Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new system for computer aided EMG-analysis was tested in 3 groups of patients with neurogenic lesions (ALS, ulnar nerve lesions, diabetic polyneuropathy). The system entails automatic segmentation and parametrization of the single MUAP as well as the automatic classification of the MUAP into motor units. Emphasis was placed on its practicability in an everyday clinical setting. All patient groups differed significantly from normal groups in most of the computed parameters of the motor units. Moreover, on the basis of the computer-aided analysis of the MUAP up to 90% of individual patients in the ALS and ulnar nerve lesion groups and up to 40% in the diabetic polyneuropathy group, who did not have any pathological spontaneous activity or paris, could be classified as pathological. It is concluded, that computer-aided EMG-analysis has become a practical tool for routine use in the clinical laboratory simplifying early diagnosis of subtle EMG-changes, and aiding the less experienced examiner.
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PMID:Computer-aided EMG-analysis in patients with neurogenic lesions. 139 99

All identified Israeli patients with amyotrophic lateral sclerosis (ALS) with onset of the disease from 1959 through 1975 (n = 318) were evaluated clinically. Most of our patients (63%) presented with weakness; only 10% presented with atrophy and 3% with fasciculations. In 31% of the cases, the onset of the disease was focal and 22% of the patients presented with bulbar signs, but only 6 patients presented with emotional lability (pseudo-bulbar). Twelve per cent of the patients presented with muscle cramps, pain or paraesthesia. Atypical signs such as motor cranial nerve lesion, dementia, sphincter disturbance and deep sensation loss are discussed. A relatively high proportion of our patients suffered from malignant tumour, but with no association with any specific tumour. The median survival time was 3 years. Patients with onset of their disease with bulbar signs had a shorter life expectancy (2.2 years): Twenty nine per cent of our patients survived for more than 5 years and 16% for more than 10 years.
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PMID:Amyotrophic lateral sclerosis. A study of its presentation and prognosis. 405 36

Our material comparises 105 patients (62 men and 43 women) aged 26-73 years with amyotrophic lateral sclerosis (ALS). EMG examination confirmed the diagnosis of multilevel lesion of spinal motor neurons. Clinically, 94 of them had classical ALS, 3 had primary bulbar palsy (PBP), 6 had primary motor spinal atrophy (PSMA), and 2 had primary lateral sclerosis (PLS). Disease duration was 18.1 month, on the average, ranging from 2-60 months. In all patients motor and sensory nerve conduction was studied in median, peroneal and sural nerves. Conduction velocity, distal latency, F-wave latency of motor nerves, amplitude of M response and of sensory potentials were evaluated. Abnormalities were found most often in the motor fibres of median nerve: lowering of the M response amplitude in 44% of nerves studied, slowing of conduction velocity and elongation of distal latency in ca. 30%, elongation of F-wave latency in 27%. In the peroneal nerve the changes were less frequent: 38%, 21%, and 3%, respectively. They were also less marked. In the sensory fibres of median nerve slowing of conduction velocity was found in 25% of nerves, in sural nerve in 11%. Some slight decrease of amplitude of sensory potentials was seen in those nerves. The results obtained indicate a possibility of peripheral nerve lesion in the course of ALS which must be remembered in clinical diagnosing.
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PMID:[Median nerve electrophysiological assessment in amyotrophic lateral sclerosis]. 963 77

