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Eye movements are fundamental diagnostic and progression markers of various neurological diseases, including those affecting the cerebellum. Despite the high prevalence of abnormal eye movements in patients with cerebellar disorders, the traditional rating scales do not focus on abnormal eye movements. We formed a consortium of neurologists focusing on cerebellar disorders. The consortium aimed to design and validate a novel Scale for Ocular motor Disorders in Ataxia (SODA). The primary purpose of the scale is to determine the extent of ocular motor deficits due to various phenomenologies. A higher score on the scale would suggest a broader range of eye movement deficits. The scale was designed such that it is easy to implement by non-specialized neurological care providers. The scale was not designed to measure each ocular motor dysfunction's severity objectively. Our validation studies revealed that the scale reliably measured the extent of saccade abnormalities and nystagmus. We found a lack of correlation between the total SODA score and the total International Cooperative Ataxia Rating Scale (ICARS), Scale for Assessment and Rating of Ataxia (SARA), or Brief Ataxia Rating Scale (BARS). One explanation is that conventionally reported scales are not dedicated to eye movement disorders; and when present, the measure of ocular motor function is only one subsection of the ataxia rating scales. It is also possible that the severity of ataxias does not correlate with eye movement abnormalities. Nevertheless, the SODA met the consortium's primary goal: to prepare a simple outcome measure that can identify ocular motor dysfunction in patients with cerebellar ataxia., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest pertinent to this work., (Published by Elsevier B.V.)

Purpose: Biallelic variants in UCHL1 have been associated with a progressive early-onset neurodegenerative disorder, autosomal recessive spastic paraplegia type 79. In this study, we investigated heterozygous UCHL1 variants on the basis of results from cohort-based burden analyses., Methods: Gene-burden analyses were performed on exome and genome data of independent cohorts of patients with hereditary ataxia and spastic paraplegia from Germany and the United Kingdom in a total of 3169 patients and 33,141 controls. Clinical data of affected individuals and additional independent families were collected and evaluated. Patients' fibroblasts were used to perform mass spectrometry-based proteomics., Results: UCHL1 was prioritized in both independent cohorts as a candidate gene for an autosomal dominant disorder. We identified a total of 34 cases from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17). The mass spectrometry-based proteomics showed approximately 50% reduction of UCHL1 expression in patients' fibroblasts., Conclusion: Our bioinformatic analysis, in-depth clinical and genetic workup, and functional studies established haploinsufficiency of UCHL1 as a novel disease mechanism in spastic ataxia., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. All rights reserved.)

Background: The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta-analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied., Methods: After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups., Results: Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%-3.2%) and 2.7% (95% CI 2.0%-3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%-22.6%) and 13.6% (95% CI 11.6%-15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75-3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta-analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14-7.40) and 2.93 times higher (95% CI 1.41-6.07), respectively, in the active treatment groups compared to placebo., Conclusions: TMS is a safe and well-tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice., (© 2019 International Neuromodulation Society.)

Introduction: Nocebo, the negative counterpart of the placebo phenomenon results in the induction of adverse events (AEs) following the administration of an inert substance. Nocebo has been demonstrated to be associated with low treatment compliance in clinical trials, thus affecting treatment outcomes. This study sought to determine the prevalence of nocebo in cerebellar ataxia., Methods: A systematic literature search was conducted on Pubmed for randomized controlled trials (RCTs) for cerebellar ataxia treatments. The number of drug-related AEs and the number of withdrawals due to drug intolerance in the placebo group were statistically analysed., Results: The literature search identified 214 studies, of which 6 studies fulfilled the inclusion criteria. Approximately 1 in 20 (4.8%) placebo-treated patients withdrew treatment due to AEs and approximately 1 in 7 (13.8%) placebo-treated participants reported at least one AE. Participants in cerebellar ataxia trials reported similar AEs across both treatment groups (active and placebo)., Conclusion: Our results demonstrate that the nocebo effect in cerebellar ataxia is amongst the lowest in neurological diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Pain is a frequent and debilitating non-motor symptom of Idiopathic Parkinson's Disease (IPD). The present study investigated the prevalence of pain and