Therapeutic hypothermia as a neuroprotective strategy in neonatal hypoxic-ischemic brain injury and traumatic brain injury.

Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury.

Metastatic gliosarcoma with a unique presentation and progression: case report and review of the literature.

A 51-year-old right-handed woman initially presented with generalized tonic-clonic seizures. MRI showed abnormal signal hyperintensity of the right temporal lobe that was thought to be consistent with ischemic stroke. Three years later, she developed an intensely enhancing centrally necrotic tumor in the right temporal-parietal lobes. A craniotomy was performed with gross total resection of the tumor followed by chemotherapy and radiation treatments. Histological examination demonstrated a gliosarcoma. A year later, she had a recurrence of the intra-axial gliosarcoma requiring a second craniotomy for tumor resection and placement of Gliadel wafers. Postoperatively, she developed plural effusions. A pulmonary workup revealed lung lesions that were biopsied and found to be gliosarcoma. After the second surgery, she underwent pleurodesis and one cycle of modified mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy, but died 5 months later from progression of the lung metastases. There are fewer than 20 reported cases of extracranial metastases of gliosarcoma. This is the first report of gliosarcoma with prolonged survival (over 2 years) and death from non-CNS metastatic gliosarcoma.

Association of surgical specialty and processes of care with patient outcomes for carotid endarterectomy.

BACKGROUND AND PURPOSE: Because there is considerable variation in practice patterns and outcomes for carotid endarterectomy (CE), there is a need to study the processes of care that are associated with adverse outcomes. The purpose of this study was to examine the impact of processes of care and surgical specialty on adverse outcomes for CE. METHODS: A retrospective cohort study based on a voluntary CE registry containing 3644 patients undergoing CE between April 1, 1997, and March 31, 1999, in New York hospitals was used in the study. A multivariable statistical model was used to identify significant independent patient risk factors and to examine the association of processes of care and surgical specialty with outcomes after adjustment for differences in patient risk factors. RESULTS: The overall adverse outcome (in-hospital death or stroke) rate was 1.84%. After adjustment for differences in 7 patient risk factors that were significantly related to adverse outcomes, the use of >/=1 specific processes of care (eversion endarterectomy, protamine, or shunts) was found to be associated with lower odds of an adverse outcome relative to patients undergoing CE without the processes (OR=0.42, P=0.006). Similarly, patients undergoing surgery performed by vascular surgeons had lower odds of experiencing an adverse outcome (OR=0.36, P=0.009). Processes of care and surgical specialty were highly correlated with one another. CONCLUSIONS: Processes of care and surgical specialty are significant interrelated determinants of adverse outcome for CE.

Workforce demand for neurosurgeons in the United States of America: a 13-year retrospective study.

OBJECT: The workforce demand for neurosurgeons was quantified by a review and an analysis of journal recruitment advertisements published over the past 13 years. METHODS: A retrospective analysis of recruitment advertisements from July 1985 through June 1998 was performed by examining issues of the Journal of Neurosurgery and Neurosurgery. Advertisement information that appeared in each journal during the last 3 years was collected from alternating months (July to May); information that appeared prior to that time was collected from alternating recruitment years back to 1985. The authors examined the following workforce parameters: practice venue, subspecialization, and practice size. They found no significant decrease in neurosurgical recruitment advertisements. There was an average of 102.7+/-22.4 (standard deviation) advertised positions per year during the most recent 3 years compared with 92.6+/-17.9 advertised positions per year during the preceding decade. Similarly, there has been no decline in advertised positions either in academic (33+/-6.1/year for the most recent 3 years compared with 32.8+/-5.9/year for 1985-1995) or private practice (69.7+/-21.6/year for the most recent 3 years compared with 59.8+/-13.4/year for 1985-1995). A shift in demand toward subspecialty neurosurgery was observed. During the past 3 years, 31.2+/-5.9% of advertised positions called for subspecialty expertise, compared with 18.5+/-2.8% for the preceding decade (p < 0.05). The largest number of subspecialty advertisements designated positions for spine and pediatric neurosurgeons. Private practice advertisements increasingly sought to add neurosurgeons to group practices. CONCLUSIONS: Contrary to previous reports and a prevailing myth, our data show no decrease in workforce demand for neurosurgeons in the United States over the past 3 years compared with the prior decade. A shift toward subspecialist recruitment, particularly for spine neurosurgeons, has been demonstrated in both academic and private practice venues.