Glial cell line derived neurotrophic factor (GDNF) is a potent trophic factor for several subpopulations of neurons including motor neurons. Two different transcripts of the GDNF gene (GDNF633 and GDNF555) have been detected in various tissues, including skeletal muscle. Denervation leads to an upregulation of GDNF633 in rat skeletal muscle, indicating that GDNF is involved in the response of skeletal muscle to denervation and possibly in reinnervation. To determine the role of GDNF in human neuromuscular disease, we investigated the expression of both transcripts in normal and denervated muscle and in muscle biopsies from Duchenne muscular dystrophy patients. GDNF expression levels were analyzed by competitive RT-PCR in 38 muscle specimens. Levels of both transcripts were significantly elevated in denervated muscle compared to normal and dystrophic muscle. Morphometric analysis of muscle-fiber calibers and its correlation to GDNF expression revealed that higher levels of GDNF were expressed in rapidly-progressive neurogenic atrophy, including four amyotrophic lateral sclerosis (ALS) cases, compared to cases of chronic atrophy. In dystrophic muscle, transcript levels were not significantly altered compared to normal controls. These data indicate that denervation, but not dystrophy, enhances GDNF expression in human skeletal muscle. Thus, the increase of GDNF expression is part of the reaction of human skeletal muscle to denervation caused by motor nerve lesion. GDNF might act on regenerating nerve fibers during muscle fiber reinnervation.
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PMID:GDNF expression is increased in denervated human skeletal muscle. 969 25

To date, delivery of neurotrophic factors has only allowed to transiently protect axotomized facial motoneurons against cell death. In the present report, long-term protection of these neurons was evaluated by continuously expressing the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) within the facial nucleus using a lentiviral vector system. The viral vector was injected unilaterally into the facial nucleus of 4-month-old Balb/C mice. In contrast to axotomy in other adult rodents, facial nerve lesion in these animals leads to a progressive and sustained loss and/or atrophy of >50% of the motoneurons. This model thus represents an attractive model to evaluate potential protective effects of neurotrophic factors for adult-onset motoneuron diseases, such as amyotrophic lateral sclerosis. One month after unilateral lentiviral vector injection, the facial nerve was sectioned, and the animals were killed 3 months later. Viral delivery of the GDNF gene led to long-term expression and extensive diffusion of GDNF within the brainstem. In addition, axotomized motoneurons were completely protected against cell death, because 95% of the motoneurons were present as demonstrated by both Nissl staining and choline acetyltransferase immunoreactivity. Furthermore, GDNF prevented lesion-induced neuronal atrophy and maintained proximal motoneuron axons, despite the absence of target cell reinnervation. This is the first evidence that viral-mediated delivery of GDNF close to the motoneuron cell bodies of the facial nucleus of adult mice can lead to complete and long-term protection against lesion-induced cell death.
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PMID:Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. 1090 95

Isolated facial weakness suggests either a contralateral hemispheric lesion or a disease of the facial nerve per se. The presence of sensory symptoms usually indicates a central facial weakness, which characteristically involves the lower part of the face. In contrast, the absence of sensory disturbances suggests a peripheral nerve lesion, some system diseases such as amyotrophic lateral sclerosis, or a stroke sparing the sensory cortex. Sporadic cases of Bell's palsy rank the first in incidence. Although its exact etiology remains unknown, accumulating evidence suggests reactivation of herpes simplex virus type I. A facial palsy that develops in patients with diabetes mellitus tends to show a more severe involvement with substantial denervation. Acoustic neuroma, strategically located at the cerebellopontine angle, may compress the facial nerve. Peripheral facial palsy may herald other symptoms of multiple sclerosis in young adults. Serial electrodiagnostic studies help delineate the course of the illness. The amplitude of the direct response elicited by stimulation of the facial nerve after the fourth to fifth day of onset serves as the best means predicting the eventual outcome of recovery. Blink reflex studies usually show an absent or delayed R1, implicating the central reflex arc, which includes the intrapontine portion of the facial nerve.
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PMID:Electrodiagnosis of the cranial nerves. 1659 78