specifically peripheral neuropathic pain (PNP) in IPD, and ascertained any impact of PNP on quality of life (QoL)., Methods: Patients with IPD and age- and gender-matched controls were screened for overall pain using the King's Parkinson's Pain Scale (KPPS). PNP was assessed using the Michigan Neuropathy Screening Instrument (MNSI). QoL was assessed using the 36-Item Short Form Survey (SF-36)., Results: Fifty-one patients and 51 age and gender matched controls were recruited. The prevalence of overall pain was similar in the two groups (88.2% versus 94.1%, p = 0.487). However, patients with IPD had higher KPPS scores in fluctuation-related (4.9 ± 6.9 vs 1.1 ± 2.6, p < 0.001), nocturnal (6.6 ± 7.5 vs 1.7 ± 4.2, p < 0.001) and oro-facial (0.6 ± 2.0 vs 0.0 ± 0.0, p = 0.040) domains compared to controls. Patients with IPD experienced more PNP compared to healthy control subjects (35.3% versus 13.7%, p = 0.011). After adjusting for age, gender, disease duration and overall KPSS score, PNP correlated negatively with physical functioning score (beta -0.290, p = 0.036), emotional role limitations score (beta -0.319, p = 0.032) and general health perception score (beta -0.342, p = 0.014) domains of SF-36., Conclusion: Peripheral neuropathic pain is prevalent in IPD and has a significant impact on QoL. The presence of burning pain is suggestive of small fibre neuropathy, but this symptom is not featured in KPSS and, therefore, a revision of the KPSS should be considered., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Nocebo is very prevalent among neurological disorders, resulting in low adherence and treatment outcome. We sought to examine the adverse events (AE) following placebo administration in placebo-controlled randomized clinical trials (RCTs) for chronic inflammatory demyelinating polyneuropathy (CIDP)., Methods: After a systematic literature search for RCTs for CIDP pharmacotherapy treatments, we assessed the number of AE in the placebo groups and the number discontinuations because of placebo intolerance., Results: Our literature search strategy revealed 82 papers. Data were extracted from three RCTs fulfilling our inclusion criteria. Approximately two in five placebo-treated patients (42.0%) reported at least one AE and approximately one in fifty placebo-treated patients discontinued placebo treatment because of AEs (2.1%). All patients participating in the CIDP trials reported similar AEs independently of the study arm they belonged., Conclusion: Compared to other neurological diseases the nocebo effect in CIDP is significantly smaller., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Axillary nerve lesions can commonly occur secondary to trauma or brachial plexopathy. Our aim was to describe our technique of axillary nerve motor conduction studies and provide the respective normal values., Methods: Active electrode was positioned over the most prominent portion of the middle deltoid, approximately 5-7 cm distal to the acromion. Reference electrode was positioned over the acromion. Ground electrode was placed between the active and the reference electrodes. Supramaximal stimulation was at the Erb's point., Results: A total of 154 participants (61% male, age range 18-84) were included. There was a significant positive correlation between the subjects' age and the onset latency (Spearman's rho 0.312, p < 0.001) and a significant negative correlation between the participants' age and the CMAP (Spearman's rho -0.481, p < 0.001). For the total male population the lower normal value for the CMAP was 7.6 mV and the higher normal value for the onset latency was 5.0 ms. For the total female population the respective normal values were 6.5 mV and 3.5 ms. In order to detect an axillary nerve lesion, asymmetry of >40% in the CMAPS between the symptomatic and the asymptomatic side show a sensitivity of 95.2% and a specificity of 96.6%., Conclusion: We described our technique of axillary nerve motor conduction studies and provided the respective normal values stratified for age and gender. When suspecting an axillary nerve lesion it is always worth performing axillary motor NCS bilaterally and compare the CMAPs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Phenytoin is an effective anticonvulsant for focal epilepsy. Its use can be associated with long-term adverse effects including cerebellar ataxia. Whilst phenytoin is toxic to Purkinje cells in vitro; the clinical and radiological phenotype and mechanism of cerebellar degeneration in vivo remain unclear. We describe the prevalence, clinical and radiological characteristics of phenytoin-related ataxia., Methods: Patients with epilepsy receiving treatment with phenytoin were recruited from the Epilepsy clinics at Royal Hallamshire Hospital, Sheffield, UK. Neurological examination was performed on all patients after recruitment. Patients were categorised into those with and without ataxia. We determined the severity of ataxia clinically (SARA score) and the pattern of cerebellar involvement by neuroimaging (MRI volumetry and MR spectroscopy)., Results: Forty-seven patients were recruited. Median duration of epilepsy was 24 years, median duration of phenytoin treatment was 15 years and current median phenytoin daily dose was 325 mg. Fifty-five percent of patients complained of poor balance. Clinical evidence