A De Novo HECW2 Variant in a Patient with Acetazolamide-Responsive Episodic Ataxia.

To the best of our knowledge, this is the first case to address episodic ataxia (EA) as a possible phenotypic feature of HECW2-related disorder. This single case study describes a 26-year-old female born at term with mild intellectual disability, neonatal hypotonia, and a history of febrile seizures who presented with paroxysmal events since the age of 2. These episodes include frequent falls due to imbalance, dilated pupils, vertigo, diaphoresis, nausea, vomiting, and nystagmus. Brain imaging was normal. A prolonged electroencephalogram (EEG) revealed interictal epileptiform discharges but failed to capture her clinical events. For several years, she was treated for presumed focal seizures with preserved awareness and trialed on adequate dosing of several antiepileptic medications without improvement. After 25 years, given the more prolonged nature of her episodes and the mild interictal cerebellar signs, empiric treatment with acetazolamide was initiated for a presumed diagnosis of EA. Acetazolamide treatment led to a dramatic reduction in event frequency and severity. The initial EA genetic panel was negative. Clinical exome sequence analysis revealed a novel pathogenic de novo missense variant in the HECW2 gene [c.3829 T > C;(p.Tyr1277His)], located in the HECT domain. HECW2 variants are associated with neurodevelopmental delay, hypotonia, and epilepsy. This study expands the genetic and clinical spectrum of HECW2-related disorder and adds EA to the phenotypic spectrum in affected individuals.

Prevalence of Fragile X-Associated Tremor/Ataxia Syndrome in Patients with Cerebellar Ataxia in Japan.

The presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS). However, its prevalence in Japan has yet to be clarified. The aim of the present study is to determine the prevalence of FXTAS in Japanese patients with cerebellar ataxia and to describe their clinical characteristics. DNA samples were collected from 1328 Japanese patients with cerebellar ataxia, referred for genetic diagnosis. Among them, 995 patients with negative results for the most common spinocerebellar ataxia subtypes were screened for FMR1 premutation. Comprehensive clinical and radiological analyses were performed for the patients harbouring FMR1 premutation. We herein identified FMR1 premutation from one female and two male patients, who satisfied both clinical and radiological criteria of FXTAS (0.3%; 3/995) as well. Both male patients presented with high signal intensity of corticomedullary junction on diffusion-weighted magnetic resonance imaging, a finding comparable to that of neuronal intranuclear inclusion disease. The female patient mimicked multiple system atrophy in the early stages of her disease and developed aseptic meningitis with a suspected immune-mediated mechanism after the onset of FXTAS, which made her unique. Despite the lower prevalence rate in Japan than the previous reports in other countries, the present study emphasises the necessity to consider FXTAS with undiagnosed ataxia, regardless of men or women, particularly for those cases presenting with similar clinical and radiological findings with multiple system atrophy or neuronal intranuclear inclusion disease.

POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients.

Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation in POLR3A. Here, we present 10 patients from 8 unrelated families with POLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a "pure" cerebellar phenotype, and one a "pure" spastic presentation. The non-neurological findings typically associated with POLR3A mutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. The POLR3A mutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14-18. Interestingly, this patient had the most "complex" presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onset POLR3A-related disorders, and therefore further expand the phenotype.

Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of literature.

Opsoclonus-myoclonus-ataxia syndrome is a heterogeneous constellation of symptoms ranging from full combination of these three neurological findings to varying degrees of isolated individual sign. Since the emergence of coronavirus disease 2019 (COVID-19), neurological symptoms, syndromes, and complications associated with this multi-organ viral infection have been reported and the various aspects of neurological involvement are increasingly uncovered. As a neuro-inflammatory disorder, one would expect to observe opsoclonus-myoclonus syndrome after a prevalent viral infection in a pandemic scale, as it has been the case for many other neuro-inflammatory syndromes. We report seven cases of opsoclonus-myoclonus syndrome presumably parainfectious in nature and discuss their phenomenology, their possible pathophysiological relationship to COVID-19, and diagnostic and treatment strategy in each case. Finally, we review the relevant data in the literature regarding the opsoclonus-myoclonus syndrome and possible similar cases associated with COVID-19 and its diagnostic importance for clinicians in various fields of medicine encountering COVID-19 patients and its complications.

