithms as well as the mathematical support and software for the proposed classifier for the data of laser correlation spectroscopy of blood plasma are presented.

Comorbidity of Deployment-Related Posttraumatic Disorders and Their Treatment with Cognitive-Behavioral Group

DTIC Science & Technology

2011-04-01

traumatised soldiers will be presented in this article . Initial experiences with the group therapy program will be discussed. 15. SUBJECT TERMS 16...clinical impression and the SCID-II questionnaire (Structurel Clinical Interview for DSM-IV1) for personality disorders. 89% showed clinical evidence...group therapy, newly developed in Berlin, for traumatised soldiers will be presented in this article . Initial experiences with the group therapy program

Identifying influenza-like illness presentation from unstructured general practice clinical narrative using a text classifier rule-based expert system versus a clinical expert.

PubMed

MacRae, Jayden; Love, Tom; Baker, Michael G; Dowell, Anthony; Carnachan, Matthew; Stubbe, Maria; McBain, Lynn

2015-10-06

We designed and validated a rule-based expert system to identify influenza like illness (ILI) from routinely recorded general practice clinical narrative to aid a larger retrospective research study into the impact of the 2009 influenza pandemic in New Zealand. Rules were assessed using pattern matching heuristics on routine clinical narrative. The system was trained using data from 623 clinical encounters and validated using a clinical expert as a gold standard against a mutually exclusive set of 901 records. We calculated a 98.2 % specificity and 90.2 % sensitivity across an ILI incidence of 12.4 % measured against clinical expert classification. Peak problem list identification of ILI by clinical coding in any month was 9.2 % of all detected ILI presentations. Our system addressed an unusual problem domain for clinical narrative classification; using notational, unstructured, clinician entered information in a community care setting. It performed well compared with other approaches and domains. It has potential applications in real-time surveillance of disease, and in assisted problem list coding for clinicians. Our system identified ILI presentation with sufficient accuracy for use at a population level in the wider research study. The peak coding of 9.2 % illustrated the need for automated coding of unstructured narrative in our study.

Interviews with children about their mental health problems: The congruence and validity of information that children report.

PubMed

Macleod, Emily; Woolford, June; Hobbs, Linda; Gross, Julien; Hayne, Harlene; Patterson, Tess

2017-04-01

To obtain a child's perspective during a mental health assessment, he or she is usually interviewed. Although researchers and clinicians generally agree that it is beneficial to hear a child's account of his or her presenting issues, there is debate about whether children provide reliable or valid clinical information during these interviews. Here, we examined whether children provide clinically and diagnostically relevant information in a clinical setting. In all, 31 children aged 5-12-years undergoing mental health assessments were asked open-ended questions about their presenting problems during a semi-structured interview. We coded the information that children reported to determine whether it was clinically relevant and could be used to diagnose their problems and to formulate and plan treatment. We also coded children's information to determine whether it was congruent with the children's presenting problems and their eventual clinical diagnoses. Most of the information that children reported was clinically relevant and included information about behaviour, affect, temporal details, thoughts, people, the environment, and the child's physical experiences. The information that children reported was also clinically valid; it was congruent with the problems that were discussed (84%) and also with the eventual diagnosis that the child received after a complete assessment (74%). We conclude that children can contribute relevant, clinically useful, valid information during clinical psychological assessments.

[Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

PubMed

Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

2010-08-01

The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

Shifting attention from objective risk factors to patients' self-assessed health resources: a clinical model for general practice.

PubMed

Hollnagel, H; Malterud, K

1995-12-01

The study was designed to present and apply theoretical and empirical knowledge for the construction of a clinical model intended to shift the attention of the general practitioner from objective risk factors to self-assessed health resources in male and female patients. Review, discussion and analysis of selected theoretical models about personal health resources involving assessing existing theories according to their emphasis concerning self-assessed vs. doctor-assessed health resources, specific health resources vs. life and coping in general, abstract vs. clinically applicable theory, gender perspective explicitly included or not. Relevant theoretical models on health and coping (salutogenesis, coping and social support, control/demand, locus of control, health belief model, quality of life), and the perspective of the underprivileged Other (critical theory, feminist standpoint theory, the patient-centred clinical method) were presented and assessed. Components from Antonovsky's salutogenetic perspective and McWhinney's patient-centred clinical method, supported by gender perspectives, were integrated to a clinical model which is presented. General practitioners are recommended to shift their attention from objective risk factors to self-assessed health resources by means of the clinical model. The relevance and feasibility of the model should be explored in empirical research.

Effect of delay in hospital presentation on clinical and imaging findings in acute pulmonary thromboembolism.

PubMed

Jenab, Yaser; Alemzadeh-Ansari, Mohammad Javad; Fehri, Seyedeh Arezoo; Ghaffari-Marandi, Neda; Jalali, Arash

2014-04-01

There is limited information on the extent and clinical importance of the delay in hospital presentation of acute pulmonary thromboembolism (PTE). The aim of this study was to investigate the delay in hospital presentation of PTE and its association with clinical and imaging findings in PTE. This prospective study was conducted on patients admitted to our hospital with a diagnosis of acute PTE between September 2007 and September 2011. Relationships between delay in hospital presentation and clinical findings, risk factors, imaging findings, and in-hospital mortality were analyzed. Of the 195 patients enrolled, 84 (43.1%) patients presented 3 days after the onset of symptoms. Patients with chest pain, history of immobility for more than 3 days, recent surgery, and estrogen use had significantly less delayed presentation. Right ventricular dysfunction was significantly more frequent in patients with delayed presentation (odds ratio [OR] = 2.38; 95% confidence interval [CI] 1.27-4.44; p = 0.006); however, no relationship was found between delay in presentation and pulmonary computed tomographic angiography or color Doppler sonography findings. Patients with delayed presentation were at higher risk of in-hospital mortality (OR = 4.32; 95% CI 1.12-16.49; p = 0.021). Our study showed that a significant portion of patients with acute PTE had delayed presentation. Also, patients with delayed presentation had worse echocardiographic findings and higher in-hospital mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Unspecific clinical manifestation of cauda equina myxopapillary ependymoma

PubMed Central

Kariev, Gayrat Maratovich; Halikulov, Elbek Shodievich; Rasulov, Shavkat Orzikuloviich

2015-01-01

A 9-year-old boy admitted to the neurosurgical hospital complaining of headache, vomiting, abdominal pain, and weakness in the arms and legs, urinary retention. Previously, the patient had a treatment of pediatricians. He was examined, magnetic resonance imaging revealed the tumor of the conus medullaris and cauda equina. The surgery was performed with removal myxopapillary ependymoma (ME). Postoperative neurological symptoms regressed; he has received radiotherapy postoperatively. This case illustrates a rare clinical presentation of ME, which simulated intracranial, thoracic, and caudal pathology. We presented features of the clinical presentation, diagnostics, and treatment options of this ependymoma. PMID:26396623

The SAPHO syndrome: a clinical and imaging study.

PubMed

Sallés, Meritxell; Olivé, Alejandro; Perez-Andres, Ricard; Holgado, Susana; Mateo, Lourdes; Riera, Elena; Tena, Xavier

2011-02-01

The purpose of this study is to describe the clinical and radiological manifestations of patients with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Retrospective study (1984-2007) was performed in a single center. All patients with the SAPHO syndrome were included. Fifty-two patients were included: 26 male, mean age at diagnosis is 42±12 years. Ostearticular involvement was present before cutaneous involvement in 59.6% of patients and concomitantly in 23.5%. Anterior chest pain was the commonest clinical manifestation, it was present in 38 patients (73%), followed by peripheral arthritis in 17 patients (32%), and sacroliliac pain in 14 patients (26.9%). Cutaneous involvement was present in 33 patients (63.5%). HLA B27 antigen was present in eight patients (17.7%). Bone scintigraphy showed an increased uptake in 42 patients (93.3%). The location of the uptake was mainly in sternoclavicular and manubriosternal joints. CT scan was performed in all "hot joints" showing sclerosis, erosions, hyperostosis, and soft tissue involvement. Refractory patients were treated mainly with pamidronate. Although SAPHO syndrome is an entity that share features that fit into a variety of established disease categories, the present study has a homogenous clinical and radiological pattern that gives support to believe that the SAPHO syndrome is an isolated clinical entity.

Developing tools for the safety specification in risk management plans: lessons learned from a pilot project.

PubMed

Cooper, Andrew J P; Lettis, Sally; Chapman, Charlotte L; Evans, Stephen J W; Waller, Patrick C; Shakir, Saad; Payvandi, Nassrin; Murray, Alison B

2008-05-01

Following the adoption of the ICH E2E guideline, risk management plans (RMP) defining the cumulative safety experience and identifying limitations in safety information are now required for marketing authorisation applications (MAA). A collaborative research project was conducted to gain experience with tools for presenting and evaluating data in the safety specification. This paper presents those tools found to be useful and the lessons learned from their use. Archive data from a successful MAA were utilised. Methods were assessed for demonstrating the extent of clinical safety experience, evaluating the sensitivity of the clinical trial data to detect treatment differences and identifying safety signals from adverse event and laboratory data to define the extent of safety knowledge with the drug. The extent of clinical safety experience was demonstrated by plots of patient exposure over time. Adverse event data were presented using dot plots, which display the percentages of patients with the events of interest, the odds ratio, and 95% confidence interval. Power and confidence interval plots were utilised for evaluating the sensitivity of the clinical database to detect treatment differences. Box and whisker plots were used to display laboratory data. This project enabled us to identify new evidence-based methods for presenting and evaluating clinical safety data. These methods represent an advance in the way safety data from clinical trials can be analysed and presented. This project emphasises the importance of early and comprehensive planning of the safety package, including evaluation of the use of epidemiology data.

Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.

PubMed

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-05-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

Scabies.

PubMed

Bielan, B

2001-08-01

The "Clinical Snapshot" series provides a concise examination of a clinical presentation including history, treatment, patient education, and nursing measures. Using the format here, you are invited to submit your "Clinical Snapshot" to Dermatology Nursing.

Examining the Clinical Correlates of Autism Spectrum Disorder in Youth by Ascertainment Source

PubMed Central

Joshi, Gagan; Faraone, Stephen V; Wozniak, Janet; Petty, Carter; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L.; McDermott, Katie; Epstien, Cecily; Walker, Rosemary; Caron, Ashley; Feinberg, Leah; Biederman, Joseph

2014-01-01

Objective To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. Methods ASD youth referred to a specialized ambulatory program for ASD (N=143) were compared to ASD youth referred to a general child psychiatry clinic (N=217). Results More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (PDD-NOS). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. Conclusion The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction. PMID:24566937

Clinically unrecognized miliary tuberculosis: an autopsy study.

PubMed

Savic, Ivana; Trifunovic-Skodric, Vesna; Mitrovic, Dragan

2016-01-01

Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy. Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities. Retrospective study of all autopsies performed between 2008 and 2014. Institute of Pathology, Belgrade, Serbia. in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy. Clinically unrecognized MT. The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death. Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery. None.

Terminal Behavioral Objectives for Teaching Clinical Toxicology to Clinical Pharmacists

ERIC Educational Resources Information Center

Veltri, Joseph C.; And Others

1976-01-01

As a first step in the development of a competency-based clinical toxicology clerkship, a set of terminal behavioral objectives were developed that reflect the anticipated role that clinical pharmacists should play as part of the clinical toxicology team. The evaluation approaches used at the University of Utah are presented. (LBH)

The Green Card Clinic: overview of a brief patient-centred intervention following deliberate self-harm.

PubMed

Wilhelm, Kay; Finch, Adam; Kotze, Beth; Arnold, Karen; McDonald, Geoff; Sternhell, Peter; Hudson, Beaver

2007-02-01

The aim of this study was to present an overview of the Green Card Clinic, a novel brief intervention service for patients presenting to the emergency department following deliberate self-harm (DSH) or with suicidal ideation, to examine its effectiveness in terms of service utilization, and patient and clinician feedback, and to explore the correlates of repeated DSH. The aims and structure of the Green Card Clinic are described. We highlight our patient-centred approach involving self-identification of difficulties from a list of problem areas, coupled with tailored intervention strategies. Relevant data are presented and characteristics of repeat DSH patients are compared to the first-episode group. Between 1998 and 2005, 456 DSH patients were referred to the clinic. Of these, 75% (n = 344) attended the first session, 43% (n = 197) the second session, 26% (n = 117) the third session, and 16% (n = 73) completed a 3-15 month follow-up. Clinic attenders (mean age 31.6 years, 57% female) reported a diverse range of self-identified problems and repeat DSH patients reported worse depression, poorer health-related behaviours, and a greater number of problems than those presenting after first-episode DSH. The clinic achieved high rates of first session attendance. This may have been attributable to the use of a few specific strategies aimed at increasing compliance, such as the green card, next-day appointments and assertive follow-up of non-attenders. For repeat self-harmers, we advocate an approach aimed at 'lifestyle change' rather than based on current psychological stressors. The Green Card Clinic service, involving a range of interventions tailored to meet the multitude of presenting needs, appears to be an acceptable and flexible approach to brief intervention for DSH.

Endemic pemphigus in the Peruvian Amazon: epidemiology and risk factors for the development of complications during treatment*

PubMed Central

Ramos, Willy; Chacon, Gina Rocio; Galarza, Carlos; Gutierrez, Ericson Leonardo; Smith, Maria Eugenia; Ortega-Loayza, Alex Gerardo

2012-01-01

BACKGROUND Pemphigus is an autoimmune blistering disease. According to a report, in areas of endemic pemphigus foliaceus (EPF) in Peru there are cases of pemphigus vulgaris with epidemiologic, clinical and histopathologic characteristics similar to those of "endemic pemphigus vulgaris" (EPV) in Brazil. OBJECTIVES To determine the clinical and epidemiologic characteristics of endemic pemphigus and the risk factors of patients for developing complications during treatment. METHODS A study was carried out from July 2003 to March 2008. The study population was 60 patients with EPF and 7 patients with EPV evaluated in hospitals and clinics in the Peruvian Amazon and Lima. A multivariate analysis was carried out using binary logistic regression. RESULTS The average age of EPF patients was 31.4 years; 55% were men; 60% presented the generalized clinical variant. Non-compliance with the treatment was seen in 57.1% of the patients. Thirty-five percent presented complications (e.g. pyodermitis and pyelonephritis) during treatment. The risk factors for developing complications during treatment were non-compliance with the treatment and having the generalized clinical form. In the EPV group, the average age was 21.7 years; 71.4% were men. All patients presented with the mucocutaneous clinical variant and the initial presentation consisted of oral mucosa lesions; 71.4% presented complications during treatment, pyodermitis being the most frequent. CONCLUSIONS Non-compliance with the treatment and the generalized clinical form are risk factors for the development of complications during treatment of patients with EPF. Peru indeed has EPV cases with epidemiologic characteristics similar to EPF. Living in a rural area may represent a risk factor for the development of complications during treatment of patients with EPV. PMID:23197201

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis.

PubMed

Bandinelli, F; Salvadorini, G; Delle Sedie, A; Riente, L; Bombardieri, S; Matucci-Cerinic, M

2016-02-01

The variability of demographic, social, genetic, and clinical factors might influence the time between the onset of symptoms and the diagnosis [diagnostic delay (DD)] of ankylosing spondylitis (AS) in different geographic areas. Different clinical manifestations in men and women affected by AS might indicate a possible role of gender in DD. The aim of the present study was to investigate the influence of demographic, social, genetic, and clinical factors on DD and the differences of DD between men and women related to the presence of different demographic, social, clinical, and genetic parameters in an Italian cohort of primary AS patients. A total of 135 Italian primary AS patients (45 female and 90 male, 27.9 ± 0.89 years old at onset) were studied. The DD, gender, education and work (manual or non-manual) levels, and type of first clinical presentation (inflammatory back pain, arthritis, enthesitis) at onset, family history of AS, and HLA B27 presence were analyzed. The DD (8.744 mean ±0.6869) was significantly higher in men (p = 0.0023), in axial presentation (p = 0.0021), and in manual work (even if with low significance, p = 0.047). The lower DD in women in comparison to that in men was likely related to higher education (p = 0.0045) and work (p = 0.0186) levels, peripheral involvement (p = 0.0009), and HLA B27 positivity (p = 0.0231). DD was higher in AS patients: male, employed in manual jobs, and with axial symptoms at onset. In men, DD seemed to be negatively influenced by lower level of education and work, axial clinical presentation, and HLA B27.

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil.

PubMed

Torres, Rafael Garcia; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Micheletti, Adilha Rua; Ribeiro, Barbara de Melo; Silva, Leonardo Eurípedes Andrade; Mora, Delio Jose; Paim, Kennio Ferreira; Silva-Vergara, Mario León

2016-10-05

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training. © The American Society of Tropical Medicine and Hygiene.

Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations.

PubMed

Joshi, Gagan; Faraone, Stephen V; Wozniak, Janet; Tarko, Laura; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L; Biederman, Joseph

2017-08-01

To compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only. A psychiatrically referred sample of autism spectrum disorder (ASD) youth with ADHD attending a specialized ambulatory program for ASD ( n = 107) and a sample of youth with ADHD attending a general child psychiatry ambulatory clinic ( n = 74) were compared. Seventy-six percent of youth with ASD met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD. The clinical presentation of ADHD in youth with ASD was predominantly similar to its typical presentation including age at onset (3.5 ± 1.7 vs. 4.0 ± 1.9; p = .12), distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity. Combined subtype was the most frequent presentation of ADHD in ASD youth. Despite the robust presentation of ADHD, a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment (41% vs. 24%; p = .02). A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

[Clinical-epidemiological profile of patients with suspicion of alimentary allergy in Mexico. Mexipreval Study].

PubMed

Medina-Hernández, Alejandra; Huerta-Hernández, Rosa Elena; Góngora-Meléndez, Marco A; Domínguez-Silva, M Gabriela; Mendoza-Hernández, David A; Romero-Tapia, Sergio J; Iduñate-Palacios, Fernando; Cisneros-Rivero, María Gozos; Covarrubias-Carrillo, Rosa Martha; Juan-Pineda, María Ángeles; Zárate-Hernández, María Carmen

2015-01-01

Adverse reaction to food has increased around the world in last years. Prevalence of food allergy raises between 2-4% in adults, and 6-8% in children. The clinical presentation is heterogeneous and varies from mild symptoms to anaphylactic reactions. Even the clinical history focused in the food is important; demonstration of allergen sensitization is mandatory. To describe the profile of the patients with suspicion of food allergy and the regular clinical practice followed in Mexico. An observational, descriptive, cross-sectional study was carried out from March 2013 to March 2014 using a convenience sample of allergic patients who were treated in the office, both private and public, of those physicians who seen food allergy patients. Clinical, epidemiological, diagnostic and therapeutic data were collected from 1,971 suspicious food allergic patients presenting for the first time in the departments of the researchers involved in the study. No difference was found in relation to gender. In relation to age, a bimodal distribution, with peaks at 2 and 35 years old, was found. A history of respiratory allergy was present in 75% of cases; 80% of patients had had any previous symptoms before seeking consultation and the most frequent clinical manifestations were cutaneous, 5% reported anaphylaxis. The foods involved in reactions change with age. The clinical presentation changes with the food, although the skin is the most frequently affected organ. Even if the suspicious were high, the confirmation with specific diagnostic tools is strongly recommended.

