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Ballard D. Wright and Byron Young

✓ The authors describe a device that monitors and automatically regulates intracranial pressure.

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Byron Young and John J. Mulcahy

✓ Ten patients with neurogenic detrusor hyperreflexia were treated by percutaneous radiofrequency sacral rhizotomy. All had low-threshold involuntary micturition. The bladder capacity of seven patients was increased to over 290 cc during a follow-up interval of 3 to 18 months. This convenient percutaneous procedure is particularly suited for controlling detrusor hyperreflexia, which has frequent failures of initial treatment and late recurrence of symptoms.

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Akira Matsuno

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Jimmi Hatton, Richard Kryscio, Melody Ryan, Linda Ott and Byron Young

Object

Hypermetabolism, hypercatabolism, refractory nitrogen wasting, hyperglycemia, and immunosuppression accompany traumatic brain injury (TBI). Pituitary dysfunction occurs, affecting growth hormone (GH) and plasma insulin-like growth factor–I (IGF-I) concentrations. The authors evaluated whether combination IGF-I/GH therapy improved metabolic and nutritional parameters after moderate to severe TBI.

Methods

The authors conducted a prospective, randomized, double-blind study comparing combination IGF-I/GH therapy and a placebo treatment. Ninety-seven patients with TBI were enrolled in the study within 72 hours of injury and were assigned to receive either combination IGF-I/GH therapy or placebo. All patients received concomitant nutritional support. Insulin-like growth factor–I was administered by continuous intravenous infusion (0.01 mg/kg/hr), and GH (0.05 mg/kg/day) was administered subcutaneously. Placebo control group patients received normal saline solution in place of both agents. Nutritional and metabolic monitoring continued throughout the 14-day treatment period.

The two groups did not differ in energy expenditure, nutrient intake, or use of insulin treatment. The mean daily serum glucose concentration was higher in the treatment group (123 ± 24 mg/dl) than in the control group (104 ± 11 mg/dl) (p < 0.03). A positive nitrogen balance was achieved within the first 24 hours in the treatment group and remained positive in that group throughout the treatment period (p < 0.05). This pattern was not observed in the control group. Plasma IGF-I concentrations were above 350 ng/ml in the treatment group throughout the study period. Overall, the mean plasma IGF-I concentrations were 1003 ± 480.6 ng/ml in the treatment group and 192 ± 46.2 ng/ml in the control group (p < 0.01).

Conclusions

The combination of IGF-I and GH produced sustained improvement in metabolic and nutritional endpoints after moderate to severe acute TBI.

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Jimmi Hatton, Bonnie Rosbolt, Philip Empey, Richard Kryscio and Byron Young

Object

Cyclosporine neuroprotection has been reported in brain injury models but safety and dosing guidelines have not been determined in humans with severe traumatic brain injury (TBI). The purpose of this investigation was to establish the safety of cyclosporine using 4 clinically relevant dosing schemes.

Methods

The authors performed a prospective, blinded, placebo-controlled, randomized, dose-escalation trial of cyclosporine administration initiated within 8 hours of TBI (Glasgow Coma Scale score range 4–8; motor score range 2–5). Four dosing cohorts (8 patients treated with cyclosporine and 2 receiving placebo treatment per cohort) received cyclosporine (1.25–5 mg/kg/day) or placebo in 2 divided doses (Cohorts I–III) or continuous infusion (Cohort IV) over 72 hours. Adverse events and outcome were monitored for 6 months.

Results

Forty patients were enrolled over 3 years (cyclosporine cohorts, 24 male and 8 female patients; placebo group, 8 male patients). Systemic trough concentrations were below 250 ng/ml during intermittent doses. Higher blood concentrations were observed in Cohorts III and IV. There was no significant difference in immunological effects, adverse events, infection, renal dysfunction, or seizures. Mortality rate was not affected by cyclosporine administration, independent of dose, compared with placebo (6 of 32 patients receiving cyclosporine and 2 of 8 receiving placebo died, p > 0.05). At 6 months, a dose-related improvement in favorable outcome was observed in cyclosporine-treated patients (p < 0.05).

Conclusions

In patients with acute TBI who received cyclosporine at doses up to 5 mg/kg/day, administered intravenously, with treatment initiated within 8 hours of injury, the rate of mortality or other adverse events was not significantly different from that of the placebo group.

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William Y. Lu, Marc Goldman, Byron Young and Daron G. Davis

✓ Gangliogliomas of the optic nerve are extremely rare. The case is reported of a 38-year-old man who presented with a visual field deficit and was discovered to have an optic nerve ganglioglioma. The possible embryological origins of this neoplasm, its histological and immunohistochemical features, and its appearance on magnetic resonance imaging are examined. The prognoses of optic nerve glioma and of gangliogliomas occurring elsewhere in the nervous system are compared.

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Byron Young, William F. Meacham and Joseph H. Allen

✓ Small aneurysms may sometimes be considered junctional dilatations but may also progressively enlarge and cause spontaneous subarachnoid hemorrhage, as in the case reported. These small aneurysms should be treated precisely as an aneurysm directly responsible for bleeding. When found in conjunction with other aneurysms, they should either be treated simultaneously or followed until clinical developments indicate the need for such surgery.

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Renee Phillips, Linda Ott, Byron Young and John Walsh

✓ Energy expenditure, nitrogen excretion, and serum protein levels were studied from the time of hospital admission until 2 weeks after severe head injury in eight adolescents and four children with peak 24-hour Glasgow Coma Scale scores ranging from 3 to 8. The mean measured energy expenditure (MEE) was 1.3 times Harris and Benedict's predicted value for energy expenditure. Seventy percent of the patients achieved caloric balance (MEE × 1.2) by 4 to 14 days after injury, but balance was not consistently maintained. Five of the 12 patients had intermittent diarrhea, and two had increased gastric residuals. In five patients fluid restrictions were imposed due to either the syndrome of inappropriate secretion of antidiuretic hormone, pulmonary complications, or intracranial pressure complications. For the adolescents (aged 11 to 17 years) the mean calorie intake during the 1st week was 752 kcal/day and for the children (aged 2 to 5 years) it was 340 kcal/day. During the 2nd week the mean calorie intake for the adolescents was 1671 kcal/day and for the children was 691 kcal/day. Mean urinary nitrogen excretion was 307 mg/kg/day for the adolescents and 160 mg/kg/day for the children. The calculated mean nitrogen balance for the eight adolescents and the four younger children was − 13.6 and −4.1, respectively. Mean albumin levels decreased from 2.9 gm/dl during the 1st week to 2.4 gm/dl during the 2nd week (normal 3.5 to 5.0 gm/dl). Mean total protein level during the 1st week was 5.4 gm/dl and increased to a mean of 6.0 gm/dl during the 2nd week (normal 6.0 to 7.8 gm/dl). Weight loss ranged from 2 to 26 lb during the 2-week period. From these studies it can be concluded that head injury in the child and adolescent induces a metabolic response that includes increased energy expenditure and decreased serum albumin levels similar to those observed for head-injured adults. Mean nitrogen excretion values are less than those in adults with a severe head injury.

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William F. Regine, Roy A. Patchell, James M. Strottmann, Ali Meigooni, Michael Sanders and Byron Young

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT).

Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months.

Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.