Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuromyelitis optica (NMO) or Devic's disease is an inflammatory neurologic disease characterized by severe optic neuritis and transverse myelitis. Other features of NMO include female preponderance, higher onset age, severe functional disability, longitudinally extensive spinal cord lesions (longer than 3 vertebral segments), and oligoclonal IgG bands negativity. Brain lesions are not uncommon in NMO. The relation between NMO and multiple sclerosis (MS) has long been a matter of controversy, but since the discovery of anti-aquaporin 4 (AQP4) antibody (NMO-IgG), an NMO-specific autoantibody, the clinical, MRI, and laboratory features that distinguish NMO from MS have been clarified. Anti-AQP4 antibody binds to the extracellular domain of AQP4, which is highly expressed in endfeet of astrocytes. Recent neuropathological studies, analysis of CSF-GFAP levels during relapse and experimental studies strongly suggest that NMO is an anti-AQP4 antibody-mediated astrocytopathic disease and that T cell-mediated CNS inflammation is necessary to develop NMO. Also, IL-6 is remarkably elevated in the CSF and appears to regulate plasmablasts to produce anti-AQP4 antibody. Therefore, from the therapeutic point of view, depletion of anti-AQP4 antibody, suppression of T cell response to trigger relapse and anti-IL-6 therapy seem to be pivotal. High-dose intravenous methylprednisolone is the first-line therapy for acute exacerbations of NMO. But plasma exchange should be started soon if corticosteroid is not efficacious. If untreated, AQP4 antibody-positive patients are highly likely to experience relapses within a year. Thus, immunosuppressive therapy (corticosteroids, immunosuppressants, rituximab) should be initiated without delay. Preliminary results suggest that eculizumab, an anti-C5 monoclonal antibody, can also prevent relapse in NMO, Meanwhile, interferon-beta, a first-line disease modifying drug of MS, is not effective in NMO. Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life.
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PMID:[Treatment of neuromyelitis optica]. 2257 70

Neuromyelitis optica (NMO; also termed Devic's disease) is a severely disabling autoimmune disorder of the central nervous system (CNS), which predominantly affects the optic nerves and spinal cord. In up to 80% of cases, NMO is associated with antibodies to aquaporin-4 (AQP4-IgG), the most abundant water channel in the CNS. AQP4-IgG have been demonstrated to be directly pathogenic. Gamma-aminobutyric acid A receptor (GABAAR) agonists are frequently used in patients with NMO, e.g., for symptomatic treatment of spasticity or epilepsy or for non-NMO-related indications such as treatment of insomnia. However, GABAAR signaling has recently been shown to strongly promote AQP4 expression. This is of potential clinical importance since any increase in AQP4 membrane expression during acute NMO attacks may enhance the complement-mediated humoral immune reaction against AQP4-expressing cells characteristic for NMO and, thus, result in more severe CNS damage. We therefore hypothesize that GABAAR agonist-induced AQP4 upregulation may be a potential risk factor in NMO. This would also include a potential role for (GABAAR-enhanced) damage to the subependymal zone neural stem cells, the major source of both glial cells and neuroblasts in the adult brain, in NMO. We also make proposals on how to test that hypothesis and underline the general need for evaluating possible detrimental effects of commonly used drugs affecting AQP4 expression in NMO.
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PMID:Gamma-aminobutyric acid receptor agonists, aquaporin-4, and neuromyelitis optica: a potential link. 2632 47