Fast forwarding: the evolution of neurosurgery. The 2005 presidential address.

Despite the major social and economic reorganization of medical practice that has taken place during the past 40 years, neurosurgery-the most fascinating specialty in all of clinical medicine-has grown and prospered. Today, this specialty is poised for an era of spectacular advancement and improvement in care; however, significant problems with the potential to retard this growth face neurosurgery. Among these problems is the medical liability situation, which has the potential to destabilize neurosurgical practices and the current health care delivery system. Other issues facing neurosurgery include the potential for loss of the unique nature of the specialty through a conversion to shift-worker surgeons and increasing reliance on profit-seeking institutions for financial stability and liability protection. Lifestyle choices are of growing importance and currently discourage women from entering the field. With a growing knowledge base, there is the recognition that it may not be possible for most individuals to master all aspects of the specialty. There is continued confusion about manpower needs. In addition, some neurosurgeons are choosing to practice in ways that fail to meet the neurosurgeon's obligations to society. There is a growing number of neurosurgeons who dislike providing trauma coverage and there is the potential for some neurosurgeons to give up intracranial neurosurgery. The author believes that it is not competition that will improve the delivery of neurosurgical care and allow for continued growth, but cooperation, and that it will be possible to alleviate many of our problems through increased regionalization of neurosurgical care delivery. This proposal has the potential to promote the formation of neurosurgical teams, ameliorate the problem of physician fatigue, allow greater development of subspecialty skills, and ease the burden of trauma call. It should allow satisfactory solutions to lifestyle considerations and encourage more women to enter the field of neurosurgery. Such a transformation would encourage advances in care to be brought rapidly into the clinical setting and allow neurosurgery to be practiced at the very highest level.

Endolymphatic sac tumor metastatic to the spine. Case report.

Endolymphatic sac tumors (ELSTs) are aggressive papillary lesions of the temporal bone. Although histologically benign, they may exhibit invasive growth and destruction of the skull base. Patients generally present with symptoms referable to the lesion's location within the middle or posterior cranial fossa. Although well characterized as a distinct entity, ELSTs involved in metastatic dissemination have never been reported. In the present report the authors describe a case of ELST metastatic to the spine treated with resection.

Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat.

The endoplasmic reticulum (ER) is emerging as a contributory component of cell death after ischemia. Since caspase-12 has been localized to the ER and is a novel signal for apoptosis, we examined the message levels and protein expression of caspase-12 after cerebral ischemia in vivo. Animals underwent permanent middle cerebral artery occlusion (MCAO) and were sacrificed 24 h after ischemia. Protein analysis revealed a significant increase in caspase-12 and a corresponding up-regulation of caspase-12 mRNA in the ischemia group compared with that in the sham group. Immunohistochemical analysis revealed diffuse positive immunostaining of caspase-12 throughout the striatum and cerebral cortex in animals that underwent ischemia, with more intense caspase-12 immunostaining in the striatum than in the cortex after ischemia. These results demonstrate that cerebral ischemia initiates an ER-based stress response that results in the transcriptional up-regulation and corresponding increased expression of caspase-12 protein, and may provide a new area for therapeutic intervention to ameliorate outcomes following stroke.

Compromised metabolic recovery following spontaneous spreading depression in the penumbra.

Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra. SD was elicited in one group of rats by injecting KCl directly into a frontal craniectomy and the wave of depolarization was recorded in two craniectomies 3 and 6 mm posterior to the first one. In a second group, the middle cerebral artery was occluded using the monofilament technique and a recording electrode was placed 5 mm lateral to the midline and 0.2 mm posterior to bregma. To determine the metabolic response in the penumbral region of the cortex ipsilateral to the occlusion, brains from both groups were frozen in situ when the deflection of the SD was maximal. The spatial metabolic response of SD in the ischemic cortex was compared to that in the non-ischemic cortex. Coronal sections of the brains were lyophilized, pieces of the dorsolateral cortex were dissected and weighed, and analyzed for ATP, P-creatine, inorganic phosphate (Pi), glucose, glycogen and lactate at varying distances anterior and posterior to the recording electrode. ATP and P-creatine levels were significantly decreased at the wavefront in both groups and the levels recovered after passage of the wavefront in the normal brain, but not in the ischemic brain. Glucose and glycogen levels were significantly decreased and lactate levels significantly increased in the tissue after the passage of the wavefront. While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex. SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised. Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra.

Steal affecting the central nervous system.

