Unexplained Ataxia Research Articles

Clinical and genetic features of a case with juvenile onset sandhoff disease

BackgroundSandhoff disease (SD) is a rare neurological disease with high clinical heterogeneity. SD in juvenile form is much rarer and it is often misdiagnosed in clinics. Therein, it is necessary to provide more cases and review the literature on juvenile onset SD.Case presentationA 14 years-old boy with eight years of walking difficulties, and was ever misdiagnosed as spinocerebellar ataxia. We found this patient after genetic testing carried rs201580118 and a novel gross deletion in HEXB (g.74012742_74052694del). Through review the literature, we found that was the first gross deletion identified at the 3’end of HEXB, associated with juvenile onset SD from China.ConclusionThis case expanded our knowledge about the genotype and phenotype correlations in SD. Comprehensive genetic testing is important for the diagnosis of unexplained ataxia.

Premutations in the FMR1 gene in Serbian patients with undetermined tremor, ataxia and parkinsonism

ABSTRACT Introduction: Although one of the most common monogenic late-onset neurodegenerative disorders, fragile-X-associated tremor/ataxia syndrome (FXTAS) is still underdiagnosed. The aim of the present study was to estimate the frequency of premutation carriers in patients with unexplained degenerative ataxias, action tremor or parkinsonism, and action tremor with or without associated cognitive impairment. Methods: The study comprised 100 consecutive patients with the disease onset >49 years who had any form of unexplained action tremor, cerebellar ataxia, followed by parkinsonism with or without incipient dementia, and in whom the FMR1 repeats size was determined. Results: Premutation in the FMR1 was identified in two patients (2%): the first, male patient had 83 CGG repeats and the second, female patient had 32 and 58 CGG repeats. Discussion/Conclusion: FXTAS was relatively rare among older patients with unexplained ataxia and action tremor, with or without parkinsonism and/or cognitive impairment. Tremor and ataxia were major clinical features in our two patients, although parkinsonism, autonomic dysfunction and psychiatric problems might be an important part of the spectrum. Probable FXTAS should be considered in the differential diagnosis of patients with unexplained action tremor and ataxia, and undetermined parkinsonism, especially when there was a positive family history for involuntary movement disorders in other family members and/or autism spectrum disorders in younger cousins.

PII: S1557-5063(16)30199-9

Malignant plasma cell neoplasms are rarely documented in ferrets. This article reviews the clinical findings for 6 ferrets with histopathologically confirmed malignant cell neoplasia. The most common clinical sign was hind limb ataxia or paresis (5/6), although hyperglobulinemia was identified as the most consistent hematologic abnormality (5/6) between cases. At the time of diagnosis, the malignancy had disseminated into >4 locations in most of the ferret patients. The clinical presentation of malignant plasma cell tumors in the ferret may be similar to that of multiple myeloma in other species. Practitioners should consider malignant plasma cell neoplasia when encountering ferrets with unexplained ataxia, paresis, and palpable masses, especially when accompanied by increases in gamma globulins.

Malignant Plasma Cell Neoplasia in Ferrets: A Review of 6 Cases

Malignant plasma cell neoplasms are rarely documented in ferrets. This article reviews the clinical findings for 6 ferrets with histopathologically confirmed malignant cell neoplasia. The most common clinical sign was hind limb ataxia or paresis (5/6), although hyperglobulinemia was identified as the most consistent hematologic abnormality (5/6) between cases. At the time of diagnosis, the malignancy had disseminated into >4 locations in most of the ferret patients. The clinical presentation of malignant plasma cell tumors in the ferret may be similar to that of multiple myeloma in other species. Practitioners should consider malignant plasma cell neoplasia when encountering ferrets with unexplained ataxia, paresis, and palpable masses, especially when accompanied by increases in gamma globulins.

Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study

Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression. In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p<0.0001). Factors that were associated with faster progression of the SARA score were short duration of follow-up (p=0.0179), older age at inclusion (0.04 [SE 0.02] per additional year; p=0.0476), and longer repeat expansions (0.06 [SE 0.02] per additional repeat unit; p=0.0128) in SCA1, short duration of follow-up (p<0.0001), lower age at onset (-0.02 [SE 0.01] per additional year; p=0.0014), and lower baseline SARA score (-0.02 [SE 0.01] per additional SARA point; p=0.0083) in SCA2, and lower baseline SARA score (-0.03 [SE 0.01] per additional SARA point; p=0·0195) in SCA6. In SCA3, we did not identify factors that affected progression of the SARA score. Our study provides quantitative data on the progression of the most common spinocerebellar ataxias based on a follow-up period that exceeds those of previous studies. Our data could prove useful for sample size calculation and patient stratification in interventional trials. EU FP6 (EUROSCA), German Ministry of Education and Research (BMBF; GeneMove), Polish Ministry of Science, EU FP7 (NEUROMICS).

65: Incidental Genetic Findings and Patient Preferences Regarding Return of Results in a Population of Patients With Unexplained Ataxia Undergoing Next-Generation Sequencing

Background: As broad-based genomics assays, such as whole exome and whole genome sequencing, are adopted as clinical diagnostic tools, the identification and reporting of incidental findings becomes a salient issue. The estimated chance of identifying a highly penetrant, pathogenic incidental finding is between 1%-5% in individuals seeking whole exome sequencing. We elicited patient preferences regarding return of incidental findings and developed methods for identifying such findings in a group of …

SPG7 mutations are a common cause of undiagnosed ataxia.

