Seizures associated with stroke in childhood.

Seventy-three consecutive children younger than 17 years of age seen from 1978 to 1992 with acute hemiplegia from stroke, were retrospectively reviewed to evaluate the incidence of seizures and the risks of recurrent seizures after stroke. The population consisted of 56 children with cerebral infarction, 12 with intracranial hemorrhage, and 5 with transient ischemic attack. Children whose strokes occurred in the neonatal period and those secondary to trauma, malignancy, or infection were excluded. Mean follow-up time was 43.5 months (range: 12-156 months). At least 1 seizure occurred in 36 patients (49.3%) and recurrent seizures occurred in 21 patients (28.8%). Recurrent seizures developed more often among patients who had initial seizures with delayed onset (P < .05). In 56 patients with cerebral infarction, 16 of 31 patients (51.6%) with cortical involvement documented by neuroradiologic studies and 1 of 25 patients (4%) without cortical involvement developed recurrent seizures (P < .01). In 12 patients with intracranial hemorrhage, 3 of 10 patients with cortical involvement and none of 2 patients without cortical involvement developed recurrent seizures. It is concluded that seizures commonly occur in childhood stroke. Risk factors for recurrent seizures include later onset of initial seizures and presence of cortical involvement.

Episodic spontaneous hypothermia with hyperhidrosis: implications for pathogenesis.

Unprovoked hypothermia is an unusual presenting sign. When occurring with diaphoresis it has been referred to as episodic spontaneous hypothermia with hyperhidrosis. Earlier reports described episodic, spontaneous hypothermia with hyperhidrosis in patients with agenesis of the corpus callosum and postulated a midline congenital malformation of the central nervous system. Since then, various endocrine, electrolyte, autonomic, and sleep disturbances have been described but the etiology remains undetermined. Three unrelated children are reported each of whom had an intact corpus callosum and normal endocrine function. Shivering was consistently absent despite marked symptomatic hypothermia. One child had spontaneous resolution of episodic spontaneous hypothermia with hyperhidrosis and two children responded to the antiserotonergic, cyproheptadine. It is hypothesized that specific serotonergic dysfunction in the anterior hypothalamic extrapyramidal shivering mechanism is central in the pathogenesis of this condition.

Muscle imaging in neuromuscular disease using computerized real-time sonography.

The results of a study utilizing computerized real-time sonography (CRS) to image muscles in patients with neuromuscular disease are presented for 67 patients, 37 with neuromuscular disease and 4 with upper motor neuron disease, and 26 age-matched healthy controls between the ages of 2 days and 59 years. CRS is a safe, noninvasive, atraumatic method for evaluating a broad range of neuromuscular diseases. It is capable of differentiating myopathies or dystrophies from neurogenic atrophies and floppy infants with "central" hypotonia from those with neuromuscular diseases.

Anticonvulsive drugs and blood levels of lactate, pyruvate, and glucose in children with seizures.

Lactate, pyruvate, and glucose were determined in groups of 10 patients, each receiving single drug therapy for their seizure disorder with either phenytoin, valproic acid, carbamazepine, or phenobarbital, and in patients not taking medication. All drug levels were in their therapeutic ranges. The characteristics of the groups were similar, except for the phenytoin group being significantly older. No significant differences were found in glucose or pyruvate concentrations. However, patients on valproic acid had reduced lactate (p less than 0.05) and L/P ratios (p less than 0.05). The reduction in lactate in patients on valproate therapy may mask inborn errors of metabolism that normally result in an increase in blood lactate levels.

Urinary sialic acid screening in neurologic disorders.

Urine sialic acid was measured in 246 patients evaluated for possible neurodegenerative disorders. Total, free, and bound sialic acid excretion declined significantly with patients' ages. Among 11 patients (4.5%) with age-related excretion rates greater than 2 standard deviations above the mean, 5 had the following disorders: free sialic acid storage disease, mucolipidosis type II, pseudohypoparathyroidism, sinus histiocytosis, and probable Sanfilippo syndrome. Although the remaining 6 were undiagnosed, 2 exhibited deteriorating courses and the other 4 presented variable combinations of organomegaly, developmental delay or mental retardation, seizures, facial dysmorphism, or bony abnormalities. Thus, these individuals also may have metabolic disorders with abnormal excretions of sialic acid-containing compounds. With awareness of age-related excretion rates, sialic acid screening is most useful for the sialidoses, mucolipidoses, and disorders of free sialic acid metabolism.

Studies on a case of HHH-syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria).

