bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the mode of sensory stimulation in presurgical brain mapping in which functional magnetic resonance imaging is used
Authors: Le Rumeur Elisabeth , Allard Michèle , Poiseau Eric , Jannin Pierre
Published: May 2009

Object. The aim of this study was to evaluate different types of sensory stimulation used to distinguish between microvasculature and venous drainage on functional magnetic resonance (fMR) images with blood oxygen level—dependent (BOLD) contrast.

Methods. Seven volunteers received three sensory stimulations. One consisted of small discontinuous automated pokes to the ventral aspect of the right thumbtip. The other two were delivered by the investigator, who vigorously brushed the ventral aspect of the right thumbtip either alone or in combination with the thenar region. Seven contiguous axial slices of the head were acquired using echoplanar fMR imaging during each mode of stimulation. Box-car analysis and Student's t-test were performed. Cluster analysis was used to determine significant differences between rest and activation phases.

The major findings were 1) that a discontinuous sensory stimulation involving a small skin area was able to evoke a limited activated area in the postcentral gyrus with a low activation index (AI [2%]); 2) that this limited activated area was included in the activated area elicited by the continuous sensory stimulations; and 3) that this also evoked multiple activated areas exhibiting AIs of either approximately 2% or greater than 5%. This indicated that the limited discontinuous tactile stimulation evoked a BOLD-contrast fMR image essentially of microvasculature, whereas the more extensive continuous stimulations evoked a BOLD-contrast fMR image in both microvasculature and venous drainage.

Conclusions. Different sensory stimulations are necessary to differentiate primary sensory cortex from venous drainage for presurgical brain mapping.
Mobile computerized tomography scanning in the neurosurgery intensive care unit: increase in patient safety and reduction of staff workload
Authors: Gunnarsson Thorsteinn , Theodorsson Annette , Karlsson Per , Fridriksson Steen , Boström Sverre , Persliden Jan , Johansson Ingegerd , Hillman Jan
Published: May 2009

Object. Transportation of unstable neurosurgical patients involves risks that may lead to further deterioration and secondary brain injury from perturbations in physiological parameters. Mobile computerized tomography (CT) head scanning in the neurosurgery intensive care (NICU) is a new technique that minimizes the need to transport unstable patients. The authors have been using this device since June 1997 and have developed their own method of scanning such patients.

Methods. The scanning procedure and radiation safety measures are described. The complications that occurred in 89 patients during transportation and conventional head CT scanning at the Department of Radiology were studied prospectively. These complications were compared with the ones that occurred during mobile CT scanning in 50 patients in the NICU. The duration of the procedures was recorded, and an estimation of the staff workload was made. Two patient groups, defined as high- and medium-risk cases, were studied. Medical and/or technical complications occurred during conventional CT scanning in 25% and 20% of the patients in the high- and medium-risk groups, respectively. During mobile CT scanning complications occurred in 4.3% of the high-risk group and 0% of the medium-risk group. Mobile CT scanning also took significantly less time, and the estimated personnel cost was reduced.

Conclusions. Mobile CT scanning in the NICU is safe. It minimizes the risk of physiological deterioration and technical mishaps linked to intrahospital transport, which may aggravate secondary brain injury. The time that patients have to remain outside the controlled environment of the NICU is minimized, and the staff's workload is decreased.
Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries
Authors: Stoodley Marcus , Macdonald R. Loch , Weir Bryce , Marton Linda S. , Johns Lydia , Du Zhang Zhen , Kowalczuk Andrew
Published: May 2009

Object. It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue.

Methods. To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7.

