Neuromuscular junction disorders

Lambert-Eaton syndrome is an antibody-mediated neuromuscular junction disorder. This disorder, which is most frequently encountered in patients with small-cell lung carcinoma, is characterized clinically by weakness and hyporeflexia. The impaired release of acetylcholine vesicles from presynaptic terminals at neuromuscular junctions that causes the weakness is a consequence of autoantibodies against small cell carcinoma epitopes that cross-react with and downregulate the expression of motor nerve terminal Ca2+ channels [39]. (See in Ch. 43.)... 

Neuropathic disorders Administer with caution in individuals with peripheral motor neuropathic diseases (eg, amyotrophic lateral sclerosis, motor neuropathy) or neuromuscular junctional disorders (eg, myasthenia gravis, Lambert-Eaton syndrome). Patients with neuromuscular disorders may be at increased risk of clinically significant P.787... 

Diseases selectively targeting spinal cord and brainstem motor neurons (e.g. amyotrophic lateral sclerosis and the familial spinal muscular atrophies) or the presynaptic component of neuromuscular junctions (e.g. Lambert-Eaton syndrome, botulism and Ixodes tick paralysis) cause weakness without sensory impairment. Disorders involving the enteric nervous system (e.g. Chagas disease and Hirschsprung s disease) impair bowel motility. 

Measuring muscle-evoked responses to repetitive motor nerve electrical stimulation permits detection of presyn-aptic neuromuscular junction dysfunction. In botulism and the Lambert-Eaton syndrome, repetitive stimulation elicits a smaller than normal skeletal muscle response at the beginning of the stimulus train, due to impaired initial release of acetylcholine-containing vesicles from presyn-aptic terminals of motor neurons followed by a normal or accentuated incremental muscle response during repeated stimulation. This incremental response to repetitive stimulation in presynaptic neuromuscular disorders can be distinguished from the decremental response that characterizes autoimmune myasthenia gravis, which affects the postsynaptic component of neuromuscular junctions. 

Whereas many metabolic defects affect only a small number of individuals, emotional illnesses including depression, schizophrenia, and other affective disorders at one time or another afflict a large fraction of the population. Autism affects thousands of children.1055 Parkinson disease and Alzheimer disease are just two of a number of degenerative neural diseases attacking older people. Less commonly, young persons contact multiple sclerosis and muscular dystrophy, which is often a disease of neuromuscular junctions. 

This chapter deals with botulinum toxin type A (BOTOX) in the treatment of strabismus, blepharospasm, and related disorders. Botulinum toxin type A (BOTOX) has been used to treat strabismus, blepharospasm, Meige s syndrome, and spasmodic torticollis. By preventing acetylcholine release at me neuromuscular junction, botulinum toxin A usually causes a temporary paralysis of the locally injected muscles. The variability in duration of paralysis may be related to me rate of developing antibodies to me toxin, upregulation of nicotinic cholinergic postsynaptic receptors, and aberrant regeneration of motor nerve fibers at me neuromuscular junction. Complications related to this toxin include double vision (diplopia) and lid droop (ptosis). 

Myasthenia gravis, LEMS, and neuromyotonia affect the neuromuscular junction. These disorders are not necessarily associated with malignancy but are sometimes associated with tumors and are regarded as PNS in these patients. 

Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH]... 

The stiff-man syndrome, a disease with excess motor unit activity, is also associated with autoimmune diseases and thyroid disorders (Layzer, 1988). Indeed, despite the heterogeneity of conditions manifesting excessive motor activity, terminal axon sprouting has been demonstrated in muscle biopsies (Oda et al, 1989). Despite elevated thyroid antibody titers in the two patients, there are no reports on the presence of TSHr, Tg, or TPO in the peripheral nerves, neuromuscular junction, or striated muscles. Hence, the role these antibodies play in the generation of neuromuscular manifestations still needs to be elucidated. 

Myasthenia Gravis and Related Disorders Biochemical Basis for Disease of the Neuromuscular Junction, ed.M.A. Agius, D.P. Richman and R.H. Fairclough in Annals of the New York Academy of Sciences, Vol. 998, New York Academy of Sciences, 2003... 

Recording activity directly from the muscle fibers themselves can be clinically valuable in identifying neuromuscular disorders [19]. Therefore, invasive electrodes are needed to access the muscle fibers or the neuromuscular junction. Fine-needle electrodes or thin stainless-steel wires are inserted or implanted to obtain local recording from the fibers or neuromuscular junctions [7]. 

Approximately 15% of patients receiving PMV or LTMV have NMD (37,64). NMD can be grouped into disorders involving the central nervous system, such as multiple sclerosis and amyotrophic lateral sclerosis the motor neuron, such as postpolio syndrome and amyotrophic lateral sclerosis the peripheral nerves, such as Guillain-Barre syndrome the neuromuscular junction, such as botulism and myasthenia gravis and the peripheral muscles, such as inflammatory myopathies, myotonic dystrophy type 1, and Duchenne s muscular dystrophy (40). 

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