bluuebunny/crossref_metadata_2025 huggingface dataset:
Mercury water and cauterizing stones: Nicolas André and tic douloureux
Authors: Brown Jeffrey A. , Coursaget Catherine , Preul Mark C. , Sangvai Devdutta
Published: May 2009

✓ In his 1756 text, Observations pratiques sur les maladies de l'urèthre et sur plusiers faits convulsifs, Nicolas André coined the term “tic douloureux.” He believed that this pain originated from compression of facial sensory peripheral nerves. Using scientific observation and experimentation to confirm this hypothesis, he reproduced the tic pain and treated it by using careful efforts to remove adhesions from the nerve with a caustic solution of mercury water. Believing that recurrence of the pain was a result of early closure of the wound, with recompression of the nerve being the direct cause, André prevented recompression by ensuring open wound drainage. André's surgical technique of using cauterizing stones ensured that there was minimal blood loss and little danger of rebleeding and recompression of the nerve by an accumulated blood clot. His case reports include lengthy follow-up periods that documented the benefits of his procedures, which were confirmed by testimonials from uninvolved colleagues. Although remembered for the two words, “tic douloureux,” Nicolas André has long been ignored for his prescient treatment and scientific analysis of a disease for which the modern standard of care has only been defined during the last generation.
Workforce demand for neurosurgeons in the United States of America: a 13-year retrospective study
Authors: Friedlich Daniel L. , Feustel Paul J. , Popp A. John
Published: May 2009

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.
Prefrontal dysfunction following unilateral posteroventral pallidotomy in Parkinson's disease
Authors: Yokoyama Tetsuo , Imamura Yoko , Sugiyama Kenji , Nishizawa Shigeru , Yokota Naoki , Ohta Seiji , Uemura Kenichi
Published: May 2009

Object. Pre- and postoperative cognitive function was evaluated in patients with Parkinson's disease (PD) who underwent unilateral posteroventral pallidotomy (PVP) to clarify the effects of this operation on cognitive function.

Methods. Cognitive function was assessed before surgery and 1 month and 3 months afterward by using a battery of neuropsychological tests consisting of orientation, digit span (forward and backward), digit learning, 5-minute memory of five words, similarities, serial sevens, animal name listing, and the kana pick-out test, as well as the Japanese version of the Mini-Mental State. Preoperative evaluation revealed that patients experienced difficulties in performing the neuropsychological tasks of reasoning and abstraction, working memory of numerals, word fluency, and concept formation compared with 36 healthy volunteers (p < 0.05). A simple regression analysis showed strong relationships in a negative fashion between preoperative (r = 0.81, p = 0.002) and 1-month (r = 0.79, p = 0.0059) and 3-month (r = 0.85, p = 0.0016) postoperative gross-total scores and Hoehn and Yahr staging. Preoperative and postoperative scores at 1 month and 3 months were analyzed by analysis of variance, but only the Fisher's post hoc test revealed the source of difference. All tasks except orientation (p = 0.0292) were unchanged in the 10 patients who underwent surgery on the right side. The scores for this task at 1 month postsurgery were significantly lower (p = 0.0203) but improved to preoperative values by 3 months. In the 15 patients who underwent surgery on the left side significant differences among tasks were revealed for serial sevens (p = 0.0471) and animal naming (p = 0.0425). The scores for these tasks were significantly lower at 1 month postoperatively (p = 0.0431 for serial sevens and p = 0.0408 for animal naming), but improved by 3 months after the operation.

Conclusions. The present data revealed that cognitive dysfunction in patients with PD relates to advancement of Hoehn and Yahr stage, but PVP is not associated with significant long-lasting cognitive deficits.
Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial
Authors: Kelly Daniel F. , Goodale David B. , Williams John , Herr Daniel L. , Chappell E. Thomas , Rosner Michael J. , Jacobson Jeff , Levy Michael L. , Croce Martin A. , Maniker Allen H. , Fulda Gerald J. , Lovett James V. , Mohan Olga , Narayan Raj K.
Published: May 2009

Object. Sedation regimens for head-injured patients are quite variable. The short-acting sedative—anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used.

Methods. Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95 ± 87 hours) and 19 patients in the morphine group (mean time of morphine usage 70 ± 54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events.

