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.

Surface electromyography using electrode arrays: a study of motor neuron disease.

The use of electromyography (EMG) is limited, particularly in the investigation of children, by the invasive nature of needle electrodes. Surface electrode techniques are an attractive alternative but the detected signals are greatly influenced by volume conductor effects, thus making their interpretation problematic. Using finite element analysis we investigated the relationship between surface potential distribution and motor unit depth, incorporating anisotropic conductivity to model muscle tissue and a range of subcutaneous fat thicknesses. The modeling results were used to analyze data recorded with a 16-channel surface electrode array, from 10 normals subjects and 12 patients with motor neuron disease. Differences in the motor units between the two groups were statistically significant (P < 0.01) and are consistent with reinnervation and increased motor unit territory in the patient group. This noninvasive technique shows promise as a more acceptable alternative to the use of conventional needle electrodes for neurophysiological investigations.

Development of an automated on-line analysis system using flow injection, ultrasound filtration and CCD detection.

The design and construction of an automated on-line analysis system is described with reference to applications in bioprocess control, clinical, and environmental analysis. The new system is built around three main elements: ultrasound filtration, a micro flow injection analysis (FIA) system, and direct readout spectrophotometry. The advantages of three on-line ultrasound filtration devices, developed for clarification of water, human blood and mammalian cell culture samples, are described. The filters avoid off-line centrifugation and do not suffer from the blockage problems associated with conventional filters. The separation efficiency of the ultrasound filters is also discussed. The delivery system is based on a gas driven FIA technique, using helium to avoid bubble formation, with the carrier and reagent flow being controlled by computer switched solenoid valves. Direct readout spectrometers are used, based on charge coupled devices (CCDs) covering the wavelength range 200-900 nm. These detectors provide near instantaneous capture of full spectra, allowing several analytes to be monitored simultaneously, and are much smaller than conventional spectrophotometers. Optical fibres are used to link the light source to the detector via a flow cell in the FIA system. Software to run the entire system was developed using the LabVIEWtrade mark graphical programming environment, enabling rapid development of the control system and user interface. The integration of these components has shown significant improvement in the application of FIA techniques to on-line analysis.

Diabetic neuropathic pain in a leg amputated 44 years previously.

The mechanism of neuropathic pain in the diabetic limb is far from clear. Phantom limb pain likewise is of obscure aetiology. The development of typical pain in an absent leg in a patient with diabetes many years after the amputation stimulates thought as to the mechanism, not only of neuropathic pain, but also of phantom limb pain. A 58-year-old man was diagnosed with type 2 diabetes 44 years after having undergone left below knee amputation for congenital AV malformation, at the age of 13. Eight months before the diagnosis of diabetes he began to complain of pain in the leg on the amputated side-pain very similar to that described in typical diabetic neuropathy. This was followed by similar pain in the right leg. MR scan of the spine revealed a small syringohydromyelia of the thoracic cord in addition to a prolapse of disc at L(5)/S(1) level on the left side, which was first noted 5 years previously. There were no other features of S(1) compression. The typical neuropathic character of the pain involving both the amputated and the intact limbs that developed with the diagnosis of type 2 diabetes suggest that the neuropathic pain may originate from centres higher than peripheral nerves.

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.

KANDID--an EMG decision support system--evaluated in a European multicenter trial.

KANDID is an advanced EMG decision support system dedicated to the support of the clinical neurophysiologist during EMG examinations. It has facilities for test planning, automatized and structured data interpretation, EMG diagnosis, explanation, and reporting. In a prospective European multicenter field trial, the agreement levels between clinical neurophysiologists and KANDID's diagnostic statements were measured under ordinary clinical EMG practice. KANDID was assessed in 159 individual patient EMG examinations by nine clinical neurophysiologists at seven different EMG laboratories. The reasoning of KANDID was considered understandable for the examiners in 80-90% of cases. The agreement level for the electrophysiological states of muscles and nerves between KANDID and the individual examiners was, on average, 81%. The corresponding diagnostic agreement with KANDID was, on average, 61%. A pronounced interexaminer variation in the agreement level related to the different EMG centers was observed. All Danish and Belgian examiners agreed with KANDID in more than 50% of their cases with regard to the EMG diagnosis, while the English examiners were in agreement with KANDID in 50% or less of their cases. These differences were possibly due to differences in epidemiology, examination techniques, control material, and examination planning strategies. It is concluded that it is possible to transfer systems like KANDID out of their development sites and apply them successfully if they can be locally customized by the clinical end users via editors.

Neuropathy in chronic obstructive pulmonary disease: a multicentre electrophysiological and clinical study.

The incidence and type of neuropathy in patients with chronic obstructive pulmonary disease (COPD) were assessed. In a selected group of 89 patients, abnormal nerve conduction studies were found in 44%. Electrophysiological signs of a generalized peripheral neuropathy were found in 5-18%, depending on diagnostic criteria. Lesions which were thought to be due to compression or other forms of trauma were present in a further 24%. In the patients with peripheral neuropathy, the changes were distally predominant, affected mainly sensory fibres, and were consistent with an axonal type of neuropathy. There was a significant correlation between age and the incidence of peripheral neuropathy. Electrophysiological evidence of neuropathy was three times as common as clinical evidence. Much of the variation in the reported incidence of neuropathy in COPD is probably due to imprecise diagnostic criteria.