Conclusions. The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.
Dysembryoplastic neuroepithelial tumor of the cerebellum and brainstem
Authors: Fujimoto Kenta , Ohnishi Hideyuki , Tsujimoto Masahiko , Hoshida Tohru , Nakazato Yoichi
Published: May 2009

✓ The authors present a case in which dysembryoplastic neuroepithelial tumors (DNETs) occurred in the cerebellum and brainstem of a 44-year-old woman. A magnetic resonance image of the brain revealed multiple cystic lesions in the right cerebellar hemisphere, vermis, tonsil, and brainstem. Partial removal of the tumors was performed. There were gray multinodular gelatinous lesions on the cerebellar hemisphere. Histologically, the tumors exhibited areas of multiple microcystic nodules in the cerebellar white matter, which were composed of oligodendroglia-like cells (OLCs), astrocytes, and neurons. There were multiple, variable nodules in the lesions, lined by OLCs. The adjacent cerebellar cortex displayed dysplastic features. Reduction of granule neurons and dislocation of Purkinje cells into the molecular layer were observed. The pathological profile of this patient agrees with that described by Daumas-Duport, et al., as a “dysembryoplastic neuroepithelial tumor.”
Metastatic solitary fibrous tumor of the meninges
Authors: Ng Ho-Keung , Choi Paul C. L. , Wong Cheuk-Wah , To Ka-Fai , Poon Wai-Sang
Published: May 2009

✓ Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic cells that was first described in the thorax and subsequently reported in diverse organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have been documented. In the nervous system, SFT has been described as a meningeal lesion although all 14 previously reported cases were benign. The authors report the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor first presented as a meningeal lesion that after three recurrences over a 10-year period metastasized to the soft tissues and lungs. The potentially malignant nature of cranial SFTs, especially those with atypical histological features and high mitotic counts, should be recognized.
A new device for endoscopic third ventriculostomy
Authors: Decq Philippe , Le Guerinel Caroline , Palfi Stéphane , Djindjian Michel , Kéravel Yves , Nguyen Jean-Paul
Published: May 2009

✓ Since its description by Dandy in 1922, several techniques have been used to perform third ventriculostomy under endoscopic control. Except for the blunt technique, in which the endoscope is used by itself to create the opening in the floor of the third ventricle, the other techniques require more than one instrument to perforate the floor of the ventricle and enlarge the ventriculostomy. The new device described is a sterilizable modified forceps that allows both the opening of the floor and the enlargement of the ventriculostomy in a simple and effective way.

The new device has the following characteristics: 1) the tip of the forceps is thin enough to allow the easy perforation of the floor of the ventricle; 2) the inner surface of the jaws is smooth to avoid catching vessels of the basal cistern; and 3) the outer surface of the jaws has indentations that catch the edges of the opening to prevent them from slipping along the instrument's jaws. The ventricle floor is opened by gentle pressure of the forceps, which is slowly opened so that the edges of the aperture are caught by the distal outer indentation of the jaws, leading to an approximately 4-mm opening of the floor. This device has been used successfully in 10 consecutive patients.

This new device allows surgeons to perform third ventriculostomy under endoscopic control in a very simple, quick, and effective way, avoiding the need for additional single-use instruments.
Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases
Authors: Jiang Ji-Yao , Yu Ming-Kun , Zhu Cheng
Published: May 2009

Object. The goal of this study was to investigate the protective effects of long-term (3–14 days) mild hypothermia therapy (33–35°C) on outcome in 87 patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score ≤ 8).

Methods. In 43 patients assigned to a mild hypothermia group, body temperatures were cooled to 33 to 35°C a mean of 15 hours after injury and kept at 33 to 35°C for 3 to 14 days. Rewarming commenced when the individual patient's intracranial pressure (ICP) returned to the normal level. Body temperatures in 44 patients assigned to a normothermia group were maintained at 37 to 38°C. Each patient's outcome was evaluated 1 year later by using the Glasgow Outcome Scale. One year after TBI, the mortality rate was 25.58% (11 of 43 patients) and the rate of favorable outcome (good recovery or moderate disability) was 46.51% (20 of 43 patients) in the mild hypothermia group. In the normothermia group, the mortality rate was 45.45% (20 of 44 patients) and the rate of favorable outcome was 27.27% (12 of 44 patients) (p < 0.05). Induced mild hypothermia also markedly reduced ICP (p < 0.01) and inhibited hyperglycemia (p < 0.05). The rates of complication were not significantly different between the two groups.