Clinical Aspects of Adult Epiglottitis

PubMed Central

Chaisson, Richard E.; Gerberding, J. Louise; Sande, Merle A.; Ross, Joel

1986-01-01

Epiglottitis in adults has been considered a medical rarity. Recent evidence suggests that this disorder is seen in adults regularly, though uncommonly, in clinical practice. We present 14 cases of adult epiglottitis. Most cases were blood culture-negative; Hemophilus influenzae was isolated from blood cultures in two cases and Hemophilus parainfluenzae in one case. There were no deaths. Epiglottitis in adults differs from pediatric epiglottitis in the mode of presentation, bacterial cause and clinical course. PMID:3524004

Pediatric Sepsis.

PubMed

Prusakowski, Melanie K; Chen, Audrey P

2017-02-01

Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care. Copyright © 2016 Elsevier Inc. All rights reserved.

Out of sight, out of mind? Does terminating the physical presence of a geriatric consultant in the community clinic reduce the implementation rate for geriatric recommendations.

PubMed

Freud, Tamar; Punchik, Boris; Biderman, Aya; Peleg, Roni; Kagan, Ella; Barzak, Alex; Press, Yan

2016-01-01

To assess the effect of moving the geriatric consultation from the primary care clinic to another setting, on the rate of implementation of geriatric recommendations by family physicians. A retrospective review of the computerized medical records of elderly patients in four primary care clinics. The rate of implementation of geriatric recommendations was compared between clinics in which a geriatric consultant was physically present (control clinics) and a clinic where the consultation took place elsewhere (study clinic). In addition, the results of the present study were compared to a previous study in which the geriatric consultation was carried out in the study clinic and the family doctor was an active participant. 127 computerized files were reviewed in the study clinic and 133 in the control clinics. The mean age of the patients was 81.1±6.3 years and 63.1% were women. The overall implementation of geriatric recommendations by family doctors in the study clinic was 55.9%, a statistically significant decrease compared to the previous study where the rate was 73.9% (p<0.0001). In contrast, there was no change in the implementation rate in the control clinics at 65.0% in the present study and 59.9% in the previous one (p=0.205). Direct, person-to-person contact between the geriatric consultant and the family doctor has a beneficial effect on the implementation of geriatric recommendations. This should be considered by healthcare policy makers when planning geriatric services in the community. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical presentation of familial exudative vitreoretinopathy.

PubMed

Ranchod, Tushar M; Ho, Lawrence Y; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

2011-10-01

To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. Case series, retrospective review. We included 273 eyes of 145 patients. Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. Demographics on presentation and clinical staging. Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, <1 month-49 years). A positive family history of FEVR was obtained in 18% of patients. A positive family history for ocular disease consistent with but not diagnosed as FEVR was obtained in an additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage 3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds were seen in 77 eyes, 64 of which were temporal or inferotemporal in location. The FEVR patient population is remarkable for the wide range of age at presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Clinical profiles, disease outcome and co-morbidities among T. b. rhodesiense sleeping sickness patients in Uganda.

PubMed

Kato, Charles D; Nanteza, Ann; Mugasa, Claire; Edyelu, Andrew; Matovu, Enock; Alibu, Vincent P

2015-01-01

The acute form of Human African Trypanosomiasis (HAT, also known as Sleeping sickness) caused by Trypanosoma brucei rhodesiense has been shown to have a wide spectrum of focus specific clinical presentation and severity in East and Southern Africa. Indeed HAT occurs in regions endemic for other tropical diseases, however data on how these co-morbidities might complicate the clinical picture and affect disease outcome remains largely scanty. We here describe the clinical presentation, presence of co-infections, and how the latter impact on HAT prognosis. We carried out a retrospective analysis of clinical data from 258 sleeping sickness patients reporting to Lwala hospital between 2005 and 2012. The mean patient age was 28.6 years with a significant number of cases below 18 years (p< 0.0001). About 93.4% of the cases were diagnosed as late stage (p< 0.0001). The case fatality rate was 10.5% with post treatment reactive encephalopathys reported in 7.9% of the cases, of whom 36.8% eventually died. Fever was significantly (p = 0.045) higher in patients under 18 years. Of the early stage patients, 26.7% and 6.7% presented with late stage signs of sleep disorder and mental confusion respectively. Among the co-infections, malaria was significantly more prevalent (28.9%; p< 0.0001) followed by urinary tract infections (4.2%). Co-infections were present in 14.3% of in-hospital deaths, 38.5% of which were recorded as Malaria. Malaria was significantly more common in patients under 18 years (45.5%; p< 0.02), and was reported in 60% of the fatal cases in this age group. We show a wide spectrum of sleeping sickness clinical presentation and disease outcome that was apparently not significantly influenced by concurrent infections. It would thus be interesting to determine the host and/or parasite factors that might be responsible for the observed diverse clinical presentation.

[Cerebellar infarction in vascular teritorry of arteria cerebelli superior].

PubMed

Savić, Dejan; Savić, Ljiljana

2010-01-01

Cerebellar vascular diseases are focal cerebrovascular diseases in posterior circulation--vertebrobasilar system. The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: arteria cerebelli inferior posterior, arteria cerebelli inferior anterior and arteria cerebelli superior. Cerebelar infarctions are rare but unpredictable disorders. The aim of this study was determination of main risk factors, clinical presentation and prognosis of the cerebellar infarctions in distal vascular teritorry of the arteria cerebelli superior. We evaluated 60 patients hospitalized after acute cerebellar infarction among other hospitalized patients in five year period. In 18 patients computerized tomography demonstrated infarction in distal vascular teritorry of the arteria cerebelli superior. All patients underwent clinical and other diagnostic investigations (computerized tomography, electrocardyography and standard blood tests) and were questioned by phone after finishing hospital treatment. Cerebellar infarcts in distal vascular teritorry of arteria cerebell superior was 30% of all cerebellar infarcts. The most frequent risk factor was hypertension (66.7%). Symptomatology and clinical signs were heterogenous but the most frequent were instability (77.8%), vertigo (72.2%) and vomiting (55.6%) followed by ataxia of the limbs (77.8%) and the body (61.1%), nystagmus (55.6%) and disarthria (33.3%) in clinical presentation. All patients had good recovery in hospital and one year afterwards. Infarctions in distribution of arteria cerebelli superior are rare and have multiple risk factors and various clinical features in majority of other studies as in this one. Mass effects are present in several studies but none in this one which reflects contraversions present in other published investigations. Cerebellar infarctions in vascular teritorry of arteria cerebelli superior have multiple risk factors, mostly heterogenous clinical presentations with predominance of instability, vertigo and vomiting with ataxia of the limbs and the body as well as nystagmus and disarthria in clinical presentation. The outcome and prognosis of disease is good despite the large amount of arteria cerebelli superior vascular teritorry.

Atypical Cutaneous Manifestations in Syphilis.

PubMed

Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

2016-05-01

Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Incidence and correlates of major bleeding after percutaneous coronary intervention across different clinical presentations.

PubMed

Loh, Joshua P; Pendyala, Lakshmana K; Torguson, Rebecca; Chen, Fang; Satler, Lowell F; Pichard, Augusto A; Waksman, Ron

2014-09-01

Bleeding after percutaneous coronary intervention (PCI) is identified as a strong predictor for adverse events, including mortality. This study aims to compare the incidence and correlates of post-PCI bleeding across different clinical presentations. The study included 23,943 consecutive PCI patients categorized according to their clinical presentation: stable angina pectoris (n = 6,741), unstable angina pectoris (UAP) (n = 5,215), non-ST-segment elevation myocardial infarction (NSTEMI) (n = 8,418), ST-segment elevation myocardial infarction (STEMI) (n = 2,721), and cardiogenic shock (CGS) (n = 848). Severity of clinical presentation was associated with a greater use of preprocedural anticoagulation, glycoprotein IIb/IIIa inhibitors, and intraaortic balloon pump (IABP). TIMI-defined major bleeding increased with increasing severity of clinical presentation: stable angina pectoris, 0.7%; UAP, 1.0%; NSTEMI, 1.6%; STEMI, 4.6%; and CGS, 13.5% (P < .001). On multivariable analysis, CGS (odds ratio [OR], 4.67; 95% CI [2.62-8.34]), STEMI (OR, 3.39; 95% CI [2.07-5.55]), and NSTEMI (OR, 2.00; 95% CI [1.29-3.10]) remained correlated with major bleeding even after adjusting for baseline and procedural differences, whereas UAP did not. The multivariable model also identified the use of IABP, female gender, congestive heart failure, no prior PCI, increased baseline hematocrit, and increased procedure time as correlates for major bleeding. In patients undergoing PCI, the worsening severity of clinical presentation corresponds to an increase in incidence of post-PCI major bleeding. The increased risk with CGS, STEMI, and NSTEMI persisted despite adjusting for more aggressive pharmacotherapy and use of IABP. Careful attention to antithrombotic pharmacotherapy is warranted in this high-risk population. Copyright © 2014 Mosby, Inc. All rights reserved.

