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Review Article Open Access
Myasthenia gravis (MG) is neuromuscular junction (NMJ) disorder caused mainly by antibodies against muscle nicotinic acetylcholine receptors (nAChRs) at the postsynaptic membrane resulting in depletion of acetylcholine (ACh) at the NMJ. Muscle fatigue is the cardinal symptom of MG. Some patients may develop comorbid nervous system manifestations and syndromes as memory difficulties, sleep abnormalities, autonomic dysfunction, peripheral neuropathy, epilepsy, psychiatric disorders and others. The present article serves as an overview of recent literature in pubmed which highlighted co-morbid nervous system diseases with MG (publications till 2011 were checked). The exact mechanism(s) of such comorbidities is unknown. Generalized cholinergic deficiency due to involvement of nervous system cholinergic systems and pathways by the immunopathogenic process responsible for MG may be suggested. The structural identities between different muscle and neuronal nAChRs subunits with the possibility of cross-reactivity between different nAChRs Abs may be contributed. Such comorbidities also may be due to the immune responses driven by muscle and neuronal nAChRs antibodies expressed by cancer (e.g. thymoma or small cell lung cancer) (i.e. paraneoplastic syndrome). Some authors claim against the generalized cholinergic deficiency as a cause of comorbid nervous system manifestations with MG and suggested that it may be a response to non-specifically acting cytokines or multiple autoimmune response in presence or absence of tumor, or as a consequence of MG itself (as mood disorder, respiratory impairment, hypoxia, sleep abnormalities) or its medications [acetylcholine esterase inhibitors (AChE-Is)]. Recognition of co-morbidities with MG is mandatory, not only for diagnosis, determining prognosis and managing patients but also for future advances in understanding the cellular and molecular mechanisms of MG and its immunopathogenic spectrum for targeted antigen-specific therapeutic strategies.
Myasthenia gravis, cognition, autonomic neuropathy, nicotinic acetyl choline receptors, thymoma, Central nervous system,Neurological disorder, Myasthenia Gravis