bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative lidocaine injection into the carotid sinus during endarterectomy
Authors: Maher Cormac O. , Wetjen Nicholas M. , Friedman Jonathan A. , Meyer Fredric B.
Published: May 2009

Object. Many surgeons inject a local anesthetic agent into the carotid sinus before carotid endarterectomy in an attempt to ameliorate perioperative hemodynamic instability. The purpose of this study is to analyze the effect of carotid sinus injection with lidocaine on perioperative hemodynamics and complications.

Methods. The authors prospectively studied 92 patients in whom 100 consecutive carotid endarterectomies were performed by a single surgeon (eight procedures were bilateral). Patients were randomly assigned to one of two groups, in which either 0.5 ml of 1% lidocaine was injected into the carotid sinus nerve or no injection of lidocaine was administered before the arteriotomy. All patients were treated postoperatively according to a standard endarterectomy protocol. There were no significant differences between the two groups in the incidence of hypertension, hypotension, or the use of vasoactive medications in the operating room following restoration of carotid artery (CA) blood flow, in the recovery room, or in the intensive care unit.

Conclusions. Injection of lidocaine into the carotid sinus at the time of endarterectomy is not associated with a significant improvement in any hemodynamic factor, from the time of restoration of CA blood flow to postoperative Day 1.
Cation dysfunction associated with cerebral ischemia followed by reperfusion: a comparison of microdialysis and ion-selective electrode methods
Authors: Stiefel Michael F. , Marmarou Anthony
Published: May 2009

Object. Disruption of ionic homeostasis during ischemia is a well-characterized event and is identified by a rise in the concentration of extracellular potassium [K+]e, with a concomitant reduction in the concentration of extracellular sodium [Na+]e. Results of clinical studies in which microdialysis has been used, however, have shown only modest changes in the levels of extracellular ions. The object of this study was to measure [K+]e and [Na+]e by using ion-selective electrodes (ISEs) and to compare these measurements with those obtained using the well-established method of microdialysis.

Methods. Fifteen Sprague—Dawley rats were separated into three groups. Five animals were subjected to a 15-minute period of ischemia, and another five animals to a 60-minute period of ischemia; animals in both of these groups received K+-free microdialysis perfusate. The third group of five rats underwent a 60-minute period of ischemia and received a reduced-Na+ microdialysis perfusate. Transient forebrain ischemia was produced by bilateral carotid artery occlusion combined with hypotension. A custom-fabricated glass Na+ electrode and a flexible plastic K+ and reference electrodes were used to monitor extracellular ion transients. Microdialysis samples were obtained with the aid of a 2-mm microdialysis probe that was perfused with K+-free mock cerebrospinal fluid at a rate of 2 µl/minute.

Baseline measurements of [K+]e and [Na+]e, obtained using ISEs, were 3.41 ± 0.09 mM and 145 ± 7.75 mM, respectively. Ischemia resulted in a rapid accumulation of [K+]e (in animals subjected to 15 minutes of ischemia, the concentration was 41.9 ± 13.7 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 66.9 ± 11.5 mM), with a concomitant decrease in [Na+]e (in animals subjected to 15 minutes of ischemia, the concentration was 71.7 ± 2.9 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 74.7 ± 1.9 mM). A comparison of microdialysis and ISE methods revealed that microdialysis underestimated the [K+]e changes and was insensitive to concomitant [Na+]e alterations that occur during ischemia.

Conclusions. Our results indicate that the flexible ISE is a reliable and accurate tool for monitoring ionic dysfunction that accompanies brain injury.
Modulation of phorbol ester—induced regulation of matrix metalloproteinases and tissue inhibitors of metalloproteinases by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase
Authors: Park Myung-Jin , Park In-Chul , Hur Jin-Heang , Kim Mi-Suk , Lee Hyung-Chan , Woo Sang-Hyeok , Lee Kyung-Hee , Rhee Chang-Hun , Hong Seok-Il , Lee Seung-Hoon
Published: May 2009

Object. Expression of matrix metalloproteinases (MMPs) has been postulated to play a central role in brain tumor invasion; however, its underlying mechanism is not yet fully understood. In the present study, by assessing the effect of a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, on the secretion of MMPs and in vitro invasion of various glioma cells, the authors attempt to define the role of the p38 MAPK pathway in the regulation of MMPs and tissue inhibitors of metalloproteinases (TIMPs) activated by phorbol ester (phorbol-12-myristate-13-acetate [PMA]) in the D54 human glioblastoma cell line.