of ataxia was seen in 40% patients. Gait, stance and heel-shin slide were the predominant features of cerebellar dysfunction. MRI demonstrated structural, volumetric and functional deficits of the cerebellum. Only one patient with ataxia had phenytoin levels above the normal range., Conclusions: Cerebellar ataxia is present in 40% of patients with epilepsy and chronic exposure to phenytoin. Patients on long-term phenytoin have reduced cerebellar volume even if they have no clinical evidence of ataxia. Evidence of structural deficits on imaging suggests a predilection for vermian involvement., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the origin and dynamic characteristics of the generalised hyper-synchronous spike and wave (SW) discharges in childhood absence epilepsy (CAE)., Methods: We applied nonlinear methods, the error reduction ratio (ERR) causality test and cross-frequency analysis, with a nonlinear autoregressive exogenous (NARX) model, to electroencephalograms (EEGs) from CAE, selected with stringent electro-clinical criteria (17 cases, 42 absences). We analysed the pre-ictal and ictal strength of association between homologous and heterologous EEG derivations and estimated the direction of synchronisation and corresponding time lags., Results: A frontal/fronto-central onset of the absences is detected in 13 of the 17 cases with the highest ictal strength of association between homologous frontal followed by centro-temporal and fronto-central areas. Delays consistently in excess of 4 ms occur at the very onset between these regions, swiftly followed by the emergence of "isochronous" (0-2 ms) synchronisation but dynamic time lag changes occur during SW discharges., Conclusions: In absences an initial cortico-cortical spread leads to dynamic lag changes to include periods of isochronous interhemispheric synchronisation, which we hypothesize is mediated by the thalamus., Significance: Absences from CAE show ictal epileptic network dynamics remarkably similar to those observed in WAG/Rij rats which guided the formulation of the cortical focus theory., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: TG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies)., Methods: This was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy., Results: Twenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy., Conclusions: We found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has also been linked to levodopa exposure., Objective: The aim of this systematic review is to clarify any evidence of peripheral nervous system involvement in idiopathic PD., Methods: A systematic computer-based literature search was conducted on PubMed database., Findings: The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on 1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber neuropathy was 56.9% (based on 72 patients). Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy and very occasional cases of acute neuropathies. Although nerve conduction studies have been performed in the majority of the studies, they included only a limited number of nerves, mainly in the lower limbs. There is little evidence to support a direct link between levodopa treatment and the development of PN in idiopathic PD. In the majority of the cases PN has been linked to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels. Additional aetiological risk factors for PN may be responsible for any apparent link between PD and PN., Conclusions: Large-scale prospective studies with long-term follow-up with detailed baseline assessments are needed in order to understand the natural history of PN in PD, both on clinical and neurophysiological parameters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: Coeliac disease (CD) is more common in people with Type 1 diabetes and is associated with poorer glycaemic control, lipid profiles, nephropathy and retinopathy. Potential CD (positive serology but normal duodenal biopsy) is associated with neuropathy but patients with coexisting Type 1 diabetes were excluded. The aim was to determine whether potential CD is associated with increased microvascular complications in patients with Type 1 diabetes., Methods and Results: Four groups were recruited; 1) patients with Type 1 diabetes and potential CD, 2) patients with Type 1 diabetes and newly identified CD, 3) patients with Type 1 diabetes alone and 4) patients with CD alone. Glycaemic control, quality of life, lipid profile and microvascular complication rates were examined. As many as 76 individuals were included in the study: 22 in group 1, 14 in group 2, 24 in group 3 and 16 in group 4. There were no differences in age, gender, BMI and diabetes duration between the groups. Patients in group 1 had significantly lower total cholesterol compared to group 3 (p = 0.003) but higher than group 2 (p = 0.027). There were no significant differences in HbA1c, HDL cholesterol, cholesterol:HDL ratio, creatinine, quality of life scores or prevalence of neuropathy between individuals in group 1 and the other groups., Conclusions: This is the first study to assess the effects of potential CD in patients with Type 1 diabetes. It appears that an enteropathy is required as well as antibody positivity in order to increase the risk of diabetes related complications. This pilot data requires further