Age dependency of apoptotic neurodegeneration was studied in the developing rat brain after percussion head trauma. In 7‐day‐old rats, mechanical trauma, applied by means of a weight drop device, was shown to trigger widespread cell death in the hemisphere ipsilateral to the trauma site, which first appeared at 6 hours, peaked at 24 hours, and subsided by 5 days after trauma. Ultrastructurally, degenerating neurons displayed features consistent with apoptosis. A decrease of bcl‐2 in conjunction with an increase of c‐jun mRNA levels, which were evident at 1 hour after trauma and were accompanied by elevation of CPP 32‐like proteolytic activity and oligonucleosomes in vulnerable brain regions, confirmed the apoptotic nature of this process. Severity of trauma‐triggered apoptosis in the brains of 3‐ to 30‐day‐old rats was age dependent, was highest in 3‐ and 7‐day‐old animals, and demonstrated a subsequent rapid decline. Adjusting the mechanical force in accordance with age‐specific brain weights revealed a similar vulnerability profile. Thus, apoptotic neurodegeneration contributes in an age‐dependent fashion to neuropathological outcome after head trauma, with the immature brain being exceedingly vulnerable. These results help explain unfavorable outcomes of very young pediatric head trauma patients and imply that, in this group, an antiapoptotic regimen may constitute a successful neuroprotective approach. Ann Neurol 1999;45:724–735

In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.

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ObjectiveTo evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS).Methods373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset).ResultsNo significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months’ duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups.ConclusionAlthough ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early.Trial registration numberNCT00444613.