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A 30-year-old woman developed symptoms, signs and neurophysiology consistent with Guillain-Barré syndrome and was admitted to the neurosciences intensive care unit owing to respiratory compromise. Here, she received a clonidine infusion for agitation, complicated by a minor hypotensive episode, following which she became unconscious. MR scan of the brain showed changes compatible with hypoxic brain injury. Urinary amino acids showed increased urinary α-ketoglutarate. Genetic testing using whole-exome sequencing identified pathogenic variants in the SLC13A3 gene known to be associated with an acute reversible leukoencephalopathy with increased urinary α-ketoglutarate. The case highlights the importance of considering inborn errors of metabolism in cases of unexplained encephalopathy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cerebrotendinous xanthomatosis (CTX) is a rare inborn error of bile acid metabolism that manifests as a triad of neurological dysfunction (usually ataxia), tendon xanthomata and early-onset cataracts. We describe three patients with CTX, two of whom presented to a specialist ataxia clinic without a diagnosis. The third patient presented to a neuromuscular clinic. We discuss the clinical features, pathophysiology and treatment of CTX. As the condition is treatable, this is a neurological rarity not to be missed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Editorial. Focuses on coeliac disease or gluten sensitivity enteropathy. History of the treatment of coeliac disease; Association between neurological disorders and adult coeliac disease; Typical clinical manifestation of a patient with gluten sensitivity.

Introduction type 1 diabetes mellitus is associated with an increase in gastrointestinal symptoms and other gastrointestinal diseases such as coeliac disease. There is conflicting data regarding the association of inflammatory bowel disease (IBD) with type 1 diabetes. The authors aimed to determine the prevalence of IBD in type 1 diabetes and assess the effect of quality of life and glycaemic control. Methods Patients with type 1 diabetes were recruited from the diabetes centre and a gastrointestinal symptom questionnaire completed. Quality of life was assessed using the short form 36 version 2 (SF-36) questionnaire and glycaemic control assessed using HbA1c. Controls were selected from the diabetes cohort matched for age and sex in a 2:1 ratio for comparison of quality of life and glycaemic control. Non-diabetic controls were recruited locally and were administered the same questionnaires. Prevalence of IBD and quality of life scores were compared between the groups. Results 662 individuals with type 1 diabetes and 602 controls were recruited into the study. The prevalence of IBD was 12/662 (1.5%) in those with type 1 diabetes and 2/602 (0.3%) in controls (OR 5.5, 1.2–24.9, p<0.013). In those with diabetes, HbA1c was 7.7 in those with IBD compared to 7.5 in those without IBD (p=NS). Symptom burden was higher in people with type 1 diabetes and IBD compared to diabetes only (median 2.0 vs 1.0, p=0.009). Quality of life scores were significantly lower in the general health and vitality domains compared to diabetes only (p=0.004 and 0.041 respectively). There was a trend to lower scores in the social functioning and mental health composite scores. Conclusion IBD is more common in type 1 diabetes than the general population although the mechanism is uncertain but may be related to autoimmunity. Quality of life is adversely affected by having both IBD and type 1 diabetes but this could not be explained by changes in glycaemic control. [ABSTRACT FROM PUBLISHER]

Introduction Gastrointestinal symptoms are more common in people with Type 1 diabetes than the non-diabetic population. Irritable bowel symptoms (IBS) are associated with reduced quality of life in non-diabetic cohorts but the prevalence in Type 1 diabetes is not clear. Similarly the effect on quality of life is unknown. The aim of this study was to examine the prevalence of IBS in Type 1 diabetes compared to non-diabetic controls and the effect upon quality of life. Methods Patients with Type 1 diabetes were recruited from the diabetes centre and a gastrointestinal symptom questionnaire completed. Quality of life was assessed using the short form 36 version 2 (SF-36) questionnaire and glycaemic control assessed using HbA1c. Non-diabetic controls were recruited locally and were administered the same questionnaires. Prevalence of IBS symptoms (as judged by the Rome II criteria) and quality of life scores were compared between the groups. Results 662 individuals with Type 1 diabetes and 602 controls were recruited into the study. The prevalence of IBS was 106/662 (16%) in those with Type 1 diabetes and 48/602 (7.9%) in controls (OR 2.2, 1.5–3.1, p<0.001). In those with diabetes, HbA1c was 8.3 in those with IBS compared to 8.0 in those without IBS (p=ns). Symptom burden was not significantly different when comparing people with Type 1 diabetes and IBS and controls with IBS. Quality of life scores were significantly lower in all domains in people with Type 1 diabetes and IBS symptoms compared to people with Type 1 diabetes without IBS symptoms and non-diabetic controls with and without IBS (p<0.001). In the non-diabetic group IBS symptoms were associated with lower quality of life scores in the bodily pain, general health and physical composite score domains (all p<0.05). Conclusion IBS symptoms are more common in people with Type 1 diabetes compared to controls. Patients with Type 1 diabetes and IBS have worse quality of life scoresthan Type 1 diabetes patients without IBS symptoms and non-diabetic controls with or without IBS. The quality of life differences between Type 1 diabetes patients with and without IBS could not be explained by glycaemic control. Quality of life scores were lower in non-diabetic subjects with IBS compared to non-diabetic controls. The relationship between IBS and Type 1 diabetes is poorly understood – however our data suggest that questioning diabetic patients about IBS and addressing these symptoms may be beneficial to the patient. [ABSTRACT FROM PUBLISHER]