Conclusions. Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.
Effects of continuous localized infusion of granulocyte—macrophage colony—stimulating factor and inoculations of irradiated glioma cells on tumor regression
Authors: Wallenfriedman Margaret A. , Conrad John A. , DelaBarre Lance , Graupman Patrick C. , Lee Gina , Garwood Michael , Gregerson Dale S. , Jean Walter C. , Hall Walter A. , Low Walter C.
Published: May 2009

Object. Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte—macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats.

Methods. The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF—treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833 ± 2284 mm3, 3294 ± 1632 mm3, and 1979 ± 1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 106 gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF—irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging.

Conclusions. These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.
Hormonal effects on glioblastoma multiforme in the nude rat model
Authors: Plunkett Robert J. , Lis Agnieszka , Barone Tara A. , Fronckowiak Mary Duffy , Greenberg Steven J.
Published: May 2009

Object. The authors studied the effect of gender and hormonal status on survival in nude rats implanted with human glioblastoma multiforme (GBM) cell lines.

Methods. Nude rats received intracerebral implants of either wild-type U87MG cells or U87MG cells transfected with the gene for endothelin-1 (U87/ET-1). In the initial study, survival was compared in males and females for each of the two cell lines. The six second-phase study groups were composed of: 1) males; 2) females; 3) ovariectomized females; 4) sham ovariectomized females; 5) ovariectomized rats given 10 µg/day estradiol benzoate for 21 days; and 6) ovariectomized rats given 20 mg/kg/day progesterone for 21 days. All rats in the second phase were implanted with U87/ET-1 cells. Animals were killed when they exhibited initial signs of neurological deterioration. Female nude rats survived longer than male rats implanted with either U87 or U87/ET-1 cells. In the second phase, ovariectomized, male, and progesterone-treated rats died at approximately 19 days, whereas the female, sham-treated, and estrogen-treated animals died 23 to 25 days after tumor cell implantation.

Conclusions. The authors demonstrate that female nude rats implanted with human GBM cells have a survival advantage over male rats and that estrogen provides the advantage.
Immediate early gene expression in vascular smooth-muscle cells synergistically induced by hemolysate components
Authors: Wang Xiaoyu , Marton Linda S. , Weir Bryce K. A. , Macdonald R. Loch
Published: May 2009

Object. Vasospasm after subarachnoid hemorrhage is associated with changes in modulators of vascular tone in the arterial wall and is related to the presence of erythrocyte hemolysate in the subarachnoid space. The purpose of this study was to determine the compounds in erythrocyte hemolysate that are responsible for changing smooth-muscle cell gene expression.

Methods. Rat aorta smooth-muscle cells were exposed to erythrocyte hemolysate in vitro and the effects on immediate early gene messenger (m)RNA levels were determined by competitive reverse transcriptase—polymerase chain reaction.

Message levels for c-fos, jun B, and c-jun were increased in the presence of hemolysate, reaching maximum expression between 30 and 60 minutes, whereas the level of jun D mRNA was unaffected. Increasing doses of hemolysate caused greater expression of c-fos and jun B, but not c-jun. Adenosine triphosphate and hemoglobin, possible spasmogens present in hemolysate, caused much smaller and more rapid increases in c-fos expression than whole hemolysate. Size fractionation showed that all of the c-fos mRNA—inducing activity of hemolysate was recovered with molecules greater than 6 kD. Following separation of hemolysate proteins by hydrophobic interaction chromatography, only one of the three fractions had partial activity. Recombining the three fractions, however, yielded greater c-fos activation than any combination of two.

Conclusions. Multiple high-molecular-weight components present in erythrocytes have synergistic effects on gene expression in smooth-muscle cells. The differences in patterns of gene induction suggest that multiple signaling pathways are activated.
Antisense preproendothelin-oligoDNA therapy for vasospasm in a canine model of subarachnoid hemorrhage
Authors: Ohkuma Hiroki , Parney Ian , Megyesi Joseph , Ghahary Aziz , Findlay J. Max
Published: May 2009

Object. The purpose of this study is twofold: 1) to test antisense genetic techniques used in the prevention of cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH), targeting the endothelin-1 (ET-1) gene; and 2) to determine if fibrinolysis of subarachnoid clot with recombinant tissue plasminogen activator (rtPA) could enhance the effect of antisense treatment.