Natural History of Polymerase Gamma-Related Ataxia.

BACKGROUND: Mutations in the mitochondrial DNA polymerase gamma are causing a wide phenotypic spectrum including ataxia as one of the most common presentations. OBJECTIVE: The objective of this study was to determine the course of disease of polymerase gamma-related ataxia. METHODS: In a prospective natural history study, we assessed 24 adult ataxia patients with biallelic polymerase gamma mutations for (1) severity of cerebellar dysfunction using the Scale for the Assessment and Rating of Ataxia score, (2) presence of nonataxia signs using the Inventory of Non-Ataxia Symptoms, (3) gray- and white-matter changes in brain MRI, and (4) findings in nerve conduction studies. RESULTS: Assessment included follow-up visits up to 11.6 years. The Scale for the Assessment and Rating of Ataxia showed a mean annual increase of 1.02 ± 0.78 points/year. Disease progression was faster in patients with age at onset ≤ 30 years (1.5 Scale for the Assessment and Rating of Ataxia points/year) than with later onset (0.5 points/year); P = 0.008. The Inventory of Non-Ataxia Symptoms count increased by 0.30 ± 0.4 points/year. External ophthalmoplegia, brain stem oculomotor signs, areflexia, and sensory deficits were the most common nonataxic features. On MRI cerebellar atrophy was mild. T2 signal alterations affected mostly cerebellar white matter, middle cerebellar peduncles, thalamus, brain stem, and occipital and frontal white matter. Within 4 years, progression was primarily observed in the context of repeated epileptic seizures. Nerve conduction studies revealed axonal sensory peripheral neuropathy with mild motor nerve involvement. Exploratory sample size calculation implied 38 patients per arm as sufficient to detect a reduction of progression by 50% in hypothetical interventions within a 1-year trial. CONCLUSION: The results recommend the Scale for the Assessment and Rating of Ataxia as a primary outcome measure for future interventional trials in polymerase gamma-related ataxia. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis.

Inherited optic neuropathies (IONs) are neurodegenerative disorders characterized by optic atrophy with or without extraocular manifestations. Optic atrophy-10 (OPA10) is an autosomal recessive ION recently reported to be caused by mutations in RTN4IP1, which encodes reticulon 4 interacting protein 1 (RTN4IP1), a mitochondrial ubiquinol oxydo-reductase. Here we report novel compound heterozygous mutations in RTN4IP1 in a male proband with developmental delay, epilepsy, optic atrophy, ataxia, and choreoathetosis. Workup was notable for transiently elevated lactate and lactate-to-pyruvate ratio, brain magnetic resonance imaging with optic atrophy and T2 signal abnormalities, and a nondiagnostic initial genetic workup, including chromosomal microarray and mitochondrial panel testing. Exome sequencing identified a paternally inherited missense variant (c.263T>G, p.Val88Gly) predicted to be deleterious and a maternally inherited deletion encompassing RTN4IP1. To our knowledge, this is the first report of a non-single nucleotide pathogenic variant associated with OPA10. This case highlights the expanding phenotypic spectrum of OPA10, the association between "syndromic" cases and severe RTN4IP1 mutations, and the importance of nonbiased genetic testing, such as ES, to analyze multiple genes and variants types, in patients suspected of having genetic disease.

Conventional MRI findings in hereditary degenerative ataxias: a pictorial review.

