Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral neuropathies constitute an important cause of neurological disability in the tropics. The clinical manifestations of tropical peripheral neuropathies are identical to those observed by neurologists elsewhere and their aetiologies are also similar. However, the frequency of occurrence, or prevalence, of the different types of neuropathy is clearly different from that observed in developed nations, ranging from epidemic outbreaks of optic and peripheral sensory neuropathy caused by malnutrition--such as in the outbreak recently observed in Cuba--to the endemic problems of leprosy and HTLV-1 infection. A large variety of plant and animal poisons and industrial neurotoxins frequently affect the peripheral nervous system in warm climates. In addition to their public health importance, tropical neuropathies constitute unexplored natural models of disease worthy of clinical and laboratory studies.
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PMID:Tropical neuropathies. 859 21

We reviewed 200 patients with paraneoplastic encephalomyelitis (PEM) and anti-Hu antibodies to show possible clinical differences with respect to previous series, and to identify patient, tumour and treatment-related characteristics associated with neurological disability and survival. The median age of the 200 patients was 63 years (range 28-82 years) and 75% were men. The predominant neurological syndromes were sensory neuropathy (54%), cerebellar ataxia (10%), limbic encephalitis (9%) and multifocal involvement (11%). Sensorimotor neuropathies with predominant motor involvement were observed in only 4% of the patients. Pathological or X-ray evidence of a tumour was obtained in 167 patients (83%) and was a small-cell lung cancer (SCLC) in 74% of those with histological diagnosis. Coexistence of extrathoracic tumours with SCLC was rare (0.5%). Positive Hu immunoreactivity was observed in the extrathoracic tumours of six out of seven patients in whom autopsy or long-term follow-up ruled out a coexisting SCLC. PEM preceded the diagnosis of the tumour in 71% of patients (mean delay +/- SD 6.5 +/- 7.0 months; range 0.1-47 months). In the 24 patients in whom the tumour diagnosis was the initial event, PEM predicted the progression or relapse of the tumour in 87% of them. No tumour was found in 33 patients, including four who had a post-mortem study and four with >5 years of follow-up. In a logistic regression analysis, treatment of the tumour, associated or not with immunotherapy, was an independent predictor of improvement/stabilization of PEM [odds ratio 4.56; 95% confidence interval (CI) 1.62-12.86]. Cox multivariate analysis indicated that the variables independently associated with mortality were: age >60 years [relative risk (RR) 1.49; 95% CI 1.05-2.12], Rankin score at diagnosis >3 (RR 1.60; 95% CI 1.12-2.28), more than one area of the nervous system affected (RR 1.61; 95% CI 1.08-2.40), and absence of treatment (RR 2.56; 95% CI 1.76-3.71). We conclude that, unlike previous series, the majority of our patients were male, and there was a low occurrence of predominantly motor neuropathies and extrathoracic tumours coexisting with SCLC. When the diagnosed extrathoracic tumour expresses Hu antigens, further tests to rule out a coexisting SCLC are probably unnecessary. Finally, the predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.
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PMID:Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. 1135 30

Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist.
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PMID:Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. 3204 May 56