Steal is a pathophysiological process in which increased blood flow through a low-resistance vascular bed is sufficient to divert flow away from a region of the central nervous system. Three disease states in which steal may cause neurological deficits due to central nervous system ischemia are reviewed. Subclavian steal occurs when stenosis of the subclavian artery proximal to the vertebral origin causes retrograde flow in the left vertebral artery. Patients with anatomic subclavian steal usually do not develop neurological symptoms but may rarely present with posterior circulation ischemia. Arteriovenous malformations alter cerebral blood flow patterns and regional perfusion pressure. It has been hypothesized that cerebral arteriovenous malformations may cause neurological deficits due to steal and that these deficits may be cured with arteriovenous malformation treatment. Intra-arterial pressure measurements and transcranial velocity studies show regional hemodynamic alterations. However, these changes have not been correlated with presenting symptoms. Evidence from single-photon emission computed tomography does suggest a relationship between regional hypoperfusion and neurological deficits. Coarctation of the aorta may divert flow from the spinal cord circulation through intercostal arteries distal to the stenosis. This is a possible but unproven mechanism of myelopathology. Steal syndromes may be amenable to treatment by open surgical or endovascular approaches. Experimental studies of the pathophysiology of steal are strengthened by precise definitions of the measured parameters and innovative applications of technology.

Primary hypertension-induced cerebellar encephalopathy causing obstructive hydrocephalus. Case report.

Hypertension-induced encephalopathy is a recognized pathological process commonly focused in the parietal and occipital lobes of the cerebral hemispheres. The parenchyma of the posterior fossa is infrequently involved. The authors report on two cases of isolated edema of the cerebellar hemispheres, which occurred in the setting of hypertensive crisis and led to complete obstruction of or significant impingement on the fourth ventricle and potentially lethal hydrocephalus. To the best of the authors' knowledge, these are the first reported cases of hypertensive encephalopathy centered in the posterior fossa. Two patients presented with profound decreases in neurological status subsequent to development of malignant hypertension. Imaging studies revealed diffusely edematous cerebellar hemispheres with effacement of the fourth ventricle, causing dilation of the lateral and third ventricles. Following emergency placement of external ventricular drains, control of systemic blood pressure was accomplished, and neurological functioning returned to baseline. Although neurological deterioration resolved swiftly following placement of ventricular catheters and administration of diuretic agents, systemic blood pressure did not fluctuate with the release of cerebrospinal fluid and resolution of increased intracranial pressure. Decrease in systemic blood pressure lagged well behind improvement in neurological status; the patients remained morbidly hypertensive until systemic blood pressure was controlled with multiple parenteral medications. The authors hypothesize that the development of hypertension beyond the limits of cerebral autoregulation led to breakdown of the blood-brain barrier in the cerebellum and development of posterior fossa edema secondary to the focal transudation of protein and fluid. Correction of the elevated blood pressure led to amelioration of cerebellar edema. In the appropriate clinical setting, hypertension as the inciting cause of cerebellar encephalopathy should be considered.

Differential grading of endolymphatic sac tumor extension by virtue of von Hippel-Lindau disease status.

OBJECTIVE: Endolymphatic sac tumors are aggressive papillary tumors of the temporal bone frequently associated with von Hippel-Lindau disease. The goal of this study was to use a newly devised classification system as a means to analyze differences between endolymphatic sac tumor extension in von Hippel-Lindau disease and non-von Hippel-Lindau disease patients. METHODS: Previously reported cases of endolymphatic sac tumor and two new cases were retrospectively reviewed and assigned to a new classification system consisting of four grades based on tumor extent and location. RESULTS: Mean age of 103 patients without von Hippel-Lindau disease was 52.5 years, whereas in 46 patients with VHL the mean age was 31.3 years. Patients with von Hippel-Lindau disease were more likely to be female (female-to male ratio of 2:1 for von Hippel-Lindau disease patients versus 1:1 for non-von Hippel-Lindau disease patients). Symptoms consisted of hearing loss (100% [mean duration, 10 yr] for VHL patients versus 97% [mean duration, 7.8 yr] for non-von Hippel-Lindau disease patients), facial weakness (38% versus 49%), and tinnitus or vertigo (41% versus 60%). Bilateral tumors were common in von Hippel-Lindau disease patients (28% versus 1%). Tumors in von Hippel-Lindau disease patients were significantly more likely to be lower grade than tumors in non-von Hippel-Lindau disease patients (Grade I, 40% versus 25%; Grade II, 50% versus 58%; Grade III, 8% versus 14%; and Grade IV, 2% versus 4%; p < 0.05). Before 1988, there were relatively fewer Grade I (15% versus 33%) and relatively more Grade II (69% versus 47%) endolymphatic sac tumors in non-von Hippel-Lindau disease patients than after 1988. CONCLUSIONS: Increased usefulness of intracranial imaging since 1988 has led to the diagnosis of sporadic endolymphatic sac tumors with lower grades. Surveillance imaging in von Hippel-Lindau disease may account for the greater proportion of endolymphatic sac tumors diagnosed with lower grades. Endolymphatic sac tumors associated with a diagnosis of von Hippel-Lindau disease appear to affect a younger population of patients than non-von Hippel-Lindau disease cases and occur in women twice as often as in men when associated with von Hippel-Lindau disease. In addition, tumors are more frequently bilateral and less advanced in the von Hippel-Lindau disease patient as opposed to the non-von Hippel-Lindau disease patient.