PURPOSE: Cerebellar ataxias are a large and heterogeneous group of disorders. The evaluation of brain parenchyma via MRI plays a central role in the diagnostic assessment of these conditions, being mandatory to exclude the presence of other underlying causes in determining the clinical phenotype. Once these possible causes are ruled out, the diagnosis is usually researched in the wide range of hereditary or sporadic ataxias. METHODS: We here propose a review of the main clinical and conventional imaging findings of the most common hereditary degenerative ataxias, to help neuroradiologists in the evaluation of these patients. RESULTS: Hereditary degenerative ataxias are all usually characterized from a neuroimaging standpoint by the presence, in almost all cases, of cerebellar atrophy. Nevertheless, a proper assessment of imaging data, extending beyond the mere evaluation of cerebellar atrophy, evaluating also the pattern of volume loss as well as concomitant MRI signs, is crucial to achieve a proper diagnosis. CONCLUSION: The integration of typical neuroradiological characteristics, along with patient's clinical history and laboratory data, could allow the neuroradiologist to identify some conditions and exclude others, addressing the neurologist to the more appropriate genetic testing.

Brain Atrophy and White Matter Damage Linked to Peripheral Bioenergetic Deficits in the Neurodegenerative Disease FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting subjects (premutation carriers) with a 55-200 CGG-trinucleotide expansion in the 5'UTR of the fragile X mental retardation 1 gene (FMR1) typically after age 50. As both the presence of white matter hyperintensities (WMHs) and atrophied gray matter on magnetic resonance imaging (MRI) are linked to age-dependent decline in cognition, here we tested whether MRI outcomes (WMH volume (WMHV) and brain volume) were correlated with mitochondrial bioenergetics from peripheral blood monocytic cells in 87 carriers with and without FXTAS. As a parameter assessing cumulative damage, WMHV was correlated to both FXTAS stages and age, and brain volume discriminated between carriers and non-carriers. Similarly, mitochondrial mass and ATP production showed an age-dependent decline across all participants, but in contrast to WMHV, only FADH2-linked ATP production was significantly reduced in carriers vs. non-carriers. In carriers, WMHV negatively correlated with ATP production sustained by glucose-glutamine and FADH2-linked substrates, whereas brain volume was positively associated with the latter and mitochondrial mass. The observed correlations between peripheral mitochondrial bioenergetics and MRI findings-and the lack of correlations with FXTAS diagnosis/stages-may stem from early brain bioenergetic deficits even before overt FXTAS symptoms and/or imaging findings.

CT myelographic diagnosis of ligamentum flavum hypertrophy in a Warmblood Gelding with progressive ataxia.

An 8-year-old Warmblood gelding presented with a history of progressive ataxia for 6 weeks. Intra- and intervertebral ratios measured from lateral radiographs of the cervical spine were within normal limits. Computed tomographic myelography of the cervical spine revealed focal compression of the dorsal and the ventral contrast column as well as a ventral displacement of the spinal cord within the spinal canal due to a bulging of soft tissue attenuating material in the dorsal half of the intervertebral junction of C6 and C7. Post-mortem histopathological examination confirmed chondroid metaplasia of the ligamentum flavum at C6-C7.

MR imaging and spectroscopy in degenerative ataxias: toward multimodal, multisite, multistage monitoring of neurodegeneration.

PURPOSE OF REVIEW: Degenerative ataxias are rare and currently untreatable movement disorders, primarily characterized by neurodegeneration in the cerebellum and brainstem. We highlight MRI studies with the most potential for utility in pending ataxia trials and underscore advances in disease characterization and diagnostics in the field. RECENT FINDINGS: With availability of advanced MRI acquisition methods and specialized software dedicated to the analysis of MRI of the cerebellum, patterns of cerebellar atrophy in different degenerative ataxias are increasingly well defined. The field further embraced rigorous multimodal investigations to study network-level microstructural and functional brain changes and their neurochemical correlates. MRI and magnetic resonance spectroscopy were shown to be more sensitive to disease progression than clinical scales and to detect abnormalities in premanifest mutation carriers. SUMMARY: Magnetic resonance techniques are increasingly well placed for characterizing the expression and progression of degenerative ataxias. The most impactful work has arguably come through multi-institutional studies that monitor relatively large cohorts, multimodal investigations that assess the sensitivity of different measures and their interrelationships, and novel imaging approaches that are targeted to known pathophysiology (e.g., iron and spinal imaging in Friedreich ataxia). These multimodal, multi-institutional studies are paving the way to clinical trial readiness and enhanced understanding of disease in degenerative ataxias.

