Late-onset Tay-Sachs disease presenting with a neuromuscular phenotype-a case series.

BACKGROUND AND PURPOSE: Tay-Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in ß-hexosaminidase leads to accumulation of GM2 ganglioside resulting in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late-onset Tay-Sachs disease (LOTS) is extremely rare, especially in the non-Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms. CASES: A case series of four unrelated patients of non-Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients. CONCLUSION: This case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.

The Diagnostic Yield of Electromyography at Detecting Abnormalities on Muscle Biopsy: A Single Center Experience.

Historically, electromyography (EMG) is utilized early in the diagnostic evaluation of neuromuscular disorders, but its importance may be diminishing with more sophisticated genetic, imaging and immunohistochemistry investigations now available. In the present study, the diagnostic yield of EMG at predicting pathological abnormalities confirmed by muscle biopsy was determined at our neuroscience center. A retrospective study of consecutive cases reviewed at neuromuscular multidisciplinary meetings between 2007 and 2016 identified patients who had EMG and muscle biopsy as part of their diagnostic evaluation. EMG and biopsy findings were categorized as myopathic, neurogenic or normal. The diagnostic accuracy was determined by calculating the concordance between EMG and pathological findings. Of the 175 cases included in the analysis, there was definite concordance between EMG and muscle biopsy findings in 134 cases (76.6%). Abnormal EMG produced sensitivity of 87% and specificity of 65% for abnormal muscle biopsy. Seventeen patients had a normal EMG and an abnormal muscle biopsy, of which 6 had histopathological findings consistent with mitochondrial myopathy, central core myopathy or glycogen storage disorder. Conflicting EMG and muscle biopsy findings were observed in 10 cases. Inclusion body myositis, chronic neuromuscular disorders and dual pathologies were associated with discordant findings. This study demonstrates that EMG has accurate predictive value in diagnosing neuromuscular disorders at our neuroscience center. EMG retains a vital role, particularly in initial diagnostic evaluations of neuromuscular disorders.

Late-Onset Tay-Sachs Disease in an Irish Family.

BACKGROUND: Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive lysosomal storage disease caused by deficient ß-hexosaminidase A activity. LOTS is rare in the Ashkenazi Jews, but even rarer in the non-Jewish population. CASES: We report an Irish family expanding the LOTS phenotype (ataxia, diffuse muscle wasting, dystonia, chorea, belly dancer's dyskinesia, and neuropsychiatric features) associated with the known HEXA variant 1073 + 1G > A and a novel variant c.459 + 24G > C. CONCLUSIONS: LOTS should be considered in patients with similar symptoms and cerebellar atrophy on brain imaging.

Acute severe sensory ganglionopathy in systemic lupus erythematous.

Sensory ganglionopathies (or neuronopathies) are a rare subgroup of neuropathies characterized by involvement of sensory neurons in the dorsal root ganglion. Although much less common than central nervous system involvement, patients with systemic lupus erythematous (SLE) can develop peripheral nervous system involvement (PNS) and most commonly a chronic length dependent symmetric sensorimotor axonal polyneuropathy as a late complication of the disease. Unlike in Sjogren's syndrome, SLE-associated sensory ganglionopathy is extremely rare and usually manifests in a chronic insidious fashion. We report a 24-year-old man with SLE-associated sensory ganglionopathy manifesting an unusually acute and severe disabling clinical course with a good response to immunosuppressive therapies. Timely recognition of this rare association and early targeted immunosuppression prevented severe neurological sequelae and preserved patient's ambulation. We demonstrate videos on the evolution of patient's neurological impairment and response to treatment, contributing to the current knowledge of the natural history of PNS involvement in SLE.

Coeliac disease presenting with chorea.

Chorea can be genetic or acquired, and often leads to a challenging diagnostic conundrum. In a significant proportion, there is no specific identifiable cause. Chorea is a rare but potentially reversible neurological manifestation of coeliac disease, usually presenting insidiously and often presumed to be associated with typical gastrointestinal symptoms. We report a patient with rapidly progressive generalised chorea, but without preceding gastrointestinal symptoms, who was subsequently diagnosed with coeliac disease. A gluten-free diet resulted in complete resolution of the chorea.

A population-based epidemiologic study of adult neuromuscular disease in the Republic of Ireland.

