Ataxic Neuropathy Research Articles

Nerve ultrasound as a diagnostic tool for sensory neuronopathy in spinocerebellar ataxia syndrome

ObjectiveThe objective was to assess if nerve ultrasound has a role in diagnosing sensory neuronopathy in spinocerebellar ataxia syndrome (SCA) by examining if proposed diagnostic cut-off criteria of ultrasound in sensory neuronopathy caused by cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) were also discriminatory for SCA-related sensory neuronopathy. MethodsOptimal diagnostic cut-off criteria for nerve size measured by diagnostic ultrasound were developed in 14 patients with CANVAS and 42 healthy controls using six peripheral nerve sites; and logistic regression and receiver operating characteristic (ROC) curves. These proposed cut-off values were tested in seven patients with spinocerebellar ataxia type 2 (SCA2) patients with sensory neuronopathy. ResultsUltrasound of upper limb nerves was highly accurate in differentiating between CANVAS and healthy controls with areas under the ROC curves between 0.97 and 0.99. Optimal cut-off measurements from the CANVAS patients also accurately diagnosed sensory neuronopathy in all patients with SCA2. ConclusionsUpper limb ultrasound is a sensitive tool for detecting sensory neuronopathy in established cases of CANVAS and SCA2. SignificanceUltrasound could aid the diagnosis of sensory neuronopathy in spinocerebellar ataxias.

Clinical characterization of anti-GQ1b antibody syndrome in Korean children

Anti-GQ1b antibody syndrome encompasses Miller Fisher syndrome and its related disorders. We retrospectively identified 11 pediatric patients (5.4–18 years old) with anti-GQ1b antibody syndrome. Diagnoses of patients included acute ophthalmoparesis (n = 6), classical Miller Fisher syndrome (n = 2), Miller Fisher syndrome/Guillain-Barré syndrome (n = 1), acute ataxic neuropathy (n = 1), and pharyngeal-cervical-brachial weakness (n = 1). Nine patients (81.8%) fully recovered. Maturational change in GQ1b antigen expression and the accessibility of anti-GQ1b antibodies might be the cause of the difference of clinical manifestations in children with anti-GQ1b antibody syndrome.

Effects of acetone cyanohydrin, a derivative of cassava, on motor activity and kidney and liver function in Wistar rats

IntroductionAcetone cyanohydrin (ACH) is a toxic substance present in cassava roots (Manihot esculenta Crantz) which results from enzymatic hydrolysis of linamarin. Long-term consumption is associated with 2 neurological disorders: konzo and tropical ataxic neuropathy. Previous studies have evaluated behavioural alterations linked to ACH consumption, but the toxic effects of this substance on physiological processes remain unknown. Method32 male Wistar rats were assigned to 4 experimental groups (n=8 per group): a vehicle group (0.3mL saline solution, IP) and 3 ACH groups (PubChem CID: 6406) dosed at 10, 15, and 20mM/24hours for 28 days. We evaluated spontaneous motor activity with the open field test and motor coordination with the rotarod and forced swimming tests at 0, 7, 14, 21, and 28 days of treatment. At the end of the assessment period (day 28), blood samples were collected by transcardiac puncture to evaluate kidney and liver function. ResultsACH caused alterations in locomotor activity and promoted both lateral swimming and spinning in the forced swimming test at 21 and 28 days of treatment. Furthermore, it led to an increase in the levels of the parameters of kidney and liver function in a concentration-dependent manner, except for glucose and total bilirubin. ConclusionOur results suggest that long-term consumption of this toxic compound present in cassava roots may be potentially dangerous for vulnerable subjects.