Dysthymic disorder: clinical characteristics in relation to age at onset.

PubMed

Barzega, G; Maina, G; Venturello, S; Bogetto, F

2001-09-01

The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. The study is retrospective and enrolls a limited number of cases. The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.

[Toxocariasis, a neglected disease in Switzerland ?

PubMed

Duréault, Amélie; Perez Valdes, Carlos; Weber, Lalensia; Ogna, Adam; Sempoux, Christine; Manuel, Oriol; Delaloye, Julie

2017-04-12

Toxocariasis is a zoonotic disease that occurs when humans are infected by the parasites Toxocara canis or Toxocara cati. Toxocariasis is highly prevalent in tropical areas, but can also be found in industrialized countries, particularly in rural areas. Clinical presentation can range from asymptomatic infection to more severe disease. Diagnosis of toxocariasis is based on suggestive clinical findings, eosinophilia and a positive serological testing. Albendazole represents the first-line treatment, associated with corticosteroids in case of severe disease. Here we describe three clinical cases of toxocariasis in order to illustrate the clinical presentation, diagnosis and treatment of this unrecognized disease.

Acute dysphagia in an octogenarian: an unusual case of tetanus.

PubMed

Giordano, Mauro; Ciarambino, Tiziana; Di Bella, Olimpia; Finelli, Angelo; Ferrara, Nicola; Paolisso, Giuseppe

2014-06-01

Tetanus is a major worldwide health problem, and its global incidence has been estimated to be approximately 1 million cases per year. In particular, tetanus is more frequent in the elderly as compared with adults. We report a case of an octogenarian who presented with dysphagia and tremors as the only clinical symptoms. During hospitalization, the patient's clinical conditions worsened rapidly, and, although in absence of the classic clinical presentation (trisma, nuchal rigidity, and opisthotonus), a diagnosis of tetanus was suspected. Thus, the patient underwent a tetanus immunoglobulin immunization and antibiotic therapy with excellent clinical recovery.

Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

PubMed

Gillespie, Mary

2010-11-01

Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Clinical presentation of nasopharyngeal carcinoma in Sarawak Malaysia.

PubMed

Tiong, T S; Selva, K S

2005-12-01

Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia. The clinical presentation in Sarawak has not been well documented. A retrospective review of 213 selected NPC cases was undertaken on the clinical records in Sarawak General Hospital, Sarawak, from June 1999 to June 2003. There were 116 patients in Kuching and 97 in Serian. There were twice as many males as females. The youngest patient was 16 and the oldest 88 years old with a mean age of 51 years. The four most common symptoms in order of frequencies were cervical lymphadenopathy, epistaxis, hearing loss and diplopia. 80.8% of the patients presented with cervical lymphadenopathy and about 85% of the patients presented in the advanced stages. Very small percentages of the patients were found to have single presenting symptoms of epistaxis (2.4%) and hearing loss (0.5%).

Clinical judgement and the medical profession

PubMed Central

Kienle, Gunver S; Kiene, Helmut

2011-01-01

Objectives Clinical judgment is a central element of the medical profession, essential for the performance of the doctor, and potentially generating information also for other clinicians and for scientists and health care managers. The recently renewed interest in clinical judgement is primarily engaged with its role in communication, diagnosis and decision making. Beyond this issue, the present article highlights the interrelations between clinical judgement, therapy assessment and medical professionalism. Methods Literature review and theory development. Results The article presents different methodological approaches to causality assessment in clinical studies and in clinical judgement, and offers criteria for clinical single case causality. The article outlines models of medical professionalism such as technical rationality and practice epistemology, and characterizes features of professional expertise such as tacit knowledge, reflection in action, and gestalt cognition. Conclusions Consequences of a methodological and logistical advancement of clinical judgment are discussed, both in regard to medical progress and to the renewel of the cognitive basis of the medical profession. PMID:20973873

Clinical audit, a valuable tool to improve quality of care: General methodology and applications in nephrology.

PubMed

Esposito, Pasquale; Dal Canton, Antonio

2014-11-06

Evaluation and improvement of quality of care provided to the patients are of crucial importance in the daily clinical practice and in the health policy planning and financing. Different tools have been developed, including incident analysis, health technology assessment and clinical audit. The clinical audit consist of measuring a clinical outcome or a process, against well-defined standards set on the principles of evidence-based medicine in order to identify the changes needed to improve the quality of care. In particular, patients suffering from chronic renal diseases, present many problems that have been set as topics for clinical audit projects, such as hypertension, anaemia and mineral metabolism management. Although the results of these studies have been encouraging, demonstrating the effectiveness of audit, overall the present evidence is not clearly in favour of clinical audit. These findings call attention to the need to further studies to validate this methodology in different operating scenarios. This review examines the principle of clinical audit, focusing on experiences performed in nephrology settings.

Pedunculated and Telangiectatic Merkel Cell Carcinoma: An Unusual Clinical Presentation

PubMed Central

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-01-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect. PMID:23723504

The role of clinician emotion in clinical reasoning: Balancing the analytical process.

PubMed

Langridge, Neil; Roberts, Lisa; Pope, Catherine

2016-02-01

This review paper identifies and describes the role of clinicians' memory, emotions and physical responses in clinical reasoning processes. Clinical reasoning is complex and multi-factorial and key models of clinical reasoning within musculoskeletal physiotherapy are discussed, highlighting the omission of emotion and subsequent physical responses and how these can impact upon a clinician when making a decision. It is proposed that clinicians should consider the emotions associated with decision-making, especially when there is concern surrounding a presentation. Reflecting on practice in the clinical environment and subsequently applying this to a patient presentation should involve some acknowledgement of clinicians' physical responses, emotions and how they may play a part in any decision made. Presenting intuition and gut-feeling as separate reasoning methods and how these processes co-exist with other more accepted reasoning such as hypothetico-deductive is also discussed. Musculoskeletal physiotherapy should consider the elements of feelings, emotions and physical responses when applying reflective practice principles. Furthermore, clinicians dealing with difficult and challenging presentations should look at the emotional as well as the analytical experience when justifying decisions and learning from practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Problems and Processes in Medical Encounters: The CASES method of dialogue analysis

PubMed Central

Laws, M. Barton; Taubin, Tatiana; Bezreh, Tanya; Lee, Yoojin; Beach, Mary Catherine; Wilson, Ira B.

2013-01-01

Objective To develop methods to reliably capture structural and dynamic temporal features of clinical interactions. Methods Observational study of 50 audio-recorded routine outpatient visits to HIV specialty clinics, using innovative analytic methods. The Comprehensive Analysis of the Structure of Encounters System (CASES) uses transcripts coded for speech acts, then imposes larger-scale structural elements: threads – the problems or issues addressed; and processes within threads –basic tasks of clinical care labeled Presentation, Information, Resolution (decision making) and Engagement (interpersonal exchange). Threads are also coded for the nature of resolution. Results 61% of utterances are in presentation processes. Provider verbal dominance is greatest in information and resolution processes, which also contain a high proportion of provider directives. About half of threads result in no action or decision. Information flows predominantly from patient to provider in presentation processes, and from provider to patient in information processes. Engagement is rare. Conclusions In this data, resolution is provider centered; more time for patient participation in resolution, or interpersonal engagement, would have to come from presentation. Practice Implications Awareness of the use of time in clinical encounters, and the interaction processes associated with various tasks, may help make clinical communication more efficient and effective. PMID:23391684

Problems and processes in medical encounters: the cases method of dialogue analysis.

PubMed

Laws, M Barton; Taubin, Tatiana; Bezreh, Tanya; Lee, Yoojin; Beach, Mary Catherine; Wilson, Ira B

2013-05-01

To develop methods to reliably capture structural and dynamic temporal features of clinical interactions. Observational study of 50 audio-recorded routine outpatient visits to HIV specialty clinics, using innovative analytic methods. The comprehensive analysis of the structure of encounters system (CASES) uses transcripts coded for speech acts, then imposes larger-scale structural elements: threads--the problems or issues addressed; and processes within threads--basic tasks of clinical care labeled presentation, information, resolution (decision making) and Engagement (interpersonal exchange). Threads are also coded for the nature of resolution. 61% of utterances are in presentation processes. Provider verbal dominance is greatest in information and resolution processes, which also contain a high proportion of provider directives. About half of threads result in no action or decision. Information flows predominantly from patient to provider in presentation processes, and from provider to patient in information processes. Engagement is rare. In this data, resolution is provider centered; more time for patient participation in resolution, or interpersonal engagement, would have to come from presentation. Awareness of the use of time in clinical encounters, and the interaction processes associated with various tasks, may help make clinical communication more efficient and effective. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Clinical utility of histological features of polyomavirus allograft nephropathy.

