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.

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.

Familial visceral neuropathy: a defined entity?

Familial visceral neuropathy (FVN) is a heterogeneous group of disorders due to abnormalities of the myenteric plexus. FVN with neuronal intranuclear inclusions is one particular form of FVN with a variable phenotype that includes achalasia, gastro-esophageal reflux, intestinal dysmotility and pseudo-obstruction, dysarthria, peripheral neuropathy and pupillary defects, and the presence of intranuclear inclusions within the neurons of the enteric nervous system. We present a four-generation family in which 10 individuals (7 of whom have been examined) are affected with FVN. The family was previously reported as familial esophageal achalasia, an autosomal recessive condition (MIM200400). At that time, several individuals in a single sibship were affected and there were no manifestations in either parent. Since that report, two individuals have had affected children and the mother has developed symptoms and has abnormalities on electromyography, thus enabling us to reclassify the family. This family provides further evidence of autosomal dominant inheritance, with marked variation in expression.

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.

The association of hereditary neuropathies and heritable skeletal disorders.

We describe two patients with associations of hereditary neuropathies and heritable skeletal disorders not previously reported. The first patient had Marfan's syndrome and hereditary motor and sensory neuropathy Type 1. The second patient had Ehlers-Danlos syndrome, Klippel-Feil syndrome and tomaculous neuropathy.

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

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.

Gliomatosis cerebri: a clinical, radiological and pathological report of four cases.

Four cases of gliomatosis cerebri are described. In only one case was the diagnosis made during life. Radiological investigations, including computed tomography and magnetic resonance imaging, showed non-specific changes in the white matter.

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.