A – C.A.N.V.A.S (CEREBELLAR ATAXIA, NEURONOPATHY AND VESTIBULAR AREFLEXIA WITH AUTONOMIC DYSFUNCTION): A FASCINATING CLINICAL PORTRAIT

57-year-old male patient with a 30-year history chronic cough, balance difficulties (most noticeable in the dark), ataxia and sensory neuropathy. There was also evidence of orthostatic hypotension and hypohydrosis. Examination revealed downbeat nystagmus, an abnormal visually-enhanced vestibulo-ocular reflex, length-dependent sensory neuropathy, high-stepping tandem ataxia and bilateral dysmetria. MRI brain shows marked vermian cerebellar atrophy (more noticeable in lobes VI and VIIa/b) and nerve conduction studies reveal absent sensory conductions (ganglionopathy). Genetic testing for Friedrich’s ataxia, spinocerebellar ataxia and hereditary motor sensory neuropathy (Charcot-Marie-Tooth disease) were all negative. Sural nerve biopsy showed pattern of severe loss of myelinated fibres. This patient was diagnosed with cerebellar ataxia, neuronopathy (ganglionopathy) and vestibular areflexia with autonomic dysfunction. Keywords: ataxia, neuronopathy, vestibular areflexia, autonomic dysfunction.

Clinical, ophthalmological, imaging and genetic features in Brazilian patients with ARSACS

BackgroundAutosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an important form of inherited ataxia with a varied clinical spectrum. Detailed studies of phenotype and genotype are necessary to improve diagnosis and elucidate this disorder pathogenesis. OBJECTIVE AND METHODS: To investigate the clinical phenotype, retinal architecture, neuroimaging features and genetic profile of Brazilian patients with ARSACS, we performed neurological and ophthalmological evaluation in thirteen Brazilian patients with molecularly confirmed ARSACS, and examined their mutation profiles. Optical coherence tomography protocol (OCT) consisted in peripapillary retinal nerve fiber layer (RNFL) measurement and qualitative analysis of perifoveal scans. Neuroimaging protocol accessed the frequency of atrophy in cerebellum, corpus callosum and parietal lobe, brainstem signal abnormalities, and posterior fossa arachnoid cysts. We reviewed the literature to delineate the ARSACS phenotype in the largest series worldwide. RESULTS: All patients had ataxia and spasticity, and 11/13 had peripheral neuropathy. Macular microcysts were present in two patients. Peripapillary striations, dentate appearance of inner retina and papillomacular fold were found in eleven cases. All individuals exhibited thickening of RNFL in OCT. The most frequent radiological signs were cerebellar atrophy (13/13), biparietal atrophy (12/13), and linear pontine hypointensities (13/13). Genetic analysis revealed 14 different SACS variants, of which two are novel. CONCLUSION: Macular microcysts, inner retina dentate appearance and papillomacular fold are novel retinal imaging signs of ARSACS. Ophthalmological and neuroimaging changes are common findings in Brazilian patients. The core clinical features of ARSACS are ataxia, spasticity and peripheral neuropathy with onset predominantly in the first decade of life.

POLG-related disorders and their neurological manifestations.

The POLG gene encodes the mitochondrial DNA polymerase that is responsible for replication of the mitochondrial genome. Mutations in POLG can cause early childhood mitochondrial DNA (mtDNA) depletion syndromes or later-onset syndromes arising from mtDNA deletions. POLG mutations are the most common cause of inherited mitochondrial disorders, with as many as 2% of the population carrying these mutations. POLG-related disorders comprise a continuum of overlapping phenotypes with onset from infancy to late adulthood. The six leading disorders caused by POLG mutations are Alpers-Huttenlocher syndrome, which is one of the most severe phenotypes; childhood myocerebrohepatopathy spectrum, which presents within the first 3 years of life; myoclonic epilepsy myopathy sensory ataxia; ataxia neuropathy spectrum; autosomal recessive progressive external ophthalmoplegia; and autosomal dominant progressive external ophthalmoplegia. This Review describes the clinical features, pathophysiology, natural history and treatment of POLG-related disorders, focusing particularly on the neurological manifestations of theseconditions.

Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron‐one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron‐two. cDNA and protein analysis indicated that no full‐length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.