Methods. The activation of MAPKs was determined using Western blot analysis after addition of phospho-specific antibodies against these kinases, the status of MMPs and TIMPs was analyzed using gelatin zymography and Western blot analysis, and the invasion rate of D54 cells and other glioma cells was analyzed using a modified Boyden chamber assay. Treatment of D54 cells with PMA activated two distinct MAPKs, extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK, but not c-Jun N-terminal kinase/stress-activated protein kinase. Induction of MMP-9 production and MMP-2 activation by PMA were blocked by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a specific inhibitor of ERK 1/2. In addition, PMA-induced downregulation of TIMP-1 and TIMP-2 secretion and upregulation of the membrane type 1 MMP, a major activator of MMP-2 on the cell surface, were reversed by SB203580 in these cells; the PMA-induced increase of invasion in vitro decreased when SB203580 was added to the top compartment of a modified Boyden chamber; and the inhibitor also reduced the MMP secretion and PMA-induced in vitro invasion in various glioma cell lines.

Conclusions. These results indicate that activation of p38 MAPK by PMA plays a central role in the regulation of MMPs and TIMPs in D54 cells, which has a major influence in tumor invasion and metastasis. Furthermore, inhibition of p38 MAPK by SB203580 blocked the secretion of MMPs and in vitro invasion of various glioma cells, underscoring a possible role of p38 MAPK inhibitors as antiinvasive and/or antimetastatic agents of malignant gliomas.
Suramin-induced reversal of chronic cerebral vasospasm in experimental subarachnoid hemorrhage
Authors: Kimura Hitoshi , Meguro Toshinari , Badr Ahmed , Zhang John H.
Published: May 2009

Object. The naphthylsulfonate derivative suramin is an inhibitor of growth factor receptors (receptor tyrosine kinases) and G protein—coupled P2Y receptors. Both types of these receptors are suspected of being involved in cerebral vasospasm after subarachnoid hemorrhage (SAH). In the current study, the authors examined the therapeutic effects of suramin and a selective P2X-receptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), in the reversal of vasospasm in an established canine double-hemorrhage model.

Methods. Twenty-four dogs underwent double blood injection into the cisterna magna, with injections given on Days 0 and 2. The dogs were divided randomly into three groups (six animals in each group) to be treated from Days 2 through 6 with the vehicle dimethyl sulfoxide, suramin, or PPADS. An additional group of six dogs received double blood injection without any treatment and served as an SAH control group. The animals were killed on Day 7. Angiography was performed on Day 0 before blood injection and again on Day 7 before the animals were killed. After the death of the animals, the basilar arteries (BAs) were collected for morphological studies and determination of tyrosine kinase expression, and the bloody cerebrospinal fluid (CSF) produced by the hemorrhages was collected for measurement of oxyhemoglobin and adenosine triphosphate (ATP).

In the SAH control group, the mean diameter of the BAs on Day 7 was 46.23 ± 6.32% of the value on Day 0 (which served as a reference of 100%). In the DMSO-treated group, the mean residual diameter of the BA was 47.77 ± 0.8% on Day 7 compared with the value on Day 0. Suramin, but not PPADS, increased the residual diameter to 74.02 ± 4.24% on Day 7. On Day 7 the level of ATP in the CSF was decreased and the level of oxyhemoglobin was increased, compared with values measured on Day 0. Suramin, but not PPADS, reduced tyrosine phosphorylation in the spastic BAs.

Conclusions. By reducing tyrosine kinase activity, suramin may be useful in the treatment of cerebral vasospasm.
Anatomical study of the orbitozygomatic transsellar—transcavernous—transclinoidal approach to the basilar artery bifurcation
Authors: Chanda Amitabha , Nanda Anil
Published: May 2009

Object. An anatomical study in which measurements were obtained was undertaken to demonstrate that the orbitozygomatic transcavernous—transclinoidal approach provides excellent exposure of the trunk of the basilar artery (BA) and its bifurcation.

Methods. Bilateral stepwise dissections were performed on 10 fixed cadaver heads with the aid of × 3 to × 40 magnifications. A frontotemporal craniotomy was made, followed by an orbitozygomatic osteotomy. After the dura mater had been opened, the sylvian fissure was widely separated. The anteromedial triangle of the cavernous sinus was opened to mobilize the internal carotid artery medially. The sella turcica and the dorsum sellae were exposed. The posterior clinoid process and the dorsum sellae were drilled to expose a length of BA that included its bifurcation. Measurements were obtained following the frontotemporal craniotomy, orbitozygomatic osteotomy, and drilling of the posterior clinoid process to quantify the exposures provided by these procedures.