Relationship between provider volume and mortality for carotid endarterectomies in New York state.

BACKGROUND AND PURPOSE: The objective of this study was to assess the relationship between each of 2 provider volume measures for carotid endarterectomies (CEs) (annual hospital volume and annual surgeon volume) and in-hospital mortality. New York's Statewide Planning and Research (SPARCS) administrative database was used to identify all 28 207 patients for whom carotid endarterectomy was the principal procedure performed in New York State hospitals between January 1, 1990, and December 31, 1995. METHODS: A statistical model was developed to predict in-hospital mortality using age, admission status, and several conditions found to be associated with higher-than-average mortality. This model was then used to calculate risk-adjusted mortality rates for various intersections of hospital and surgeon volume ranges. RESULTS: Risk-adjusted in-hospital mortality ranged from 1.96% (95% confidence interval, 1.47 to 2.57) for patients having surgeons with annual CE volumes of <5 in hospitals with annual CE volumes of /=5 in hospitals with annual CE volumes of >100. These 2 rates were statistically different. CONCLUSIONS: We conclude that the in-hospital mortality rates for carotid endarterectomies performed by surgeons with extremely low annual volumes (<5) and for hospitals with low volumes (

The fall and rise of carotid endarterectomy in the United States and Canada.

BACKGROUND: Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy in the prevention of stroke when the procedure is performed in regional centers of surgical excellence. However, the relative effects of these studies on the rates of carotid endarterectomy in the United States and Canada have been unclear. METHODS: We calculated the annual rate of carotid endarterectomy in the U.S. states of California and New York and in the Canadian province of Ontario from 1983 through 1995. We also studied whether patients in the early 1990s were selectively referred to hospitals with high volumes of procedures and historically low in-hospital mortality rates. RESULTS: Rates of carotid endarterectomy fell in all three regions from 1984 to 1989 (from 126 to 66 per 100,000 adults 40 years of age or older in California, from 65 to 40 per 100,000 in New York, and from 40 to 15 per 100,000 in Ontario), after the publication of studies demonstrating that the rates of complications of carotid endarterectomy were unacceptably high. However, the clinical trials of the 1990s, which showed benefit from carotid endarterectomy, were associated with a dramatic resurgence in the rates of the procedure from 1989 to 1995 (from 66 to 99 per 100,000 in California, from 40 to 96 per 100,000 in New York, and from 15 to 38 per 100,000 in Ontario). These increased rates were not associated with proportionally greater numbers of referrals of patients to hospitals with low mortality rates. CONCLUSIONS: There have been a dramatic fall and rise in the rates of carotid endarterectomy in both the United States and Canada, which correlate with the publication of first unfavorable and then favorable clinical studies. The absence of selective referral of patients to centers with the lowest mortality rates raises questions about whether the benefits of carotid endarterectomy in the general population are similar to those demonstrated in the clinical trials.

Crossroads at Salerno: Eldridge Campbell and the writings of Theodorico Borgognoni on wound healing.

During Eldridge Campbell's tour of duty as the neurosurgical consultant to the Mediterranean theater of World War II operations, he was introduced to a then-revolutionary method of wound treatment. Ironically, Campbell's diligent research efforts later revealed that this method of wound treatment had first been advocated seven centuries earlier--in the same geographical location--by the Italian surgeon Theodoric. Although controversial, this method of wound care was subsequently applied and supported by Theodoric's outspoken pupil, Henri de Mondeville, despite intense opposition from the prevailing medical authorities who supported the doctrine of "laudable pus" for wound management. With Mondeville's death, Theodoric's technique lapsed into obscurity, relegated to a historical footnote until modern biology and the discoveries of Lister and Pasteur would again bring to light the benefits of nonsuppurative wound treatment. In this article the author discusses the work of Theodoric, Mondeville, and Campbell in light of the medical climate of their times and explores the contemporary parallels noted by Campbell in terms of the neglect of other, more recent medical discoveries. These examples encourage us to accept or reject medical treatments based on a thorough examination of their efficacy and not on the stature of their advocates within the medical community.

Nerve entrapment and calf atrophy caused by a Baker's cyst: case report.

