Juvenile form of alexander disease caused by a previously undescribed mutation in the GFAP gene. a case report

Alexander disease is a form of leukoencephalopathy caused by mutations in the GFAP gene. There are three forms of the disease: infant, juvenile and adult. We present the clinical case of a patient born in 2004 (16 years old) with a debut of the disease at the age of 4 years with complex ticks. further neurological symptoms progressed and appeared atactic gait, intention tremor by performing coordination tests, muscle hypotension, decreased tendon reflexes, nasal voices, and behavior changes.Magnetic resonance imaging revealed changes in the white matter of both frontal lobes. An analysis was made of 59 genes of the panel “Leukodystrophy/leukoencephalopathy” by the method of mass parallel sequencing on the Ion S5. A mutation of the GFAP gene (Nm_002055), 4 exon c.758C>A, p.ALA253Asp in a heterozygous state, not described in Human Gene mutation Database, was detected. The patient was confirmed to have a diagnosis of Alexander disease. According to tractography, a decrease in the number of fibers in the frontal lobes was found.The patient is currently receiving symptomatic treatment.

Men with FMR1 premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset condition characterised by cerebellar ataxia and intention tremor, usually found in individuals with FMR1 premutation alleles (PM—CGG expansion of 55–199 repeats). Population studies estimate that between 1 in 250 and 1 in 1600 men have a PM, with up to 45% of these men suggested to develop FXTAS by age 80. We used a Bayesian approach to compare the probability of finding a specific PM genotype in an ataxia population to a population control group and found an estimated penetrance of <1% (0.031%; CI 0.007% to 0.141%) for men with ≤70 CGGs. These findings suggest that men with a PM of ≤70 CGGs, who comprise the vast majority of those with a PM, have a much lower risk of being affected with FXTAS than previously suggested. This is an issue of growing importance for accurate genetic counselling, as those with a PM of ≤70 CGGs are increasingly detected through community carrier screening or neurodevelopmental assessment programmes.

A state hospital survey of movement disorders including intention tremor

AimsIn a survey of movement disorders in patients in a State Hospital the finger-nose test was included because of increasing interest in the cerebellum in schizophrenia. It was expected that this would reflect the pathobiology of schizophrenia and be unrelated to the type of medication.BackgroundAbnormalities of movement and involuntary movements have gone from being considered part of schizophrenia to side-effects of medication to now demonstrably present in those who have never taken anti-psychotic medication. Soft neurological signs (SNS) are increased in schizophrenia, unrelated to medication, considered not to indicate brain localization, yet often include the finger-nose test which localizes to the cerebellum.MethodAll available patients in a State Hospital were examined for movement disorders. They were rated on the following scales: Abnormal Involuntary Movement Scale (AIMS) for Tardive Dyskinesia (TD), Simpson-Angus Neurological Rating Scale for Parkinsonism (SANRS), Barnes Akathisia Scale (BAS), a Dystonia scale and the finger-nose test.Result250 patients were included, 174 were examined or observed for movement disorder: 120 had no missing data, 54 refused part of the exam. Their mean age was 47, 62% male, 53% black, 26% Hispanic, 17% white.Medication: First Generation Antipsychotic (FGA) 35 (mean CPZ equivalent dose:1177mg), Second Generation Antipsychotic (SGA) 159 (734mg), both FGA and SGA 56 (1907mg), no antipsychotic 3; anticholinergic or amantidine: FGA 57%, SGA 16%, both FGA and SGA: 50%.Tardive Dyskinesia: all 23%, FGA 36%, SGA 25%, both 7%Parkinsonism: all 38%, FGA 43%, SGA 33%, both 34%Akathisia: all 3%, FGA 0%, SGA 4%, both 3%Pseudo-akathisia: FGA 11%, SGA 4%, both13%Dystonia: all 10%, FGA 13%, SGA 11%, both 8%Intention Tremor: all 16%, FGA 0%, SGA 21%, both 16%Half of those with Intention Tremor had Parkinsonism, a third had TD and a half were on anti-Parkinson medication.None of these differences were statistically significant at p = 0.05 though intention tremor did show a trend (p = 0.08). The difference between FGA and SGA only became significant when all movement disorders were added together with those on anticholinergics with no movement disorder.When compared with rates in similar State Hospitals in the 1970s tardive dyskinesia was now half the rate and Parkinsonism about the same.ConclusionOverall rates of movement disorder are not very different between FGA and SGA. The surprise was that intention tremor only occurred with SGAs. Why?