Ataxia Associated with CADASIL: a Pathology-Confirmed Case Report and Literature Review.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is primarily characterized by migraine, stroke, mood disturbances, and cognitive decline. Ataxia has seldom been reported as a presenting symptom. Here, we review reports of CADASIL presenting as ataxia and compare these to the first pathologically confirmed case of CADASIL presenting with progressive ataxia. A 50-year-old woman presented with progressive truncal ataxia. Brain magnetic resonance imaging (MRI) revealed white matter hyperintensities in the bilateral anterior temporal lobes, external capsules, and periventricular areas, but not the cerebellum. Electron microscopy of skin biopsy material revealed multiple granular osmiophilic materials. Genetic testing confirmed a c.4552C > A mutation in exon 25 of the NOTCH3 gene. CADASIL is a rare cause of progressive ataxia, and only four cases of CADASIL presenting with ataxia have been reported in the literature. We also discuss the possible pathophysiology of cerebellar ataxia associated with CADASIL.

Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy.

Mutations in the mitochondrial alanyl-tRNA synthetase gene, AARS2, have been reported to cause leukoencephalopathy associated with early ovarian failure, a clinical presentation described as "ovarioleukodystrophy." We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous for AARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131del AARS2 dramatically impairs gene function and that p.Ile328Met AARS2 is a hypomorphic allele. This work expands the phenotypic spectrum of AARS2-associated disease to include ataxia without leukoencephalopathy.

Infantile Onset of Spinocerebellar Ataxia Type 5 (SCA-5) in a 6 Month Old with Ataxic Cerebral Palsy.

Spinocerebellar ataxia type 5 (SCA-5) is a predominantly slowly progressive adult onset ataxia. We describe a child with a presentation of ataxic cerebral palsy (CP) and developmental delay at 6 months of age. Genetic testing confirmed a c.812C>T p.(Thr271Ile) mutation within the SPTBN2 gene. Seven previous cases of infantile onset SCA-5 are reported in the literature, four of which had a CP presentation. Early onset of SCA-5 presents with ataxic CP and is a rare cause of cerebral palsy.

Imaging correlates of hand motor performance in multiple sclerosis: A multiparametric structural and functional MRI study.

BACKGROUND: Hand motor impairment has considerable effects on daily-life activities of patients with multiple sclerosis (pwMS). Understanding its anatomo-functional substrates is relevant to provide more specific therapeutic interventions. OBJECTIVES: To investigate the association between hand motor performance and anatomo-functional magnetic resonance imaging (MRI) abnormalities in pwMS. METHODS: A total of 134 healthy controls (HC) and 366 pwMS underwent the Nine-Hole-Peg-Test (9HPT), structural and resting state (RS) functional MRI. Multivariate analyses identified the independent predictors of hand motor performance. RESULTS: PwMS versus HC showed widespread gray matter atrophy, microstructural white matter abnormalities, and decreased RS functional connectivity in motor and cognitive networks. Predictors of worse right-9HPT (R2 = 0.52) were decreased right superior cerebellar peduncle and right lemniscus fractional anisotropy (FA) (p ⩽ 0.02), left angular gyrus atrophy (p < 0.003), decreased RS connectivity in left superior frontal gyrus, and left posterior cerebellum (p < 0.001). Worse left 9HPT (R2 = 0.56) was predicted by decreased right corticospinal FA (p = 0.003), atrophy of left anterior cingulum and left cerebellum (p ⩽ 0.02), decreased RS connectivity of left lingual gyrus and right posterior cerebellum in cerebellar and executive networks (p ⩽ 0.02). CONCLUSION: Structural and functional abnormalities of regions involved in motor functions contribute to explain motor disability in pwMS. The integration of clinical and advanced MRI measures contributes to improve our understanding of multiple sclerosis clinical manifestations.