Bi-allelic ADPRHL2 Mutations Cause Neurodegeneration with Developmental Delay, Ataxia, and Axonal Neuropathy

ADP-ribosylation is a reversible posttranslational modification used to regulate protein function. ADP-ribosyltransferases transfer ADP-ribose from NAD+ to the target protein, and ADP-ribosylhydrolases, such as ADPRHL2, reverse the reaction. We used exome sequencing to identify five different bi-allelic pathogenic ADPRHL2 variants in 12 individuals from 8 families affected by a neurodegenerative disorder manifesting in childhood or adolescence with key clinical features including developmental delay or regression, seizures, ataxia, and axonal (sensori-)motor neuropathy. ADPRHL2 was virtually absent in available affected individuals' fibroblasts, and cell viability was reduced upon hydrogen peroxide exposure, although it was rescued by expression of wild-type ADPRHL2 mRNA as well as treatment with a PARP1 inhibitor. Our findings suggest impaired protein ribosylation as another pathway that, if disturbed, causes neurodegenerative diseases.

Identification of a novel DNMT1 mutation in a Chinese patient with hereditary sensory and autonomic neuropathy type IE

BackgroundDNA methyltransferase 1 (EC 2.1.1.37), encoded by DNMT1 gene, is one of key enzymes in maintaining DNA methylation patterns of the human genome. It plays a crucial role in embryonic development, imprinting and genome stability, cell differentiation. The dysfunction of this group of enzymes can lead to a variety of human genetic disorders. Until now, mutations in DNMT1 have been found to be associated with two distinct phenotypes. Mutations in exon 20 of this gene leads to hereditary sensory and autonomic neuropathy type IE, and mutations in exon 21 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy.Case presentationHere we report a novel DNMT1 mutation in a sporadic case of a Chinese patient with cerebellar ataxia, multiple motor and sensory neuropathy, hearing loss and psychiatric manifestations. Furthermore, we elucidated its pathogenic effect through molecular genetics studies and revealed that this defective DNMT1 function is responsible for the phenotypes in this individual.ConclusionOur findings expand the spectrum of DNMT1-related disorders and provide a good example of precision medicine through the combination of exome sequencing and clinical testing.

An efficient approach on alcohol dependence syndrome

Alcohol consumption results in multiple end-organ damages. Predominantly the nervous system is affected in the form of Wernicke encephalopathy, Korsakoff psychosis, cerebellar ataxia and peripheral neuropathy. Neuropathy due to alcohol consumption depends on the period and extent of total lifetime of alcohol consumption. Cultural and racial factors also play a role in the development of alcohol neuropathy. Alcohol consumption results in multiple end-organ damages. Alcoholic neuropathy is the most common harmful effects of excessive alcohol intake. The incidence of alcoholic neuropathy in the standard population is not accurate as the percentage varies extensively contingent on the description of chronic alcoholism and the criteria used to detect and classify neuropathy. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), studies involving clinical and electrodiagnostic tests prove that neuropathy is present in 25-66%. Alcoholic neuropathy depends on the extent and extent of total lifetime of alcohol consumption. Cultural and racial factors also play a role in resulting in alcohol neuropathy. Few studies suggest that the incidence of peripheral neuropathy is higher in alcoholic patients who have a family history of alcohol dependence syndrome. This is study finds the Common peroneal and sural nerves are the most common nerves to be involved in neuropathy. Predominantly axonal degeneration is the main pathology. Units of alcohol and CAGE criteria score has a 100% specificity in detecting patients prone to neuropathy.

MITOCHONDRIAL DISEASES (Posters): P.188Novel POLG mutations and variable clinical phenotypes in 5 Chinese patients with mitochondrial diseases

POLG related mitochondrial disorders has rarely been reported in China. Here we report 5 unrelated Chinese patients (2 males and 3 females) with mitochondrial disease caused by POLG gene mutations. Two of them had a dominant family history and 3 were sporadic cases. The ages of onset were from 15 to 40 years old, with disease course ranging from 1 to 26 years. Clinically, 1 case were conformed with SANDO (sensory ataxic neuropathy, dysarthria and ophthalmoparesis) syndrome, 2 cases with autosomal dominant progressive external ophthalmoplegia (PEO), 1 case with autosomal recessive PEO, and 1 case with sensory axonal neuropathy and mental retardation. Laboratory examination revealed normal or mild elevation of serum creatine kinase level. Electromyography revealed myopathic or neurogenic pattern. Nerve conduction studies showed decreased amplitude of nerve action potential in 3 cases, with sensory nerve predominantly involved. Mitochondrial abnormality appeared in 4 patients who underwent muscle biopsies. Sural nerve biopsy revealed chronic axonal neuropathy in the patient with sensory axonal neuropathy and mental retardation. Genetic test revealed compound heterozygous POLG mutations in 3 sporadic patients and single heterozygous mutations in 2 dominant inherited patients. c.914G>A (p.S305N), c.924G>T (p.Q308H), c.1613A>T (p.E538V), c.1612G>T (p.E538*), c.1790 G>A (p.R597Q) and c.3002delG. were novel mutations. Novel mutations found in this study expanded the mutational spectrum of POLG.