PubMed

Gaber, Lillian W; Egidi, M Francesca; Stratta, Robert J; Lo, Agnes; Moore, Linda W; Gaber, A Osama

2006-07-27

The purpose of this study was to determine if histological features of polyomavirus allograft nephropathy (PVAN) are associated with the clinical presentation and outcomes of PVAN. We examined the histological features of initial and follow-up biopsies of 20 kidney and kidney-pancreas transplant recipients with PVAN during a time prior to routine surveillance. The subjects' demographics, clinical characteristics, and outcomes were compared based upon classification of histological features of PVAN on initial biopsy. Diabetes mellitus (45%) and a history of tacrolimus-induced nephrotoxicity (35%) appeared to be prevalent in subjects with PVAN. Although histological severity of PVAN did not predict or correlate with the clinical course of PVAN, subjects with pattern C on initial PVAN biopsy presented later posttransplant, had higher serum creatinine level at presentation, and had significant allograft deterioration at follow-up than subjects with either pattern A or B on initial biopsy. Resolution of PVAN was noted in 60% of follow-up biopsies and occurred more frequently in subjects with pattern B on initial biopsy. Most subjects developed chronic allograft nephropathy after PVAN and viral clearance did not abrogate the progression to chronic allograft nephropathy. These data indicate that histologic patterns of PVAN may have clinical correlation to disease presentation and prognosis.

Depression in Adults with Intellectual Disability: Symptoms and Challenging Behaviour

ERIC Educational Resources Information Center

Hurley, A. D.

2008-01-01

Background: Psychiatric evaluation of adults with intellectual disability (ID) remains complex because of limitations in verbal abilities, atypical clinical presentation and challenging behaviour. This study examines the clinical presentation of adults with depression compared with bipolar disorder, anxiety disorders and non-psychiatric control…

When a seizure is not a real seizure!

PubMed

Talebi, Soheila; Ghobadi, Farzaneh; Chaudhari, Sameer; Gracia, Ely; Olatunde, Ola; Pekler, Gerald; Visco, Ferdinand; Hassen, Getaw Worku

2016-04-01

We report here 2 cases of methadone induced Torsades de Pointes with a clinical presentation mimicking convulsive seizures in a substance abuser. These cases highlight the importance of being aware of methadone-induced Torsades de Pointes and the occasional atypical clinical presentations of this condition.

Paroxysmal Atrial Fibrillation in a Mission-Assigned Astronaut

NASA Technical Reports Server (NTRS)

Bauer, Peter A.; Polk, J. D.

2010-01-01

This presentation will explore the clinical and administrative conundrums faced by the flight surgeon upon discovering asymptomatic paroxysmal atrial fibrillation seven months prior to scheduled long duration spaceflight. The presenter will discuss the decision-making process as well as the clinical and operational outcomes.

Clinical manifestations of primary hyperthyroidism in the elderly patients at the out-patient clinic of Srinagarind Hospital.

PubMed

Limpawattana, Panita; Sawanyawisut, Kittisak; Mahankanukrau, Ajanee; Wongwipaporn, Chaiyasit

2006-02-01

The authors reviewed the outpatient charts diagnosed as hyperthyroidism at Srinagarind Hospital from June 1998-June 2004. The objective was to compare the clinical features of hyperthyroidism in patients older and younger than 60 years old. There were 922 cases enrolled, 84 cases (9.11%) were 60 years old and above. The female: male ratio was 3.4:1 and 4:1 and the mean ages were 64.2 +/- 3.7 and 37.4 +/- 11.2 years old in the elder and younger group, respectively. The common presentations were dyspnea (94.1, 96.5%), weight loss (93.8, 87.9%) and palpitation (83.3, 93.1%) in the elder and younger, respectively. The more significant clinical presentations in the elder group were atrial fibrillation, weakness and anorexia whereas exophthalmos, goiter, heat intolerance and hyperhidrosis were not as frequent. Thus, the classic presentations often lacked in the elder group. Therefore, unexplained AF, weakness and anorexia should not exclude hyperthyroidism even with paucity of typical clinical features.

Clinical management of occupational low back pain in Australia: what is the real picture?

PubMed

Hush, Julia M

2008-12-01

The aim of this study was to compare the clinical management of patients with occupational low back pain (LBP) presenting to secondary care practitioners in Australia with national and international practice guidelines. A consecutive cohort of 401 patients with LBP following a work injury was assembled at the time of referral to secondary rehabilitation. A comprehensive assessment was performed to collect demographic, clinical and occupational data, which were analysed using descriptive statistics. Clinical and occupational management data were compared with evidence-based guidelines for the management of LBP. This study revealed that in this cohort presenting to secondary care, referral for guideline-based active treatment was delayed until, on average, 10 months post-injury; radiographic investigations had been ordered for almost every patient, including those presenting in the first three months of their injury; the prevalence of co-morbidities was high and there were signs that psychological distress was under-diagnosed. This study reveals a lack of compliance with clinical guidelines for occupational back pain management in Australia.

[Bartonella henselae, an ubiquitous agent of proteiform zoonotic disease].

PubMed

Edouard, S; Raoult, D

2010-06-01

Bartonella henselae is the causative agent of cat scratch disease, a human infection usually characterized by persistent regional lymphadenopathy. It is transmitted to humans by cat scratches or bites. Cats are the major reservoir for this bacterium thus B. henselae has a worldwide distribution. The bacterial pathogenicity may bay emphasized by the immune status of the infected host. Angiomatosis or hepatic peliosis are the most frequent clinical manifestations in immunocompromised patients. B. henselae is also responsible for endocarditis in patients with valvular diseases, and may induce various clinical presentations such as: bacteriemia, retinitis, musculoskeletal disorders, hepatic or splenic diseases, encephalitis, or myocarditis. Several diagnostic tools are available; they may be combined and adapted to every clinical setting. B. henselae is a fastidious bacterium; its diagnosis is mainly made by PCR and blood tests. No treatment is required for the benign form of cat scratch disease. For more severe clinical presentations, the treatment must be adapted to every clinical presentation.

Music therapy with disorders of consciousness: current evidence and emergent evidence-based practice.

PubMed

Magee, Wendy L; O'Kelly, Julian

2015-03-01

Patients with prolonged disorders of consciousness (PDOC) stemming from acquired brain injury present one of the most challenging clinical populations in neurological rehabilitation. Because of the complex clinical presentation of PDOC patients, treatment teams are confronted with many medicolegal, ethical, philosophical, moral, and religious issues in day-to-day care. Accurate diagnosis is of central concern, relying on creative approaches from skilled clinical professionals using combined behavioral and neurophysiological measures. This paper presents the latest evidence for using music as a diagnostic tool with PDOC, including recent developments in music therapy interventions and measurement. We outline standardized clinical protocols and behavioral measures to produce diagnostic outcomes and examine recent research illustrating a range of benefits of music-based methods at behavioral, cardiorespiratory, and cortical levels using video, electrocardiography, and electroencephalography methods. These latest developments are discussed in the context of evidence-based practice in rehabilitation with clinical populations. © 2014 New York Academy of Sciences.

[Granulomatous sporotrichosis: report of two unusual cases].

PubMed

Ramírez-Soto, Max; Lizárraga-Trujillo, José

2013-10-01

Sporotrichosis is a subcutaneous mycosis caused by Sporothrix complex, endemic in Abancay, Peru. Is acquired by traumatic inoculation with plant material. Common clinical presentations are lymphatic cutaneous and fixed cutaneous disease. We report 2 cases of fixed cutaneous sporotrichosis with granulomatous appearance. The first case was a patient of 65 years old with no risk factors and the second case was a 67 year old diabetic patient. Subjects underwent mycological culture with Sabouraud agar, with isolation of Sporothrix schenckii and clinical dignosis of fixed cutaneous sporotrichosis with granulomatous appearance. One patient received oral treatment with saturated solution of potassium iodide (SSKI) with a initial dose of 3 drops tid up to a maximum dose of 40 drops tid. Mycological and clinical cure was achieved after 2 months of treatment. We should consider the unusual clinical presentations of fixed cutaneous sporotrichosis with granulomatous appearance that present morphological and clinical features in diabetic and nondiabetic patients older than 60 years from endemic areas and communicate adequate response to treatment with SSKI in one case.

Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.

PubMed

Lyon, Alexander R; Bossone, Eduardo; Schneider, Birke; Sechtem, Udo; Citro, Rodolfo; Underwood, S Richard; Sheppard, Mary N; Figtree, Gemma A; Parodi, Guido; Akashi, Yoshihiro J; Ruschitzka, Frank; Filippatos, Gerasimos; Mebazaa, Alexandre; Omerovic, Elmir

2016-01-01

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Is Diabetes a Risk Factor for a Severe Clinical Presentation of Dengue? - Review and Meta-analysis

PubMed Central

Htun, Nan Shwe Nwe; Odermatt, Peter; Eze, Ikenna C.; Boillat-Blanco, Noémie; D’Acremont, Valérie; Probst-Hensch, Nicole

2015-01-01

Background The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. Methodology/Findings A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08–2.84, p = 0.022). Conclusions/Significance Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue. PMID:25909658

Sleeping Sickness in Travelers - Do They Really Sleep?

PubMed Central

Urech, Karin; Neumayr, Andreas; Blum, Johannes

2011-01-01

The number of imported Human African Trypanosomiasis (HAT) cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed) using the terms “Human African Trypanosomiasis”, “travelers” and “expatriates”; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%), headache (50% each) and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%). While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%), diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none). Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%), motor deficit (64.3%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21.4%) or depression (21.4%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses and chancres are frequently seen. The diagnosis of HAT in Africans living outside the endemic region is often missed or delayed, leading to presentation with advanced stages of the disease. PMID:22069503

Sleeping sickness in travelers - do they really sleep?

PubMed

Urech, Karin; Neumayr, Andreas; Blum, Johannes

2011-11-01

The number of imported Human African Trypanosomiasis (HAT) cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed) using the terms "Human African Trypanosomiasis", "travelers" and "expatriates"; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%), headache (50% each) and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%). While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%), diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none). Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%), motor deficit (64.3%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21.4%) or depression (21.4%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses and chancres are frequently seen. The diagnosis of HAT in Africans living outside the endemic region is often missed or delayed, leading to presentation with advanced stages of the disease.