longitudinal validation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To introduce a new method of quantitative EEG analysis in the time domain, the error reduction ratio (ERR)-causality test. To compare performance against cross-correlation and coherence with phase measures., Methods: A simulation example was used as a gold standard to assess the performance of ERR-causality, against cross-correlation and coherence. The methods were then applied to real EEG data., Results: Analysis of both simulated and real EEG data demonstrates that ERR-causality successfully detects dynamically evolving changes between two signals, with very high time resolution, dependent on the sampling rate of the data. Our method can properly detect both linear and non-linear effects, encountered during analysis of focal and generalised seizures., Conclusions: We introduce a new quantitative EEG method of analysis. It detects real time levels of synchronisation in the linear and non-linear domains. It computes directionality of information flow with corresponding time lags., Significance: This novel dynamic real time EEG signal analysis unveils hidden neural network interactions with a very high time resolution. These interactions cannot be adequately resolved by the traditional methods of coherence and cross-correlation, which provide limited results in the presence of non-linear effects and lack fidelity for changes appearing over small periods of time., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The term gluten-related disorders (GRD) encompasses a spectrum of systemic autoimmune diseases with diverse manifestations. GRD are characterized by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Celiac disease (CD) or gluten-sensitive enteropathy is only one of a number of GRD. Extraintestinal manifestations include dermatitis herpetiformis (DH) and neurologic dysfunction. Furthermore it is only recently that the concept of extraintestinal manifestations without enteropathy has become accepted. In this chapter we review the spectrum of neurologic manifestations in GRD, discuss recent advances in their diagnosis, and look at their possible pathophysiologic mechanisms., (© 2014 Elsevier B.V. All rights reserved.)

The cerebellum, and in particular the Purkinje cells within it, appear to be a frequent immunological target in the context of some systemic diseases. This is perhaps more often the case with the cerebellum by comparison to other structures within the central nervous system. This observation may relate to the fact that the cerebellum is one of the largest, oldest, and most structurally conserved structures in the vertebrate nervous system and/or that Purkinje cells possess good and multiple antigenic targets. Immune-mediated ataxias include paraneoplastic cerebellar degeneration and post-infective cerebellitis, but these will be discussed elsewhere. This chapter covers in detail the epidemiology, clinical characteristics, pathophysiology, and treatment of some other examples of immune-mediated ataxias, including gluten ataxia and ataxia associated with anti-GAD antibodies. There is particular emphasis on gluten ataxia as this is one of the commonest immune-mediated cerebellar ataxias and one of the few ataxias that are potentially treatable. The chapter also introduces the concept of primary autoimmune cerebellar ataxia as a form of organ-specific autoimmune disease for the first time. The pathophysiology leading to cerebellar damage, loss of Purkinje cells, and the development of ataxia remains speculative, but existing clues are discussed in detail., (2012 Elsevier B.V. All rights reserved.)

Background: Familial amyloidotic polyneuropathy (FAP) TTR Val30Met is a lethal autosomal dominant sensorimotor and autonomic neuropathy due to a substitution of methionine for valine at position 30 of the transthyretin (TTR) gene. Amyloid, composed of mutated TTR, is deposited in the peripheral nervous system, myocardium and kidneys. Considerable variability in the age of onset and penetrance of the disease occurs in different countries. Penetrance in Sweden, Cyprus and Portugal is 2%, 28% and 80% respectively. Environmental and genetic factors are believed to contribute to this variability. So far, no single modifier gene has been unequivocally associated with age of onset or penetrance., Methods: Candidate modifier genes were chosen from among those coding for chaperone proteins co-localized with TTR deposits in peripheral nerves. Seventy one TTRVal30Met carriers, 51 affected and 20 asymptomatic, belonging to 22 unrelated Greek-Cypriot families, and 59 normal controls were recruited for this study. Sequencing of the coding regions of TTR, serum amyloid P (APCS) and complement C1Q (A, B and C) genes was performed and APOE genotypes were determined. We searched for correlations between various polymorphisms of chaperone proteins and age of disease onset., Results: Four new and 4 previously described single nucleotide substitutions were identified. One polymorphic site in C1QA (rs172378) and one in C1QC (rs9434) as well as the epsilon2 allele correlated with age of onset (p<0.05)., Conclusions: Our study has identified polymorphisms which may influence the FAP-TTR Val30Met phenotype. Identifying modifier genes and their protein products may contribute to therapeutic advances.

