Jack E. Riggs

Osmotic Demyelination Syndrome Following Correction of Hyponatremia

The treatment of hyponatremia is controversial: some authorities have cautioned that rapid correction causes central pontine myelinolysis, and others warn that severe hyponatremia has a high mortality rate unless it is corrected rapidly. Eight patients treated over a five-year period at our two institutions had a neurologic syndrome with clinical or pathological findings typical of central pontine myelinolysis, which developed after the patients presented with severe hyponatremia. Each patients condition worsened after relatively rapid correction of hyponatremia (greater than 12 mmol of sodium per liter per day)--a phenomenon that we have called the osmotic demyelination syndrome. Five of the patients were treated at one hospital, and accounted for all the neurologic complications recorded among 60 patients with serum sodium concentrations below 116 mmol per liter; no patient in whom the sodium level was raised by less than 12 mmol per liter per day had any neurologic sequelae. Reviewing published reports on patients with very severe hyponatremia (serum sodium less than 106 mmol per liter) revealed that neurologic sequelae were associated with correction of hyponatremia by more than 12 mmol per liter per day; when correction proceeded more slowly, patients had uneventful recoveries. We suggest that the osmotic demyelination syndrome is a preventable complication of overly rapid correction of chronic hyponatremia.

Effect of carbamazepine and valproate on bone mineral density

OBJECTIVE To examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children. METHODS Axial (second, third, and fourth lumbar vertebrae) and appendicular (distal third of radius) bone mineral density was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26 children with uncomplicated idiopathic epilepsy treated with either carbamazepine (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and patients were similar with respect to age, race (all white), and geographic area, and had no dietary restrictions, neurologic impairment, or physical handicaps. RESULTS Subjects were seizure-free for more than 6 months on a regimen of carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/- 2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium intake was similar in control and treated groups. After correction for gender and age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005) reduction in bone mineral density at the axial and appendicular sites, respectively. The reduction in bone mineral density increased with the duration of valproate therapy. Carbamazepine did not significantly reduce bone mineral density. CONCLUSION Valproate montherapy, but not carbamazepine therapy, significantly reduces axial and appendicular bone mineral density in children with idiopathic epilepsy and may increase their risk of osteoporotic fractures.

Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita

The periodic paralyses are a group of autosomal dominant muscle diseases sharing a common feature of episodic paralysis. In one form, paramyotonia congenita (PC), the paralysis usually occurs with muscle cooling. Electrophysiologic studies of muscle from PC patients have revealed temperature-dependent alterations in sodium channel (NaCh) function. This observation led to demonstration of genetic linkage of a skeletal muscle NaCh gene to a PC disease allele. We now report the use of the single-strand conformation polymorphism technique to define alleles specific to PC patients from three families. Sequencing of these alleles defined base pair changes within the same codon, which resulted in two distinct amino acid substitutions for a highly conserved arginine residue in the S4 helix of domain 4 in the adult skeletal muscle NaCh. These data establish the chromosome 17q NaCh locus as the PC gene and represent two mutations causing the distinctive, temperature-sensitive PC phenotype.

Clinicopathological features of genetically confirmed Danon disease

Background: Danon disease is due to primary deficiency of lysosome-associated membrane protein-2. Objective: To define the clinicopathologic features of Danon disease. Methods: The features of 20 affected men and 18 affected women in 13 families with genetically confirmed Danon disease were reviewed. Results: All patients had cardiomyopathy, 18 of 20 male patients (90%) and 6 of 18 female patients (33%) had skeletal myopathy, and 14 of 20 male patients (70%) and one of 18 female patients (6%) had mental retardation. Men were affected before age 20 years whereas most affected women developed cardiomyopathy in adulthood. Muscle histology revealed basophilic vacuoles that contain acid phosphatase–positive material within membranes that lack lysosome-associated membrane protein-2. Heart transplantation is the most effective treatment for the otherwise lethal cardiomyopathy. Conclusions: Danon disease is an X-linked dominant multisystem disorder affecting predominantly cardiac and skeletal muscles.

Neurologic manifestations of electrolyte disturbances.