Introduction Coeliac disease (CD) is more common in people with type 1 diabetes than in the general population. We have previously shown that patients with type 1 diabetes and newly identified CD have worse glycaemic control, lipid profile, renal involvement and retinal disease. Patients with positive antibodies but a normal duodenal biopsy may also have gluten related complications but this has not been investigated in patients with coexisting type 1 diabetes. Methods 1000 patients with type 1 diabetes were recruited and 14 new cases CD were identified. Patients with positive EMA and/or tissue transglutaminase but a normal duodenal biopsy were compared to the newly diagnosed CD and a matched cohort of patients with negative antibodies. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined. Results 51 patients were included in the study (14 CD/diabetes, 22 potential CD and 14 diabetes only). There were no differences in age, gender, BMI and diabetes duration between the groups. Median HbA1c, total cholesterol, HDL cholesterol and cholesterol:HDL ratio was not significantly different in those with potential CD compared to diabetes only controls unlike those with CD/diabetes. There were no significant differences in quality of life scores between any of the groups. The prevalence of retinopathy was not significantly different between the groups but the prevalence of advanced lesions was higher in those with CD/diabetes (p=0.02). The prevalence of nephropathy was not significantly different between groups but patients with CD/diabetes had a higher prevalence of advanced renal disease (p=0.009). There was no difference in the prevalence of neuropathy between the groups. Conclusion In type 1 diabetes, enteropathy as well as antibody positivity is required to increase diabetes related complications whereas antibody positivity alone does not. The numbers in this study are small and therefore confirmation in a larger study would be desirable. [ABSTRACT FROM PUBLISHER]

Introduction Historically Brunner's glands were thought to interfere with interpretation of villous atrophy in the duodenal bulb. Recent reports suggest that the duodenal bulb may be the only site to demonstrate villous atrophy (VA) in coeliac disease (CD). There are few data on the prevalence of lesions in non-coeliac patients. Methods We aimed to compare the histological findings in the duodenal bulb and distal duodenum of patients with CD against controls having gastroscopy with duodenal biopsy. Indications included positive coeliac serology, family history, diarrhoea, and iron deficiency anaemia. A total of 461 patients were prospectively recruited. Biopsies were graded using the Marsh criteria by a single pathologist blinded to the clinical information. Results 461 patients, (300 female, 161 male) median age 50 years (range 16–89) were analysed. 24 patients had VA in the bulb only, 6 had VA in distal duodenum only (p=0.001) (). 1 control patient with HIV enteropathy had VA at both sites. CD in remission showed greater histological variability than new diagnosis CD (p=0.0018) and controls (p=0.0001) OC-105 Histology and serology in new diagnosis coeliac disease, coeliac disease in remission, and controls Conclusion Villous atrophy may be present only in the duodenal bulb. In this study 11/126 (9%) of new diagnosis CD and 12/85 (14%) of CD in remission demonstrated VA in the bulb alone. We recommend taking a biopsy from the bulb as well as the distal duodenum to diagnose suspected coeliac disease and reassess known cases. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Previous investigators have suggested that the only role for enteroscopy in coeliac disease (CD) is in the assessment of refractory cases. We assessed the value of enteroscopy in making the diagnosis of CD. Methods: 31 patients (22 female, 9 male) were recruited prospectively from September 2001 to October 2002. Mean age 52.7 years (range 20-80 years). Clinical indications for investigating For CD were anaemia (n = 12), diarrhoea (n = 9), irritable bowel syndrome (n = 7), family history of CD (n = 1), elevated transaminases (n = 1), and abdominal pain (n = 1). All patients were tested using a combination of immunoglobulins, IgG and IgA gliadin antibodies (AGA) and endomysial antibody (EMA). Of the 31 cases, 8 were EMA positive (alone or in combination with either AGA) and 23 had positive IgG and/or IgA AGA. Initial quadrantic duodenal biopsies showed intraepithelial lymphocytes in 16 cases and normal mucosa in the other 15. In view of the clinical indications and positive antibody titres we proceeded to enteroscopy with repeat quadrantic duodenal biopsies (×4) and separate distal small bowel biopsy (×4). Results: A single investigator performed push enteroscopy. Mean depth of insertion was 115 cm beyond the pylorus (range 95-135 cm). All samples were reviewed by a gastrointestinal histopathologist and compared with the initial duodenal biopsy. The diagnosis of CD could not be confirmed from either the 2nd duodenal biopsy or small bowel biopsy in all 23 cases that were only AGA positive. For the 8 EMA positive cases, repeat biopsy proved the diagnosis of CD in 5 cases (AGA group vs EMA: Fisher exact t test p < 0.0001). Of these 5 cases, 3 only had evidence of villous atrophy in the distal small bowel biopsy. Conclusion: EMA positive patients in whom the diagnosis of CD has not been confirmed after duodenal biopsy may benefit from repeat biopsy. In 3 of the 5 cases the diagnostic information was only apparent in the distal small... [ABSTRACT FROM AUTHOR]

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.)

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.