Clinical, MRI, and histopathological findings of congenital focal diplomyelia at the level of L4 in a female crossbred calf.

BACKGROUND: This case report describes the clinical signs of a calf with focal diplomyelia at the level of the fourth lumbar vertebra. Magnetic resonance imaging (MRI) images and histological findings of the affected spinal cord are included in this case report. This case differs from previously reported cases in terms of localization and minimal extent of the congenital anomaly, clinical symptoms and findings during further examinations. CASE PRESENTATION: The calf was presented to the Farm Animal Health clinic, Faculty of Veterinary Medicine, Utrecht University, with an abnormal, stiff, 'bunny-hop' gait of the pelvic limbs. Prominent clinical findings included general proprioceptive ataxia with paraparesis, pathological spinal reflexes of the pelvic limbs and pollakiuria. MRI revealed a focal dilated central canal, and mid-sagittal T2 hyperintense band in the dorsal part of the spinal cord at the level of the third to fourth lumbar vertebra. By means of histology, the calf was diagnosed with focal diplomyelia at the level of the fourth lumbar vertebra, a rare congenital malformation of the spinal cord. The calf tested positive for Schmallenberg virus antibodies, however this is not considered to be part of the pathogenesis of the diplomyelia. CONCLUSIONS: This case report adds value to future clinical practice, as it provides a clear description of focal diplomyelia as a previously unreported lesion and details its diagnosis using advanced imaging and histology. This type of lesion should be included in the differential diagnoses when a calf is presented with a general proprioceptive ataxia of the hind limbs. In particular, a 'bunny-hop' gait of the pelvic limbs is thought to be a specific clinical symptom of diplomyelia. This case report is of clinical and scientific importance as it demonstrates the possibility of a focal microscopic diplomyelia, which would not be evident by gross examination alone, as a cause of hind-limb ataxia. The aetiology of diplomyelia in calves remains unclear.

Novel UCHL1 mutations reveal new insights into ubiquitin processing.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 has been implicated in early-onset progressive neurodegeneration (MIM no. 615491), so far only in one family. In this study a second family is characterized, and the functional consequences of the identified mutations in UCHL1 are explored. Three siblings developed childhood-onset optic atrophy, followed by spasticity and ataxia. Whole exome sequencing identified compound heterozygous variants in UCHL1, c.533G > A (p.Arg178Gln) and c.647C > A (p.Ala216Asp), cosegregating with the phenotype. Enzymatic activity of purified recombinant proteins analysed by ubiquitin hydrolase assays showed a 4-fold increased hydrolytic activity of the recombinant UCHL1 mutant Arg178Gln compared to wild type, whereas the Ala216Asp protein was insoluble. Structural 3D analysis of UCHL1 by computer modelling suggests that Arg178 is a rate-controlling residue in catalysis which is partly abolished in the Arg178Gln mutant and, consequently, the Arg178Gln mutant increases the enzymatic turnover. UCHL1 protein levels in fibroblasts measured by targeted mass spectrometry showed a total amount of UCHL1 in control fibroblasts about 4-fold higher than in the patients. Hence, studies of the identified missense variants reveal surprisingly different functional consequences as the insoluble Ala216Asp variant leads to loss of function, whereas the Arg178Gln leads to increased enzyme activity. The reported patients have remarkably preserved cognition, and we propose that the increased enzyme activity of the Arg178Gln variant offers a protective effect on cognitive function. This study establishes the importance of UCHL1 in neurodegeneration, provides new mechanistic insight about ubiquitin processing, and underlines the complexity of the different roles of UCHL1.

