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)

Although the etiology and pathogenesis of ALS is unknown, increasing evidence supports a role for autoimmune mechanisms in motoneuron degeneration and death. An animal model, experimental autoimmune gray matter disease, can be induced by the inoculation of spinal cord gray matter. The experimental disease is characterized by weakness secondary to the loss of upper and lower motoneurons, accompanied by inflammatory foci within the spinal cord, and IgG at the neuromuscular junction and within UMN and LMN. In human ALS, IgG is present within the UMN and LMN, and T-lymphocytes and activated microglia have been identified within spinal cord gray matter and motor cortex. ALS IgG can passively transfer physiological changes of the neuromuscular junction to mice resulting in enhanced release of acetylcholine. The ALS IgG selectively interact with calcium channels and alter channel function. These data suggest a potential role for autoimmune mechanisms in the destruction and loss of motoneurons in ALS.
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PMID:Evidence for autoimmunity in amyotrophic lateral sclerosis. 780 36

Motor neurone disease, or amyotrophic lateral sclerosis, is a serious progressive neurological disorder, characterized by loss of UMN and LMN. Pathological features include characteristic intracytoplasmic MN inclusion bodies and appearances on ubiquitin staining. The aetiopathogenesis of the disease remains unknown and there is, to date, no effective treatment. Several abnormalities have been demonstrated in neurotransmitter, neuropeptide and gene expression studies. Abnormalities in glutamate metabolism have led to the excitotoxin hypothesis of MN destruction. Other theories include deficits in MN trophic factors, trans-synaptic degeneration, impaired ability to detoxify putative toxic agents and impaired DNA/RNA metabolism. The existence of familial forms, some of which show linkage to markers in chromosome 21, allows a genetic approach to the mechanisms of disease. Recent studies suggest that mutations in the Cu/Zn SOD gene may be important in some of the familial forms. The atypical forms seen in the Western Pacific have stimulated a search for environmental agents. Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue.
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PMID:Motor neurone disease. 792 18

Although the etiology and pathogenesis of ALS is unknown, increasing evidence supports a role for autoimmune mechanisms in motoneuron degeneration and death. An animal model, experimental autoimmune gray matter disease, can be induced by the inoculation of spinal cord gray matter. The experimental disease is characterized by weakness secondary to the loss of upper and lower motoneurons, accompanied by inflammatory foci within the spinal cord, and IgG at the neuromuscular junction and within UMN and LMN. In human ALS, IgG is present within the UMN and LMN, and T-lymphocytes and activated microglia have been identified within spinal cord gray matter and motor cortex. ALS IgG can passively transfer physiological changes of the neuromuscular junction to mice resulting in enhanced release of acetylcholine. The ALS IgG selectively interact with calcium channels and alter channel function. These data suggest a potential role for autoimmune mechanisms in the destruction and loss of motoneurons in ALS.
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PMID:Evidence for autoimmunity in amyotrophic lateral sclerosis. 822 65

For many years, the only published criteria for the electrodiagnostic (EDX) recognition of amyotrophic lateral sclerosis (ALS) were those formulated by Lambert (1957; 1969). In 1990, different EDX guidelines were incorporated in the all-inclusive diagnostic criteria formulated by a subcommittee on ALS of the World Federation of Neurology, which met in El Escorial, Spain. Unfortunately, particularly in regard to the EDX requirements, the 'El Escorial criteria' have several flaws which compromise their usefulness. These include: (1) they ignore the fact that whenever upper and lower motor neuron disorders co-exist, as they characteristically do with ALS, the motor unit potential firing pattern is controlled by the upper motor neuron lesion; (2) they markedly devalue the usefulness of detecting fasciculations and, through presumably typographical error, state that the 'absence' rather than the 'presence' of fasciculations supports the diagnosis of ALS; this view is in direct conflict with the opinions expressed by most electromyographers; (3) they contain a statement regarding how the diagnosis of ALS is confirmed by the EDX studies which is confusing and, for two of the body regions (bulbar; thoracic), unrealistic; (4) finally, many of the EDX features they listed supporting the recognition of possible LMN degeneration appear to be mislabeled, while a few features in the EDX criteria are incorrect.
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PMID:Clinical neurophysiology in the diagnosis of amyotrophic lateral sclerosis: the Lambert and the El Escorial criteria. 780 56