Conclusions. The data produced by this study demonstrate that long-term mild hypothermia therapy significantly improves outcomes in patients with severe TBI.
Risk of rupture from incidental cerebral aneurysms
Authors: Tsutsumi Kazuo , Ueki Keisuke , Morita Akio , Kirino Takaaki
Published: May 2009

Object. Controversy still exists about the risk estimation for rupture of untreated saccular aneurysms presenting for causes other than subarachnoid hemorrhage (SAH). The object of this study was to address this issue.

Methods. Between January 1976 and December 1997 in the Aizu Chuou Hospital, 62 patients underwent observation for more than 6 months for saccular, nonthrombotic, noncalcified unruptured aneurysms at locations not related to the cavernous sinus, which were detected in cerebral angiography studies performed for causes other than SAH. Clinical follow-up data in those 62 patients were reviewed to identify the risk of SAH.

All patients were followed until July 1998, with the observation period ranging from 6 months to 17 years (mean 4.3 years). Seven patients (11.3%) developed SAH confirmed on computerized tomography (CT) scanning at a mean interval of 4.8 years, six of whom died and one of whom recovered with a major deficit. In addition, one patient died of the mass effect of the aneurysm, and another after sudden onset of headache and vomiting. The 5- and 10-year cumulative risks of CT-confirmed SAH calculated by the Kaplan—Meier method were 7.5% and 22.1%, respectively, for total cases, 33.5% and 55.9%, respectively, for large (> 10 mm) aneurysms, and 4.5% and 13.9%, respectively, for small (< 10 mm) aneurysms.

Conclusions. Although based on a relatively small, single-institution series, our data indicated that the risk of rupture from incidental, intradural, saccular aneurysms was higher than previously reported, and may support preventive surgical treatment of incidental aneurysms, considering the fatality rate of SAH.
Continuous electromyography monitoring of motor cranial nerves during cerebellopontine angle surgery
Authors: Romstöck Johann , Strauss Christian , Fahlbusch Rudolf
Published: May 2009

Object. Electromyography (EMG) monitoring is expected to reduce the incidence of motor cranial nerve deficits in cerebellopontine angle surgery. The aim of this study was to provide a detailed analysis of intraoperative EMG phenomena with respect to their surgical significance.

Methods. Using a system that continuously records facial and lower cranial nerve EMG signals during the entire operative procedure, the authors examined 30 patients undergoing surgery on acoustic neuroma (24 patients) or meningioma (six patients). Free-running EMG signals were recorded from muscles targeted by the facial, trigeminal, and lower cranial nerves, and were analyzed off-line with respect to waveform characteristics, frequencies, and amplitudes. Intraoperative measurements were correlated with typical surgical maneuvers and postoperative outcomes.

Characteristic EMG discharges were obtained: spikes and bursts were recorded immediately following the direct manipulation of a dissecting instrument near the cranial nerve, but also during periods when the nerve had not yet been exposed. Bursts could be precisely attributed to contact activity. Three distinct types of trains were identified: A, B, and C trains. Whereas B and C trains are irrelevant with respect to postoperative outcome, the A train—a sinusoidal, symmetrical sequence of high-frequency and low-amplitude signals—was observed in 19 patients and could be well correlated with additional postoperative facial nerve paresis (in 18 patients).

Conclusions. It could be demonstrated that the occurrence of A trains is a highly reliable predictor for postoperative facial palsy. Although some degree of functional worsening is to be expected postoperatively, there is a good chance of avoiding major deficits by warning the surgeon early. Continuous EMG monitoring is superior to electrical nerve stimulation or acoustic loudspeaker monitoring alone. The detailed analysis of EMG-waveform characteristics is able to provide more accurate warning criteria during surgery.
Diffuse axonal injury due to lateral head rotation in a rat model
Authors: Xiao-Sheng He , Sheng-Yu Yi , Xiang Zhang , Zhou Fei , Jian-Ning Zhang , Li-Sun Yang
Published: May 2009

Object. The authors investigated the ramifications of producing diffuse axonal injury (DAI) by lateral head rotation in a rat model.

