Cause:Genetic in 10%, autosomal dominant, on chromosome 21 at least half the time (Nejm 1991;324:1381)
Pathophys: Degeneration of anterior horn cells and motor Betz cells of cerebrum progressively up from caudad portion of body. Can start anywhere in cord. Circulating antibody inhibits protein stimulation of axonal sprouting secreted by denervated muscle, primary or secondary effect? (Nejm 1984;311:933). Perhaps defective glutamate transport systems permit neurotoxic levels to build up (Nejm 1992;326:1464) or autoimmune IgG against calcium channels (Nejm 1992;327:1721)
1/250 000 persons in US will die of it; 50× increased prevalence in Guam (Nejm 1970;282:947) along with a unique dementing variant of Parkinson's; both associated with a specific HLA genotype
Sx: Paresis and leg weakness
Si:Marked muscle atrophy, usually upper extremity, accompanied by asymmetric fasciculations of many muscle groups including tongue, and hyperreflexia of the atrophic muscles; paraplegia; and no sensory abnormality or sx that distinguishes it from cervical disc disease. Pseudobulbar palsies, why? (HMS 6/08)
Dysphagia, respiratory paralysis, dysphonia, and dysarthria; cognitive impairment c/w frontotemporal dementia (Arch Neurol 2006;63:345)
With paraplegia, r/o mass lesion, syphilis, B12 deficiency, parasagittal meningioma, Shy-Drager syndrome (Parkinson's Disease (Paralysis Agitans), Dysautonomias), postpolio muscular atrophy (Nejm 1986;314:959)
Lab:
Path:Muscle biopsy shows neuronal degenerative changes; cord shows atrophy with decreased anterior horn cells and lipofuscin in degenerated corticospinal tracts
Rx:Riluzole (an antiglutamate) 50-200 mg po qd slows progression minimally (Lancet 1996;347:1425), perhaps in pts w bulbar onset but not with limb onset disease (Med Let 1995;37:113; Nejm 1994;330:585, 636)