Eli Reichenthal

Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial.

OBJECTIVE To establish the safety of intravenous dexanabinol in severe head injury. DESIGN Prospective, randomized, double-blind, placebo- (vehicle) controlled, multicenter, escalating dose study of a single administration of drug (48 or 150 mg) or vehicle (1 or 3 mL). SETTING All Israeli neurosurgical intensive care units (a total of six units). PATIENTS Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment. MEASUREMENTS AND MAIN RESULTS Intracranial pressure, cerebral perfusion pressure, blood pressure, and heart rate were measured continuously in the intensive care unit. Adverse medical events were recorded and clinical outcome was assessed by the Glasgow outcome scale throughout a 6-month follow-up period. A highly significant reduction in the percentage of time with intracranial pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm Hg was observed in the drug-treated group. The nature and incidence of adverse medical events were similar in the two groups. The percentage of patients achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14% higher in the drug-treated group at 3 and 6 months, respectively. Statistical analysis of these differences by a logistic model using dose, entry Glasgow coma scale score, and computed tomograph as covariates yielded p values for the effect of treatment of .03 and .14 at 3 and 6 months, respectively. CONCLUSIONS Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.

Frequent Blood-Brain Barrier Disruption in the Human Cerebral Cortex

Abstract1. The blood–brain barrier (BBB) protects the brain from circulating xenobiotic agents. The pathophysiology, time span, spatial pattern, and pathophysiological consequences of BBB disruptions are not known.2. Here, we report the quantification of BBB disruption by measuring enhancement levels in computerized tomography brain images.3. Pathological diffuse enhancement associated with elevated albumin levels in the cerebrospinal fluid (CSF) was observed in the cerebral cortex of 28 out of 43 patients, but not in controls. Four patients displayed weeks-long focal BBB impairment. In 19 other patients, BBB disruption was significantly associated with elevated blood pressure, body temperature, serum cortisol, and stress-associated CSF “readthrough” acetylcholinesterase. Multielectrode electroencephalography revealed enhanced slow-wave activities in areas of focal BBB disruption. Thus, quantification of BBB disruption using minimally invasive procedures, demonstrated correlations with molecular, clinical, and physiological stress-associated indices.4. These sequelae accompany a wide range of neurological disorders, suggesting that persistent, detrimental BBB disruption is considerably more frequent than previously assumed.

Early outcome and complications of the extended subcranial approach to the anterior skull base

Objectives: To present the technique of the extended subcranial approach to the anterior skull base and to review the results in 55 patients who underwent the procedure. Study Design: Retrospective review of the records of 55 patients who underwent the extended subcranial approach to the anterior skull base between 1994 and 1998 for the treatment of various neoplasms originating in the nasal cavity, nasopharynx, paranasal sinuses, orbit, or meninges, as well as for the repair of complex craniofacial trauma and/or cerebrospinal fluid (CSF) leak. Preoperative patient evaluation and the surgical technique are also reviewed. Methods: Patient records were retrospectively reviewed and tabulated for age, sex, and indications for procedure, with special focus on early outcome and complications. Results: Twenty‐six patients underwent oncologic resections, 22 patients had reduction of complex fronto‐naso‐orbital and skull base fractures, and seven patients had repair of CSF leak. Significant complications in the oncologic group consisted of one hematoma requiring needle aspiration and two cases of temporary nontension pneumocephalus. In the fracture group, one patient died because of extensive intracerebral damage and multiorgan failure, and one patient had nontension pneumocephalus coupled with CSF leakage and one patient had temporary nontensisn pneumocephalus. The most common late complication in all three groups was anosmia. Conclusions: Based on their review, the authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

Neurosurgical management of single brain metastasis

A series of 74 consecutive cases undergoing craniotomy for single brain metastasis in the Beilinson Medical Center between October 1975 and October 1981 were reviewed. All patients underwent radiation therapy after craniotomy. The most common metastasis was that of unknown origin (35%), followed by lung (24%) and breast (16%). Overall median survival after craniotomy was 6.6 months. Overall 1- and 2-year survival rates were 30 and 15%, respectively. Operative mortality (30 days) was 15%. For the patients with metastases to the lung, median survival was 7.5 months and 1-year survival rate was 33%. It appears from this report that two dominant factors affect the prognosis of these patients. The first is the long latent interval (time between diagnosis of primary tumor and detection of metastasis). The second is the location of the metastasis; those with lesions in the cerebral hemispheres had a far better outcome than those with cerebellar lesions (p less than 0.0001).