Methods. Using a special injury-producing device, the rat's head was rapidly rotated 90° in the coronal plane at an angular velocity of at least 753.13 rad/second and an angular acceleration of at least 1.806 × 105 rad/second2; the rotation was complete within 2.09 msec. There were no statistically significant changes in PO2, PCO2, pH, or blood pressure values at 5, 15, or 60 minutes after head rotation compared with their respective preinjury baseline values. The rats exhibited posttraumatic behavior suppression for an average of 12.6 minutes. The mortality rate was 17%. The rats that survived had diffuse subarachnoid hemorrhage around the brainstem and upper cervical cord, but no obvious brain contusion. In sections stained with silver or hematoxylin and eosin, axonal swelling and bulblike protrusions at the axonal axis were observed in the medulla oblongata, midbrain, upper cervical cord, and corpus callosum between 6 hours and 144 hours postinjury. The axonal injuries were most severe in the brainstem and were accompanied by parenchymal bleeding. The density of bulblike axonal protrusions peaked 6 hours postinjury in the medulla oblongata and 24 hours postinjury in the midbrain.

Conclusions. Rapid lateral head rotation can produce DAI characterized by severe damage to the rat brainstem.
Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study
Authors: Badie Behnam , Schartner Jill M. , Paul Jasmeet , Bartley Becky A. , Vorpahl Jessica , Preston J. Keith
Published: May 2009

Object. Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model.

Methods. Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c—highly positive, CD45—slightly positive cell), macrophage (CD11b/c—highly positive, CD45—highly positive cell), lymphocyte (CD11b/c-negative, CD45—highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry.

Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 ± 3% and 33 ± 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 ± 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42).

Conclusions. Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.
Role of calcium channels in oxyhemoglobin-induced apoptosis in endothelial cells
Authors: Meguro Toshinari , Klett Christoph P. R. , Chen Betty , Parent Andrew D. , Zhang John H.
Published: May 2009

Object. Oxyhemoglobin (OxyHb) released from hemolysed erythrocytes has been considered to be responsible for cerebral vasospasm after subarachnoid hemorrhage. The authors previously reported that OxyHb produced apoptosis in cultured vascular endothelial cells. The change in intracellular Ca++ homeostasis was expected to be one of the possible mechanisms of the cytotoxic effects of OxyHb. This study was undertaken to investigate the protective effects of Ca++-channel blockers on OxyHb-induced apoptosis.

Methods. Cultured bovine coronary artery and brain microvascular endothelial cells (passages 5–9) were used. A cell density study, immunohistochemical staining, and DNA fragmentation analysis were performed to confirm apoptosis. Various concentrations (1–50 µM) of OxyHb were used for 24- to 72-hour incubations with and without Ca++-channel blockers.

Oxyhemoglobin produced cytotoxicity leading to cell detachment from the culture dish in time- and concentration-dependent manners. The highest dose (50 µM) of OxyHb produced cell detachment after a 24-hour incubation, and the lower doses (1–10 µM) produced cell detachment after 48 to 72 hours. Immunohistochemical analysis showed that apoptosis occurred in cells that were still attached to the side of the culture dish after 48 to 72 hours of OxyHb treatment (5 µM). The OxyHb (10 µM) produced DNA ladders at 48 to 72 hours. Three Ca++-channel blockers were used to prevent the toxic effect of OxyHb. The voltage-dependent Ca++-channel blocker nicardipine (1 µM), the voltage-independent Ca++-channel blocker econazole (10 µM), and the inorganic Ca++-channel blocker lanthanum (100 µM) all failed to prevent cell detachment or DNA ladders produced by OxyHb. These results were similar in both cell lines.

Conclusions. Oxyhemoglobin produced apoptotic changes in cultured vascular endothelial cells, and Ca++-channel blockers did not prevent OxyHb-induced apoptosis.
Relationship between residual cerebral blood flow and oxygen metabolism as predictive of ischemic tissue viability: sequential multitracer positron emission tomography scanning of middle cerebral artery occlusion during the critical first 6 hours after stroke in pigs
Authors: Sakoh Masaharu , Østergaard Leif , Røhl Lisbeth , Smith Donald F. , Simonsen Claus Z. , Sørensen Jens Christian , Poulsen Peter V. , Gyldensted Carsten , Sakaki Saburo , Gjedde Albert
Published: May 2009

Object. The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke.