The number of autoimmune disorders that may involve the nervous system is increasing. The diagnosis of neurological involvement in the context of systemic diseases may be helped by the detection of autoantibodies reacting against neural autoantigens. If the autoantigen is not known but the target tissue is suspected, immunohistochemistry is one of the main techniques used to certify the presence of autoantibodies. Autoreactive antibodies are also present in the healthy population but in low quantity compared to patients with such diseases. Quantification of such autoantibodies could help to discriminate between disease and healthy states. We have developed a densitometric immunohistological method for the evaluation of human serum anti-neural reactivity. Using a densitometric analysis of rat brain sections incubated with the serum from 107 healthy subjects, we have defined the baseline of natural anti-neural autoreactivity, and the cut-off for subsequent quantification of anti-neural reactivity in patients with neurological involvement in the context of autoimmune diseases, including systemic lupus erythematosus, paraneoplastic cerebellar degeneration, and stiff person syndrome. The test sensitivity was 81% with a positive predictive value of 52%, a specificity of 89% with a negative predictive value as high as 97%. In conclusion, this standardised semi-quantitative procedure makes immunohistochemistry a reliable diagnostic test for autoimmune neuropathologies and represents an excellent exclusion test for anti-neural autoimmunity.

Background: Ataxia is the commonest neurological manifestation of coeliac disease. Some individuals with genetic susceptibility to the disease have serological evidence of gluten sensitivity without overt gastrointestinal symptoms or evidence of small-bowel inflammation. The sole manifestation of disease in such patients may be ataxia. We describe the clinical, radiological, and neurophysiological features of this disorder., Methods: Patients with ataxia attending the neurology outpatient clinics at the Royal Hallamshire Hospital, Sheffield, UK, were screened for gluten sensitivity as shown by the titre of antibody to gliadin. Those with other causes of ataxia were excluded. We carried out clinical, neurophysiological, neuroradiological, and, in two cases, neuropathological examinations., Findings: 28 patients with gluten ataxia were identified. All had gait ataxia and most had limb ataxia. Those with more severe gait ataxia had longer disease duration. No patient had tremor or other extrapyramidal features. 19 patients showed some form of peripheral neuropathy on neurophysiological examination. 16 patients had no gastrointestinal symptoms. Distal duodenal biopsy showed lymphocytic infiltration in two patients, and changes compatible with coeliac disease in 11. Six patients had evidence of cerebellar atrophy on magnetic-resonance imaging. Necropsy was done on two patients who died; there was lymphocytic infiltration of the cerebellum, damage to the posterior columns of the spinal cord, and sparse infiltration of the peripheral nerves., Interpretation: Gluten sensitivity is an important cause of apparently idiopathic ataxia and may be progressive. The ataxia is a result of immunological damage to the cerebellum, to the posterior columns of the spinal cord, and to peripheral nerves. We propose the term gluten ataxia to describe this disorder.

Background: Antigliadin antibodies are a marker of untreated coeliac disease but can also be found in individuals with normal small-bowel mucosa. Because neurological dysfunction is a known complication of coeliac disease we have investigated the frequency of antigliadin antibodies, as a measure of cryptic gluten sensitivity, and coeliac disease in neurological patients., Methods: Using ELISA, we estimated serum IgG and IgA antigliadin antibodies in 147 neurological patients who were divided into two groups. There were 53 patients with neurological dysfunction of unknown cause despite full investigation (25 ataxia, 20 peripheral neuropathy, 5 mononeuritis multiplex, 4 myopathy, 3 motor neuropathy, 2 myelopathy). The remaining 94 patients were found to have a specific neurological diagnosis (16 stroke, 12 multiple sclerosis, 10 Parkinson's disease, 56 other diagnoses) and formed the neurological control group. 50 healthy blood donors formed a third group., Findings: The proportions of individuals with positive titres for antigliadin antibodies in the three groups were 30/53, 5/94, and 6/50 respectively (57, 5, and 12%). The difference in proportion between group 1 and the combined control groups was 0.49 (95% CI 0.35-0.63). Distal duodenal biopsies in 26 out of 30 antigliadin-positive patients from group 1 revealed histological evidence of coeliac disease in nine (35%), non-specific duodenitis in ten (38%), and no lesion in seven (26%) individuals., Interpretation: Our data suggest that gluten sensitivity is common in patients with neurological disease of unknown cause and may have aetiological significance.