Faculty Bibliography

A 61-year-old man with muscle aches and persistently elevated serum creatine kinase had aggregates of randomly oriented, rhomboidal or rectangular protein crystalline inclusions in the sarcoplasm of type II fibers. Immunochemical studies showed strong reactivity of the inclusions to tubulin antibodies, suggesting that these unique crystalline inclusions may be a consequence of altered synthesis, processing, or degradation of tubulin

Forty years ago, a patient with MG probably had a fifty-fifty chance of surviving a myasthenic crisis, defined as the need for mechanical ventilatory support. Approximately 16% of all patients experience a crisis, a figure that has not changed appreciably since then. Progressive weakness, oropharyngeal symptoms, refractoriness to anticholinesterase medication, intercurrent infection, and invasive procedures including needle biopsies of thymic gland masses, and reactions to contrast agents used in the performance of CT of the chest have been implicated in the development of crisis. It is now standard practice to treat severe crisis in an intensive care unit. The ready availability of intensive care in most hospitals belies the fall in the mortality of myasthenic crisis to 6% over the past several decades. Crisis is a temporary exacerbation, regardless of the proximate cause, and the goal is to keep the patient alive until it subsides, usually in 2 weeks. In the past, edrophonium was used to differentiate myasthenic crisis from cholinergic crisis, but that is now moot because withdrawal of cholinesterase medication is necessary for improvement in both situations. The underlying immunologic derangements in myasthenic crisis are not well understood, but there is a rapidly fatal antibody-mediated syndrome that bears resemblance to crisis and is associated with inflammation and necrosis of the end-plate region

The therapy of myasthenia gravis and inflammatory myopathy are discussed in detail in this article. The discussion of these two disorders illustrates the extraordinary progress that has been achieved in the therapy of neuromuscular disease

Quantitative immunocytochemical analysis of complement proteins (CP) was performed on sural nerve biopsies from 15 patients with diabetic neuropathy (DN) and 18 nondiabetic patients with other forms of chronic neuropathy (ON). The mean age of the patients and the pathological severity of the neuropathy were similar in both groups. The percentage of patients that expressed strongly immunoreactive CP in the walls of endoneurial microvessels was significantly greater in DN than in ON for all proteins tested. C3d neoantigen was expressed in 100% of DN cases compared with 17% of ON; and membrane attack complex (MAC), C5b-9 neoantigen, in 93% of DN and 17% of ON. In the cases with DN, 81% of endoneurial microvessels, as identified by the endothelial marker, Ulex europaeus, contained C5b-9 neoantigen deposits, compared with 22% in those of ON, and the staining in DN was significantly more intense. Expression of the neoantigens of C3d and C5b-9 in nerve implies local activation of the complement system. In DN, activation of the complement pathway and formation of the MAC could injure blood vessels and adversely affect the circulation in the endoneurium