An unusual case of leg pain and atrophy in a patient with gastrocnemius due to tibial nerve branch compression by a Baker's cyst is presented. The clinical findings and electrodiagnostic studies were supportive of isolated medial gastrocnemius denervation. Treatment by synovectomy along with decompression of the branch of the posterior tibial nerve to the medial head of the gastrocnemius muscle resulted in clinical improvement. No other cases of such selective branch compression have been previously reported.

Continuous measurement of jugular venous oxygen saturation in response to transient elevations of blood pressure in head-injured patients.

Following traumatic brain injury, continuous jugular venous oxygen saturation (SjvO2) measurements have been made and used to assess cerebral oxygenation. Transients of SjvO2 may reflect cerebral blood flow (CBF) changes if measurements are made over a short period of time during which cerebral metabolic rate for oxygen is assumed unchanged. In response to alterations in perfusion pressure, transients of SjvO2 may indicate the extent to which autoregulation has been preserved after injury. The effect of arterial pressure changes on SjvO2 was measured in 14 severely head-injured patients (Glasgow Coma Scale score < 8) within 36 hours of injury. Mean arterial blood pressure (MABP), arterial oxygen saturation, and intracranial pressure (ICP) data were also continuously recorded by a computer at the patients' bedside. The reliability of the SjvO2 oximetry measurements varied among patients, and an average 38% of SjvO2 measurements were off by more than 6% saturation, necessitating recalibration. During periods of satisfactory catheter performance, 120 instances were found in which MABP was elevated more than 8 torr (mean +/- standard deviation: 32 +/- 13 torr) due to endotracheal suctioning. In 94 of these measurements, there was an associated increase in the ICP of 5 torr or more, averaging 16.6 +/- 10.2 torr. The SjvO2 was 0.62 +/- 0.10 before the increase in MABP and rose to a peak of 0.77 +/- 0.10 during the maximum MABP elevation, suggesting increased CBF during the transient hypertension. In 34 of 37 instances of persistent blood pressure elevations lasting for more than 10 minutes (mean 16.0 +/- 8.0 minutes), the SjvO2 elevation persisted (average duration 15.0 +/- 12.4 minutes), suggesting impaired or lost autoregulatory vasoconstriction. The presence or absence of hyperemia was unrelated to the extent of the autoregulation response. Results indicate that SjvO2 rises with increasing perfusion pressure during and after endotracheal suctioning, suggesting a feeble or absent autoregulatory response following traumatic brain injury.

Institutional Review Board evaluation of neuroscience protocols involving human subjects.

We analyzed our Institutional Review Board's (IRB) critiques of neuroscience protocols to identify areas of difficulty for investigators. Minutes from IRB meetings were reviewed, and criticisms were collated under applicable Code of Federal Regulations sections, coalescing into four categories: procedural issues, protocol critique, consent critique, and patient rights. Better communication with research subjects would have avoided a majority (66%) of criticisms. Procedural criticisms could have been reduced by adherence to IRB technical requirements. The small number of protocol design criticisms suggests either a lack of rigor in committee analysis or reliance on prior reviewers; it may also reflect the ongoing debate about the role of the IRB in evaluating scientific merit.

Neurons of layer Vb of rat sensorimotor cortex atrophy but do not die after thoracic cord transection.

Albino rats six weeks (wk) of age underwent transection of the spinal cord at the level of the seventh thoracic vertebra. They were killed ten wk later by several schedules of formaldehyde-glutaraldehyde, formaldehyde and formaldehyde-ethanol-acetic acid perfusion-fixation. Layer Vb of the sensorimotor cortex, the site of origin of corticospinal axons severed by the operation, was searched by light and electron microscopic methods for evidence of neuronal necrosis. Cord-transected rats were compared with control, unoperated animals of identical age. Nerve cell death was not evident to qualitative study, although shrunken, deeply-staining neurons of artefactitious origin occurred capriciously in paraffin sections when fixation was initiated with a dilute formaldehyde-glutaraldehyde solution. Quantitative light and electron microscopic studies were also negative for indications of neuronal death. However, mild somal atrophy could be substantiated for layer Vb neurons of cord-transected rats by light microscopic, morphometric methods. Neuronal atrophy was unaccompanied by qualitative or quantitative ultrastructural alterations. Subcellular organelles and the per cent of neuronal plasma membrane apposed by axosomatic boutons were unchanged. Neuroglia and neuronal processes always had a normal electron microscopic appearance.

Duplex scanning of the internal carotid artery: an assessment of cerebral blood flow.