Methods. A total of 39 dogs were studied in this experiment. Placebo (six animals), rtPA (six animals), antisense preproET-1 oligodeoxynucleotide (ASOD; five animals), or rtPA plus ASOD (combined treatment; six animals) was injected into the cisterna magna 30 minutes after a second SAH was induced on the 2nd day of the experiment. The animals were observed until Day 7, when they underwent follow-up angiography and then were killed; their basilar arteries were removed for analysis. Control animals included in this study (two animals in each group) received placebo, rtPA, ASOD, or rtPA plus ASOD without induction of SAH, or rtPA with mismatched (nonsense) preproET-1 oligodeoxynucleotide following SAH. Six additional dogs were analyzed earlier following SAH.

Dogs that received placebo developed severe vasospasm (51 ± 8% of baseline caliber). Administration of ASOD alone resulted in a mild reduction in vasospasm (64 ± 13% of baseline caliber) and rtPA alone resulted in a moderate reduction in vasospasm (81 ± 5% of baseline caliber); however, the combined therapy of rtPA plus ASOD almost completely prevented vasospasm (95 ± 6% of baseline caliber), which was significantly different from all other groups (p < 0.05). Morphological analysis of the basilar arteries yielded results similar to angiography with respect to vasospasm severity. The ASOD treatment combined with rtPA resulted in reduced ET-1 expression, as demonstrated by immunohistochemical staining of the arteries, and reduced preproET-1 levels on Day 4, as measured by reverse transcription—polymerase chain reaction. Nonsense DNA sequences had no effect on the vessels.

Conclusions. Antisense preproET-1 oligodeoxynucleotide treatment, when combined with clot lysis caused by rtPA, reduced vasospasm in the canine model of SAH, and this effect appeared to be related to reduced ET-1 synthesis. The results of this experiment support a causative role for ET-1 early in the course of vasospasm development in dogs. The apparent additive therapeutic effects of antisense and fibrinolytic treatments could be due to clot lysis, which allows better delivery of oligodeoxynucleotides to arteries within the subarachnoid space.
Treatment of intracranial gliomas with bone marrow—derived dendritic cells pulsed with tumor antigens
Authors: Liau Linda M. , Black Keith L. , Prins Robert M. , Sykes Steven N. , DiPatre Pier-Luigi , Cloughesy Timothy F. , Becker Donald P. , Bronstein Jeff M.
Published: May 2009

Object. An approach toward the treatment of intracranial gliomas was developed in a rat experimental model. The authors investigated the ability of “professional” antigen-presenting cells (dendritic cells) to enhance host antitumor immune responses when injected as a vaccine into tumor-bearing animals.

Methods. Dendritic cells, the most potent antigen-presenting cells in the body, were isolated from rat bone marrow precursors stimulated in vitro with granulocyte—macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Cultured cell populations were confirmed to be functional antigen-presenting cells on the basis of expressed major histocompatibility molecules, as analyzed by fluorescence-activated cell sorter cytofluorography. These dendritic cells were then pulsed (cocultured) ex vivo with acid-eluted tumor antigens from 9L glioma cells. Thirty-eight adult female Fischer 344 rats harboring 7-day-old intracranial 9L tumors were treated with three weekly subcutaneous injections of either control media (10 animals), unpulsed dendritic cells (six animals), dendritic cells pulsed with peptides extracted from normal rat astrocytes (10 animals), or 9L tumor antigen—pulsed dendritic cells (12 animals). The animals were followed for survival. At necropsy, the rat brains were removed and examined histologically, and spleens were harvested for cell-mediated cytotoxicity assays.

The results indicate that tumor peptide-pulsed dendritic cell therapy led to prolonged survival in rats with established intracranial 9L tumors implanted 7 days prior to the initiation of vaccine therapy in vivo. Immunohistochemical analyses were used to document a significantly increased perilesional and intratumoral infiltration of CD8+ and CD4+ T cells in the groups treated with tumor antigen—pulsed dendritic cells compared with the control groups. In addition, the results of in vitro cytotoxicity assays suggest that vaccination with these peptide-pulsed dendritic cells can induce specific cytotoxic T lymphocytes against 9L tumor cells.

