Objectives-To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. Methods-A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. Results-In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). Conclusions-Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment eVects. Weakness in hypothyroidism is more diYcult to treat, suggesting myopathy. (J Neurol Neurosurg Psychiatry 2000;68:750-755 and possibly also polyneuropathy.5 6 The reported prevalence of these signs and symptoms is variable. Few prospective studies on this topic have been performed. [7][8][9][10] In retrospective studies, published in the early 1980s, 1 11 the prevalence of neuropathy in hypothyroid patients varied between 10% and 70% and that of myopathy between 20% and 80%, whereas the prevalence of myopathic features in hyperthyroidism varied between 60% and 80% of the patients. The aims of this study were (1) to investigate the prevalence of neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism or hyperthyroidism; (2) to evaluate electrodiagnostic evidence of neuromuscular dysfunction; (3) to study the eVects of treatment; (4) to correlate the severity and duration of thyroid dysfunction with the serum creatine kinase (CK) concentration and the presence of neuropathy and myopathy; and (5) to compare the patterns of neuromuscular involvement between hypothyroidism and hyperthyroidism. Patients and methods PATIENTSAll adult patients with newly diagnosed thyroid dysfunction (abnormal serum concentrations of thyroid stimulati...

The recently described human anion channel Anoctamin (ANO) protein family comprises at least ten members, many of which have been shown to correspond to calcium-activated chloride channels. To date, the only reported human mutations in this family of genes are dominant mutations in ANO5 (TMEM16E, GDD1) in the rare skeletal disorder gnathodiaphyseal dysplasia. We have identified recessive mutations in ANO5 that result in a proximal limb-girdle muscular dystrophy (LGMD2L) in three French Canadian families and in a distal non-dysferlin Miyoshi myopathy (MMD3) in Dutch and Finnish families. These mutations consist of a splice site, one base pair duplication shared by French Canadian and Dutch cases, and two missense mutations. The splice site and the duplication mutations introduce premature-termination codons and consequently trigger nonsense-mediated mRNA decay, suggesting an underlining loss-of-function mechanism. The LGMD2L phenotype is characterized by proximal weakness, with prominent asymmetrical quadriceps femoris and biceps brachii atrophy. The MMD3 phenotype is associated with distal weakness, of calf muscles in particular. With the use of electron microscopy, multifocal sarcolemmal lesions were observed in both phenotypes. The phenotypic heterogeneity associated with ANO5 mutations is reminiscent of that observed with Dysferlin (DYSF) mutations that can cause both LGMD2B and Miyoshi myopathy (MMD1). In one MMD3-affected individual, defective membrane repair was documented on fibroblasts by membrane-resealing ability assays, as observed in dysferlinopathies. Though the function of the ANO5 protein is still unknown, its putative calcium-activated chloride channel function may lead to important insights into the role of deficient skeletal muscle membrane repair in muscular dystrophies.

The question whether symptom-free migraine patients show cognitive impairments compared to matched control subjects is addressed, and also whether migraine patients show transient cognitive impairments induced by an attack. The Neuropsychological Evaluation System (NES2) was administered once in an interictal period and twice within 30 h after different migraine attacks. Since cognitive impairments could be related to attack duration or severity, cognitive performance was compared during a postictal period after sumatriptan use and during a postictal period after habitual nonvasoactive medication use. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched headache-free controls participated in the study. During a headache-free period, migraineurs without aura responded as quickly as controls, while migraineurs with aura were slower than controls during all tasks specifically requiring selective attention. These effects were not aggravated by a preceding migraine attack, irrespective of medication use and attack duration. studies have provided evideficits in migraine patients, control. These results, along with limited food tolerance, tiredness, altered mood state, and diurincluding psychomotor deficiencies (1, 2), memory deficits (2,3), and dysfunctions in the early stages of visual processing (4, 5), especially in migraineurs with aura (3, 6, 7). However, in other studies, neither detrimental cognitive effects in migraine patients nor differences between migraineurs with and without aura have been found (8, 9). Factors that could contribute to these inconsistent results are patient selection biases, a lack of distinction between migraineurs with aura and migraineurs without aura, the absence of matched control groups, and the presence of type I errors as a result of multiple testing without adjustment of the nominal alpha level. The time interval between a migraine attack and task performance can also be an important factor. Inter&al brain functioning can be influenced by functional or structural effects of migraine on the one hand, and temporal and reversible effects of an attack on the other. Cognitive performance can be temporarily adversely affected by the physiological dynamics of a preceding or upcoming migraine attack. Post-attack effects can be pronounced, since a migraine 'headache is followed by transient physiological alterations remaining for up to 48 h after an attack, e.g., regional cerebral blood flow abnormalities (lo), a reduction of alpha activity within the background EEG (11), and a reduction of the Contingent Negative Variation amplitude (12+an event-related cortical potential reflecting noradrenergic arousal and dopaminergic motor esis (13), suggest a physiological recovery phase which could also lead to an impaired cognitive performance in the post-attack period.The present study addresses two main questions: the first whether migraine patients show cognitive impairments in an interictal period compared to matched headache-free control subjects; the second whether migra...

Background: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. Aim: To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. Methods: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. Results: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). Conclusions: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.

Occasionally, patients who clinically present as an idiopathic inflammatory myopathy may lack mononuclear cell infiltrates in their muscle biopsy specimens. This subacute-onset progressive necrotising myopathy should not deter the clinician from timely and appropriate treatment as we consider this myopathy to be steroid-responsive with a possible immune-mediated pathogenesis.