Methods. Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12–30 ml/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour.

Conclusions. The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.
Ependymal cyst producing alpha-fetoprotein
Authors: Kanazawa Ryuzaburo , Kogure Kazunari , Kominami Shushi , Kobayashi Shiro , Teramoto Akira , Mori Osamu
Published: May 2009

✓ This 17-year-old man was admitted to the hospital due to progressive headache and diplopia. Neuroradiological studies revealed a cystic mass in the pineal region without a parenchymal lesion. In addition, serum alpha-fetoprotein (AFP) levels were elevated. A cyst-to-third-ventricle and cistern fenestration was performed, but the cyst enlarged 3 months after the first operation. In the second operation, subtotal resection of the cyst was performed. The AFP level in the cyst fluid was very high preoperatively but was decreased postoperatively. The patient was discharged with no neurological deficit. Pathological examination of resected tissue showed a single layer of cuboidal cells that resembled an ependymal structure. The cells were immunoreactive for AFP immunostain, which indicated AFP production from these cells.
Neuroblastomatous recurrence of ganglioglioma
Authors: David Karoly M. , de Sanctis Stefano , Lewis Paul D. , Noury Ana M. S. , Edwards J. Martin Rice
Published: May 2009

✓ This case is believed to be the first reported recurrent intracranial ganglioglioma with purely neuroblastomatous malignant transformation. A complete macroscopic resection of a right frontal lobe tumor in an 18-year-old woman revealed differentiated ganglioglioma. Seven years later a large, well-demarcated recurrent tumor was again macroscopically totally resected in the same patient. Histological analysis showed malignant transformation in only the neuronal component of the original tumor. A review of the literature on recurrent gangliogliomas and their malignant transformation is included.
Multicentric intracranial smooth-muscle tumor in a woman with human immunodeficiency virus
Authors: Citow Jonathan S. , Kranzler Leonard
Published: May 2009

✓ A 31-year-old woman with acquired immunodeficiency syndrome (AIDS) was found to harbor both a pulmonary smooth-muscle tumor and an intracranial extraaxial smooth-muscle tumor of the parasellar region. The frequency of smooth-muscle tumors (leiomyoma and leiomyosarcoma) has increased with AIDS, but much more so in children than in adults. Only nine cases of human immunodeficiency virus—related smooth-muscle tumors have been previously reported in adults, and only one of these was located intracranially.
Electrophysiological localization of the substantia nigra in the parkinsonian nonhuman primate
Authors: Starr Philip A. , Subramanian Thyagarajan , Bakay Roy A. E. , Wichmann Thomas
Published: May 2009

✓ During ablative surgery and implantation of deep-brain stimulators for the treatment of movement disorders, electrophysiological techniques are often used for localization of subcortical targets. New restorative therapies for Parkinson disease, aimed at delivering drugs or cells to the substantia nigra (SN), are becoming available. Therefore, precise surgical approaches to the dopaminergic cell—containing region of the SN are required to avoid damage to nearby structures such as the corticospinal tract and subthalamic nucleus. In a study conducted in nonhuman primates, the authors evaluated the utility and accuracy of electrophysiological techniques in localizing the SN.

Three adult rhesus monkeys were used as hosts for intranigral cell transplants. The monkeys were rendered hemiparkinsonian by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. With the aid of stereotactic guidance, chronic recording chambers were placed on the skull of each monkey and directed at the SN. In each monkey, 20 to 40 trajectories were explored with a microelectrode. Spontaneous and movement-related single-unit activities were recorded in the SN, pars reticulata, subthalamic nucleus, globus pallidus, striatum, thalamus, and red nucleus. Motor and ocular responses to microstimulation in the subthalamic area were noted. Using the electrophysiological and stereotactic information that was obtained, three-dimensional maps of the nigral complex were constructed to infer the location of the SN pars compacta. The maps were subsequently used to guide intranigral placement of fetal dopaminergic cells. Accurate delivery was verified by histological analysis.