Conclusions. Based on these results, dendritic antigen-presenting cells pulsed with acid-eluted peptides derived from autologous tumors represent a promising approach to the immunotherapy of established intracranial gliomas, which may serve as a basis for designing clinical trials in patients with brain tumors.
Selective motor hyperreinnervation by using contralateral C-7 motor rootlets in the reconstruction of an avulsion injury of the brachial plexus
Authors: Bertelli Jayme A. , Ghizoni Marcos F.
Published: May 2009

✓ Brachial plexus avulsion injuries are a clinical challenge. In recent experimental studies the authors have demonstrated the high degree of muscle reinnervation attained when a C-4 motor rootlet was directly connected to the musculocutaneous nerve. This degree of reinnervation was attributed to the good chance that a muscle fiber can be reinnervated by a motor fiber when the number of regenerating motor neurons is increased and when competitive sensory fibers are excluded from the process. The authors present the first clinical case in which this phenomenon has been observed. This 26-year-old man, who was involved in an automobile accident, presented with an upper brachial plexus avulsion, for which he underwent operation 4 months later. The axillary and suprascapular nerves were directly surgically connected to the motor rootlets of the C-7 contralateral root by using two cables of sural nerve graft. Two years postsurgery, the patient was able to perform shoulder abduction of 120° and hold an 800-g weight at 90°. These results are encouraging, and in selected patients motor rootlet transfer might prove to be a useful surgical strategy.
Hemodynamic characterization of intracranial pressure plateau waves in head-injured patients
Authors: Czosnyka Marek , Smielewski Piotr , Piechnik Stefan , Schmidt Eric A. , Al-Rawi Pippa G. , Kirkpatrick Peter J. , Pickard John D.
Published: May 2009

Object. Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves.

Methods. One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed.

The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p <0.05) and TCD pulsatility increased (p <0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury.

Conclusions. The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.
Ventricular volume following third ventriculostomy
Authors: Schwartz Theodore H. , Ho Brian , Prestigiacomo Charles J. , Bruce Jeffrey N. , Feldstein Neil A. , Goodman Robert R.
Published: May 2009

Object. Ventricular size often shows no obvious change following third ventriculostomy, particularly in the early postoperative period, making postoperative evaluation difficult without expensive and often invasive testing in patients with equivocal clinical responses. The authors hypothesized that performing careful volumetric measurements would show decreases in size within the first 3 weeks after surgery.

Methods. Volumetric measurements were calculated from standard 3 × 3—mm axial computerized tomography (CT) scans obtained immediately before and 3 and 21 days after surgery. Two independent investigators measured third ventricular volume in a series of 16 patients and lateral ventricular volume in 10 of the patients undergoing stereotactically guided endoscopic third ventriculostomy for noncommunicating hydrocephalus.

Fifteen patients were symptomatically improved at the time the follow-up scan was obtained. Third ventricular volume decreased in all patients by a mean of 35% (range 7.8–95.1%) and lateral ventricular volume decreased in all patients by a mean of 33% (range 4.5–80.3%). The degree of change correlated with the length of preoperative symptoms (p <0.005). The one patient who experienced no improvement showed no decrease in third ventricular volume. In seven of 10 patients, the decrease in third ventricular volume exceeded the decrease in lateral ventricular volume. Repeated measurements indicated that the 95% confidence interval for the authors' calculations varied around the mean by 2.5% for third ventricular volume and 1.2% for lateral ventricular volume. Long-term outcome was excellent, with only one case of delayed failure. The mean follow-up duration was 12 months.

Conclusions. Volumetric measurements calculated from standard CT scans will show a demonstrable decrease in ventricular volume soon after successful third ventriculostomy and can be helpful in assessing patients postoperatively. Although the third ventricle may exhibit a greater decrease, the lateral ventricular measurements are more accurate. Patients with more indolent symptoms show the smallest change.
Low incidence of delayed intracerebral hemorrhage secondary to ventriculoperitoneal shunt insertion
Authors: Savitz Martin H. , Bobroff Lewis M.
Published: May 2009

Object. Bleeding into the brain parenchyma or ventricles is an infrequently reported complication in adults who undergo insertion of a ventriculoperitoneal (VP) shunt. The purpose of this study was to establish the incidence of delayed intracerebral hemorrhage secondary to ventricular cannulation during shunting procedures.