Assessment of the impact of an exercise program on the physical and functional capacity in patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay: An exploratory study.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neuromuscular disorder caused by the mutation of the SACS gene. Clinical symptoms of this disease include progressive ataxia, spasticity, and peripheral neuropathy. Similar to other neuromuscular disorders, these patients are prone to physical deconditioning which may lead to a loss of functional capacity. This paper aims to evaluate the impact of a training program on the physical fitness and the functional capacity of ARSACS patients. Twelve patients (age: 28.1 ± 8.2 years) participated in this study. They followed an eight-week training program including physical activities, strength-power and aerobic training. Compared to the initial evaluation, measures of physical fitness and functional capacity were significantly improved (p ≤ 0.05) for 11 of the 12 tests. Positive gains were also observed for fall frequency and for upper-limb incoordination. This paper supports the importance of a training program for ARSACS patients in order to improve their quality of life. Through these types of interventions, it may be possible to slow down the progression of the disease and help maintain functional capacity.

SCA2 presenting as a focal dystonia

BackgroundSpinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in ATXN2 on chromosome 12q24. Patients present with adult-onset progressive gait ataxia, slow saccades, nystagmus, dysarthria and peripheral neuropathy. Dystonia is known to occur as SCA2 advances, but is rarely the presenting symptom.Case presentationA 43-year-old right handed woman presented with focal dystonia of the right hand which started two years earlier with difficulty writing. There were only mild cerebellar signs. Her mother was reported to have a progressive gait disorder and we subsequently learned that she had SCA2. A total of 10 maternal family members were similarly affected. Over the course of 10 years, the patient’s cerebellar signs progressed only mildly however the dystonia worsened to the extent of inability to use her right hand. Dystonia did not improve significantly with botulinum toxin, levodopa or trihexyphenidyl, but has shown marked improvement since DBS implantation in the GPi.ConclusionsWe describe a patient with SCA2 who presented with focal dystonia of the right upper extremity. Subtle cerebellar signs as well as the family history became especially important given the absence of predominant gait ataxia. Our case emphasizes that focal dystonia is not only a feature of SCA2, but can also rarely be the presenting sign as well as the most prominent feature during the disease course.

Neurological complications associated with arboviruses during Zika outbreak in Salvador, Bahia-Brazil

