Familial Kearns-Sayre syndrome.

The Kearns-Sayre syndrome (KSS) is a distinctive type of progressive external ophthalmoplegia, characterized by pigmentary degeneration of the retina, heart block, elevated concentration of cerebrospinal fluid protein, and abnormal muscle mitochondria. Previously described cases have all been sporadic. Consequently, viral infections and autoimmune disorders have been proposed as etiologies. The occurrence of KSS in two brothers suggests that genetic factors may play a role in the pathogenesis of some cases.

Ophthalmoplegic migraine in infancy.

Isolated oculomotor nerve palsy is an unusual finding in the pediatric patient. Third nerve weakness is a rare complication of vascular headaches, and there are few reported cases of so-called ophthalmoplegic migraine (OM) in young children. Recently we have seen a 12-month-old girl with OM that appeared to respond to treatment with propranolol.

Methylphenidate dosing: twice daily versus three times daily.

OBJECTIVE: To evaluate the short-term efficacy and side effects associated with two methylphenidate hydrochloride (MPH) dosing patterns. METHODS: Twenty-five boys with attention deficit hyperactivity disorder (ADHD) participated in a 5-week, triple-blind, placebo-controlled, crossover evaluation of MPH administered twice (b.i.d.) versus thrice (t.i.d.) per day (mean dose = 8.8 +/- 5 mg, .30 +/- .1 mg/kg/dose). Four dosing conditions (placebo, titration [gradual increase to target dose], b.i.d., and t.i.d.) were used. Dependent measures obtained on a weekly basis included: parent and teacher ratings of child behavior, parent-child conflicts, parent report of stimulant side effects, child self-report of mood symptoms, a sleep log, laboratory measures of attention, and actigraphic recording of sleep activity. RESULTS: All dosing conditions resulted in significant effects on ADHD symptoms when compared with baseline. Relative to placebo, t.i.d. dosing was characterized by improvement on the greatest number of behavioral measures, and both b.i.d. and t.i.d. were generally more effective than titration. Direct comparisons of b.i.d. and t.i.d. dosing revealed that t.i.d. was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor, with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor. The analysis of clinically significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention. Compared with placebo, appetite suppression was rated, on average, as more severe in the t.i.d. and titration conditions, but not in the b.i.d. condition. However, the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d. and t.i.d. schedules. Although there was no difference in sleep duration for children on b.i.d. and t.i.d. schedules, total sleep time appeared to decrease slightly on t.i.d. relative to placebo according to both parent ratings and actigraphic assessment. There were no significant differences between b.i.d. and t.i.d. on any other side effects or sleep variables. CONCLUSIONS: For many children with ADHD, t.i.d. dosing may be optimal. There are few differences in acute side effects between b.i.d. and t.i.d. MPH dosing. The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects.

The Dubowitz syndrome: further observations.

An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal retardation, microcephaly, sparse hair, toe syndactyly, and characteristic facial appearance is now recognized as the Dubowitz syndrome. Five addition additional cases of the Dubowitz syndrome are reported, including 2 with documented vascular abnormalities.

Cerebellar medulloblastoma. An analysis of four cases of extraneural metastasis.

In four of 28 patients (14%) with medulloblastoma who were treated at the University of Wisconsin, Madison, over a 20-year period, extraneural metastases developed. In an effort to delineate the causal factors involved in extraneural metastases, salient features of patients with metastases and without metastases were compared. Suboccipital craniectomy, radiation therapy, and patient longevity were not well correlated with metastases. However, subarachnoid tumor spread was a consistent precursor. A ventriculoatrial shunt may have been a factor in one patient and a serious infection that preceded diffuse metastasis may have been a factor in another patient. Half of the patients with metastases were found to have the desmoplastic variety of medulloblastoma while only one of 24 patients without metastases had this tumor type.

Pharmacokinetics of lorazepam in critically ill neonates with seizures.

Pharmacokinetic data were evaluated in 10 term neonates with seizures after intravenous administration of lorazepam, 0.05 mg/kg or 0.1 mg/kg. All seizure activity ceased, with no adverse effects. Pharmacokinetic data revealed a decreased volume of distribution and clearance, and a prolonged half-life in comparison with data from older children and adults. These findings are consistent with physiologic differences in the neonate.