Methods. Over a 24-year period, in a series of 125 adult patients with hydrocephalus, postoperative computerized tomography scans were obtained in every case within 48 hours of shunt surgery performed by the same neurosurgeon. The rate of delayed intracerebral hematoma or intraventricular hemorrhage after VP shunt placement was documented by routine neuroradiological follow up to be 4%.

Conclusions. In adult patients with no coagulopathy or occult vascular lesions, the rate of bleeding after VP shunt insertion may be low if the procedure is uncomplicated by multiple attempts at perforation, puncture of the choroid plexus, or improper placement of the tubing within the parenchyma of the brain.
Inhibition of NF2-negative and NF2-positive primary human meningioma cell proliferation by overexpression of merlin due to vector-mediated gene transfer
Authors: Ikeda Keiro , Saeki Yoshinaga , Gonzalez-Agosti Charo , Ramesh Vijaya , Chiocca E. Antonio
Published: May 2009

Object. The absence of in vitro models of neurofibromatosis Type 2 (NF2)—defective meningiomas has limited investigative efforts to study the biological effects of this gene in the pathogenesis of these tumors. The goals of this report are to show that gene transfer vectors can efficiently express the wild-type NF2 transgene into primary meningioma cells and to determine effects on cellular proliferation.

Methods. In this study, the authors have compared the transducing capacities of a retrovirus, an adenovirus, and a herpes simplex virus amplicon vector for use in primary human meningioma cells harvested from human tumors excised from patients with and without NF2. Transduction efficiencies with the latter vector approached 100% and it was selected to transfer the wild-type NF2 transgene into these cells. Western blot analysis confirmed that vector-mediated gene transfer mediated the expression of the NF2-encoded polypeptide merlin. Overexpression of merlin significantly inhibited the proliferation of both NF2-negative and NF2-positive human meningioma cells when compared to the proliferation of cells transduced with a control vector.

Conclusions. This study demonstrates the feasibility of using vector-mediated gene transfer to study wild-type NF2 gene function in short-term cultures of primary human meningioma cells.
Growth hormone receptor expression and function in meningiomas: effect of a specific receptor antagonist
Authors: Friend Keith E. , Radinsky Robert , McCutcheon Ian E.
Published: May 2009

Object. This study was undertaken to explore the effects of growth hormone (GH) and the GH-stimulated peptide insulin-like growth factor—1 (IGF-1) on the growth rate of meningiomas.

Methods. Polymerase chain reaction and ribonuclease protection assays were used to demonstrate that GH receptor messenger RNA was present in all 14 meningioma specimens studied, regardless of tumor grade. Both wild type (GHRwt) and a previously described exon 3 deletion isoform (GHRd3) of the GH receptor were identified in individual tumor specimens. The importance of the GH receptor was assessed using a GH receptor antagonist (B2036). Blockade of the GH receptor with B2036 reduced serum-induced DNA synthesis, as measured by thymidine incorporation, by 8 to 33% (mean 20%) in primary meningioma cultures. Tumors that expressed the GHRwt and GHRd3 isoforms, or a combination of the two, were all responsive to antagonist treatment. The importance of IGF-1 in stimulating meningioma cell growth was also assessed. It was found that IGF-1 increased thymidine incorporation in primary meningioma cultures in a dose-dependent manner: 1 ng/ml, 5 ng/ml, and 10 ng/ml resulted in increases in thymidine incorporation of 21%, 43%, and 176%, respectively, over baseline values.

Conclusions. In these studies the authors demonstrate that activation of the GH/IGF-1 axis significantly increases the growth rate of meningiomas. Blockade of the GH receptor on tumor cells inhibited tumor growth. If these findings are confirmed in animal studies, agents that downregulate the GH/IGF-1 axis might represent a potential adjuvant therapy in the management of patients with meningioma.
Influence of rewarming conditions after hypothermia in gerbils with transient forebrain ischemia
Authors: Nakamura Takehiro , Miyamoto Osamu , Yamagami Shin-Ichi , Hayashida Yoshiaki , Itano Toshifumi , Nagao Seigo
Published: May 2009

Object. Recently, several studies have demonstrated that hypothermia has a beneficial effect on clinical outcome; however, it is difficult to determine the appropriate rewarming conditions in clinical use. The purpose of the present study was to examine the influence of rewarming conditions in gerbils with transient forebrain ischemia.