Ataxia as the main manifestation of tumor-like primary angiitis of the central nervous system: a case report and literature review.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare disease, and tumor-like primary angiitis of the central nervous system is even rarer. Histopathology is the gold standard for tumor-mimicking PACNS. However, pathological diagnosis is relatively limited due to fewer biopsy opportunities. CASE PRESENTATION: A 68-year-old male presented with ataxia, and was diagnosed with tumor-like primary angiitis of the central nervous system. The patient underwent Intravenous drip glucocorticoid therapy (10 mg of dexamethasone, daily). After 10 days, the symptoms of the patient were completely relieved. Radiology revealed that the low density lesion in the right cerebellar hemisphere obviously narrowed. Cyclophosphamide therapy was not initiated. CONCLUSION: It is crucial for clinicians to be aware of changes in radiology that indicate PACNS, since the diagnosis of tumor-like PACNS remains quite challenging. Glucocorticoid therapy is an effective therapy in this condition, and the prognosis can be favorable.

Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Refractory Holmes Tremor.

Three right-handed patients diagnosed with Holmes tremor (HT), who suffered from pharmacotherapy-refractory tremor, were eligible for unilateral posterior subthalamic area deep brain stimulation (PSA-DBS). All patients were evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Clinical Global Impression scale (CGI) before DBS, 6, and 12 months after the PSA-DBS as well as at the last follow-up. In all patients, we observed a significant improvement of tremor control as demonstrated by changes in the FTMTRS and the CGI scales. Mean improvement of tremor in all patients was 56% for the FTMRTS with a corresponding change in the CGI scale. Our study demonstrates that PSA-DBS is efficacious in the treatment of HT. Indeed, PSA is a promising target for DBS for intractable proximal and distal tremor, even in cases of previous, suboptimal functional neurosurgery. The beneficial effect lasts over a long-term follow-up. PSA-DBS may be considered as an alternative target of DBS in tremor treatment.

Utility of Neuroimaging in Children Presenting to a Pediatric Emergency Department With Ataxia.

OBJECTIVES: The aim of this study was to evaluate the utility of neuroimaging in children who present to the pediatric emergency department with acute-/subacute-onset ataxia. Neuroimaging is performed in many children with ataxia to rule out serious intracranial pathology. There is, however, limited evidence to support such practice. METHODS: This was a retrospective review of electronic medical records of children who presented to the emergency department with ataxia between 2007 and 2013. Patient demographics, historical features, physical examination findings, laboratory results, and neuroimaging results were collected. Neuroimaging studies that were classified as abnormal by a neuroradiologist were further reviewed and classified by the study neurologist as clinically significant or not. RESULTS: The records of 141 subjects were analyzed. The most common causes of ataxia were infectious/postinfectious (36.2%) and ingestion (15.6%). Neuroimaging was performed in 104 children (73.8%). Neuroimaging was abnormal in 63 children (60.6%). However, these abnormalities were clinically significant in only 14 children (13.5%). Focal neurological findings were noted in 12 of 14 children (85.7%) with clinically significant neuroimaging. CONCLUSIONS: Clinically significant neuroimaging was noted in a minority of children who presented with acute/subacute ataxia. The majority of patients with clinically significant neuroimaging had focal neurological findings on examination. Neuroimaging may not be required in all children presenting to the ED with acute ataxia, but further large-scale studies are needed to validate these findings and identify a subset of patients with ataxia in whom imaging can be deferred.

Acute-Onset Ataxia and Transient Cerebellar Diffusion Restriction Associated with a PRRT2 Mutation.

PRRT2 gene mutations cause paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions, hemiplegic migraine, and episodic ataxia. A 21-year-old woman reported an episode of dizziness and ataxic gait occurring after swimming. Brain MRI showed a hyperintense cerebellar lesion on diffusion-weighted imaging (DWI) with decreased apparent diffusion coefficient. The clinical course was favorable. Both clinical and MRI abnormalities regressed. Her brother had presented PKD since adulthood. A C.649dupC PRRT2 truncating mutation was identified in both patients. To our knowledge, this is the first case of an acute cerebellar ataxia associated with heterozygous PRRT2 mutation and transient cerebellar hyperintensity on DWI. Among the clinical and genetic heterogeneities of familial paroxysmal disorders, PRRT2 mutation may be considered in patients with episodic cerebellar ataxia and diffusion restriction on neuroimaging.