Frontal fibrosing alopecia in a postmenopausal woman.

PubMed

Lee, W S; Hwang, S M; Ahn, S K

1997-12-01

A case is presented of a 52-year-old woman in whom clinical and histopathologic findings suggested cicatricial alopecia. Our patient had an uncommon, but distinctive, clinical presentation. It was characterized by bandlike frontal hair loss. This was recently described as patterned cicatricial alopecia, presented in a recent study as postmenopausal frontal hairline recession with scarring. Our patient's case should be differentiated from recognized forms of scarring alopecia.

Cognitive Behavioral Treatment of Panic Disorder and Agoraphobia in a Multiethnic Urban Outpatient Clinic: Initial Presentation and Treatment Outcome

ERIC Educational Resources Information Center

Friedman, Steven; Braunstein, Jeffrey W.; Halpern, Beth

2006-01-01

Few studies examine the effectiveness of panic control treatment across diverse ethnic groups. In this paper we present data on 40 patients (African American, n = 24; Caucasian, n = 16) with panic disorder and comorbid agoraphobia who presented at an anxiety disorder clinic in an inner-city area. On initial assessment both groups were similar on…

Clinical Cancer Genetics and Prevention

Cancer.gov

Olufunmilayo F. Olopade MD, FACP, Professor of Medicine and Human Genetics and Director of the Cancer Risk Clinic Department of Medicine, BSD Section of Hematology/Oncology University of Chicago, presented "Clinical Cancer Genetics and Prevention".

Nursing students' viewpoints toward two methods of clinical conference and clinical nursing round.

PubMed

Gheidanzadeh, Maryam; Baghersad, Zahra; Abazari, Parvaneh

2017-01-01

Clinical education provides a chance to combine theoretical knowledge and clinical skills. Students are the key elements in the evaluation of clinical education efficacy. The present study was aimed to define nursing students' viewpoints concerning conformity to the characteristics of clinical conference and clinical round. This descriptive analytical study was conducted on the bachelor's students of the 4 th -6 th semester of nursing. Sampling was conducted using census sampling method during the 2 nd semester of 2014-2015 school year. Data collection tool was a three-section researcher-made questionnaire containing demographic, nursing round, and clinical conference characteristics. Descriptive and inferential statistical tests (independent t -test, ANOVA, and Spearman and Pearson correlation coefficients) were used for data analysis. Participants were 134 bachelor's students of the 4 th -6 th semester of nursing. According to half of the participants, conformity to the characteristics of clinical conference (45.5%, 53%) and clinical round (44%, 51.5%) were poor and medium, respectively. Paired t -test showed a significant difference between students' viewpoints toward the planning of clinical conference and clinical nursing round ( P = 0.006, t = 2.77). According to the results of the present study on students' viewpoints, clinical education faces a serious challenge with regard to clinical education methods. Considering the necessity and importance of clinical education, more investigation should be conducted to detect its relevant factors and plan for its improvement.

Development of Multimedia Computer Applications for Clinical Pharmacy Training.

ERIC Educational Resources Information Center

Schlict, John R.; Livengood, Bruce; Shepherd, John

1997-01-01

Computer simulations in clinical pharmacy education help expose students to clinical patient management earlier and enable training of large numbers of students outside conventional clinical practice sites. Multimedia instruction and its application to pharmacy training are described, the general process for developing multimedia presentations is…

Familial spinal neurofibromatosis due to a multiexonic NF1 gene deletion.

PubMed

Pizzuti, Antonio; Bottillo, Irene; Inzana, Francesca; Lanari, Valentina; Buttarelli, Francesca; Torrente, Isabella; Giallonardo, Anna Teresa; De Luca, Alessandro; Dallapiccola, Bruno

2011-08-01

We report the detailed clinical presentation and molecular features of a spinal neurofibromatosis familial case where a 40-year-old woman, presenting with multiple bilateral spinal neurofibromas and no other clinical feature of neurofibromatosis type 1 (NF1), inherited a paternal large multiexonic deletion (c.5944-?_7126+?del) which resulted in NF1 gene haploinsufficiency at the RNA level. In the clinically unaffected 73-year-old father, spinal cord MRI disclosed bilateral and symmetrical hypertrophy of spinal lumbosacral roots. Our study widens the phenotypic and mutational spectrum of NF1 and illustrates the difficulties of counseling patients with border-line or atypical presentation of this disorder.

Unraveling Diagnostic Uncertainty Surrounding Lyme Disease in Children with Neuropsychiatric Illness.

PubMed

Koster, Michael P; Garro, Aris

2018-01-01

Lyme disease is endemic in parts of the United States, including New England, the Atlantic seaboard, and Great Lakes region. The presentation has various manifestations, many of which can mimic psychiatric diseases in children. Distinguishing manifestations of Lyme disease from those of psychiatric illnesses is complicated by inexact diagnostic tests and misuse of these tests when they are not clinically indicated. This article aims to describe manifestations of Lyme disease in children with an emphasis on Lyme neuroborreliosis. Clinical scenarios will be presented and discussed. Finally, recommendations for clinical psychiatrists who encounter children with possible Lyme disease are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

'BeAWARE': supporting non-clinical staff within general practice to promptly identify patients presenting with warning signs of heart attack or stroke.

PubMed

Poulter, Christopher; Stewart, Michelle; Fitzpatrick, Cliona; Keech, Wendy; Stavreski, Bill; Grenfell, Robert

2014-06-01

General practice requires systems to deal with patients presenting with urgent needs. BeAWARE was developed to support non-clinical staff to promptly identify patients with symptoms of heart attack or stroke. Data were collected from May 2012 to December 2012 on participants completing the BeAWARE learning module, including pre- and post-assessments on knowledge, confidence and intended action. From May 2012 to December 2012, 1865 participants completed the module. There were significant increases in recall of heart attack and stroke symptoms among non-clinical participants, including chest tightness (23.4-48.7%, P DISCUSSION: BeAWARE fulfils a practice gap in patient safety by improving non-clinical staff's knowledge, confidence and intended action in response to patients presenting with heart attack or stroke warning signs.

National Institutes of Health eliminates funding for national architecture linking primary care research.

PubMed

Peterson, Kevin A

2007-01-01

With the ending of the National Electronic Clinical Trial and Research Network (NECTAR) pilot programs and the abridgement of Clinical Research Associate initiative, the National Institutes of Health Roadmap presents a strategic shift for practice-based research networks from direct funding of a harmonized national infrastructure of cooperating research networks to a model of local engagement of primary care clinics performing practice-based research under the aegis of regional academic health centers through Clinical and Translational Science Awards. Although this may present important opportunities for partnering between community practices and large health centers, for primary care researchers, the promise of a transformational change that brings a unified national primary care community into the clinical research enterprise seems likely to remain unfulfilled.

FRAX(®) Clinical Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

PubMed

McCloskey, Eugene V; Binkley, Neil

2011-01-01

The World Health Organization fracture risk assessment tool, FRAX(®), is an advance in clinical care that can assist in clinical decision-making. However, with increasing clinical utilization, numerous questions have arisen regarding how to best estimate fracture risk in an individual patient. Recognizing the need to assist clinicians in optimal use of FRAX(®), the International Osteoporosis Foundation (IOF) in conjunction with the International Society for Clinical Densitometry (ISCD) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX(®) usage. As part of the process, the charge of the FRAX(®) Clinical Task Force was to review and synthesize data surrounding a number of recognized clinical risk factors including rheumatoid arthritis, smoking, alcohol, prior fracture, falls, bone turnover markers and glucocorticoid use. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the Clinical Task Force composition and charge is presented here. Copyright © 2011. Published by Elsevier Inc.

Implementation of a Clinical Reasoning Course in the Internal Medicine trimester of the final year of undergraduate medical training and its effect on students' case presentation and differential diagnostic skills.

PubMed

Harendza, Sigrid; Krenz, Ingo; Klinge, Andreas; Wendt, Ulrike; Janneck, Matthias

2017-01-01

Background: Clinical reasoning, comprising the processes of clinical thinking, which form the basis of medical decisions, constitutes a central competence in the clinical routine on which diagnostic and therapeutic steps are based. In medical curricula in Germany, clinical reasoning is currently taught explicitly only to a small extend. Therefore, the aim of this project was to develop and implement a clinical reasoning course in the final year of undergraduate medical training. Project description: A clinical reasoning course with six learning units and 18 learning objectives was developed, which was taught by two to four instructors on the basis of 32 paper cases from the clinical practice of the instructors. In the years 2011 to 2013, the course of eight weeks with two hours per week was taught seven times. Before the first and after the last seminar, the participating students filled out a self-assessment questionnaire with a 6-point Likert scale regarding eight different clinical reasoning skills. At the same times, they received a patient case with the assignment to prepare a case presentation and differential diagnoses. Results: From 128 participating students altogether, 42 complete data sets were available. After the course, participants assessed themselves significantly better than before the course in all eight clinical reasoning skills, for example in "Summarizing and presentation of a paper case" or in the "Skill to enumerate differential diagnoses" (p<0.05). The greatest increase occurred in the skill to recognize typical cognitive errors in medicine and to identify risk situations for their occurrence (pre: 2.98±0.92 and retro-pre: 2.64±1.01, respectively, versus post: 4.38±0.88). Based on the ratio of number of words used per keywords used the problem presentation of the paper case was significantly more focused after the course (p=0.011). A significant increase in the number of gathered differential diagnoses was not detected after the course. Conclusion: The newly developed and established Clinical Reasoning Course leads to a gain in the desired skills from the students' self-assessment perspective and to a more structured case presentation. To establish better options to exercise clinical reasoning, a longitudinal implementation in the medical curriculum seems to be desirable. Faculty training would be useful to implement the concept as standardized as possible.