In view of the conflicting results about the links between lower and upper motor neuron (LMN, UMN) dysfunction in amyotrophic lateral sclerosis (ALS), we undertook this study to correlate their changes over time. Single motor units (MUs) were characterized by their macro-MU potentials, twitch amplitude, and excitatory responses to transcranial magnetic stimulation (TMS). Ten ALS patients were studied 2 to 4 times and their data were subdivided into epochs corresponding to mean disease duration of 12 (58 MUs), 20 (60 MUs), 32 (50 MUs), 43 (40 MUs), and 168 months (55 MUs). The MU size increased and the contractile effectiveness and the excitatory response rates decreased significantly with time. The contractile effectiveness of MUs producing normal excitatory responses decreased with time, whereas a gradual loss of excitatory responses was observed among MUs with normal electromechanical properties. Since no correlation was found between UMN and LMN dysfunction, we conclude that UMN and LMN probably degenerate independently in ALS.
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PMID:Progression of cortical and spinal dysfunctions over time in amyotrophic lateral sclerosis. 1808 Sep 98

A new amyotrophic lateral sclerosis (ALS) category named 'UMN-dominant ALS' and defined as 'due predominantly to UMN signs but with minor electromyogram (EMG) denervation or LMN signs on examination' has been proposed. The clinical and laboratory features of 20 patients with UMN-dominant ALS are described here, their disease course is analysed longitudinally according to their disability progression, and all these parameters are compared with those of typical ALS patients. Ten women and 10 men diagnosed with UMN-dominant ALS were evaluated. Their mean age at disease onset was 58.6 years. At the most recent evaluation, after a mean disease duration of 7.7 years, all patients progressed to a tetrapyramidal syndrome with pseudobulbar features of varying degree. No patient had respiratory problems. Cognitive impairment was observed in eight patients. The differences in disease progression between the UMN-dominant ALS and typical ALS patients proved significant (p <0.02) both with regard to the total ALSFRS-R score at six months and to each single region subscore at 12 months. Our findings suggest that there is both a different pattern of disability and longer survival in UMN-dominant ALS compared to classic ALS patients.
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PMID:Natural history of upper motor neuron-dominant ALS. 1992 48

PLS is a disease of the UMN, distinguished from ALS in prognosis and absence of LMN signs. We present, to our knowledge, the first conventional MR imaging visualization of the callosal motor segment, a concept previously supported by primate models, electrophysiologic studies, and postmortem examinations. Modification of the Witelson topographic scheme of the CC is supported by MR tractography. On the basis of 2 cases of PLS, we present conventional imaging confirmation of the revised topographic scheme of fiber distribution across the CC.
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PMID:High T2 signal in primary lateral sclerosis supports the topographic distribution of fibers in the corpus callosum: assessing disease in the primary motor segment. 2147 32

Amyotrophic lateral sclerosis is the most common motor neuron disorder in adults. Although the diagnosis appears obvious in theory, clinical practice shows the contrary as diagnosis is delayed in many patients; the average time between symptom onset and diagnosis can reach 12 months. The delay can be explained by the variability of the clinical presentation and by the absence of diagnostic markers. In order to standardize diagnosis for enrollment in clinical research, diagnostic criteria for ALS were created and revisited during the last 20 years. In 2006, the Awaji criteria for the diagnosis of ALS were proposed, adding two major points to the diagnostic criteria: electromyography is considered equivalent to clinical examination for the identification of LMN signs and fasciculation potentials resume their prominent place in the diagnosis. Comparisons of the accuracy of the revisited El Escorial and Awaji criteria support improved diagnostic sensitivity without any effect on specificity with the new classification. The only weakness of the new classification involves patients with UMN signs in one region and LMN in two regions; these patients were previously classified as laboratory-supported probable ALS and currently as possible ALS, a lower level of diagnostic certainty. In all other instances the accuracy appears to be improved by the Awaji criteria. Nevertheless, there is a body of evidence suggesting the need for a revision of these new criteria, giving more weight to clinical and complementary findings of UMN involvement. The need to diagnose and treat ALS quickly could be facilitated by the inclusion of complementary investigations that detect UMN signs.
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PMID:[Awaji criteria: new diagnostic criteria for amyotrophic lateral sclerosis]. 2326 Dec 62

The misdiagnosis of MND (particularly of the ALS phenotype), is uncommon. Atypical presentations, particularly of focal onset and with pure LMN or UMN signs, present a more difficult diagnostic challenge, although perhaps reassuringly, treatable mimics are rare. A working knowledge of potential alternative conditions and MND diagnostic pitfalls should help to reduce the misdiagnosis rate, particularly if the key points are considered.
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PMID:Motor neurone disease: diagnostic pitfalls. 2347 5

Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs.
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PMID:Zebrafish models of human motor neuron diseases: advantages and limitations. 2470 36


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