Integration of neurosurgical image guidance and an intraoperative magnetic resonance scanner. The University Hospitals of Cleveland experience.

BACKGROUND: Intraoperative magnetic resonance (MR) imaging has been employed as an alternative to image guidance using preoperative images. We integrated both systems to evaluate their clinical use. METHODS: The BrainLAB VectorVision system was integrated in an intraoperative Siemens Open Viva 0.2-tesla MR system. Clinical experience was assessed. RESULTS: Patterns of intraoperative imaging emerged, and benefit was seen in registering preoperative and intraoperative images. CONCLUSIONS: This integrated system has clinically observed effects on imaging, navigation, and surgery.

Ischemic cell death: dynamics of delayed secondary energy failure during reperfusion following focal ischemia.

Reperfusion injury is believed to contribute to the pathophysiology of ischemic cell death, but the precipitating factors have yet to be completely elucidated. The goal of this study was to examine if reflow-induced secondary energy failure is a component in the events that lead to cell death following increasing periods of middle cerebral artery (MCA) occlusion in Wistar rats. Discrete sections within the MCA distribution were dissected and analyzed for high-energy phosphates and glucose. Regional cerebral blood flow was determined by [14C]-iodoantipyrine technique in representative groups. The levels of ATP + P-creatine were initially depressed at the end of the focal ischemia and the concentrations in the penumbra were unchanged for up to 8 h after 2 h of ischemia which contrasts with response in the ischemic core, striatum, and penumbra where the HEP generally recovered to values near those of control only to decrease with increasing periods of reflow. The possibility of a rebound ischemia in secondary energy failure (SEF) was precluded by regional CBF values and concentrations of glucose that were significantly higher than the threshold for an ischemic effect. The depletion of cellular energy stores following SEF strongly indicates that the evolution of infarct during reflow results from loss of ATP and its synthesis.

Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia.

Cerebral ischemia initiates a program of cell death known as apoptosis. Early steps in these death promoting events are the release of cytochrome c from the mitochondria and activation of caspase-9. The purpose of this report is to determine if the administration of a specific caspase-9 inhibitor, Z-Leu-Glu(Ome)-His-Asp(Ome)-FMK x TFA (Z-LEHD-FMK) would attenuate apoptosis and the resultant brain injury after ischemia. Adult Wistar rats underwent 3 h of temporary middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. An intraventricular injection of 4.8 microg of Z-LEHD-FMK was given 15-min postreperfusion. Administration of the caspase-9 inhibitor, Z-LEHD-FMK, to the experimental group (n = 12) reduced total infarction volume by 49% (p < 0.05) and improved neurological outcome by 63% (p < 0.01) as compared to the control group (n = 12). Western blot analysis of animals that underwent ischemia-reperfusion showed the appearance of the active form of caspase-9. Inhibition of caspase-9, the apical caspase in cytochrome-c-dependent apoptosis, is an effective intervention to attenuate neurological injury after focal ischemia.

Delayed changes in regional brain energy metabolism following cerebral concussion in rats.

Traumatic brain injury (TBI) results in an acute altered metabolic profile of brain tissue which resolves within hours of initial insult and yet some of the functional deficits and cellular perturbations persist for days. It is hypothesized that a delayed change in energy status does occur and is a factor in the neural tissue's ability to survive and regain function. Regional metabolic profile and glucose consumption were determined at either 1 or 3 days following two different intensities of parasagittal fluid-percussion (F-P). A significant decrease in both 1CMRgluc and levels of ATP and P-creatine was evident in the hemisphere ipsilateral to the trauma at 1 day after the insult. The effect was greater in the cortical than the subcortical regions and was more pronounced at the higher trauma intensity. Normalization of glucose consumption and energy levels was essentially complete by 3 days. It would appear that the delayed metabolic changes at 1 day postinsult cannot be explained by a secondary ischemia since the changes in the metabolite profile do not elicit an increase in the consumption of glucose. These changes in energy metabolites may account for and contribute to the chronic neurological deficits following TBI.