Electrolyte disturbances occur commonly and are associated with a variety of characteristic neurologic manifestations involving both the central and peripheral nervous systems. Electrolyte disturbances are essentially always secondary processes. Effective management requires identification and treatment of the underlying primary disorder. Since neurological symptoms of electrolyte disorders are generally functional rather than structural, the neurologic manifestations of electrolyte disturbances are typically reversible. The neurologic manifestations of serum sodium, potassium, calcium, and magnesium disturbances are reviewed.

Longitudinal Gompertzian analysis of amyotrophic lateral sclerosis mortality in the U.S., 1977-1986: evidence for an inherently susceptible population subset.

Age-adjusted mortality rates for amyotrophic lateral sclerosis (ALS) for men and women in the United States from 1977 to 1986 were determined and subjected to longitudinal Gompertzian analysis. The exponential decline in the rate of increase of age-adjusted ALS mortality rates after age 55 years is most consistent with the existence of an inherently susceptible population subset that is decreasing faster than the general population. In the U.S. between 1977 and 1986, annual age-adjusted ALS mortality rate distributions were determined by a common fixed intersect point (for men, the death rate at age 46.38 years was 0.91/100,000; for women, the death rate at age 45.85 years was 0.46/100,000); and an environmental factor that varied erratically during the decade by a factor of 7.21 for men and 11.64 for women. On the average, the U.S. environment during this period was 4.33 times more conducive to mortality from ALS in men than in women. Overall ALS mortality between 1977 and 1986 increased 46% and 49% for men and women, respectively. The common fixed intersect point in mortality rate distributions suggests that these increases were real and not merely the result of improved diagnosis and/or better reporting. The overall increase in ALS mortality most likely results from an effective increase in the susceptible population subset due to increasing life expectancy, rather than to environmental factors. That is, as life expectancy increases, more of the susceptible population subset live long enough to express the disease.

Parietal Occipital Edema in Hypertensive Encephalopathy: A Pathogenic Mechanism

Eight patients with hypertensive encephalopathy from diverse etiologies developed cerebral edema in the vertebrobasilar distribution which resolved after blood pressure was lowered. Parietal occipital edema is a recognized feature of hypertensive encephalopathy. The explanation for this regional pathological variation in hypertensive encephalopathy remains undefined. Some evidence suggests that sympathetic innervation of the anterior cerebral vasculature may be protective, and conversely, the relative lack of sympathetic innervation in the vertebrobasilar vasculature may predispose the parietal occipital region to the development of cerebral edema in hypertensive encephalopathy.

Longitudinal gompertzian analysis of adult mortality in the U.S., 1900–1986

Analysis of mortality data for the United States from 1900 through 1986 demonstrates near perfect Gompertzian mortality rate distributions for adult American men and women. In the U.S. between 1900 and 1986, annual age-adjusted mortality rate distributions were determined by a fixed common intersect point (for men, the mortality rate at age 87.41 years was 18,810/100,000; for women, the extrapolated mortality rate at age 108.69 years was 75,365/100,000) and a variable environmental factor. Despite living in the same environment, the environmental factor contributing to adult mortality is at present significantly less for women than men. However, analysis predicts that in an environment less conducive to human survival than has existed in the United States during this century, the environmental factor contributing to adult mortality was less for men than women. The study further implies that as the environment becomes more favorable for human survival, men will experience an effective lowering of their theoretical maximal life span toward a limit of 87.4 years. The calculated maximal life span for men has already decreased 7 years during this century. This negative effect of a more favorable environment also occurs in women, although the theoretical maximal life span in women is lowered only toward a limit of 108.7 years.

Mitochondria1 encephalomyopathy with decreased succinate‐cytochrome c reductase activity

We report two siblings with a mitochondrial encephalomyopathy. The syndrome was characterized by ataxia, intellectual impairment, myoclonic jerks, rare seizures, and small stature. Muscle biopsy specimens showed abnormal accumulations of mitochondria and lipid droplets. Biochemical studies on muscle demonstrated decreased succinate-cytochrome c reductase activity in the mitochondrial respiratory chain.

Upper extremity ischemic monomelic neuropathy: a complication of vascular access procedures in uremic diabetic patients.

Combining the previous reports with our own, all 14 patients who developed UF-IMN following vascular access procedures for hemodialysis and in whom the etiology of their renal failure was noted had long-standing diabetes mellitus