The adult brain retains the capacity to rewire mature neural circuits in response to environmental changes, brain damage or sensory and motor experiences. Two plastic processes, synaptic remodeling and neurogenesis, have been the subject of numerous studies due to their involvement in the maturation of the nervous system, their prevalence and re-activation in adulthood, and therapeutic relevance. However, most of the research looking for the mechanistic and molecular events underlying synaptogenic phenomena has been focused on the extensive synaptic reorganization occurring in the developing brain. In this stage, a vast number of synapses are initially established, which subsequently undergo a process of activity-dependent refinement guided by target-derived signals that act as synaptotoxins or synaptotrophins, promoting either loss or consolidation of pre-existing synaptic contacts, respectively. Nitric oxide (NO), an autocrine and/or paracrine-acting gaseous molecule synthesized in an activity-dependent manner, has ambivalent actions. It can act by mediating synapse formation, segregation of afferent inputs, or growth cone collapse and retraction in immature neural systems. Nevertheless, little information exists about the role of this ambiguous molecule in synaptic plasticity processes occurring in the adult brain. Suitable conditions for elucidating the role of NO in adult synaptic rearrangement include physiopathological conditions, such as peripheral nerve injury. We have recently developed a crush lesion model of the XIIth nerve that induces a pronounced stripping of excitatory synaptic boutons from the cell bodies of hypoglossal motoneurons. The decline in synaptic coverage was concomitant with de novo expression of the neuronal isoform of NO synthase in motoneurons. We have demonstrated a synaptotoxic action of NO mediating synaptic withdrawal and preventing synapse formation by cyclic GMP (cGMP)-dependent and, probably, S-nitrosylation-mediated mechanisms, respectively. This action possibly involves the participation of other signaling molecules working together with NO. Brain-derived neurotrophic factor (BDNF), a target-derived synaptotrophin synthesized and released postsynaptically in an activity-dependent form, is a potential candidate for effecting such a concerted action. Several items of evidence support an interrelationship between NO and BDNF in the regulation of synaptic remodeling processes in adulthood: i) BDNF and its receptor TrkB are expressed by motoneurons and upregulated by axonal injury; ii) they promote axon arborization and synaptic formation, and modulate the structural dynamics of excitatory synapses; iii) NO and BDNF each control the production and activity of the other at the level of individual synapses; iv) the NO/cGMP pathway inhibits BDNF secretion; and finally, v) BDNF protects F-actin from depolymerization by NO, thus preventing the collapsing and retracting effects of NO on growth cones. Therefore, we propose a mechanism of action in which the NO/BDNF ratio regulates synapse dynamics after peripheral nerve lesion. This hypothesis also raises the possibility that variations in this NO/BDNF balance constitute a common hallmark leading to synapse loss in the progression of diverse neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases.
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PMID:Nitric oxide and synaptic dynamics in the adult brain: physiopathological aspects. 1687 2

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease manifested by progressive muscle atrophy and paralysis due to the loss of upper and lower motoneurons (MN). Spasticity appears in ALS patients leading to further disabling consequences. Loss of the inhibitory tone induced by downregulation of the potassium chloride cotransporter 2 (KCC2) in MN has been proposed to importantly contribute to the spastic behavior after spinal cord injury (SCI). The aim of the present study was to test whether the alterations in the expression of KCC2 are linked to the appearance of spasticity in the SOD(G93A) ALS murine model. We compared SOD(G93A) mice to wild type mice subjected to SCI to mimic the spinal MN disconnection from motor descending pathways, and to sciatic nerve lesion to mimic the loss of MN connectivity to muscle. Electrophysiological results show that loss of motor function is observed at presymptomatic stage (8 weeks) in SOD(G93A) mice but hyperreflexia and spasticity do not appear until a late stage (16 weeks). However, KCC2 was not downregulated despite MN suffered disconnection both from muscles and upper MNs. Further experiments revealed decreased gephyrin expression, as a general marker of inhibitory systems, accompanied by a reduction in the number of Renshaw interneurons. Moreover, 5-HT fibers were increased in the ventral horn of the lumbar spinal cord at late stage of disease progression in SOD1(G93A) mice. Taken together, the present results indicate that spasticity appears late in the ALS model, and may be mediated by a decrease in inhibitory interneurons and an increase of 5-HT transmission, while the absence of down-regulation of KCC2 could rather indicate an inability of MNs to respond to insults.
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PMID:Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons. 2447 30