Neurologic Outcome with Hemorrhagic Hypotension after Closed Head Trauma in Rats: Effect of Early versus Delayed Conservative Fluid Therapy

OBJECTIVE This study examined (1) whether two previously reported, well-established models in rats, one a model of hemorrhagic hypotension and the other a model of closed head trauma, could be combined to evaluate neurologic outcome when hemorrhage occurs subsequent to head injury, and (2) the ability of the traditional, conservative approach to fluid therapy (3 mL of intravenous fluid for 1 mL of blood loss) to reverse the detrimental effects of hemorrhagic hypotension after closed head trauma. In addition, two strategies of fluid therapy (early and delayed) were examined. METHODS Fifty-six Sprague-Dawley male rats were divided into five groups with head injury at time 0 in groups 3 to 5, hemorrhage at 1 hour in groups 1, 2, 4, and 5, and intravenous fluid at 15 minutes (groups 2 and 5) or 60 minutes (groups 1 and 4) after hemorrhage. Head injury was delivered using a weight-drop impact of 0.5 J onto the closed cranium. Neurologic Severity Score (NSS) was determined at 1 hour (just before hemorrhage) and at 4 hours. RESULTS NSS at 1 hour did not differ between groups 3 to 5 (15.5 (9-24) to 16 (2-21), median (range)). The amount of bleeding did not differ between groups during the first 15 minutes of hemorrhage (2.8 +/- 0.8 to 3.7 +/- 2.0 mL, mean +/- SD). After 60 minutes, cumulative blood loss in the delayed fluid therapy groups was less (3.1 +/- 1.13 mL in group 1 and 4.25 +/- 2.39 mL in group 4) than in the early fluid therapy groups (7.73 +/- 4.41 mL in group 2 and 6.85 +/- 2.36 mL in group 5) (analysis of variance, p < 0.01). The NSS of group 3 (head injury only) improved at 4 hours after injury (12 (5-20)), whereas the NSS of groups 4 and 5 (head injury followed by hemorrhage) deteriorated (24 (17-25) and 19.5 (9-25), respectively) (Kruskal-Wallis test,p < 0.05). In all the hemorrhage groups, fluid therapy failed to restore blood pressure to prehemorrhage levels. CONCLUSION It is concluded that the two individual models of hemorrhagic hypotension and closed head trauma in rats can be combined to evaluate outcome when hemorrhage occurs subsequent to head injury. Furthermore, traditional, conservative fluid therapy, whether early or delayed, failed to restore blood pressure or to improve NSS when hemorrhage occurred after head injury. Blood loss was greater with early fluid therapy whether or not head injury was present.

0.45% saline and 5% dextrose in water, but not 0.9% saline or 5% dextrose in 0.9% saline, worsen brain edema two hours after closed head trauma in rats.

In this study, we examined the effect of four IV fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats.CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 +/- 0.0025 and 1.0368 +/- 0.0028, respectively; mean +/- SD) caused by CHT (1.0395 +/- 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 +/- 0.0042 and 1.0389 +/- 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 +/- 6 mOsm/L), D5W increased blood glucose (1095 +/- 173 mg/dL), D5NS increased blood osmolality (350 +/- 5 mOsm/L) and glucose (1695 +/- 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar IV fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. Implications: We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given IV compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia. (Anesth Analg 1998;86:1225-9)

Trigeminal neuropathy: Improved imaging with a dental computed tomography software program

PURPOSE This study evaluated the use of images obtained by a dental computed tomography (CT) software program in the diagnosis and treatment of trigeminal neuropathy associated with jaw abnormality. PATIENTS AND METHODS Twelve patients with jaw abnormality associated with trigeminal neuropathy as the presenting symptom were studied by plain film radiography (PFR) and by a dental CT software program (DS) that displays multiple panoramic and cross-sectional views of the mandible and maxilla. The two modalities were compared for delineation of the integrity of mandibular foramen, mandibular canal, mental foramen, incisive foramen, and incisive canal. Also, displacement of the neurovascular bundle was evaluated and scored. RESULTS The DS was superior to PFR in showing the bony integrity of the foramina and canals in the jaws, as well as the degree of displacement of the neurovascular bundle. CONCLUSION DS should be the study of choice for evaluating trigeminal neuropathy associated with abnormalities of the jaws.