Background: An unprecedented and concurrent outbreak of Dengue (DENV), Chikungunya (CHIKV) and Zika (ZIKV) virus happened in Brazil in 2015. Approximately 18.372 cases of an acute exanthematous illness were notified in Salvador, Bahia and several cases of Guillain-Barré Syndrome (GBS) raised. Methods & Materials: We started a hospital surveillance for GBS and other neurological syndromes in two general hospitals in Salvador, northeastern Brazil. Results: Twenty-seven cases were included, of which 18 (66%) were female. The mean age was 40 years and 26 (93%) of them had acute symptoms suggestive of arbovirus infection before the onset of neurological symptoms. The main symptoms were skin rash, pruritus, myalgia, and fever. The median time between onset of acute symptoms and neurological symptoms was 10.5 days. Seventeen cases (63%) were classified as GBS, 3 (11%) as acute encephalitis, 2 (7%) as opsoclonus-myoclonus ataxia syndrome (OMS), 2 (7%) as myelitis, 1(4%) as Carpal tunnel syndrome and 1 (4%) as acute disseminated encephalomyelitis (ADEM). GBS cases presented in a variety of clinical spectrum, with 8 (47%) as acute ataxic neuropathy, 5 (29%) as classic GBS, 2 (11%) as bifacial weakness with paraesthesias, 1 (5%) as paraparetic GBS and 1 (5%) as classic Miller-Fischer syndrome. Twelve (44%) patients were admitted to semi-intensive or intensive care units and none died. The arbovirus diagnosis was established in 21(77.8%) of the cases. Serological evaluation by ELISA singly detected IgM-specific DENV antibodies in 3 cases (2 SGB and 1 Myelitis), IgM-specific CHIKV antibodies in 4 cases (3 SGB and 1 myelitis) and IgM-specific ZIKV antibodies in 3 cases (SGB). Six cases had both anti-ZIKV and anti-DENV (2 SGB, 2 encephalitis, 1 ADEM, 1 OMS) with a presumptive ZIKV diagnosis. One case of OMS had a coinfection by CHIKV and DENV-4 established by RT-PCR. Conclusion: Herein, we describe 28 cases of GBS and other neurological syndromes associated with arboviruses. Besides GBS, we also identified cases of encephalitis, ADEM and OMS, a rare syndrome characterized by chaotic eyes movement and ataxia. Thereafter, clinicians and health care providers should be aware of the potential severe neurological complications associated with arbovirus infection in epidemic areas.

Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome

BackgroundLeigh Syndrome (LS, OMIM 256000) is an early-onset, progressive neurodegenerative disorder characterized by broad clinical and genetic heterogeneity; it is the most frequent disorder of mitochondrial energy production in children. LS inheritance is complex because patients may present mutations in mitochondrial DNA (mtDNA) or in nuclear genes, which predominantly encode proteins involved in respiratory chain structure and assembly or in coenzyme Q10 biogenesis. However, during the last 15 years, the discovery of several genetic mutations and improved knowledge of the natural history of LS has significantly increased our understanding of this mitochondrial disorder.Case presentationHere we describe a 19-year-old male with clinical and neuroimaging LS diagnosed at 3 years of age. Genetic analyses of the whole mtDNA for maternally inherited LS (MILS) and neuropathy ataxia retinitis pigmentosa (NARP) syndrome failed to reveal any pathogenic mutations.ConclusionsRecently, a missense mutation in ECHS1 and a ~ 35 kb deletion in 10q26.3 involving the region including the gene were identified by WES (whole exome sequencing), uncovering the genetic diagnosis clinically hypothesized for 15 years. We also report the long-term follow-up of this patient, showing a comparison with classical LS or other Leigh-like pictures.

Eye-tracking technology: A quantitative approach of visual compensation during gait in patients with ataxic neuropathy

Proprioceptive impairment, as in the case of ataxic neuropathy, leads to visual compensation. The techniques of gaze analysis in static condition have been widely explored, but only recent technological innovations have allowed them to be associated with dynamic movements. In this context, we chose to use the eye-tracker glasses to analyze gaze and possible visual strategies established by these patients during gait. Three groups were selected: 15 health young subjects, 15 elderly subjects and 15 subjects with ataxic neuropathy. The experimental protocol consists of walk in a corridor with three different segments wearing the eye-tracker glasses. As for the gaze direction analysis we pre-defined classifications of the image called “observables”: these classifications consists on the time spent looking at the floor, the middle and the side parts of the corridor. We observed a significant difference between the two groups of health subjects and the patients regarding the time spent looking at the “observables”. Fisher's post-hoc results were: floor ( F 2.132 = 37; P ≤ .0001); middle ( F 2.132 = 9,8; P ≤ .0001) and the side parts ( F 2.132 = 11,5; P ≤ .0001). We observed a better reproducibility of the evaluation in the three different segments by analyzing the time spent looking at the floor ( F 4.84 = 1.4; P = .244), where no significant statistical difference on the performance of the subjects were found. The eye-tracker glasses have proven to be a relevant tool for the analysis of visual compensation, both reproducible and sensitive to the pathology. This technology has helped us to quantitatively characterize the visual strategy implemented by ataxic patients during gait.

