High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis.

The muscle mitochondria of a patient with Kearns-Sayre/chronic external ophthalmoplegia plus syndrome were found to be completely deficient in respiratory complex I activity and partially deficient in complex IV and V activities. Treatment of the patient with coenzyme Q10 and succinate resulted in clinical improvement of respiratory function, consistent with the respiratory deficiencies. Restriction enzyme analysis of the muscle mtDNA revealed a 4.9-kilobase deletion in 50% of the mtDNA molecules. Polymerase chain reaction analysis demonstrated that the deletion was present in the patient's muscle but not in her lymphocytes or platelets. Furthermore, the deletion was not present in the muscle or platelets of two sisters. Hence, the mutation probably occurred in the patient's somatic cells. Direct sequencing of polymerase chain reaction-amplified DNA revealed a 4977-base-pair deletion removing four genes for subunits ofcomplex I, one gene for complex IV, two genes for complex V, and five genes for tRNAs, which paralleled the respiratory enzymes affected in the disease. A 13-base-pair direct repeat was observed upstream from both breakpoints. Relative to the direction of heavy-strand replication, the first repeat was retained and the second repeat was deleted, suggesting a slip-replication mechanism. Sequence analysis of the human mtDNA revealed many direct repeats of 10 base pairs or greater, indicating that this mechanism could account for other reported deletions. We postulate that the prevalence of direct repeats in the mtDNA is a consequence of the guanine-cytosine bias of the heavy and light strands.

Eleven patients with demyelinating polyneuropathy associated with monoclonal IgM antibodies were randomized to receive IVIg or placebo, monthly, for 3 months in a double-blind study. After a washout period, they crossed over to the alternate therapy. Response was gauged by evaluating muscle strength, sensation, and neuromuscular symptoms at baseline, after 3 months, and at treatment's end. After IVIg therapy, the strength improved in only 2 of 11 patients, by 28 and 38.5 points from baseline, and declined after placebo. In 1 other patient, the sensory score improved by 13 points. Antibody titers to MAG/SGPG or gangliosides did not appreciably change. We conclude that IVIg has only a modest benefit to not more than 18% of patients with IgM paraproteinemic demyelinating neuropathy.

We report the treatment of four patients with inclusion-body myositis (IBM) and severe slowly progressive weakness using high-dose intravenous immunoglobulin (IVIg). After two monthly infusions, the strength of the proximal and less atrophic muscle groups improved or normalized in three of the four patients. The improvement lasted from 2 to 4 months. Intravenous immunoglobulin is the first treatment modality to improve the strength of some muscles in patients with this disabling inflammatory myopathy. In view of the high cost of IVIg, the unexpected but encouraging results from this pilot study warrant a controlled trial.