Rosalind Kandler

Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia

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.

Clinical review: Sleep measurement in critical care patients: research and clinical implications

Sleep disturbances are common in critically ill patients and have been characterised by numerous studies using polysomnography. Issues regarding patient populations, monitoring duration and timing (nocturnal versus continuous), as well as practical problems encountered in critical care studies using polysomnography are considered with regard to future interventional studies on sleep. Polysomnography is the gold standard in objectively measuring the quality and quantity of sleep. However, it is difficult to undertake, particularly in patients recovering from critical illness in an acute-care area. Therefore, other objective (actigraphy and bispectral index) and subjective (nurse or patient assessment) methods have been used in other critical care studies. Each of these techniques has its own particular advantages and disadvantages. We use data from an interventional study to compare agreement between four of these alternative techniques in the measurement of nocturnal sleep quantity. Recommendations for further developments in sleep monitoring techniques for research and clinical application are made. Also, methodological problems in studies validating various sleep measurement techniques are explored.Trial registration Current Controlled Trials ISRCTN47578325.

Neuropathy associated with gluten sensitivity

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.

An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease

Background New criteria for the neurophysiological diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) were recently proposed at an international symposium in Awaji-shima, Japan. They differ from the accepted revised El-Escorial criteria by considering fasciculation potentials to be evidence of acute denervation. In addition, when assessing diagnostic certainty, the Awaji-shima criteria equate electrodiagnostic evidence of lower motor neuron dysfunction with clinical examination findings. Methods A retrospective review of 205 consecutive sets of notes was performed, from patients who underwent neurophysiological assessment for suspected MND. The clinical signs and neurophysiological findings were combined according to the two sets of criteria (revised El-Escorial and Awaji-shima), and the diagnoses reached were compared with the interval diagnosis, to establish the sensitivities and specificities of each protocol. Results An interval diagnosis of MND was recorded in 107 patients. The sensitivity of the Awaji-shima criteria in reaching a diagnosis of MND was 60.7% and the revised El-Escorial 28%, with a specificity of 95.9% for both criteria. The Awaji-shima criteria increased the sensitivity of diagnosis without affecting the specificity. Conclusion Accepting EMG evidence of fasciculations as evidence of acute denervation increases the diagnostic certainty of MND, and the new criteria allow earlier diagnosis of MND without increasing the false-positive rate.

Myopathy associated with gluten sensitivity

Ataxia and peripheral neuropathy are the most common neurological manifestations of gluten sensitivity. Myopathy is a less common and poorly characterized additional neurological manifestation of gluten sensitivity. We present our experience with 13 patients who presented with symptoms and signs suggestive of a myopathy and in whom investigation led to the diagnosis of gluten sensitivity. Three of these patients had a neuropathy with or without ataxia in addition to the myopathy. The mean age at onset of the myopathic symptoms was 54 years. Ten patients had neurophysiological evidence of myopathy. Inflammatory myopathy was the most common finding on neuropathological examination. One patient had basophilic rimmed vacuoles suggestive of inclusion‐body myositis. Six patients received immunosuppressive treatment in addition to starting on a gluten‐free diet; five improved and one remained unchanged. Among seven patients not on immunosuppressive treatment, four showed clinical improvement of the myopathy with a gluten‐free diet. The improvement was also associated with reduction or normalization of serum creatine kinase level. The myopathy progressed in one patient who refused the gluten‐free diet. Myopathy may be another manifestation of gluten sensitivity and is likely to have an immune‐mediated pathogenesis. A gluten‐free diet may be a useful therapeutic intervention. Muscle Nerve, 2006

Dietary treatment of gluten neuropathy

We studied the effect of a gluten‐free diet in patients with idiopathic sensorimotor axonal neuropathy and circulating antigliadin antibodies. Consecutive patients underwent baseline neurophysiological assessment and were offered a gluten‐free diet. Those who went on the diet formed the intention‐to‐treat group and those who did not were the control group. Repeat neurophysiological assessment and subjective evaluation of neuropathy symptoms were performed at 1 year. A total of 35 patients participated in the study, with 25 patients going on the diet and 10 not doing so. There was a significant difference in the change of sural sensory action potentials (pre‐defined primary endpoint), with evidence of improvement in the intention‐to‐treat group and deterioration in the control group. Subjective change in neuropathy symptoms also showed significant differences, with patients in the intention‐to‐treat group reporting improvement and those in the control group reporting deterioration. Gluten‐free diet may thus be a useful therapeutic intervention for patients with gluten neuropathy. Muscle Nerve, 2006

Patients' and neurologists' perception of epilepsy and psychogenic nonepileptic seizures

Although differences in illness perceptions between neurologists and patients with epilepsy or psychogenic nonepileptic seizures (PNES) are likely to be clinically relevant, this is the first study to attempt a direct comparison. In addition, this study compares the illness perceptions of patients with epilepsy with those of patients with PNES.