Duplex ultrasound scanning (B-mode imaging and pulsed Doppler shift analysis) was used to measure internal carotid artery blood flow (ICBF) in 20 volunteers. The effect of changes in end tidal CO2 on cerebral blood flow was measured. When corrected to a PCO2, of 40 torr (5.32 kPa) internal carotid artery blood flow was 286 +/- 16 ml min-1 (mean +/- s.e.m.). Specific CO2 reactivity (the change in flow per torr change in CO2) was 8.16 +/- 0.69 ml min-1 torr-1 which was equivalent to 2.0 +/- 0.1 per cent of the flow at 40 torr per torr change in CO2 (percentage CO2 reactivity). The mean value and the CO2 reactivity compare favourably with previously reported measurements by other techniques. These data suggest that the non-invasive measurement of internal carotid artery blood flow by Doppler ultrasound scanning is an assessment of cerebral blood flow that can be used to study both normal and pathological changes within the cerebral circulation.

Improved recovery from a traumatic-hypoxic brain injury in cats by intracisternal injection of an anion transport inhibitor.

Cats, injured by a mechanical plus hypoxic model of traumatic brain injury, were treated by intracisternal injection of a modified loop diuretic (L-644,711). This drug inhibits the chloride/bicarbonate anion exchange transport system. The treatment resulted in a significant decrease in mortality from 61 to 21%, and an improvement in both neurological status and EEG activity of the surviving animals. The dose of drug given intracisternally was at least 175 times less than the dosage we previously found was needed to achieve a comparable effect when the drug was given intravenously. The present results suggest that certain types of head injury can be treated by drugs which affect cellular anion transport processes in the brain.

Glucose utilization is unchanged in red nucleus after axotomy.

Separate series of adult rats were subjected to unilateral high cervical and low thoracic section of the rubrospinal tract and sacrificed 1-30 (cervical series) and 3-100 days (thoracic series) later. Local cerebral glucose utilization ([14C]2-DG method of Sokoloff et al.) was determined in the red nucleus and in the inferior colliculus, nucleus interpositus and sensorimotor cortex of both sides in operates and controls. Although severe atrophy of rubral neurons follows cervical tractotomy while reversible chromatolytic alterations occur after thoracic lesions, glucose utilization did not differ in the red nucleus of operated and control rats. However, glucose utilization increased slightly in the inferior colliculus of all operated animals, a finding of indeterminate significance. The failure of axotomized intrinsic neurons of red nucleus and their surround to show altered glucose utilization stands in sharp contrast to the marked increase which occurs in cranial nerve nuclei after axotomy of their contained extrinsic neurons. The data are held to constitute another indication that there is a fundamental difference in the metabolic responses of extrinsic and intrinsic mammalian neurons to axotomy and may support the contention that, in mammals, the axon reaction of intrinsic neurons is fundamentally different from that of extrinsic nerve cells. This difference may have significance for failure of axon regeneration in mammalian CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed pulmonary dysfunction in head-injured patients.

Intracranial pressure (ICP), cardiopulmonary function, and the degree of neurological dysfunction were measured in 13 patients with serious head injury to determine the relationship of these indices to the development of delayed pulmonary dysfunction. All patients had serious isolated head injury with Glasgow Coma Scale scores of 7 or less 6 hours after injury and elevated ICP at the time of admission to the protocol. Three patients developed arterial pO2 of less than or equal to 80 torr despite the initiation of elevated inspired oxygen fraction (FIO2 greater than or equal to 0.5) and positive end expiratory pressure (greater than or equal to 5 cm H2O. One of these three patients had a decline in neurological function, quantified by the Albany Head-Injury Watch Sheet, associated with hypoxemia. The only patients who developed intrapulmonary shunt fractions of more than 15% were five patients who had increased pulmonary vascular resistance (PVR) and elevated or increasing cardiac index, suggesting persistent perfusion to areas of the lung which normally are hypoperfused due to hypoxic pulmonary vasoconstriction. This mismatching of the distribution of ventilation and perfusion was confirmed using the multiple inert gas elimination technique in two patients with an increased shunt fraction. Unperfused gas exchange units were also found to be present, as confirmed by an abnormal multiple inert gas elimination techniques, high PVR and dead space/tidal volume ratio (VD/VT), and low extravascular lung water. Abnormalities of ICP and cerebral perfusion pressure could not be correlated with changes in any of the cardiopulmonary functions studied.