A patient with the hyperornithinemia, hyperammonemia, homocitrullinuria syndrome is described. This patient represents the 12th documented case of this rare, presumably autosomal recessive condition. Increased levels of ammonia, ornithine and homocitrulline were demonstrated in blood and cerebrospinal fluid. The blood ammonia concentration could be lowered by supplementation of the diet with low doses of arginine. High doses of arginine precipitated seizures, although plasma levels of arginine and ornithine were not altered. The uptake of ornithine by the particulate fraction of the patient's fibroblasts was lower than that of controls, but still measurable. It is suggested that HHH patients have a partial impairment of the uptake of ornithine by mitochondria.

Serum carnosinase deficiency: a non-disabling phenotype?

Serum carnosinase deficiency (McKusick 21220) is a rare condition, described in 13 cases. Ten additional individuals with serum carnosinase deficiency have been identified. All continued to excrete increased amounts of carnosine in their urine despite a meat-free diet for 3 days. Serum carnosinase activity ranged from 0-30% of normal. In four individuals a normal Km for carnosine of 0.12 mM was observed, while in five individuals an increased Km was found. Homocarnosine levels in CSF in three individuals ranged from 3.4 to 15 mM. Clinical symptoms in these individuals were as follows: attention deficit disorder: 4; non progressive developmental delay: 1; neurofibromatosis: 1; absences seizures: 1; severe, but non-progressive mental retardation, seizures and neurosensory hearing loss: 1; progressive childhood dementia; 1; clinically normal: 1. There was no correlation between severity and type of the neurological symptoms and residual serum carnosinase activity. Although a definite conclusion can only be made after a considerably higher number of individuals has been analyzed, the suspicion that serum carnosinase deficiency is unrelated to the neurological symptoms is strengthened by these observations. There may, however, be an association with a predisposition for mental deficiency.

Electrocardiographic abnormalities in pediatric neuromuscular disease: a review.

Cardiac abnormalities, often heralded by electrocardiographic alterations, at times may become a serious problem in patients with neuromuscular disorders and occasionally lead to death. Electrocardiographic monitoring can identify patients whose conduction defects will benefit from the use of demand pacemakers.

Prenatal diagnosis of metachromatic leukodystrophy in a family with pseudo arylsulfatase A deficiency by the cerebroside sulfate loading test.

Prenatal diagnosis was requested by a family at risk for metachromatic leukodystrophy (MLD). An examination of the family leukocyte arylsulfatase A profile revealed that the mother had pseudo arylsulfatase A deficiency. Cultured amniotic fluid cells were deficient in arylsulfatase A, so two possibilities were indicated: the fetus was affected with MLD or had the pseudodeficiency phenotype. The only known biochemical test to differentiate the two enzyme deficient phenotypes is cerebroside sulfate loading of growing fibroblasts. The pseudodeficient cells hydrolyze the incorporated sulfatide as efficiently as control cells, whereas MLD cells show no hydrolysis. Application of this test to the at risk cultured amniotic fluid cells resulted in appreciable uptake of the sulfolipid, but no hydrolysis. Control amniotic fluid cell cultures hydrolyzed 82 to 95% of the incorporated sulfatide. Therefore, an affected fetus was indicated. Fibroblasts derived from the aborted fetus showed a deficiency of arylsulfatase A and a similar inability to hydrolyze cerebroside sulfate in the loading test. The loading technique allowed the prenatal diagnosis of MLD when the arylsulfatase A analysis was equivocal.

Phosphorylase isoenzymes in normal and myophosphorylase-deficient human heart.

Phosphorylase isoenzymes were studied by acrylamide-slab electrophoresis in normal tissues and in the heart of a child with a fatal infantile form of myophosphorylase deficiency. Of the three bands present in normal human heart, two were missing in the patient's heart: the slow "muscle" isoenzyme and the intermediate band. Only the fast "cardiac" isoenzyme remained. When extracts of normal skeletal muscle and the patient's heart were mixed in appropriate conditions, the intermediate band reappeared in the electropherogram. Phosphorylase activity in extracts of the patient's heart was not inhibited by antibodies against purified enzyme from mature human muscle, whereas normal human heart phosphorylase was inhibited by approximately 50%. These results suggest that the intermediate band of human heart phosphorylase is a hybrid of skeletal and cardiac muscle isoenzymes. Retained activity of the cardiac isoenzyme may explain why patients genetically lacking skeletal muscle phosphorylase do not have clinical heart disease.

Fatal infantile form of muscle phosphorylase deficiency.

A girl had generalized, rapidly progressive weakness beginning at age 4 weeks, and causing severe respiratory insufficiency and death at age 13 weeks. Histochemical and biochemical investigations of a muscle biopsy showed increased glycogen concentration and complete lack of phosphorylase activity. The enzyme protein appeared to be absent by immunodiffusion, and the metabolic block was documented by studies of anaerobic glycolysis in vitro. The biochemical basis for the unusual clinical picture is obscure, but muscle phosphorylase deficiency has to be considered in the differential diagnosis of the "floppy baby syndrome".