OBJECTIVE: To estimate the prevalence rates (PRs) of acquired and inherited neuromuscular diseases (NMD) in the adult Irish population, reflecting the burden of these conditions in a single country. METHODS: This population-based study was performed in the Republic of Ireland (RoI), with a PR estimated for December 2013. Multiple case ascertainment sources were utilized. Demographic and clinical information and relevant diagnostic results were registered. RESULTS: A total of 2,641 adults were identified, giving a PR of 62.6/100,000 (95% confidence interval [CI] 59.95-65.24) for all NMD in RoI. Disease-specific PR include chronic inflammatory demyelinating polyradiculoneuropathy 5.87/100,000 (95% CI 5.06-6.68), Charcot-Marie-Tooth 10.52/100,000 (95% CI 9.44-11.61), hereditary neuropathy with liability to pressure palsies 0.84/100,000 (95% CI 0.54-1.15), myotonic dystrophy type I 6.75/100,000 (95% CI 5.88-7.61), Duchenne muscular dystrophy 3.0/100,000 (95% CI 2.33-3.70), Becker muscular dystrophy 2.2/100,000 (95% CI 1.64-2.88), facioscapulohumeral dystrophy 2.59/100,000 (95% CI 2.05-3.13), limb-girdle muscular dystrophy 2.88/100,000 (95% CI 2.31-3.45), periodic paralysis 1.72/100,000 (95% CI 1.28-2.15), myotonia congenita 0.32/100,000 (95% CI 0.18-0.56), paramyotonia congenita 0.15/100,000 (95% CI 0.06-0.34), Kennedy disease 0.83/100,000 (95% CI 0.40-1.27), Lambert-Eaton myasthenic syndrome 0.29/100,000 (95% CI 0.11-0.47), myasthenia gravis 15.12/100,000 (95% CI 13.82-16.42), and sporadic inclusion body myositis 11.7/100,000 (95% CI 9.82-13.58). PR for amyotrophic lateral sclerosis was established from an existing Register as 7.20/100,000 (95% CI 6.34-8.15). CONCLUSIONS: The PR of all adult NMD in RoI is relatively high when compared with other chronic neurologic disorders, although some figures may be an underestimate of the true prevalence. The data provide a framework for international comparison and service planning.

A novel MYH7 Leu1453pro mutation resulting in Laing distal myopathy in an Irish family.

Authors describe clinical, pathological, imaging and genetic findings in the first Irish family with Laing distal myopathy in whom a novel mutation in the human slow ß-myosin heavy chain (MYH7) gene has been identified. A kindred of 14 over 6 generations included 6 individuals with childhood onset distal lower limb weakness in a scapula-peroneal distribution with subsequent proximal upper and lower limb weakness. Finger extensor weakness especially in the 3rd-5th fingers was present in each and two patients had "hanging big toe" sign. Three patients were non-ambulatory by middle-age. One patient developed cardiomyopathy and two patients had respiratory muscle impairment. Intriguingly, brain white matter lesions and epilepsy were present in three patients. Muscle biopsy revealed fibre-size variation, rimmed vacuoles, mild-extensive central nucleation, redundant and folded sarcolemmal membrane and Z band streaming. Genetic analysis revealed a novel heterozygous mutation in the MYH7 gene in one patient which co-segregated perfectly in the remaining 5 affected members and was absent in six unaffected members.

Andersen-Tawil syndrome with early fixed myopathy.

Andersen-Tawil syndrome (ATS) is a rare autosomal dominant potassium channelopathy characterized by a triad of periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic abnormalities. We present a 19-year-old man with characteristic skeletal dysmorphic features of ATS, early nonfluctuating proximal lower limb weakness from childhood, and neonatal focal seizures. He later developed fluctuating weakness in addition to a fixed proximal myopathy. A 12-lead electrocardiogram showed prominent "U" waves, and McManis protocol prolonged exercise test showed an unusually early decline in the compound motor action potential amplitude by 51%. Genetic testing revealed a de novo heterozygous mutation (R218W) in KCNJ2 associated with ATS. This is the first reported case of ATS in an Irish population with an unusual fixed myopathy from early childhood.

Methodology and design of a national epidemiological study on adult neuromuscular disease.