Late-onset ataxias are clinically and etiologically diverse. Patients rarely have defining clinical features, and many remain classified as idiopathic, despite extensive clinical, metabolic, and genetic investigations. Here we show that mutations in a gene known to cause hereditary spastic paraplegia ( SPG7 ) are a major cause of unexplained ataxia presenting in mid-adult life.

Chronic Inflammatory Demyelinating Polyneuropathy Presenting with Recurrent Ataxia, Bulbar Weakness, and Respiratory Dysfunction (P06.135)

Objective: To report a case of chronic inflammatory demyelinating polyneuropathy in a patient presenting with recurrent bouts of ataxia, bulbar weakness, and respiratory dysfunction. Background Chronic inflammatory demyelinating polyneuropathy (CIDP) can have a variable presentation leading to delay in diagnosis and treatment. We present a case of a 55-year-old man with recurrent bouts of ataxia and bulbar weakness as his initial presentation of CIDP. Design/Methods: A literature search was performed to look for comparable reports. Results: A 55-year-old diabetic man developed progressive ataxia, fatigue, dysarthria and dysphagia over a six-month period. He then presented to the hospital with acute bilateral upper extremity weakness and respiratory distress requiring intubation. He was found to be areflexic except at the biceps tendon and had difficulty weaning the ventilator. An MRI of the brain as well as initial CSF studies were normal. The patient was presumed to have a variant of Guillain-Barre syndrome and was treated empirically with plasmapheresis. He improved and was extubated. He went on to develop neck extensor weakness, followed by two further episodes of ataxia and respiratory failure at 6 and 9 months thereafter. Each time, he was treated with plasmapheresis and improved. Repeat CSF analysis at 9 months showed 1 RBC, 2 WBCs, 92 glucose, and 60 protein. Complete metabolic, autoimmune, infectious, and paraneoplastic workup was negative. Anti-GQ1b antibodies were negative. Acetylcholine receptor and anti-musk antibodies were negative. Nerve conduction study showed mild to moderate, motor and sensory, mixed axonal and demyelinating polyneuropathy. EMG showed evidence of denervation/reinnervation changes. Single fiber EMG demonstrated mildly increased jitter, though not in the neuromuscular junction disorder range. The patient was started on prednisone and is currently doing well. Conclusions: Chronic inflammatory demyelinating polyneuropathy can have a variable presentation and should be considered in patients with recurrent, unexplained ataxia and bulbar weakness. Disclosure: Dr. Malka has nothing to disclose. Dr. Muntean has nothing to disclose.

Characterizing POLG Ataxia: Clinics, Electrophysiology and Imaging

Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich's ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.

Episodic ataxia and hemiplegia caused by the 8993T→C mitochondrial DNA mutation

The m.8993T→C MTATP6 mutation of mitochondrial DNA (mtDNA) usually causes mitochondrial disease in childhood, but was recently described in a family with adult onset ataxia and polyneuropathy. Cytochrome c oxidase...

Molecular identification of Ehrlichia ewingii infection in dogs: 15 cases (1997–2001)

To determine historical, physical examination, hematologic, and serologic findings in dogs with Ehrlichia ewingii infection. Retrospective study. 15 dogs. In all dogs, infection with E ewingii was confirmed with a polymerase chain reaction (PCR) assay. Follow-up information and clarification of information recorded in the medical records was obtained by telephone interviews and facsimile correspondence with referring veterinarians and owners. Fever and lameness were the most common findings with each occurring in 8 dogs. Five dogs had neurologic abnormalities including ataxia, paresis, proprioceptive deficits, anisocoria, intention tremor, and head tilt. Neutrophilic polyarthritis was identified in 4 dogs. No clinical signs were reported in 3 dogs. The predominant hematologic abnormality was thrombocytopenia, which was identified in all 12 dogs for which a platelet count was available. Reactive lymphocytes were seen in 5 of 13 dogs. Concurrent infection with another rickettsial organism was identified in 4 dogs. Of the 13 dogs tested, 7 were seroreactive to E canis antigens. Morulae consistent with E ewingii infection were identified in neutrophils in 8 dogs. Treatment with doxycycline, with or without prednisone, resulted in a rapid, favorable clinical response in the 9 dogs for which follow-up information was available. Results suggest that PCR testing for E ewingii infection should be considered in dogs with fever, neutrophilic polyarthritis, unexplained ataxia or paresis, thrombocytopenia, or unexplained reactive lymphocytes, and in dogs with clinical signs suggestive of ehrlichiosis that are seronegative for E canis. Following treatment with doxycycline, the prognosis for recovery is good.

Tick paralysis; of a case.

The bite of certain female wood and dog ticks results in a generalized flaccid paralysis, which terminates fatally unless the tick is found and removed. Although this syndrome has been recognized for almost 50 years, a cursory review of the literature indicates that this fact is not generally known. Tick infestation is widespread, but the few case reports come from limited areas, many states never having reported its occurrence. The following case is presented to call attention to the tick as the possible cause of unexplained ataxia and paralysis and to the fact that its removal results in rapid and complete recovery from an otherwise fatal illness. There have been no other cases reported from Tennessee. REPORT OF CASE A healthy 4-year-old girl awoke in the morning with incoordination of both upper and lower extremities. She refused to get out of bed or to feed herself. She did not complain