Myasthenia gravis in a collegiate football player.

A 17-yr-old Division I-AA collegiate offensive lineman developed unilateral ptosis shortly after minor head trauma during a scrimmage. The subsequent temporal profile of the ptosis, a history of a similar event lasting a short period of time 2 yr earlier, and the results of his clinical and electrophysiologic examinations established a diagnosis of very mild, generalized, antibody-negative myasthenia gravis (MG). His desire to continue playing football posed several additional management problems for which there was no published guidance. We started him on alternate-day, high-dose prednisone therapy with potassium and calcium supplementation, and allowed him to partake in conditioning but no contact. Except for residual decreased exercise tolerance, he improved symptomatically and experienced no serious adverse effects from the illness or the treatment during his first season, despite imperfect drug compliance. His MG eventually came under excellent symptomatic control, allowing initiation of a slow taper of the prednisone before his second season. Shortly thereafter, he abruptly stopped the prednisone without seeking medical advice. He continued to experience mild left ptosis and a mild decrease in intense exercise tolerance. He decided to forego his senior season of collegiate football after a bout of severe mechanical low-back pain incurred during spring football practice and limited his athletic activity thereafter to recreational sports.

Identification of a new autosomal dominant limb-girdle muscular dystrophy locus on chromosome 7.

We report the identification of a new locus for autosomal dominant limb-girdle muscular dystrophy (LGMD1) on 7q. Two of five families (1047 and 1701) demonstrate evidence in favor of linkage to this region. The maximum two-point LOD score for family 1047 was 3.76 for D7S427, and that for family 1701 was 2.63 for D7S3058. Flanking markers place the LGMD1 locus between D7S2423 and D7S427, with multipoint analysis slightly favoring the 9-cM interval spanned by D7S2546 and D7S2423. Three of five families appear to be unlinked to this new locus on chromosome 7, thus establishing further heterogeneity within the LGMD1 diagnostic classification.

Exclusion of identified LGMD1 loci from four dominant limb-girdle muscular dystrophy families.

The limb-girdle muscular dystrophies are a clinically and genetically heterogeneous group of disorders. Recent linkage analyses and positional cloning studies have identified numerous loci responsible for the recessive and dominant forms, underscoring the inherent heterogeneity. In this report, we investigate four large autosomal dominant limb-girdle pedigrees and exclude these pedigrees from linkage to these loci. In addition, there is no evidence for linkage to any of the seven recessive LGMD loci.

Evidence for locus heterogeneity in autosomal dominant limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophy (LGMD) is a diagnostic classification encompassing a broad group of proximal myopathies. A gene for the dominant form of LGMD (LGMD1A) has recently been localized to a 7-cM region of chromosome 5q between D5S178 and IL9. We studied three additional dominant LGMD families for linkage to these two markers and excluded all from localization to this region, providing evidence for locus heterogeneity within the dominant form of LGMD. Although patterns of muscle weakness were similar in all families studied, the majority of affected family members in the chromosome 5-linked pedigree have a dysarthric speech pattern, which is not present in any of the five unlinked families. The demonstration of heterogeneity within autosomal dominant LGMD is the first step in attempting to subclassify these families with similar clinical phenotypes on a molecular level.

Randomized controlled trial of testosterone in myotonic dystrophy.

Because testosterone has an anabolic effect in myotonic dystrophy, we conducted a 12-month, randomized, double-blind therapeutic trial of testosterone enanthate (3 mg/kg/wk) in 40 men with myotonic dystrophy. We evaluated strength by manual muscle tests, quantitative myometry, pulmonary function, and quantitative functional assessment. A sustained, significant elevation of testosterone levels was produced but there was no effect on any measurement of muscle strength. Muscle mass as estimated by creatinine excretion and lean body mass (40K method) increased significantly. We conclude that testosterone does not improve strength in myotonic dystrophy despite increasing muscle mass.

Posterior femoral cutaneous neuralgia.

A middle-aged male developed a right posterior femoral cutaneous neuralgia that persisted for 10 years without any associated neurologic, electrophysiologic, or radiologic findings. Five years after onset, surgical exploration of the subgluteal area identified a venous malformation surrounding the nerve. The syndrome appears unique and exemplifies all major aspects of the sensory distribution of the nerve complex.

Monozygotic female twin carriers discordant for the clinical manifestations of Duchenne muscular dystrophy.

We studied twin sisters, in their sixth decade, who were obligate carriers of Duchenne dystrophy. One had a slowly progressing limb-girdle myopathy since her mid-20s. The other sister showed no evidence of neuromuscular disease by history or on physical examination but had high serum CK values and degeneration and regeneration of fibers in a muscle biopsy. Otherwise, they were phenotypically identical, karyotypically normal females with cytogenetically normal X-chromosomes. Based on red cell and HLA loci antigen determinations, there was a 99.2% probability that they were monozygotic. The mutant gene segregating in the family is probably linked to the Xp21 DNA marker pERT87.

Adult-onset autosomal dominant limb-girdle muscular dystrophy.

We describe a kindred with a rare autosomal dominant myopathy limited to the limb-girdle muscles, beginning insidiously any time from the late second through the sixth decades and followed by slow progression. Pelvifemoral precedes scapulohumeral weakness, and proximal appendicular involvement antedates limited distal paresis. Expressivity varies and includes an asymptomatic myopathy (preclinical or subclinical) and a nonmanifesting carrier state that extends well into the eighth decade. A variety of nonspecific changes are present in muscle on light, enzyme histochemical, and electron microscopic examination; of these changes, "rimmed" or autophagic vacuoles are the most characteristic. We identified one very similar previously reported genealogy. The similarities between the two unrelated families clearly establish this dystrophic process as a distinct genetic entity; their differences suggest genetic heterogeneity.

Brain norepinephrine, dopamine, and 5-hydroxytryptamine in magnesium-deprivation encephalopathy in rats.

The effect of Mg deficiency on the regional concentrations of norepinephrine, dopamine, and 5-hydroxytryptamine in the brain was studied in clinically symptomatic young rats fed a diet low in magnesium for 10 days. Decreases in magnesium concentration in the brain were not accompanied by any significant changes in these monoamines.