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.

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.

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.

Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids.

Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

Extracranial to intracranial vascular anastomosis for occlusive cerebrovascular disease: experience in 110 patients.

In an attempt to ascertain the value of extra- to intracranial arterial bypass for cerebrovascular disease, the general topic of bypass surgery is reviewed and the results of this procedure in 110 patients are analyzed. The feasibility of high patency rates of the anastomosis with acceptably low permanent morbidity and operative mortality rates is demonstrated. Lesions producing transient ischemic attacks which previously were considered to be inoperable or inaccessible can be bypassed by this procedure, and there appears to be a dramatic improvement in the symptomotology of virtually all patients. Patients with a mild stroke or "progressive stroke" also appear to benefit from bypass, but the erratic natural history of these entities precludes irrefutable substantiation of this conclusion. Patients with moderate-to-serve neurological deficits do not appear to be improved by this procedure. In our group of 20 patients presenting with transient ischemic attacks who have had more than 3 years of follow-up, only one patient has suffered a stroke and that was located in the opposite hemisphere.

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)

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.

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.

Sensory Jacksonian seizures.

Sensory Jacksonian seizures were analyzed in 42 patients with regard to anatomical and temporal sequences. The origin of sensory Jacksonian seizures, in contrast to motor Jacksonian seizures, often began at peripheral sites with littel cortical representation. The progression of seizure activity across the cerebral cortex followed a course that was neither rectilinear, radiate, nor random; it appeared to preceed in an organized manner to involve functionally coherent units. The patterns analyzed conformed more closely to cortical somatosensory maps reported for the chimpanzee than the sensory sequences presently available for the cortex of man. Complete diagnostic studies are indicated in patients presenting with sensory Jacksonian seizures because of the frequency of related focal pathology.

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.

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.

Camurati-Engelmann disease (progressive hereditary craniodiaphyseal dysplasia). Case report.

In a patient with Camurati-Engelmann disease, orbital and optic nerve decompression resulted in improvement of papilledema. Subsequent x-ray films of the optic canals, however, revealed reconstitution of osseous optic canals bilaterally, and papilledema has returned in one eye. Definitive treatment of this dysplastic metabolic bone disorder rests in the control of rapid abnormal bone formation.

Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative.

The intact cerebral cortices of cats were exposed in vivo under normothermic conditions and superfused with isotonic artificial cerebrospinal fluid containing added 0.125 mM adenosine. This resulted in chloridecation-rich cerebrocortical swelling which was shown by electron microscopy to be associated with an expanded astroglial compartment. The addition of DCPIB, a non-diuretic acylaryloxyacid analogue of ethacrynic acid and an inhibitor of coupled chloride-cation transport in cerebral cortex in vitro, totally blocked astroglial swelling and the concomitant increases in tissue ion contents. These studies support our previous experiments on the mechanism of formation of astroglial swelling. The pathological consequences of astroglial swelling and the clinical applications of these findings are discussed.

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.

Biology of glial swelling in experimental brain edema.

Most studies of clinically relevant cerebral edema emphasize the effect of added tissue fluid in white matter on gross distortion with transtentorial and subfalcine brain herniation. Our recent studies on altered tissue fluid compartmentation in cerebral gray matter suggest that significant microdistortion of relationships of capillaries to subserved tissue follows swelling of astroglia therein. Grave consequences to solute and gas exchange in focal regions may well be expected and are emphasized. The elucidation of the mechanisms of formation and inhibition of astroglial swelling by chemical agents, including chemically useful acylaryloxyacetic acid derivatives, are discussed. Furthermore, the effect of these agents in altering mortality and morbidity in a controlled, random study of animal head injury is presented.

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.

Delayed impairment of arterial blood oxygenation in patients with severe head injury: preliminary report.

A drop in the arterial PO2 occurring 24 hours after head injury was identified in eight patients. Traditional modes of therapy include administration of supplemental oxygen and provision of an unobstructed airway. The latter proved to be inadequate to continually maintain the PaO2 at a level consistent with the O2 content of the inspired air. Initially, determination of the PaO2, after institution of supplemental oxygen, may demonstrate adequate oxygenation, but blood gas monitoring should be continued since a delayed fall in arterial oxygen tension may occur 24 hours after head injury. This period of potentially deficient blood oxygenation, if severe enough, may further aggravate preexisting brain damage and profoundly affect the ultimate outcome of the patient. The delayed fall in PaO2 is the result of intrapulmonary shunting principally due to a ventilation/perfusion mismatch. The precise mechanism of the ventilation/perfusion inequality in the brain-injured patient awaits further elucidation, but may differ from the alteration in pulmonary function seen in the Respiratory Distress Syndrome.

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.