Factors affecting the development of hypothalamus and pituitary lesions in fatal closed head injury: a prospective study.

OBJECTIVES: To determine the factors affecting the development of pituitary and hypothalamic lesions after fatal closed head injury. MATERIALS: Thirty-four patients with severe closed head injury succumbing to the effects of brain trauma before or during admission, whether managed conservatively or surgically, formed the study group. Clinical parameters, injury to death interval, radiologic data, and management details were taken into consideration. Autopsy was performed within 48 hours of death; hypothalamus and pituitary were carefully removed and evaluated for the presence of lesions on hematoxylin and eosin and immunohistochemical staining. RESULTS: Patients were categorized into early death group (n = 11, those succumbing before/on admission) and late death group (n = 23, those succumbing after admission). Histopathologic evaluation of pituitary revealed capsular hemorrhages in 50%, posterior pituitary hemorrhage in 25%, anterior pituitary infarct in 21.8%, and anterior pituitary hemorrhage in 6.2% patients. Hypothalamic hemorrhage was observed in 65.2% patients and infarcts in 17.3%. Lesions in hypothalamus and pituitary were significantly related to the presence of ventricular compression on computed tomography scan and survival of >24 hours after injury (p < 0.05). Capsular hemorrhage, anterior pituitary hemorrhage, and posterior pituitary hemorrhage were present in 40%, 10%, and 30% of the patients in the early death group when compared with 54.5%, 4.5%, and 22.7% of the patients in the late death group. Anterior pituitary infarcts were present in 10% of the patients with early deaths and 27.3% patients in the late death group. Hypothalamic hemorrhages were present in 44.4% of patients in early death and 78.6% in late death groups. Hypothalamic infarcts (40%) were present in the late death group only. Two patients (25%) in the early death group and 11 (84.6%) in the late death group had lesions in pituitary as well as hypothalamus (p < 0.05). CONCLUSIONS: Presence of ventricular compression on computed tomography scan and survival >24 hours after severe head injury has a significant correlation with the development of hypothalamic and pituitary lesions. Secondary insults account for a proportion of pituitary and hypothalamic lesions after trauma, which may be amenable to prevention by early intervention to treat raised intracranial pressure (ICP)/herniation.

Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury.

Sixty-eight patients were entered into a randomized, prospective, double-blinded controlled trial of supplemental zinc versus standard zinc therapy to study the effects of zinc supplementation on neurologic recovery and nutritional/metabolic status after severe closed head injury. One month after injury, the mortality rates in the standard zinc group and the zinc-supplemented group were 26 and 12%, respectively. Glasgow Coma Scale (GCS) scores of the zinc-supplemented group exceeded the adjusted mean GCS score of the standard group at day 28 (p = 0.03). Mean motor GCS score levels of the zinc-supplemented group were significantly higher on days 15 and 21 than those of the control group (p = 0.005, p = 0.02). This trend continued on day 28 of the study (p = 0.09). The groups did not differ in serum zinc concentration, weight, energy expenditure, or total urinary nitrogen excretion after hospital admission. Mean 24-h urine zinc levels were significantly higher in the zinc-supplemented group at days 2 (p = 0.0001) and 10 (p = 0.01) after injury. Mean serum prealbumin concentrations were significantly higher in the zinc-supplemented group (p = 0.003) at 3 weeks after injury. A similar pattern was found for mean serum retinol binding protein level (p = 0.01). A significantly larger number of patients in the standard zinc group had craniotomies for evacuation of hematoma; thus a bias may have been present. The results of this study indicate that zinc supplementation during the immediate postinjury period is associated with improved rate of neurologic recovery and visceral protein concentrations for patients with severe closed head injury.

A trial of the effect of nimodipine on outcome after head injury.

We performed a randomised prospective double blind trial to study the effect of the calcium antagonist nimodipine on the outcome of head injured patients. The subjects were not obeying commands at the time of entry to the study, within 24 hours of injury. One hundred and seventy-five patients received nimodipine IV, 2 mg per hour for up to 7 days and 176 received placebo. The two groups were well matched for important prognostic features. Six months after injury 93 (53%) of the nimodipine group and 86 (49%) of the control group had a favourable outcome (moderate/good recovery). The relative increase in favourable outcomes (8%) was not significant but is compatible (95% C.I.) with an increase in favourable outcomes in treated patients by 33% or a decrease by 12%. Nimodipine was well tolerated and there were few adverse reactions; means of systolic and diastolic blood pressures and the intracranial pressure did not differ between the groups. It is unlikely that nimodipine has a marked effect on outcome (ie an increase in favourable outcome of greater than 15%) after head injury of this severity but the study does not exclude a modest but clinically useful benefit.