Implementation of a Clinical Reasoning Course in the Internal Medicine trimester of the final year of undergraduate medical training and its effect on students' case presentation and differential diagnostic skills

PubMed Central

Harendza, Sigrid; Krenz, Ingo; Klinge, Andreas; Wendt, Ulrike; Janneck, Matthias

2017-01-01

Background: Clinical reasoning, comprising the processes of clinical thinking, which form the basis of medical decisions, constitutes a central competence in the clinical routine on which diagnostic and therapeutic steps are based. In medical curricula in Germany, clinical reasoning is currently taught explicitly only to a small extend. Therefore, the aim of this project was to develop and implement a clinical reasoning course in the final year of undergraduate medical training. Project description: A clinical reasoning course with six learning units and 18 learning objectives was developed, which was taught by two to four instructors on the basis of 32 paper cases from the clinical practice of the instructors. In the years 2011 to 2013, the course of eight weeks with two hours per week was taught seven times. Before the first and after the last seminar, the participating students filled out a self-assessment questionnaire with a 6-point Likert scale regarding eight different clinical reasoning skills. At the same times, they received a patient case with the assignment to prepare a case presentation and differential diagnoses. Results: From 128 participating students altogether, 42 complete data sets were available. After the course, participants assessed themselves significantly better than before the course in all eight clinical reasoning skills, for example in “Summarizing and presentation of a paper case” or in the “Skill to enumerate differential diagnoses” (p<0.05). The greatest increase occurred in the skill to recognize typical cognitive errors in medicine and to identify risk situations for their occurrence (pre: 2.98±0.92 and retro-pre: 2.64±1.01, respectively, versus post: 4.38±0.88). Based on the ratio of number of words used per keywords used the problem presentation of the paper case was significantly more focused after the course (p=0.011). A significant increase in the number of gathered differential diagnoses was not detected after the course. Conclusion: The newly developed and established Clinical Reasoning Course leads to a gain in the desired skills from the students’ self-assessment perspective and to a more structured case presentation. To establish better options to exercise clinical reasoning, a longitudinal implementation in the medical curriculum seems to be desirable. Faculty training would be useful to implement the concept as standardized as possible. PMID:29226234

Determinants and Long-Term Outcomes of Percutaneous Coronary Interventions vs. Surgery for Multivessel Disease According to Clinical Presentation.

PubMed

Hong, Sung-Jin; Kim, Byeong-Keuk; Shin, Sanghoon; Suh, Yongsung; Kim, Seunghwan; Ahn, Chul-Min; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

2018-03-23

The long-term outcome of percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG), particularly for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), remains controversial.Methods and Results:We retrospectively analyzed 2,827 patients (stable coronary artery disease [SCAD], n=1,601; NSTE-ACS, n=1,226) who underwent either PCI (n=1,732) or CABG (n=1,095). The 8-year composite of cardiac death and myocardial infarction (MI) was compared between PCI and CABG before and after propensity matching. For patients with NSTE-ACS, PCI was performed more frequently for those with higher Thrombolysis in Myocardial Infarction risk score and 3-vessel disease, and PCI led to significantly higher 8-year composite of cardiac death and MI than CABG (14.1% vs. 5.9%, hazard ratio [HR]=2.22, 95% confidence interval [CI]=1.37-3.58, P=0.001). There was a significant interaction between clinical presentation and revascularization strategy (P-interaction=0.001). However, after matching, the benefit of CABG vs. PCI was attenuated in patients with NSTE-ACS, whereas it was pronounced in those with SCAD. Interactions between clinical presentation and revascularization strategy were not observed (P-interaction=0.574). Although the determinants of PCI vs. CABG in real-world clinical practice differ according to the clinical presentation, a significant interaction between clinical presentation and revascularization strategy was not noted for long-term outcomes. The revascularization strategy for patients with NSTE-ACS can be based on the criteria applied to patients with SCAD.

Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients.

PubMed

Ebner, Lukas; Walti, Laura N; Rauch, Andri; Furrer, Hansjakob; Cusini, Alexia; Meyer, Andreas M J; Weiler, Stefan; Huynh-Do, Uyen; Heverhagen, Johannes; Arampatzis, Spyridon; Christe, Andreas

2016-01-01

Pneumocystis jirovecii pneumonia (PCP) is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV) infection and renal transplant recipients (RTRs). We conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared. Forty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02), more ground glass nodules 5-10 mm (69% vs. 4%; p = <0.001) and enlarged hilar lymph nodes were found only in HIV patients (44%). Cough and dyspnea were the most common clinical signs (>80%) in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02)), implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable. While important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success.

Special Education Microteaching Clinic: Final Report.

ERIC Educational Resources Information Center

Shea, Thomas M.; And Others

Presented is the final report on the Special Education Microteaching Clinic at Southern Illinois University (Edwardsville) which incorporates a practice teaching technique in which a student teaches a lesson, is critiqued and shown a videotape, then reteaches the lesson. Section I, the overview, includes a presentation of the Microteaching…

77 FR 49865 - Geriatrics and Gerontology Advisory Committee, Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

... Clinical Centers. No time will be allocated at this meeting for receiving oral presentations from the... Veterans and evaluates VA programs designated as Geriatric Research, Education, and Clinical Centers. The meeting will feature presentations and discussions on VA's geriatrics and extended care programs, aging...

Bleeding Duodenal: Varices Treatment by TIPS and Transcatheter Embolization

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

Lopera, Jorge E.; Arthurs, Blain; Scheuerman, Christian

2008-03-15

We describe our clinical experience in 4 patients with portal hypertension who presented with bleeding mesenteric varices originating from the superior mesenteric vein with retrograde filling of collaterals draining into the inferior vena cava. The clinical presentation, imaging findings, and potential therapeutic management are discussed.

[Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

PubMed

Renisch, B; Lauer, W

2014-12-01

An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

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.

Assessing mental imagery in clinical psychology: A review of imagery measures and a guiding framework

PubMed Central

Pearson, David G.; Deeprose, Catherine; Wallace-Hadrill, Sophie M.A.; Heyes, Stephanie Burnett; Holmes, Emily A.

2013-01-01

Mental imagery is an under-explored field in clinical psychology research but presents a topic of potential interest and relevance across many clinical disorders, including social phobia, schizophrenia, depression, and post-traumatic stress disorder. There is currently a lack of a guiding framework from which clinicians may select the domains or associated measures most likely to be of appropriate use in mental imagery research. We adopt an interdisciplinary approach and present a review of studies across experimental psychology and clinical psychology in order to highlight the key domains and measures most likely to be of relevance. This includes a consideration of methods for experimentally assessing the generation, maintenance, inspection and transformation of mental images; as well as subjective measures of characteristics such as image vividness and clarity. We present a guiding framework in which we propose that cognitive, subjective and clinical aspects of imagery should be explored in future research. The guiding framework aims to assist researchers in the selection of measures for assessing those aspects of mental imagery that are of most relevance to clinical psychology. We propose that a greater understanding of the role of mental imagery in clinical disorders will help drive forward advances in both theory and treatment. PMID:23123567

Dis-integration of communication in healthcare education: Workplace learning challenges and opportunities.

PubMed

Rosenbaum, Marcy E

2017-11-01

The purpose of this paper, based on a 2016 Heidelberg International Conference on Communication in Healthcare (ICCH) plenary presentation, is to examine a key problem in communication skills training for health professional learners. Studies have pointed to a decline in medical students' communication skills and attitudes as they proceed through their education, particularly during their clinical workplace training experiences. This paper explores some of the key factors in this disintegration, drawing on selected literature and highlighting some curriculum efforts and research conducted at the University of Iowa Carver College of Medicine as a case study of these issues. Five key factors contributing to the disintegration of communication skills and attitudes are presented including: 1) lack of formal communication skills training during clinical clerkships; 2) informal workplace teaching failing to explicitly address learner clinical communication skills; 3) emphasizing content over process in relation to clinician-patient interactions; 4) the relationship between ideal communication models and the realities of clinical practice; and 5) clinical teachers' lack of knowledge and skills to effectively teach about communication in the clinical workplace. Within this discussion, potential practical responses by individual clinical teachers and broader curricular and faculty development efforts to address each of these factors are presented. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene therapy clinical trials worldwide to 2017: An update.

PubMed

Ginn, Samantha L; Amaya, Anais K; Alexander, Ian E; Edelstein, Michael; Abedi, Mohammad R

2018-03-25

To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward. Copyright © 2018 John Wiley & Sons, Ltd.

A novel and dedicated multidisciplinary service to manage breech presentation at term; 3 years of experience in a tertiary care maternity unit.