Methods. Ischemia was induced in the gerbils by a 5-minute bilateral common carotid artery occlusion, after which the animals were immediately subjected to moderate or deep hypothermia. After moderate hypothermia (30.5°C for 4 hours) the animals were rewarmed over standard, fast, or slow time periods. After deep hypothermia (24°C for 2 hours) the animals were rewarmed in a standard, fast, slow, or stepwise manner. Cerebral blood flow (CBF), extracellular glutamate, and lactate were monitored. Hippocampal CA1 cell damage was assessed 7 days after induction of ischemia.

In animals treated with moderate hypothermia, the rewarming rate had no influence on the number of surviving neurons. However, fast rewarming from deep hypothermia (to 37°C for 30 minutes) failed to provide the neuroprotective effect of hypothermia. Furthermore, this group showed a poor recovery of CBF (p < 0.01) and, consequently, an increase in extracellular glutamate (p < 0.01) and lactate (p < 0.01) in the hippocampus.

Conclusions. The results of this study indicate a transient uncoupling of CBF and cerebral metabolism during fast rewarming from deep hypothermia, whereas slow and stepwise rewarming periods were found to be useful for protection against uncoupling of CBF and cerebral metabolism during rewarming.
Painful supernumerary phantom arm following motor cortex stimulation for central poststroke pain
Authors: Canavero Sergio , Bonicalzi Vincenzo , Castellano Giancarlo , Perozzo Paola , Massa-Micon Barbara
Published: May 2009

✓ In this report, the authors describe a case in which the patient began to experience a supernumerary phantom arm after she received motor cortex stimulation for central pain. The patient had a history of right thalamocapsular stroke. It is speculated that the motor cortex activation triggered a response in the patient's parietal lobe, precipitating perception of the phantom limb.

To the authors' knowledge this is the first reported case of its kind.
Postoperative swelling of pericranial pedicle graft producing intracranial mass effect
Authors: Jensen Ric , McCutcheon Ian E. , DeMonte Franco
Published: May 2009

✓ Two cases of florid swelling of pericranial pedicle grafts are reported. Intracranial mass effect produced by the grafts necessitated reoperation with graft removal in one case and graft revision in the other. No permanent neurological deficits were incurred by either patient. Venous congestion and associated swelling within the graft were considered to be related to constriction of the graft base at the frontal bone flap-skull base interface in one patient and torsion of the graft base in the other.
Rare occurrence of intracerebellar colloid cyst
Authors: Müller Adolf , Büttner Andreas , Weis Serge
Published: May 2009

✓ Colloid cysts are rare intracerebral lesions that are preferentially encountered within the third ventricle. There are only a few reports in which colloid cysts are described in other locations such as the fourth ventricle.

A symptomatic intracerebellar colloid cyst in a 45-year-old woman is described. The patient presented with headache, gait disturbance, and nausea. Neuroradiological imaging revealed compression of the fourth ventricle, hydrocephalus, and an intracerebellar cystic lesion measuring 4 × 5 cm that had a small peripheral solid portion. The cyst was successfully removed via a paramedian suboccipital approach. Postoperatively, the patient recovered quickly.

The findings in the present report represent an additonal example of the broad spectrum of cystic lesions encountered in the cerebellum.
The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma
Authors: Arita Kazunori , Ikawa Fusao , Kurisu Kaoru , Sumida Masayuki , Harada Kunyu , Uozumi Tohru , Monden Shuji , Yoshida Jun , Nishi Yoshikazu
Published: May 2009

Object. Hypothalamic hamartoma is generally diagnosed based on its magnetic resonance (MR) imaging characteristics and the patient's clinical symptoms, but the relationship between the neuroradiological findings and clinical presentation has never been fully investigated. In this retrospective study the authors sought to determine this relationship.

Methods. The authors classified 11 cases of hypothalamic hamartoma into two categories based on the MR findings. Seven cases were the “parahypothalamic type,” in which the hamartoma is only attached to the floor of the third ventricle or suspended from the floor by a peduncle. Four cases were the “intrahypothalamic type,” in which the hamartoma involved or was enveloped by the hypothalamus and the tumor distorted the third ventricle.