F33. Cross sectional peripheral nerve area in canvas syndrome (cerebellar ataxia neuropathy vestibular areflexia syndrome)

Introduction Patients with Cerebellar Ataxia Neuropathy Vestibular Areflexia Syndrome (CANVAS) have sensory impairment due to dorsal root ganglionopathy. After preliminary findings of small nerves on ultrasound in CANVAS, we sought to systematically study a larger cohort of CANVAS patients to see if this is a feature of this ganglionopathy and thus distinct from the ultrasound findings in axonal neuropathy. Methods The ultrasound cross sectional area (CSA) of median and ulnar nerves of 14 CANVAS patients was compared with 14 age- and gender-matched healthy controls (HCONT) and 14 age-and gender-matched patients with acquired axonal neuropathy (PNCONT). The individual CSAs of CANVAS and PNCONT patients were also compared with the mean CSA of our reference population. Results The nerve CSA of CANVAS patients was significantly smaller than the CSA of both HCONT and PNCONT at all sites ( P > 2 SDs below a reference mean. Conclusion The small nerves in CANVAS probably reflect nerve thinning from axonal loss secondary to ganglion cell loss. This is in contradistinction to the ultrasound abnormality in PNCONT, in which the nerves are mildly enlarged. Our data show a role for ultrasound in the diagnosis of CANVAS ganglionopathy. This may also be applicable to sensory neuronopathy from other causes.

CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA).

CANOMAD/CANDA are syndromes characterized by ataxic neuropathy, ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl antibodies. A retrospective review of our neuromuscular autoantibody panel database was performed. Anti-GD1b seropositive patients with ataxia were included. Eleven patients were identified. Median age at onset was 56years. Median disease duration was 6years. All patients had gait disorders. Nine had ocular motility abnormalities. Most had a monoclonal protein and all had elevated serum IgM. Electrodiagnostic studies showed a mixed axonal/demyelinating pattern (6), an axonal pattern (4), or a pure demyelinating pattern (1). Ultrasounds showed nerve enlargement patterns consistent with acquired demyelination. A nerve biopsy showed near complete loss of myelinated axons with preservation of smaller axons. Rituximab was the most effective immunotherapy. CANOMAD/CANDA are rare and debilitating disorders with characteristic clinical and diagnostic findings. In our cohort, nerve ultrasound showed regional nerve enlargement and rituximab was the most effective immunomodulatory therapy.

Protein molecular modeling shows residue T599 is critical to wild-type function of POLG and description of a novel variant associated with the SANDO phenotype

Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) is a rare phenotype resulting from pathogenic variants of mitochondrial DNA polymerase gamma (POLG). We modeled a novel POLG variant, T599P, that causes the SANDO phenotype and another variant at the same residue, p.T599E, to observe their effect on protein function and confirm the pathogenicity of T599P. Through neoteric molecular modeling techniques, we show that changes at the T599 residue position introduce extra rigidity into the surrounding helix–loop–helix, which places steric pressure on nearby nucleotides. We also provide a clinical description of the T599P variant, which was found in a 42-year-old female proband. The proband presented a 1-year history of progressive gait instability, dysarthria and foot numbness. Her neurologic examination revealed ataxic dysarthria, restricted eye movements, head and palatal tremors, reduced lower limb reflexes, distal multimodal sensory loss and a wide, unsteady ataxic gait. Electromyography studies indicated a sensory neuropathy. Whole-exome sequencing was pursued after tests for infectious, inflammatory and paraneoplastic causes were negative.

Peripheral nerves are pathologically small in cerebellar ataxia neuropathy vestibular areflexia syndrome: a controlled ultrasound study.

Sensory neuronopathy is a cardinal feature of cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these patients with CANVAS and seven healthy controls. We compared the ultrasound cross-sectional area of median, ulnar, sural and tibial nerves of 14 patients with CANVAS with 14 healthy controls and 14 age- and gender-matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross-sectional areas of patients with CANVAS and neuropathy with the reference values of our laboratory control population. The nerve cross-sectional area of patients with CANVAS was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites (P < 0.001). Conversely, the nerve cross-sectional areas in the upper limb were larger in neuropathy controls than healthy controls (P < 0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one patient with CANVAS. Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy.