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Background: Biallelic expansion of AAGGG in the replication factor complex subunit 1 ( RFC1 ) was identified as a major cause of cerebellar ataxia, neuropathy (sensory ganglionopathy, or SG) and vestibular areflexia syndrome (CANVAS). We wanted to clarify if RFC1 expansions can present with pure ataxia and if such expansions could be responsible for some cases where an alternative diagnosis had been made., Methods: We identified patients with a combination of ataxia and SG and no other cause found, patients where an alternative diagnosis had been made, and patients with pure ataxia. Testing for RFC1 expansions was done using established methodology., Results: Among 54 patients with otherwise idiopathic sporadic ataxia without SG, none was found to have RFC1 expansions. Among 38 patients with cerebellar ataxia and SG in which all other causes were excluded, 71% had RFC1 expansions. Among 27 patients with cerebellar ataxia and SG diagnosed with coeliac disease or gluten sensitivity, 15% had RFC1 expansions., Conclusions: Isolated cerebellar ataxia without SG makes the diagnosis of CANVAS due to RFC1 expansions highly improbable, but CANVAS is frequently the cause of the combination of idiopathic cerebellar ataxia with SG. It is important to screen patients diagnosed with other causes of acquired ataxia and SG as a small percentage were found to have RFC1 expansions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia., Methods: All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated., Results: A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%., Conclusions: Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To examine the extent of brain abnormality in patients with coeliac disease referred for neurological opinion and evaluate MR imaging sequences as biomarkers for neurological dysfunction, given the lack of readily available serological markers of neurological disease in this cohort., Methods: Retrospective examination of a consecutive cohort of patients (n = 33, mean age = 44 ± 13 years (range 19-64)) with biopsy proven coeliac disease referred for neurological opinion. Patients were divided into subgroups based on their primary neurological complaint (balance disturbance, headache and sensory loss). 3T MR was used to evaluate differences in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between subjects and controls., Results: Cerebellar volume was significantly less in the patient group than in controls (6.9 ± 0.7% vs 7.4 ± 0.9% of total intracranial volume, p<0.05). Significantly less grey matter density was found in multiple brain regions, both above and below the tentorium cerebelli, than in controls (p<0.05). 12 (36%) patients demonstrated WMAs unexpected for the patient's age, with the highest incidence occurring in the headache subgroup. This subgroup averaged almost twice the number of WMAs per MR imaging than the subgroup with balance disturbance and six times more than the subgroup with sensory loss., Conclusion: Patients with established coeliac disease referred for neurological opinion show significant brain abnormality on MR imaging. MR imaging may provide valuable biomarkers of disease in this patient cohort.

We describe a 47-year-old male who presented with acute renal failure and later developed bilateral facial weakness, complete ophthalmoplegia, flaccid tetraparesis and diminished sensation in the extremities. Renal biopsy and urine toxicology were consistent with ethylene glycol intoxication. Sequential neurophysiological examinations revealed sensory nerve axonal loss, proximal motor nerve conduction block and a proximodistal type of axonal degeneration. Seven months after ingestion, the patient improved and was able to walk unaided but with residual bilateral facial weakness and distal sensory loss.

We report a novel transthyretin variant, Gly53Ala, in a 44-year-old British woman who presented with severe episodic headaches, often with focal neurological deficit, before developing progressive ataxia, depression, dementia and eventually peripheral neuropathy. Transthyretin amyloidosis was confirmed on biopsy of the heart muscle. Serum amyloid P component scintigraphy did not show visceral amyloid in extra-cardiac sites, but magnetic resonance imaging indicated diffuse leptomeningeal amyloidosis.

Objectives: To prospectively study the clinical, neurophysiological and neuropathological characteristics of axonal neuropathies associated with positive antigliadin antibodies and the prevalence of such neuropathies in a cohort of patients with sporadic axonal neuropathy., Methods: Prospective screening (using antigliadin, antiendomysium and tissue transglutaminase antibodies) of patients with peripheral neuropathy attending a neurology clinic., Results: 215 patients with axonal neuropathy were screened. 141 patients had symmetrical sensorimotor neuropathy, 47 had mononeuropathy multiplex, 17 had motor neuropathy and 10 had small-fibre neuropathy. Despite extensive investigations of the 215 patients, 140 had idiopathic neuropathy. Positive immunoglobulin (Ig)G with or without IgA antigliadin antibodies was found in 34% (47/140) of the patients with idiopathic neuropathy. This compares with 12% prevalence of these antibodies in the healthy controls. The prevalence of coeliac disease as shown by biopsy in the idiopathic group was at least 9% as compared with 1% in the controls. The clinical features of 100 patients (47 from the prevalence study and 53 referred from elsewhere) with gluten neuropathy included a mean age at onset of 55 (range 24-77) years and a mean duration of neuropathy of 9 (range 1-33) years. Gluten-sensitive enteropathy was present in 29% of patients. The human leucocyte antigen types associated with coeliac disease were found in 80% of patients., Conclusions: Gluten sensitivity may be aetiologically linked to a substantial number of idiopathic axonal neuropathies.

Gluten sensitivity can manifest with ataxia. The metabolic status of the cerebellum was investigated in 15 patients with gluten ataxia and 10 controls using proton MR spectroscopy. Significant differences were present in mean N-acetyl aspartate levels at short echo time and N-acetyl aspartate/choline ratios at long echo time between the patient and control groups. These data support the hypothesis that cerebellar neuronal physiology differs between patients with gluten ataxia and healthy controls.

Background: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken., Objective: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity., Methods: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis., Results: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy., Conclusions: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

Background: Spontaneous intracranial hypotension (SIH) is characterised by postural headache and low opening pressure at lumbar puncture without obvious cause. Cranial magnetic resonance imaging often shows small subdural collections without mass effect, dural enhancement, venous sinus dilatation, or downward displacement of the brain. The condition is thought to be benign., Objectives: To evaluate the incidence of subdural haematoma as a serious complication of SIH., Methods: A prospective survey of all cases of SIH presenting to a large neuroscience unit over a two year period., Results: Nine cases of SIH were seen. Four of these were complicated by acute clinical deterioration with reduced conscious level because of large subdural haematomas requiring urgent neurosurgical drainage., Conclusions: SIH should not be considered a benign condition. Acute deterioration of patients' clinical status may occur secondary to large subdural haematomas, requiring urgent neurosurgical intervention.

Objectives: To describe the range of neuromuscular disorders which may be associated with cryptic coeliac disease., Methods: Nine patients were described with neuromuscular disorders associated with circulating antigliadin antibodies, whose duodenal biopsies later confirmed the diagnosis of coeliac disease. Neurological symptoms antedated the diagnosis of coeliac disease in all, and most had minimal or no gastrointestinal symptoms at the onset of the neuromuscular disorder., Results: Three patients had sensorimotor axonal peripheral neuropathy, one had axonal motor peripheral neuropathy, one had probable inclusion body myositis and axonal motor peripheral neuropathy, one had polymyositis and sensorimotor peripheral neuropathy, one had mononeuropathy multiplex, one had neuromyotonia, and one had polyneuropathy., Conclusion: A wide range of neuromuscular disease may be the presenting feature of coeliac disease. This represents the first report of inclusion body myositis and neuromyotonia associated with coeliac disease. Estimation of circulating antigliadin antibodies should be considered in all patients with neuromuscular disease of otherwise obscure aetiology.