Excellent exposure of the trunk of the BA and its bifurcation was achieved. The structures in the interpeduncular cistern and the prepontine cistern were also exposed. There was an average gain of a 13.4-mm-long segment of the BA, which in some surgeries can be invaluable. The angle of exposure that was achieved with the BA bifurcation located at the apex increased markedly. Moreover, this method widened the oculomotor nerve—carotid artery corridor for easier access to the BA bifurcation region.

Conclusions. This approach combines the advantages granted by most conventional approaches to aneurysms of the BA bifurcation. The approach is suitable for aneurysms situated at a high, normal, or low position on the BA bifurcation. It exposes a sufficient length of the BA trunk to place a temporary clip.
Complete asymptomatic thrombosis and resorption of a congenital giant intracranial aneurysm
Authors: Krapf Hilmar , Schöning Martin , Petersen Dirk , Küker Wilhelm
Published: May 2009

✓ Intracranial aneurysms in infants are rare, but are associated with a high risk of rupture and subarachnoid hemorrhage. The authors report a case of an incidentally diagnosed, probably congenital, asymptomatic giant aneurysm of the posterior communicating artery in a 9-month-old girl, which completely thrombosed following a diagnostic superselective angiography without any neuropathological incident. Follow-up magnetic resonance imaging revealed that the aneurysm decreased further in size and was largely resorbed within 3 years after the initial finding. In single cases the natural history of congenital giant aneurysms may be better than previously assumed.
Focal motor seizures with secondary generalization arising in the cerebellum
Authors: Mesiwala Ali H. , Kuratani John D. , Avellino Anthony M. , Roberts Theodore S. , Sotero Marcio A. , Ellenbogen Richard G.
Published: May 2009

✓ The issue of whether seizures can arise in the cerebellum remains controversial. The authors present the first known case of focal subcortical epilepsy with secondary generalization thought to arise from a dysplastic lesion within the cerebellum. A newborn infant presented with daily episodes of left eye blinking, stereotyped extremity movements, postural arching, and intermittent altered consciousness lasting less than 1 minute. These episodes began on his 1st day of life and progressively increased in frequency to more than 100 events per day. Antiepileptic medications had no effect, and interictal and ictal scalp electroencephalography (EEG) recordings demonstrated bilateral electrical abnormalities. Magnetic resonance imaging revealed a mass in the left cerebellar hemisphere, and ictal and interictal single-photon emission computerized tomography revealed a focal perfusion abnormality in the region of the cerebellar mass. The patient subsequently underwent intraoperative EEG monitoring with cortical scalp electrodes and cerebellar depth electrodes. Intraoperative EEG recordings revealed focal seizure discharges that arose in the region of the cerebellar mass and influenced electrographic activity in both cerebral hemispheres. Resection of this mass and the left cerebellar hemisphere led to complete resolution of the patient's seizures and normalization of the scalp EEG readings. Neuropathological findings in this mass were consistent with ganglioglioma. A review of the literature on the cerebellar origins of epilepsy is included.
Intraventricular neurocysticercosis mimicking colloid cyst
Authors: Gupta Arti , Nadimpalli Surya Prakash Rao , Cavallino Robert P.
Published: May 2009

✓ The authors recently encountered a unique case of anterior third ventricular neurocysticercosis in which the cyst exhibited an unusually high signal on T1-weighted magnetic resonance imaging. The lesion's signal intensity and location made differentiation from colloid cyst difficult. Intraventricular neurocysticercosis should be included in the differential diagnosis of a colloid cyst.
Eagle syndrome: entrapment of the glossopharyngeal nerve?
Authors: Slavin Konstantin V.
Published: May 2009

✓ Eagle syndrome is characterized by unilateral pain in the oropharynx, the side of the face, and the earlobe. It is caused by an elongated styloid process; resection of the elongated process eliminates the pain. Although quite rare, this syndrome is well represented in the oral, ear, nose, and throat surgery literature. In the neurosurgical literature, on the other hand, there is little if any mention of Eagle syndrome.

The author presents a case of a woman who suffered from severe pain in the throat, the side of the face, and the ear. After the diagnosis of Eagle syndrome was made based on radiographic findings and was confirmed using a local anesthetic block, resection of the elongated styloid process was performed, resulting in complete and lasting pain relief.