The natural history of motor neuron disease: Assessing the impact of specialist care

Many centres in the UK care for patients with motor neuron disease (MND) in a multidisciplinary clinic (MDC). It has been demonstrated that such care results in better prognosis for survival than care from a general neurology clinic (GNC). Whether this is due to higher use of disease-modifying interventions or an independent factor of attendance at a specialist clinic has not been established. Hence, we performed a retrospective review of hospital notes of patients with MND who were diagnosed and followed up in a GNC between 1998 and 2002 and in an MDC between 2006 and 2010. Overall, 162 patients attended a GNC, and 255 attended the MDC. The median survival from diagnosis was 19 months for patients who attended the MDC, compared to 11 months for those attending the GNC (hazard ratio 0.51, 95% CI 0.41–0.64). The Cox hazards model identified attendance at an MDC as an independently positive prognostic factor (HR 1.93, 95% CI 1.37–2.72, p < 0.001). We concluded that care at an MDC improves survival. While this effect is augmented by the increased use of riluzole, NIV and PEG, the data suggest that coordinated care independently improves the prognosis of MND patients.

154 The natural history of motor neurone disease (MND): assessing the impact of specialist care

Background Many centres in the UK offer care to patients with MND in a multi-disciplinary clinic (MDC). It is has been demonstrated that MDC care results in a better outcome than care from a General Neurology Clinic (GNC). Whether this is due to higher use of disease modifying interventions or an independent factor of attendance at an MDC has not been established. Objectives To compare survival of patients followed-up in a GNC with those in a MDC. Methods A retrospective review was undertaken of hospital notes of patients with MND, who were diagnosed and followed-up in a GNC between 1998 and 2002 and in a MDC between 2006 and 2010. Survival modelling between the groups was assessed using Kaplan–Meier analysis and significance measured by the log rank test. Multivariate analysis of risk was assessed using the Cox proportional hazard model. Results In all, 162 patients attended a GNC, and 255 attended a MDC. Patients attending the MDC used riluzole, non-invasive ventilation (NIV) and percutaneous endoscopic gastrostomy (PEG) more often, and had an improved survival time of 7–8 months (p<0.001). In Cox multivariate analysis, attending an MDC was found to be a significant positive prognostic factor (HR 1.72, 95% CI 1.37 to 2.16, p<0.001). Mean survival for MND patients not using riluzole, NIV or PEG improved by an average of 3 months from symptom onset and date of diagnosis. Discussion Attendance at a specialist clinic is associated with improved survival, independently of disease modifying interventions. This suggests that coordinated care improves the prognosis of MND patients. This effect is augmented by the increased use of riluzole, NIV and gastrostomy.

The safety of UK video telemetry units: Results of a national service evaluation §

PURPOSE To assess patient safety during seizures occurring on UK video telemetry units and identify factors in unit infrastructure which may improve safety with the intention of producing national guidelines. METHODS A prospective multicentre national service evaluation of the occurrence of adverse events and level of nurse attendance during seizures occurring on video telemetry units was performed. Data from 272 seizures from 27 video telemetry units across the UK were analysed. RESULTS Adverse events occurred in 12% of seizures: 7% were physical events such as falls or respiratory compromise and 5% were unnoticed seizures. Nursing staff did not attend the patients in 44% of seizures and attendance was delayed beyond 30s in a further 29%. Only 27% of seizures were attended by a Healthcare Professional within half a minute. The most important factor shown to improve timely attendance of patients during seizures was the presence of a nurse dedicated to the telemetry bed(s). The site of the telemetry bed (bay or cubicle) and method of observation (direct or indirect) was less important. An optimal nurse-to-patient ratio was difficult to identify but the study suggests that a ratio of at least 1 nurse to 4 patients is appropriate. CONCLUSION The results provide an evidence base for the production of national standards and guidelines for surveillance of patients during video telemetry to improve patient safety.