Hypertension and neurofibromatosis. Case report.

A 14-year-old girl with neurofibromatosis presented with severe hypertension. She was subsequently found to have a cerebellar glioblastoma multiforme and vascular lesions producing coarctation of the abdominal aorta and 50% and 95% stenosis of the left and right renal arteries respectively. No evidence of pheochromocytoma was found. After removal of the cerebellar tumor, marked amelioration of the hypertension suggested that the tumor had a major role in the pronounced elevation of her blood pressure. Patients who have both neurofibromatosis and hypertension should be carefully evaluated for these several potential lesions.

Carotid-retinal embolism with coexistent mitral valve prolapse.

A 63-year-old hypertensive woman with a prolapsing mitral valve developed sudden blindness of the left eye secondary to a central retinal artery embolus. The decision to perform carotid arteriography led to discovery of an ulcerated plaque in the left internal carotid artery, which was found at the time of endarterectomy to bear a large friable platelet thrombus. The frequent occurrence of mitral valve prolapse in normal populations suggests that this anomaly may be incidental rather than etiologic in patients with cerebral embolic phenomena. The finding of mitral valve prolapse should not routinely exclude evaluation for other sources of embolic stroke.

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.

Computed tomographic findings in cerebral arterial ectasia.

The computed tomographic findings in 15 patients with angiographically documented cerebral arterial ectasia are reported. In addition to demonstrating the majority of pathologic arterial segments, computed tomography also documents the presence and extent of associated intracranial abnormalities. In this study these included cerebral atrophy (10 patients), infarction (three patients), and subarachnoid hemorrhage (one patient).

Evaluation of traumatic atlantooccipital dislocations.

The diagnosis of traumatic atlantooccipital dislocation (AOD) from the cross-table lateral radiograph is difficult because of problems in demonstrating the complex anatomy of this area and the intricate radiographic methods used to diagnose AOD. Although CT or polytomography seem to be the most accurate diagnostic methods, it is often the lateral radiograph from which the diagnosis and further decisions are made. To determine both the best radiographic method for diagnosing AOD from the lateral radiograph and the role of CT and tomography in the diagnosis of AOD, the literature was reviewed concerning how the diagnosis of AOD has been obtained. In addition, the Wholey dens-basion line, the Powers ratio, the Dublin method of diagnosing AOD, and measurement of the atlantooccipital joint width were applied to 12 cases of traumatic AOD; and the Wholey dens-basion line and the Powers ratio were determined in 100 normal adults and 50 normal children. An alternative plain radiographic method for diagnosing AOD was developed, called the X-line method. This was the most accurate of the methods tested, correctly diagnosing AOD in 75% of cases. The Wholey dens-basion line and direct measurement of the atlantooccipital joint width were each correct in 50% of cases, the Powers ratio in 33% of cases, and the Dublin method in only 25% of cases. Ultimately, either CT or polytomography should provide the definitive diagnosis. In this regard high-resolution CT with reformatted coronal and sagittal images generated from 2-mm thin axial slices appeared to have the most promise as the first study of choice.

Ceftazidime versus tobramycin/ticarcillin in treating hospital acquired pneumonia and bacteremia.

Thirty-five patients in a neurosurgical intensive care unit who had nosocomial pneumonia and bacteremia were randomly assigned to receive either ceftazidime (Cef) or the combination of ticarcillin and pharmacokinetically adjusted doses of tobramycin (T/T). Fifteen of 17 patients (88%) who received Cef were cured or improved compared to 15 of 18 (83%) who received T/T. The original pathogen was eradicated from the respiratory secretion in 10 of 15 patients receiving Cef compared to only 6 of 18 patients receiving T/T (p = 0.12). All patients in both treatment groups who had positive blood cultures cleared the organism from the bloodstream. No cases of drug toxicity, including renal toxicity, were seen in either group. Cef used as a single agent in nosocomial pneumonias and bacteremias performed at least as well as T/T.

Diverse clinical applications of percutaneous lumboperitoneal shunts.

A population of 28 patients underwent the percutaneous placement of a shunt in the lumbar region with a single tube, the other end of which was placed in the peritoneal cavity by laparotomy. The clinical indications for the procedure were: communicating hydrocephalus (16 patients), pseudotumor cerebri (3 patients), cranial cerebrospinal fluid fistula (4 patients), and a bulging postcraniotomy site (2 patients). An additional 3 patients were treated by lumbar subcutaneous-peritoneal shunt for a cerebrospinal fluid (CSF)-subcutaneous fistula after the removal of a leptomyelolipoma. The mean time of follow-up was 18.8 +/- 7.8 months. All patients with pseudotumor cerebri and subcutaneous lumbar CSF fistula and all but 1 of the patients with a cranial CSF fistula improved without further therapy. Twelve of the 16 patients with communicating hydrocephalus improved and did not require other shunt procedures. There was one shunt infection, one wound dehiscence that led to shunt removal, and one shunt migration into the spinal canal. Shunt obstruction that led to revision of the shunt occurred on three occasions in 2 patients. The shunt functioned in only 1 of 4 infants under 4 months of age.