Six patients with the parahypothalamic type exhibited precocious puberty, which was controlled by a luteinizing hormone—releasing hormone analog, and one patient was asymptomatic. No seizures or mental retardation were observed in this group. All patients with the intrahypothalamic type had medically intractable seizures, and precocious puberty was seen in one. Severe mental retardation and behavioral disorders including aggressiveness were seen in two patients. The seizures were controlled in only one patient, in whom stereotactically targeted irradiation of the lesion was performed.

This topology/symptom relationship was reconfirmed in a review of 61 reported cases of hamartoma, in which the MR findings were clearly described. The parahypothalamic type is generally associated with precocious puberty but is unaccompanied by seizures or developmental delay, whereas the intrahypothalamic type is generally associated with seizures. Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty.

Conclusions. Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.
Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas
Authors: Hiraga Shoju , Arita Norio , Ohnishi Takanori , Kohmura Eiji , Yamamoto Kazumi , Oku Yuzuru , Taki Takuyu , Sato Masaharu , Aozasa Katsuyuki , Yoshimine Toshiki
Published: May 2009

Object. Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results.

Methods. In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (> 60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months.

Conclusions. Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.
Intraoperative validation of functional magnetic resonance imaging and cortical reorganization patterns in patients with brain tumors involving the primary motor cortex
Authors: Fandino Javier , Kollias Spyros S. , Wieser Heinz G. , Valavanis Anton , Yonekawa Yasuhiro
Published: May 2009

Object. The purpose of the present study was to compare the results of functional magnetic resonance (fMR) imaging with those of intraoperative cortical stimulation in patients who harbored tumors close to or involving the primary motor area and to assess the usefulness of fMR imaging in the objective evaluation of motor function as part of the surgical strategy in the treatment of these patients.

Methods. A total of 11 consecutive patients, whose tumors were close to or involving the central region, underwent presurgical blood oxygen level—dependent fMR imaging while performing a motor paradigm that required them to clench and spread their hands contra- and ipsilateral to the tumor. Statistical cross-correlation functional maps covering the primary and secondary motor cortical areas were generated and overlaid onto high-resolution anatomical MR images. Intraoperative electrical cortical stimulation was performed to validate the presurgical fMR imaging findings. In nine (82%) of 11 patients, the anatomical fMR imaging localization of motor areas could be verified by intraoperative electrical cortical stimulation. In seven patients two or more activation sites were demonstrated on fMR imaging, which were considered a consequence of reorganization phenomena of the motor cortex: contralateral primary motor area (nine patients), contralateral premotor area (four patients), ipsilateral primary motor area (two patients), and ipsilateral premotor area (four patients).

Conclusions. Functional MR imaging can be used to perform objective evaluation of motor function and surgical planning in patients who harbor lesions near or involving the primary motor cortex. Correlation between fMR imaging findings and the results of direct electrical brain stimulation is high, although not 100%. Based on their study, the authors believe that cortical reorganization patterns of motor areas might explain the differences in motor function and the diversity of postoperative motor function among patients with central tumors.
Surgical anatomy for direct hypoglossal—facial nerve side-to-end “anastomosis”
Authors: Asaoka Katsuyuki , Sawamura Yutaka , Nagashima Masabumi , Fukushima Takanori
Published: May 2009

Object. In this study the authors investigated the histomorphometric background and microsurgical anatomy associated with surgically created direct hypoglossal—facial nerve side-to-end communication or nerve “anastomosis.”

Methods. Histomorphometric analyses of the facial and hypoglossal nerves were performed using 24 cadaveric specimens and three surgically obtained specimens of severed facial nerve. Both the hypoglossal nerve at the level of the atlas and the facial nerve just distal to the external genu were monofascicular. The number of myelinated axons in the facial nerve (7228 ± 950) was 73.2% of those in the normal hypoglossal nerve (9778 ± 1516). Myelinated fibers in injured facial nerves were remarkably decreased in number. The cross-sectioned area of the normal facial nerve (0.948 mm2) accounted for 61.5% of the area of the hypoglossal nerve (1.541 mm2), whereas that of the injured facial nerve (0.66 mm2) was less than 50% of the area of the hypoglossal nerve. Surgical dissection and morphometric measurements were performed using 18 sides of 11 adult cadaver heads. The length of the facial nerve from the pes anserinus to the external genu ranged from 22 to 42 mm (mean 30.5 ± 4.4 mm). The distance from the pes anserinus to the nearest point on the hypoglossal nerve ranged from 14 to 22 mm (mean 17.3 ± 2.5 mm). The former was always longer than the latter; the excess ranged from 6 to 20 mm (mean 13.1 ± 3.4 mm). Surgical anatomy and procedures used to accomplish the nerve connection are described.