The role of magnetic stimulation in the diagnosis of multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck, and head and lumbar region, as well as amplitude of the motor evoked potential (MEP) in normal subjects and patients with multiple sclerosis (MS). Patients with definite MS had significantly longer MCTs and smaller amplitude MEPs than normal subjects when recording from arm and leg muscles. In a comparison with visual evoked potential (VEP) recordings, head to neck MCTs were abnormal less often than VEPs, and VEPs detected more silent lesions. Recording from leg as well as arm muscles significantly increased the yield of abnormal MCT measurements. The detection of silent lesions in the patients with definite MS was improved, but there was no improvement in the non-definite cases. Amplitude measurements provided very little extra diagnostic information over MCT measurements alone and did not improve the detection of silent lesions. Interside MCT differences yielded extra abnormalities when recording from the arms but not the legs. Interside MCT abnormalities increased the detection of silent lesions in both the definite and non-definite categories. It was concluded that the majority of useful diagnostic information in patients with MS should be obtainable from bilateral MCT (head to neck) measurements, together with estimation of interside MCT differences. However, VEP recording is a better diagnostic test for MS than MEP recording as more silent lesions are detected. This may be because MCT abnormalities tend to reflect the degree of pyramidal disability.

The role of magnetic stimulation as a quantifier of motor disability in patients with multiple sclerosis.

Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck in a prospective longitudinal study of patients with multiple sclerosis (MS) and normal subjects. MCT measurements showed a high degree of reproducibility in normal subjects and patients with stable MS. In patients with definite MS, there was significant positive correlation between MCT and motor disability. In patients treated with steroids for relapse of MS, there was significant shortening of MCT following treatment in those who clinically improved, but not in those who were clinically unchanged. In a smaller group of patients followed for 3 months, MCT changes tended to mirror the clinical pattern. Magnetic stimulation should prove a useful tool for the quantification of motor disability, and monitoring the response to new treatments in MS.

Abnormalities of central motor conduction in Parkinson's disease.

The new technique of magnetic stimulation was used to measure amplitude of the motor evoked potential (MEP) recorded from abductor digiti minimi whilst stimulating at the head, and motor conduction time (MCT) between head and neck. Bilateral studies were made in 12 normal subjects and 56 patients with Parkinson's disease. The amplitudes of the MEPs were significantly larger (P less than 0.05) in the patients (mean 1.6 mV, SD 1.4) compared with the normal subjects (mean 0.9 mV, SE 0.6). MCTs were significantly shorter (P less than 0.001) in patients (mean 8.1 ms, SD 1.3) compared with the normal subjects (mean 9.4 ms, SD 1.2). Although the pathophysiological basis of these changes has not been determined, they provide objective measurements which may be clinically valuable in monitoring therapy.

Pre- and postoperative motor conduction times, measured using magnetic stimulation, in patients with cervical spondylosis.

Motor conduction time (MCT) between head and neck in pathways to abductor digiti minimi was measured pre- and postoperatively in 15 patients. There was a significant improvement in MCTs in patients with myelopathy who improved clinically, but preoperative MCTs provided no clear, predictive information. Magnetic stimulation may be of value in quantifying motor function before and after surgery in patients with cervical spondylosis.

Clinical evaluation of magnetic stimulation in cervical spondylosis.

Conduction in central motor pathways and motor roots was assessed, using the new technique of magnetic stimulation, in 39 patients with cervical spondylosis. Recordings were taken from abductor digiti minimi in all patients and from biceps brachii and abductor hallucis in some. Findings were abnormal ipsilaterally in 27 out of 63 muscles examined in patients with myelopathy, and in 2 out of 38 muscles in patients with radiculopathy. No abnormality was found in 11 muscles examined in patients with negative radiology. There was some correlation between the degree of electrophysiological change and clinical disability. Abnormal conduction was found in some patients with cord compression at the C3/4 or C4/5 interspace but not in a small group with compression at the C5/6 interspace. It seems that magnetic stimulation will provide objective confirmation of upper motor neurone involvement and may provide some measure of its degree, but at present it does not appear to be superior to clinical methods in diagnosing its presence. It may also aid the selection of the correct level for surgical decompression.

Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an initial clinical evaluation.

This report describes a novel method of stimulating the motor cortex and deep peripheral nerves in humans. The technique, developed in the Department of Medical Physics of Sheffield University, uses a large pulse of magnetic field to induce currents within the body and is painless. The basic principles of magnetic stimulation are described, and the technique is compared with conventional electrical stimulation. Safety aspects are discussed with reference to established clinical electrical and magnetic procedures. The results of the first clinical study using magnetic stimulation are described and show clear central motor pathway slowing in multiple sclerosis patients.

Small vessel disease in progressive diabetic neuropathy associated with good metabolic control.

Clinical, electrophysiological, and electron microscopical data are presented on 10 diabetic patients with severe progressive neuropathy, predominantly motor in type, in the presence of good blood glucose control, and for one patient with painful neuropathy and third cranial nerve palsy. Endothelial cell hyperplasia was seen in small vessels in all cases, and seven patients showed plugging of the vascular lumen by degenerate cellular material and electron dense protein. It is suggested that these cells desquamate and occlude smaller peripheral vessels at a point of narrowing. In one case the lumen of a vessel was occluded by thrombus. Electron microscopical examination showed a vessel occluded by degranulated platelets. Electrophysiological studies showed a pattern of denervation that was asymmetrical and distally predominant in some patients, suggesting that the neuropathy, at least in part, relates to multiple small infarcts.