Based on the characteristic electrophysiological properties of the SN and surrounding structures in the parkinsonian state, microelectrode recording techniques may be used to ensure accurate placement of cell transplantation in the intranigral region.
Use of titanium mesh for reconstruction of large anterior cranial base defects
Authors: Badie Behnam , Preston J. Keith , Hartig Gregory K.
Published: May 2009

✓ The authors evaluated the role of titanium mesh used in combination with vascularized pericranium to provide rigid support during reconstruction of anterior skull base defects.

Thirteen patients with large anterior skull base defects caused by tumor invasion or traumatic injury involving the cribriform plate, orbital roof, and planum sphenoidale were included in the study. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. Surgical glue and routine lumbar cerebrospinal fluid (CSF) drainage were not used in any patient.

At a mean postoperative follow-up time of 22 months (range 8–39 months), none of the patients had developed infection or meningocele. Postoperative CSF rhinorrhea occurred in two patients with extensive dural defects, which resolved with temporary lumbar drainage.

Use of titanium mesh and a two-layer vascularized pericranial graft is a safe, reproducible, and feasible method for reconstructing the anterior skull base. Patients with large dural defects may need temporary CSF diversion to avoid postoperative fistula formation.
Neurosurgery: a historical prologue to the future
Authors: Weiss Martin H.
Published: May 2009

✓ The author provides a brief history of the genesis of organized neurosurgery and, in particular, the formation and evolution of the American Association of Neurological Surgeons. The legacy of neurosurgery is noted and the author discusses the present and future practice of neurosurgery.
Radiosurgery for Cushing's disease after failed transsphenoidal surgery
Authors: Sheehan Jonas M. , Vance Mary L. , Sheehan Jason P. , Ellegala Dilantha B. , Laws Edward R.
Published: May 2009

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.

Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.

Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.

Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.
Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report
Authors: Kelly Daniel F. , Gaw Gonzalo Irene T. , Cohan Pejman , Berman Nancy , Swerdloff Ronald , Wang Christina
Published: May 2009

Object. Recognition of pituitary hormonal insufficiencies after head injury and aneurysmal subarachnoid hemorrhage (SAH) may be important, especially given that hypopituitarism-related neurobehavioral problems are typically alleviated by hormone replacement. In this prospective study the authors sought to determine the rate and risk factors of pituitary dysfunction after head injury and SAH in patients at least 3 months after insult.

Methods. Patients underwent dynamic anterior and posterior pituitary function testing. Results of the tests were compared with those of 18 age-, sex-, and body mass index—matched healthy volunteers. The 22 head-injured patients included 18 men and four women (mean age 28 ± 10 years at the time of injury) with initial Glasgow Coma Scale (GCS) scores of 3 to 15. Eight patients (36.4%) had a subnormal response in at least one hormonal axis. Four were growth hormone (GH) deficient. Five patients (four men, all with normal testosterone levels, and one woman with a low estradiol level) exhibited an inadequate gonadotroph response. One patient had both GH and thyrotroph deficiency and another had both GH deficiency and borderline cortisol deficiency. At the time of injury, all eight patients with pituitary dysfunction had an initial GCS score of 10 or less and, compared with the 14 patients without dysfunction, were more likely to have had diffuse swelling, seen on initial computerized tomography scans (p < 0.05), and to have sustained a hypotensive or hypoxic insult (p = 0.07). Of two patients with SAH who were studied (Hunt and Hess Grade IV) both had GH deficiency.

Conclusions. From this preliminary study, some degree of hypopituitarism appears to occur in approximately 40% of patients with moderate or severe head injury, with GH and gonadotroph deficiencies being most common. A high degree of injury severity and secondary cerebral insults are likely risk factors for hypopituitarism. Pituitary dysfunction also occurs in patients with poor-grade aneurysms. Postacute pituitary function testing may be warranted in most patients with moderate or severe head injury, particularly those with diffuse brain swelling and those sustaining hypotensive or hypoxic insults. The neurobehavioral effects of GH replacement in patients suffering from head injury or SAH warrant further study.
High level of extracellular potassium and its correlates after severe human head injury: relationship to high intracranial pressure
Authors: Reinert Michael , Khaldi Ahmad , Zauner Alois , Doppenberg Egon , Choi Sung , Bullock Ross
Published: May 2009

Object. Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction.