BACKGROUND: There have been no previous population-based studies of adult neuromuscular disease (NMD) in the Republic of Ireland (RoI). This article describes methods and case-ascertainment strategies used to identify patients with inherited and acquired NMD for the purpose of obtaining the prevalence of these disorders in the RoI. METHODS: This epidemiological study was conducted between January 2012 and January 2014. Prospective and retrospective (until 1990) case identification of adults with inherited and acquired NMD have been carried out. Multiple countrywide patient identification sources including neuromuscular clinics, hospital neurology databases, the hospital in-patient enquiry (HIPE) system of each hospital and the records of Muscular Dystrophy Ireland, a nonprofit organisation, were used. RESULTS: In total, 3,724 potential cases were identified. Of these, 1,083 were excluded because 869 cases represented duplicates or triplicates, 133 were coded incorrectly in HIPE, 74 patients were deceased and 7 patients had moved out of the country. The highest number of cases was identified in neurology databases and HIPE (1,724 and 884, respectively). A total of 2,641 individuals fulfilled the inclusion criteria and were included in the study. CONCLUSION: Detailed epidemiological data of this nature is difficult to acquire in the current structure of the Irish health service, requiring multiple sources including input from voluntary patient organisations. The development of a national patient registry for some or all of these conditions would greatly facilitate standardised data recording, giving a true picture of the burden of neuromuscular diseases in a population.

Clues to diagnosing culture negative Listeria rhombencephalitis.

A previously healthy 35-year-old Caucasian woman developed left body (including facial) hemianaesthesia, asymmetrical lower cranial nerve palsies and cerebellar signs after a 4-day history of headache, nausea and vomiting. Serial blood and cerebrospinal fluid (CSF) cultures returned negative for a culprit organism. CSF examination revealed a lymphocytic pleocytosis and an elevated protein count. CSF cytological examination identified plasma cells. MRI of brain showed multiple ring-enhancing 'abscess-like' lesions in the brainstem and upper cervical cord together with abnormal meningeal enhancement. A decision was made to treat her empirically for Listeria rhombencephalitis to which she responded completely. CSF PCR eventually returned positive for Listeria monocytogenes. This case illustrates the utility of clinical features, MRI, CSF cytology and PCR in diagnosis and treatment of culture negative L monocytogenes rhombencephalitis in an immunocompetent individual.

Clinical and EEG features of seizures in adults with down syndrome.

In this study, the authors characterized the clinical and EEG features of adult patients with Down syndrome who were referred, for more than a 10-year period, to the Epilepsy Clinic in the Cork University Hospital. A retrospective audit of the charts of 28 patients with Down syndrome who had an EEG performed in the Cork University Hospital between January 1, 2000, and September 30, 2009, including clinical follow-up, was carried out. Demographics, age at first seizure, seizure types, EEG findings, antiepileptic drugs, psychoactive medications, and seizure control were documented. Seizures most commonly began in the fourth decade of life. Generalized tonic-clonic seizures were the most common type of seizures (15 patients, 54%), followed by complex partial seizures (5 patients, 18%) and generalized myoclonus (4 patients, 15%). A number of patients had more than one type of seizure. Diffuse background slowing was the dominant EEG abnormality seen in 17 patients (60%). Epileptiform activity was present in 5 patients (18%): 2 had focal epileptiform discharges in the frontal regions, 1 in the central region, 1 in the central posterior region bilaterally, and 1 in the temporal regions. The six patients who had poor seizure control were those who had seizure onset from the fourth decade onward and clinically had complex partial seizures in combination with either generalized tonic-clonic or generalized myoclonus; four of them had epileptiform activity on EEG, with two having focal frontal epileptiform discharges: one in the central posterior areas bilaterally and one in the temporal regions. Five of the 28 patients had a normal EEG and 3 of these had a seizure disorder. There was no correlation found between use of psychoactive drugs and increased frequency/poor seizure control in patients in our study. This study documents the variability of clinical and electrophysiologic features in a well-characterized cohort of patients with Down syndrome with adult-onset epilepsy.

A 27-year-old man with diplopia, fatiguable ptosis and rash: a rare presentation of angiocentric T cell lymphoma with lymphomatoid vasculitis.

A 27-year-old man presented with a 36-h history of ptosis and diplopia and a 10-day history of a lower limb rash. Skin biopsy revealed an aggressive angiocentric γδ-T cell lymphoma. The patient's symptoms and signs disappeared within 1 week of commencement of chemotherapy and there are plans for allogeneic stem cell transplantation.