Myoclonus Associated with Celiac Disease Responsive to Anti-Epileptics and a Gluten-Free Diet

We report on the case of a 61-year-old male who initially presented with a progressive myoclonus and an intention tremor and was subsequently diagnosed with celiac disease. His neurological symptoms improved with anti-epileptic therapy and a gluten-free diet. Possible explanations include a milder disease phenotype or an epileptic component to his myoclonic movement disorder. This case highlights findings of a progressive myoclonic movement disorder, likely linked to celiac disease, and stresses the importance of a gluten-free diet in the management of the neurological manifestations of celiac disease.

Transcranial Direct Current Stimulation Combined with Botulinum Neurotoxin Type A Injections for Treatment of Upper Limb Intention Tremor in Multiple Sclerosis: A Case Report

Upper limb intention tremor is a common cause of disability in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) is an emerging form of brain stimulation used to improve sensorimotor impairments in many neurological disorders. Here, we describe a combined therapeutic approach with botulinum neurotoxin type A (BoNT-A) and tDCS for the treatment of upper limb tremor in a patient with MS. We administered a cathodal tDCS 15 days after the injections of BoNT-A. Both post-injection and post-stimulation evaluation revealed a considerable improvement of the tremor. This approach positively affected the patient’s activities of daily living. Our case report shows a safe and beneficial effect of tDCS in the treatment of action tremor in MS especially as a possible adjunctive synergic treatment with BoNT-A injections.

Fragile-X-Associated Tremor/Ataxia Syndrome or Alcohol-Induced Cerebellar Degeneration? A Case Report

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that manifests with intention tremor, progressive gait ataxia, and cognitive impairment. The disease is genetically characterized by a premutation of the <i>FMR1</i>gene on the X-chromosome manifesting with a CGG triplet expansion between 55 and 200. Given the phenotypical variety of this disease, diagnosis is frequently delayed. We present and discuss a male patient whose diagnosis of FXTAS was delayed due to his concomitant alcohol abuse.

Endurance of Short Pulse Width Thalamic Stimulation Efficacy in Intention Tremor

The benefit of short pulse width stimulation in patients suffering from essential tremor (ET) refractory to thalamic deep brain stimulation remains controversial. Here, we add to the minimal body of evidence available by reporting the effect of this type of stimulation in 3 patients with a persistent and severe intention tremor component despite iterative DBS setting adjustments. While a reduction in pulse width to 30 μs initially showed promise in these patients by improving tremor control and mitigating cerebellar side effects arguably by widening the therapeutic window, these benefits seemed to dissipate during early follow-up. Our experience supports the need for measuring longer-term outcomes when reporting the usefulness of this mode of stimulation in ET.

A Case Report of Coronavirus Disease 2019 Presenting with Tremors and Gait Disturbance

Introduction: Neurologic symptoms present as significant complications of coronavirus disease 2019 (COVID-19) infection. This report describes a novel manifestation of tremors triggered by severe acute respiratory syndrome coronavirus 2 infection. Case Presentation: We describe a case of a 46-year-old man with COVID-19 infection complicated by a bilateral intention tremor and wide-based gait. Although neurological manifestations have been reported related to COVID-19, tremulousness has not yet been described. Conclusion: Considering the evolving diversity of neurologic manifestations in this infection, emergency physicians should be vigilant of possible COVID-19 infection in patients presenting with unexplained neurologic symptoms.