Methods. Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients.

In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019).

Conclusions. Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.
Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolisms in patients with aneurysmal subarachnoid hemorrhage
Authors: Schulz Mette K. , Wang Lars Peter , Tange Mogens , Bjerre Per
Published: May 2009

Object. The success of treatment for delayed cerebral ischemia is time dependent, and neuronal monitoring methods that can detect early subclinical levels of cerebral ischemia may improve overall treatment results. Cerebral microdialysis may represent such a method. The authors' goal was to characterize patterns of markers of energy metabolism (glucose, pyruvate, and lactate) and neuronal injury (glutamate and glycerol) in patients with subarachnoid hemorrhage (SAH), in whom ischemia was or was not suspected.

Methods. By using low-flow intracerebral microdialysis monitoring, central nervous system extracellular fluid concentrations of glucose, pyruvate, lactate, glutamate, and glycerol were determined in 46 patients suffering from poor-grade SAH. The results in two subgroups were analyzed: those patients with no clinical or radiological signs of cerebral ischemia (14 patients) and those who succumbed to brain death (five patients).

Significantly lower levels of energy substrates and significantly higher levels of lactate and neuronal injury markers were observed in patients with severe and complete ischemia when compared with patients without symptoms of ischemia (glucose 0 compared with 2.12 ± 0.15 mmol/L; pyruvate 0 compared with 151 ± 11.5 µmol; lactate 6.57 ± 1.07 compared with 3.06 ± 0.32 mmol/L; glycerol 639 ± 91 compared with 81.6 ± 12.4 µmol; and glutamate 339 ± 53.4 compared with 14 ± 3.33 µmol). Immediately after catheter placement, glutamate concentrations declined over the first 4 to 6 hours to reach stable values. The remaining parameters exhibited stable values after 1 to 2 hours.

Conclusions. The results confirm that intracerebral microdialysis monitoring of patients with SAH can be used to detect patterns of cerebral ischemia. The wide range from normal to severe ischemic values calls for additional studies to characterize further incomplete and possible subclinical levels of ischemia.
Neurobehavioral protection by the neuronal calcium channel blocker Ziconotide in a model of traumatic diffuse brain injury in rats
Authors: Berman Robert F. , Verweij Bon H. , Muizelaar J. Paul
Published: May 2009

Object. Abnormal accumulation of intracellular calcium following traumatic brain injury (TBI) is thought to contribute to a cascade of cellular events that lead to neuropathological conditions. Therefore, the possibility that specific calcium channel antagonists might exert neuroprotective effects in TBI has been of interest. The focus of this study was to examine whether Ziconotide produces such neuroprotective effects.

Methods. The authors report that the acceleration—deceleration model of TBI developed by Marmarou, et al., induces a long-lasting deficit of neuromotor and behavioral function. The voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) exerts neuroprotective effects in this model of diffuse brain injury (DBI) in rats. The dose and time of injection of Ziconotide chosen for the present study was based on the authors' previous biochemical studies of mitochondria. Rats were trained in a series of motor and memory tasks, following which they were subjected to DBI using the Marmarou, et al., model. At 3, 5, and 24 hours, all rats were injected with 2 mg/kg Ziconotide for a total cumulative dose of 6 mg/kg Ziconotide. Control brain-injured animals were injected with an equal volume of saline vehicle at each of these time points. The rats were tested for motor and cognitive performance at 1, 3, 7, 14, 21, 28, 35, and 42 days postinjury. Saline-treated rats displayed severe motor and cognitive deficits after DBI. Compared with saline-treated control animals, rats treated with Ziconotide displayed better motor performance during inclined plane, beam balance, and beam walk tests; improved memory while in the radial arm maze; and improved learning while in the Morris water maze.