PubMed

Hickland, Patrick; Gargan, Phyl; Simpson, Jacquie; McCabe, Niamh; Costa, Janitha

2017-08-09

In order to provide uniform and unbiased multidisciplinary counselling on the options available, including vaginal breech delivery (VBD) and external cephalic version (ECV), the latter of which could then be performed, a weekly Breech Clinic was introduced to a tertiary care maternity unit in Northern Ireland in June 2013, replacing the traditional ECV Clinic introduced in June 2012. Retrospective data collection was undertaken using clinic proformas, Northern Ireland Maternity System data and case notes of women who attended the clinics (ECV and Breech) from June 2012 to May 2015. There were 434 referrals to the clinic over the 3-year period; 356 women attended. The proportion of women attending increased from 69% to 85% since the introduction of the Breech Clinic. Two hundred and thirty-two were deemed eligible and 179 of these underwent ECV after counselling. Although the proportion of women undergoing ECV decreased from 69% to 46%, 11 women opted for and achieved VBD during the 2 years of the Breech Clinic, compared with one woman in the year of the ECV Clinic. Seventy-one of the attempted ECVs were successful, with 61 women having a normal vaginal delivery. Notably, the success rate of ECV increased from 33% to 42%. The number of caesarean sections performed solely for breech at term decreased from 199 in the 12 months before the introduction of ECV clinic, to 188 during the ECV clinic, and 154 in the final 12 months of Breech Clinic. A dedicated service to counsel women on the management of breech presentation can decrease caesarean sections for breech presentation through increased uptake and success of ECV, and encouraging suitable women to opt for VBD when ECV is unsuccessful, contraindicated or declined.

Clinical Presentation and Outcome of Patients With Optic Pathway Glioma.

PubMed

Robert-Boire, Viviane; Rosca, Lorena; Samson, Yvan; Ospina, Luis H; Perreault, Sébastien

2017-10-01

Optic pathway gliomas (OPGs) occur sporadically or in patients with neurofibromatosis type 1 (NF1). The purpose of this study was to evaluate the clinical presentation at diagnosis and at progression of patients with OPGs. We conducted a chart review of patients with OPGs diagnosed in a single center over a period of 15 years. Demographic data including age, sex, NF1 status, clinical presentation, and outcome were collected. Of the 40 patients who were identified, 23 had sporadic tumors (57.5%) and 17 had NF1-related tumors (42.5%). Among the children with NF1, there was a significant overrepresentation of girls (82.3%) (P = 0.02), while among the children without NF1, there were slightly more boys (56.5%) than girls (43.5%). The presence of nystagmus was strongly associated with sporadic optic pathway gliomas. Poor visual outcome was related to tumor affecting both optic pathways, hydrocephalus at diagnosis, and optic nerve atrophy. Of the 40 patients, five died of OPG complications (12.5%) and all had sporadic tumors. Our cohort is one of the largest with OPGs and a detailed description of the clinical presentation both at diagnosis and at progression. We observed a significant difference between sporadic and NF1 optic pathway gliomas in terms of demographics, clinical presentation, and outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Tacrolimus Optic Neuropathy.

PubMed

Rasool, Nailyn; Boudreault, Katherine; Lessell, Simmons; Prasad, Sashank; Cestari, Dean M

2018-06-01

Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. Case series and review of the literature. We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.

77 FR 61767 - The Science of Small Clinical Trials; Notice of Course

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

...] The Science of Small Clinical Trials; Notice of Course AGENCY: Food and Drug Administration, HHS... announcing a course entitled ``The Science of Small Clinical Trials.'' The course is intended to present an overall framework and provide training in the scientific aspects of designing and analyzing clinical...

Microwave and radiofrequency techniques for clinical hyperthermia.

PubMed Central

Cheung, A. Y.

1982-01-01

Biological and practical constraints on the use of clinical hyperthermia for the management of cancer are discussed. Commonly used electromagnetic techniques for producing clinical hyperthermia are reviewed and compared. Innovative engineering designs leading to the realization of an integrated, safe and reliable clinical hyperthermia system are also presented. PMID:6950753

Panic Disorder in Clinically Referred Children and Adolescents

ERIC Educational Resources Information Center

Doerfler, Leonard A.; Connor, Daniel F.; Volungis, Adam M.; Toscano, Peter F., Jr.

2007-01-01

The present study examined the frequency and characteristics of panic disorder in children and adolescents who had been referred to a pediatric psychopharmacology clinic. Of the 280 children and adolescents evaluated in this clinic, 35 were diagnosed with panic disorder using a semi-structured clinical interview (K-SADS) and other objective…

Anterior cruciate ligament injury: A persistently difficult diagnosis.

PubMed

Parwaiz, Hammad; Teo, Alex Q A; Servant, Christopher

2016-01-01

Historically anterior cruciate ligament (ACL) injuries have been diagnosed poorly. A paper published in Injury in 1996 showed that less than 10% of patients with an ACL injury had the diagnosis made by the first physician to see them and that the average delay from first presentation to diagnosis was 21 months. The aim of our study was to investigate whether an improvement has been made over the last two decades in diagnosing ACL injuries. We identified 160 patients who had an ACL reconstruction performed by a single surgeon between October 2004 and December 2011 and for whom a complete data set was available. Data was extracted retrospectively from the hospital notes and a dedicated patient database. We performed a sub-group analysis comparing patients seen prior to the introduction of an acute knee injury clinic in April 2007 and patients seen after the introduction of the clinic. 75.1% (120/160) of patients presented first to an emergency department (ED) or to their general practitioner (GP), but only 14.4% (23/160) were diagnosed on initial presentation. The median number of healthcare professionals a patient saw prior to a diagnosis of ACL injury was 3. The median delay from injury to presentation was 0 weeks (range 0-885), injury to diagnosis 13 weeks (0-926), presentation to diagnosis 10 weeks (0-924), presentation to a specialist knee clinic 24 weeks (0-1006), and specialist knee clinic to surgery 13 weeks (0-102). The median total time from injury to surgery was 42 weeks (0-1047). Following the implementation of an acute knee injury clinic in 2007, the median delay from presentation to surgery dropped from 59 weeks to 36 weeks (p = 0.050) and there was a significant decrease in the median delay from specialist knee clinic to surgery from 23 to 11 weeks (p=0.002). Over the past two decades there appears to have been little improvement in the early diagnosis of ACL injuries, with only 14.4% of patients being diagnosed correctly at initial presentation. We recommend further education of emergency and primary care clinicians in the diagnosis of ACL injuries, emphasising the importance of the typical history of an ACL injury. The implementation of an acute knee injury clinic may help minimise delays to surgery, which should result in better patient outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

The presentation of rickets to orthopaedic clinics: return of the English disease.

PubMed

Naseem, Haris; Wall, Alun P; Sangster, Marshall; Paton, Robin W

2011-04-01

Rickets is a potentially treatable disease of the bone that is most commonly due to deficiency of vitamin D and is increasing in incidence in developed countries. Risk factors include dietary factors, the practice of covering up and darker skin pigmentation. This small retrospective case study set out to examine all cases of rickets presenting to the Paediatric Orthopaedic clinic over a 15-month period. Rickets presented in a bimodal fashion in the 6 cases identified: in males and females aged 3 or less and female adolescents aged 10 and above. This is in keeping with what is known regarding the rapid phases of growth during development. Five cases were from ethnic minority groups. Both female adolescents presented with genu valgum. Rickets can present primarily to Orthopaedic clinics with vague musculoskeletal symptoms. We recommend that biochemical screening be performed on patients from ethnic minorities who may be 'at risk'.

[Clinical laboratory tests supporting respiratory disease treatment--chairman's introductory remarks].

PubMed

Takai, Daiya

2014-12-01

The symposium consisted of four parts: history of lung function tests, nitric oxide for diagnosis and monitoring of bronchial asthma, radiological and functional changes of the lung in COPD, and combined pulmonary fibrosis and emphysema (CPFE) occasionally showing almost normal results in lung function tests. The history of lung function tests was presented by Dr. Naoko Tojo of the Tokyo Medical and Dental University. Nitric oxide tests in clinical use for diagnosis and monitoring of bronchial asthma were presented by Dr. Hiroyuki Nagase of Teikyo University. Radiological and functional changes of the lung in COPD were presented by Dr. Shigeo Muro of Kyoto University. Clinical features of combined pulmonary fibrosis and emphysema and their associated lung function were presented by Dr. Daiya Takai of the University of Tokyo. I hope that discussing the history of lung function tests until the present was useful for many medical technologists. (Review).

Clinical interventions for late-life anxious depression.

PubMed

Diefenbach, Gretchen J; Goethe, John

2006-01-01

Anxiety symptoms are frequently present in patients with late-life depression. The designation "anxious depression" has been used to describe major depressive disorder (MDD) accompanied by clinically significant but subsyndromal anxiety symptoms. MDD may also present comorbid with diagnosable anxiety disorders, although this presentation is less common in late life. Diagnosis of anxious depression in the elderly is complicated by several factors (eg, their tendency to experience and report psychiatric symptoms as somatic illness) and is associated with a more severe clinical presentation, increased risk for suicidal ideation, increased disability, and poorer prognosis. Standard pharmacotherapy for depression may be sufficient but for many patients must be modified or augmented. Psychosocial interventions may also be an important component in the treatment of these patients, although no specific psychosocial treatments have been developed for late-life anxious depression.

Clinical predictors of high risk histopathology in retinoblastoma.

PubMed

Kashyap, Seema; Meel, Rachna; Pushker, Neelam; Sen, Seema; Bakhshi, Sameer; Sreenivas, Vishnubhatla; Sethi, Sumita; Chawla, Bhavna; Ghose, Supriyo

2012-03-01

Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma. We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF. Three hundred twenty-six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis. Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study. Copyright © 2011 Wiley Periodicals, Inc.