Conclusions. The size of a half-cut end of the hypoglossal nerve matches a cut end of the injured facial nerve very well. By using the technique described, a length of facial nerve sufficient to achieve a tensionless communication can consistently be obtained.
Convection-enhanced selective excitotoxic ablation of the neurons of the globus pallidus internus for treatment of parkinsonism in nonhuman primates
Authors: Lonser Russell R. , Corthésy Marc-Etienne , Morrison Paul F. , Gogate Nitin , Oldfield Edward H.
Published: May 2009

Object. Selective treatment of central nervous system (CNS) structures holds therapeutic promise for many neurological disorders, including Parkinson's disease (PD). The ability to inhibit or augment specific neuronal populations within the CNS reliably by using present therapeutic techniques is limited. To overcome this problem, the authors modeled and developed a method in which convection was used to deliver compounds to deep brain nuclei in a reproducible, homogeneous, and targeted manner. To determine the feasibility and clinical efficacy of convective drug delivery for treatment of a neurological disorder, the investigators selectively ablated globus pallidus internus (GPi) neurons with quinolinic acid (QA), an excitotoxin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)—induced model of primate parkinsonism.

Methods. After the parameters of convective distribution to the GPi were confirmed by infusion of biotinylated albumin into the GPi of a primate (Macaca mulatta), seven adult monkeys of this species were rendered either fully parkinsonian by intravenous injections of MPTP (five animals) or hemiparkinsonian by a right-sided intracarotid injection of this agent (two monkeys). Using convection-enhanced delivery to the GPi, animals were infused with either QA (three fully parkinsonian, two hemiparkinsonian) or saline (two fully parkinsonian).

The three fully parkinsonian animals that underwent GPi lesioning with QA had substantial improvement of PD symptoms, manifested by a marked increase in activity (34 ± 2.5%; mean ± standard deviation) and dramatic improvement of parkinsonian clinical scores. In contrast, the control animals did not improve (activity monitor change = −1.5 × 0.5%). The two hemiparkinsonian animals that underwent QA lesioning of the GPi had dramatic recovery of extremity use. Histological examination revealed selective neural ablation of GPi neurons (mean loss 87%) with sparing of surrounding gray and white matter structures. No animal developed worsening signs of PD or neurological deficits after infusion.

Conclusions. Convection-enhanced delivery of QA permits selective, region-specific (GPi), and safe lesioning of neuronal subpopulations, resulting in dramatic improvement in parkinsonian symptomatology. The properties of convection-enhanced delivery indicate that this method could be used for chemical neurosurgery for medically refractory PD and that it may be ideal for cell-specific therapeutic ablation or trophic treatment of other targeted structures associated with CNS disorders.
Arteriovenous fistula with associated aneurysms coexisting with dural arteriovenous malformation of the anterior inferior falx
Authors: Ratliff John , Voorhies Rand M.
Published: May 2009

✓ This 24-year-old man presented with an unusual case of a high-flow arteriovenous fistula (AVF). This lesion was similar to giant AVFs in children that have been previously described in the literature. In patients in whom abnormalities of the vein of Galen have been excluded and in whom presentation occurs after 20 years of age, a diagnosis of congenital AVF is quite unusual.

The fistula in this case originated in an enlarged callosomarginal artery and drained into the superior sagittal sinus via a saccular vascular abnormality. Two giant aneurysmal dilations of the fistula were present. In an associated finding, a small falcine dural arteriovenous malformation (AVM) was also present. Arterial supply to the AVM arose from both external carotid arteries and the left vertebral artery, with drainage through an aberrant vein in the region of the inferior sagittal sinus into the vein of Galen.

Craniotomy with exposure and trapping of the AVF was performed, with subsequent radiosurgical (linear accelerator) treatment of the dural AVM. Through this combination of microsurgical trapping of the AVF and radiotherapy of the dural AVM, an excellent clinical outcome was achieved.