Cerebellar hemangioblastoma symptomatic during pregnancy.

An 18-year-old woman presented during the 2nd month of her pregnancy with noncommunicating hydrocephalus due to a cerebellar hemangioblastoma. The tumor rapidly enlarged over a 12-day period after ventriculoperitoneal shunting, probably because of expansion of the vascular compartment. Serial computed tomography and magnetic resonance imaging observations support previous speculations in the literature that vascular engorgement of hemangioblastomas probably accounts for the rapid deterioration of some patients during pregnancy.

Cutaneous reactions in head-injured patients receiving phenytoin for seizure prophylaxis.

Two types of adverse effects are caused by phenytoin, reversible dose-dependent central nervous system effects and non-dose dependent hypersensitivity effects. The most common presenting symptom of the hypersensitivity reaction is the development of a morbilliform rash. During a 45-month period, 151 head-injured patients received phenytoin for seizure prophylaxis using an 11-mg/kg i.v. and a 13-mg/kg i.m. parenteral loading dose followed by an i.m. or p.o. maintenance dose for therapeutic blood concentrations (10 to 20 micrograms/ml). The patients were followed for 18 months. The incidence of skin reaction to phenytoin was 19.4%, or 24 of 124 patients. Cutaneous reactions occurred from Day 5 through Day 91 of phenytoin therapy. Two patients had more serious reactions after the cutaneous reaction. One patient developed exfoliative dermatitis, and 1 had a pseudolymphoma type syndrome. Both recovered. Patients with cutaneous reactions had higher absolute eosinophil counts (P = 0.01). Other laboratory parameters of the white blood count and the total lymphocyte counts did not differ significantly. Patients receiving dexamethasone had a higher incidence of rash, but this did not reach statistical significance. Because recent data have not documented a seizure-prophylactic effect of phenytoin, only a head-injured patient who has experienced a first posttraumatic seizure should receive the drug.

Prospective randomized study of therapy in cerebrospinal fluid shunt infection.

Thirty patients who met the rigid criteria for a prospective randomized study of cerebrospinal fluid (CSF) shunt infections underwent therapy with the three currently advocated treatment modalities to determine the efficacy of each form of therapy. Ten patients (Group A) underwent shunt removal and, in addition to receiving systemic antibiotics, were treated by either external ventricular drainage or intermittent ventricular taps for decompression and antibiotic administration; 10 patients (Group B) were treated by removal and immediate replacement of the shunt and intrashunt antibiotic therapy; and 10 patients (Group C) received antibiotics without removal or replacement of the shunt. All patients were given intravenous and intraventricular antibiotics as follows: in Group A, antibiotics were given by both the intravenous and the intraventricular routes for a minimal period of 7 days; in Group B, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks; in Group C, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks. In all patients, CSF was obtained from the shunt and cultured 48 hours after the cessation of antibiotic therapy, and the cultures were repeated within 4 months of the completion of treatment. All patients in Group A and 9 of 10 patients in Group B were treated successfully. They were clinically asymptomatic, and cultures after treatment were sterile. However, only 3 patients in Group C responded to treatment. The remaining patients of Group C had persistent infections requiring additional therapy. The mean follow-up of the study group was 23 +/- 14 (SD) months. The mean hospitalization time for the study group was 33 +/- 21 days; the hospitalization time was 24.7 +/- 17 days for Group A alone, 32.7 +/- 8 days for Group B, and 47 +/- 37 days Group C.

Revising appointment, promotion, and tenure procedures to incorporate an expanded definition of scholarship: the University of Kentucky College of Medicine experience.

Scholarly activity and scholarly productivity are key features of the academic health center (AHC) and the work of college of medicine faculty. Recent changes in the academic environment of the University of Kentucky (UK) College of Medicine led to an examination of its appointment, promotion, and tenure procedures. This, in turn, led to a re-examination of the college's definition of scholarship. This article describes three of UK's scholarship-related challenges, particularly those related to clinical departments. The authors describe some of the new procedures being implemented to address these challenges; these include new faculty designations, clearer articulation of promotion procedures, explicit recognition of multiple forms of scholarship, expectations for investment in junior faculty, and mandatory discussion of faculty success in chairs' annual reviews. Faculty reactions, positive and negative, to these changes in procedures are also presented.

Recurrent subarachnoid hemorrhage complicating cerebral arterial ectasia. Case report.

A case of subarachnoid hemorrhage (SAH) complicating cerebral arterial ectasia is reported. While ischemia and cranial nerve palsies are commonly associated with this condition, review of the literature reveals that SAH is exceedingly rare. The pathogenesis, radiographic findings, and clinical complications of cerebral arterial ectasia are discussed.

Isolated histiocytosis X of the hypothalamus. Case report.

Failure to consider histiocytosis X in the differential diagnosis of hypothalamic masses may lead to inappropriate empirical radiotherapy. This report concerns a case of histiocytosis X of the hypothalamus, unassociated with systemic histiocytic lesions, in which early biopsy allowed specific therapy with subsequent total regression of the lesion.

Studies of experimental cervical spinal cord transection. Part III: Effects of acute cervical spinal cord transection on cerebral blood flow.

Regional cerebral blood flow (CBF) was measured by the microsphere technique in anesthetized, mechanically ventilated dogs before and after cervical laminectomy in four (control group), or cervical laminectomy followed by cervical cord transection (CCT) at the C-6 level in six (experimental group). No significant differences in arterial pH, pO2 or pCO2 were observed between control and experimental dogs. Baseline values for mean arterial pressure (MAP) were also similar in the two groups, but MAP fell in all experimental dogs after CCT (p less than 0.025). At 120 minutes after CCT, three of the six dogs had an MAP greater than 60 torr (66 +/- 4 torr), and in three the MAP was greater than 50 torr (45 +/- 3 torr). Regional CBF in cortical gray matter, white matter, and medulla did not change significantly after CCT in dogs with MAP greater than 60 torr. The CBF fell significantly at 120 minutes after CCT in all regions sampled in the dogs with MAP less than 50 torr (p less than 0.025). At 30 and 120 minutes after CCT, cerebellar blood flow fell significantly in all experimental animals (p less than 0.05). These findings indicate that, despite hypotension and sympathetic denervation of cerebral vessels, CBF in cortical gray matter, white matter, and medulla is maintained at normal levels after CCT by autoregulation as long as MAP exceeds 60 torr. Decreased cerebellar blood flow in the experimental group suggests redistribution of CBF after CCT with relative preservation of flow to gray matter, white matter, and medulla. Reduced CBF in the acutely cord-injured patient with significant hypotension (MAP less than 60 torr) may stimulate or complicate coexistent head injury.

Studies of experimental cervical spinal cord transection. Part II: Plasma norepinephrine levels after acute cervical spinal cord transection.

Plasma concentrations of norepinephrine (NE) were measured by a radioenzymatic assay technique before and serially after laminectomy at the C-6 level in 14 anesthetized dogs. In half the animals, no further procedures were carried out (control group); in the other dogs, cervical cord transection was performed in addition to laminectomy (experimental group). Mean plasma NE levels were similar in both groups after laminectomy and before cord interruption. In the control group, NE levels increased gradually for 2 hours after the procedure. In the group with cord transection, however, NE rose immediately after transection to 267% of the baseline value, then fell to 25% of the plasma NE level in the control group at 30 minutes, 29% at 60 minutes, and 15% at 120 minutes. Cervical spinal cord transection, therefore, results in an abrupt but short-lived increase in plasma NE concentrations. These changes in plasma NE levels may explain, at least in part, the hemodynamic alterations and the acute central hemorrhagic necrosis that occur after high spinal cord trauma.

Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures.

A randomized double-blind placebo-controlled study was carried out to determine whether phenytoin administered soon after injury lessens the incidence of epilepsy in the 1st week after severe head trauma. In this study, 244 patients were randomized into either a phenytoin or placebo group. The patients in the phenytoin group were administered phenytoin intravenously or intramuscularly within 24 hours of hospital admission. Patients in the placebo group received intravenous or intramuscular diluent. The patients were switched from parenterally administered phenytoin or placebo as soon as oral doses could be tolerated. Over 78% of the phenytoin patients had plasma concentrations of at least 10 micrograms/ml at 1, 3, and 7 days after injury. There was no significant difference in the percentage of patients having early seizures in the treated and placebo groups (p = 0.99). There was no significant difference in the interval from injury to first seizure between the treated and placebo groups (p = 0.41). The early administration of phenytoin did not lessen the occurrence of seizures in the 1st week after head injury. Since the effectiveness of seizure prophylaxis has not been established, the authors suggest that anticonvulsant drugs be administered only after an early seizure has occurred.

Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures.