Conclusions. These results demonstrated that the acceleration—deceleration model, which had been developed by Marmarou, et al., induces severe motor and cognitive deficits. We also demonstrated that Ziconotide exhibits substantial neuroprotective activity in this model of TBI. Improvement was observed in both motor and cognitive tasks, even though treatment was not initiated until 3 hours after injury. These findings support the development of neuronal N-type calcium channel antagonists as useful therapeutic agents in the treatment of TBI.
Improvement in mitochondrial dysfunction as a new surrogate efficiency measure for preclinical trials: dose—response and time-window profiles for administration of the calcium channel blocker Ziconotide in experimental brain injury
Authors: Verweij Bon H. , Muizelaar J. Paul , Vinas Federico C. , Peterson Patti L. , Xiong Ye , Lee Chuan P.
Published: May 2009

Object. Determining the efficacy of a drug used in experimental traumatic brain injury (TBI) requires the use of one or more outcome measures such as decreased mortality or fewer neurological and neuropsychological deficits. Unfortunately, outcomes in these test batteries have a fairly large variability, requiring relatively large sample sizes, and administration of the tests themselves is also very time consuming. The authors previously demonstrated that experimental TBI and human TBI induce mitochondrial dysfunction. Because mitochondrial dysfunction is easy to assess compared with neurobehavioral endpoints, it might prove useful as an outcome measure to establish therapeutic time windows and dose—response curves in preclinical drug testing. This idea was tested in a model of TBI in rats.

Methods. Animals treated with the selective N-type voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) after cortical impact displayed significant improvement in brain mitochondrial function. When a single intravenous bolus injection of 4 mg/kg Ziconotide was given at different time intervals, ranging from 15 minutes before injury to 10 hours after injury, mitochondrial function was improved at all time points, but more so between 2 and 6 hours postinjury. The authors evaluated the effects on mitochondrial function of Ziconotide at different doses by administering 0.5 to 6 mg/kg as a single bolus injection 4 hours after injury, and found 4 mg/kg to be the optimum dose.

Conclusions. The authors established these time-window profiles and dose—response curves on the basis of mitochondrial outcome measures in a total of 42 rats because there were such low standard deviations in these tests. Establishing similar time-window profiles and dose—response curves by using neurobehavioral endpoints would have required using 114 rats in much more elaborate experiments.
No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia
Authors: Westermaier Thomas , Zausinger Stefan , Baethmann Alexander , Steiger Hans-Jakob , Schmid-Elsaesser Robert
Published: May 2009

Object. Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses—the gold standard of neuroprotection during neurovascular procedures—provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question.

Methods. Thirty-two Sprague—Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33°C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy.

Conclusions. The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.
Aberrant p21 regulation in radioresistant primary glioblastoma multiforme cells bearing wild-type p53
Authors: Kraus Alison , Gross Markus W. , Knuechel Ruth , Münkel Kristin , Neff Frauke , Schlegel Jürgen
Published: May 2009

Object. A clearer understanding of the cellular mechanisms involved in the response to ionizing radiation is pivotal to the development of new therapeutic strategies for glioblastoma multiforme (GBM). To gain insight into dynamic functional aspects of cell cycle regulation and the control of apoptosis in GBMs, the authors investigated the molecular changes induced by ionizing radiation in genetically characterized primary GBMs in vitro compared with secondary GBMs, Grades II and III gliomas, and three GBM cell lines.

Methods. Irradiation of primary GBMs bearing wild-type (wt) p53 invariably fails to invoke the G1 checkpoint and apoptosis in vitro. In approximately half of these primary GBMs a defect lies at or above the level of p53 because transcriptional activation of p21 and bax after irradiation does not occur. The failure of a p21 response to irradiation is invariably accompanied by overexpression of p21 mRNA under nonirradiated conditions. In all remaining primary GBMs transcriptional activation of p21 after irradiation does occur, suggesting that a defect downstream from p21 prevents G1 arrest.

Conclusions. These results show that the G1 checkpoint and the p53 pathway are dysfunctional in primary GBMs in vitro, despite the presence of an intact p53 gene. The data also suggest that primary GBMs may be divided into two categories on the basis of their p21 response to irradiation.