This randomized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy. When delayed hypersensitivity to phenytoin developed, the patient was switched to phenobarbital. The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations. There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups (p = 0.75). The time between injury and seizures did not significantly differ between the two groups. The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures. It cannot be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy. The finding that no patient with a phenytoin plasma concentration of 12 microgram/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy, and should be studied further. Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study, or other currently available or newly developed drugs, can prevent the occurrence of posttraumatic epilepsy.

Early prediction of outcome in head-injured patients.

The relationship between Glasgow Coma Scale (GSC) scores obtained during the 1st week after head injury and outcome at 1 year was analyzed in 170 patients. Seventy-two of 76 patients with initial GCS scores of 3 or 4 lived, and only one had a favorable outcome. Favorable and unfavorable outcomes were almost equally divided when the initial GCS scores were in the intermediate range of 5, 6, or 7. No patients with an initial GCS score in this intermediate range that subsequently worsened had a favorable outcome, while over 80% of those improving to a score higher than 7 had a favorable outcome. Only 12% of those persisting with a score of 5, 6, or 7 for 1 week had favorable outcome. Outcome predictions using the multiple logistic model were made for this intermediate group of patients based on GCS scores and data on midline shift derived from computerized tomography (CT). The patients with initial scores of 5, 6, or 7 with midline shifts of less than 4.1 mm on initial CT scanning had a significantly higher favorable outcome rate compared with patients with a larger shift. However, outcome prediction made by combining shift data and initial GCS scores are not significantly more accurate than predictions based solely on initial GCS scores. Combining 48-hour GCS scores and shift data significantly improves predictive accuracy based only on coma scores. The data obtained by combining GCS scores at 72 hours and 1 week and shift data is marginally significant for improving accuracy of outcome predictions. It is concluded that GCS scores and shift data are highly accurate indicators of outcome in head-injured patients.

Studies of experimental cervical spinal cord transection. Part I: Hemodynamic changes after acute cervical spinal cord transection.

Two distinct and sequential patterns of hemodynamic alteration were observed after acute cervical spinal cord transection in anesthetized dogs. Interruption of the cord initially caused a 45% increase in mean arterial pressure (p less than 0.01), a 34% increase in systemic vascular resistance (p less than 0.05), and a 92% increase in left ventricular dp/dt (p less than 0.01), reflecting a generalized sympathetic response to trauma. Concomitant bradycardia and escape arrhythmias suggested relative parasympathetic hyperactivity. Resolution of the brief pressor response was followed by a second, more prolonged, period characterized by a fall in arterial pressure to 71% of control levels (p less than 0.05), a 16% decrease in systemic vascular resistance, and a 58.5% decrease in left ventricular dp/dt (p less than 0.01). These latter hemodynamic changes are consistent with sympathetic denervation and failure of regulatory mechanisms mediated by both alpha- and beta-adrenergic peripheral vascular and myocardial receptors.

Intolerance to enteral feeding in the brain-injured patient.

Calorie and protein supplementation improves nutritional status. This support may improve outcome and decrease morbidity and mortality in acutely brain-injured patients. Investigators have observed a poor tolerance to enteral feedings after brain injury and have noted that this persists for approximately 14 days postinjury. This delay has been attributed to increased gastric residuals, prolonged paralytic ileus, abdominal distention, aspiration pneumonitis, and diarrhea. In the present investigation, 23 brain-injured patients with an admission 24-hour peak Glasgow Coma Scale (GCS) score between 4 and 10 were studied for 18 days from hospital admission. The mean duration from injury to initiation of full-strength, full-rate enteral feeding was 11.5 days. Seven of the 23 patients tolerated enteral feedings within the first 7 days following hospital admission (mean 4.3 days), four patients tolerated feedings between 7 and 10 days postadmission (mean 9 days), and 12 patients did not tolerate feedings until after 10 days postinjury (mean 15.9 days). There was a marginally significant relationship between low GCS scores on admission and length of days to enteral feeding tolerance (p = 0.07). A significant inverse relationship was observed between daily peak intracranial pressure (ICP) and time to tolerance of feedings (p = 0.02). There was no significant relationship between feeding tolerance and days to return of bowel sounds (p = 0.12). Serum albumin levels decreased during the investigation (mean +/- standard error to the mean: 3.2 +/- 0.12 gm/dl on Day 1; 2.7 +/- 0.23 gm/dl on Day 16; normal = 3.5 to 5.0 gm/dl), whereas the percentage of patients tolerating feedings increased over the course of the study. The authors conclude that patients with acute severe brain injury do not adequately tolerate feedings via the enteral route in the early postinjury period. Tolerance of enteral feeding is inversely related to increased ICP and severity of brain injury. It is suggested that parenteral nutritional support is required following brain injury until enteral nutrition can be tolerated.