Eagle syndrome, which is caused by compression of the glossopharyngeal nerve as it passes the elongated styloid process, may be classified as an entrapment syndrome deserving of neurosurgical attention. The goal of this report is to familiarize neurosurgeons with Eagle syndrome and its diagnostic work up and treatment.
Cerebral revascularization performed using posterior inferior cerebellar artery—posterior inferior cerebellar artery bypass
Authors: Lemole G. Michael , Henn Jeffrey , Javedan Sam , Deshmukh Vivek , Spetzler Robert F.
Published: May 2009

✓ Cerebral revascularization is often required for the surgical treatment of complex intracranial aneurysms. In certain anatomical locations, vascular anatomy and redundancy make in situ bypass possible. The authors present four patients who underwent revascularization performed using the rarely reported posterior inferior cerebellar artery (PICA)—PICA in situ bypass after their aneurysms had been trapped.

At Barrow Neurological Institute, between 1991 and the present, four male patients underwent PICA—PICA bypasses to treat aneurysms involving the vertebral artery, the PICA, or both. The mean age of these patients was 34 years (range 5–49 years). Follow-up studies revealed patent bypasses and no evidence of infarction. Patient outcomes were excellent or good.

Multiple surgical techniques have been described for revascularization of at-risk cerebral territories. Often, the blood supply must be derived from extracranial sources through a mobilized pedicle or interposited graft. Certain anatomical locations such as the vertebrobasilar junction, the anterior circle of Willis, and the middle cerebral artery bifurcation are amenable to in situ bypass because there is vessel redundancy or proximity to the contralateral analogous vessel. The advantages of an in situ bypass include one suture line, a short bypass distance, and a close match with the caliber of the recipient graft. Although technically challenging, this technique can be successful and should be considered for appropriate candidates.
Cushing's Case XLV: Minnie G.
Authors: Lanzino Giuseppe , Maartens Niki F. , Laws Edward R.
Published: May 2009

✓ A 23-year-old patient who was examined in 1910 by Harvey Cushing triggered his lifelong interest in the syndrome that bears his name. “Minnie G.,” as she became historically known, presented with a “… syndrome of painful obesity, hypertrichosis, and amenorrhea with overdevelopment of secondary sexual characteristics accompanying a low grade of hydrocephalus and increased cerebral tension.” This case stimulated Harvey Cushing's inquisitive mind and sparked an interest that 20 years later culminated in his seminal report, “The basophil adenomas of the pituitary gland and their clinical manifestations (pituitary basophilism).” In this classic work, Cushing reported in detail the cases of two patients encountered from his own practice and 10 similar cases collected from the literature. Minnie G. was the first case that Cushing reported. The clinical course of that case is briefly reviewed in this article.
Ultra-early surgery for aneurysmal subarachnoid hemorrhage: outcomes for a consecutive series of 391 patients not selected by grade or age
Authors: Laidlaw John D. , Siu Kevin H.
Published: May 2009

Object. This study was undertaken to determine the outcomes in an unselected group of patients treated with semiurgent surgical clipping of aneurysms following subarachnoid hemorrhage (SAH).

Methods. A clinical management outcome audit was conducted to determine outcomes in a group of 391 consecutive patients who were treated with a consistent policy of ultra-early surgery (all patients treated within 24 hours after SAH and 85% of them within 12 hours). All neurological grades were included, with 45% of patients having poor grades (World Federation of Neurosurgical Societies [WFNS] Grades IV and V). Patients were not selected on the basis of age; their ages ranged between 15 and 93 years and 19% were older than 70 years. The series included aneurysms located in both anterior and posterior circulations. Eighty-eight percent of all patients underwent surgery and only 2.5% of the series were selectively withdrawn (by family request) from the prescribed surgical treatment. In patients with good grades (WFNS Grades I–III) the 3-month postoperative outcomes were independence (good outcome) in 84% of cases, dependence (poor outcome) in 8% of cases, and death in 9%. In patients with poor grades the outcomes were independence in 40% of cases, dependence in 15% of cases, and death in 45%. There was a 12% rate of rebleeding with all cases of rebleeding occurring within the first 12 hours after SAH; however, outcomes of independence were achieved in 46% of cases in which rebleeding occurred (43% mortality rate). Rebleeding was more common in patients with poor grades (20% experienced rebleeding, whereas only 5% of patients with good grades experienced rebleeding).

Conclusions. The major risk of rebleeding after SAH is present within the first 6 to 12 hours. This risk of ultra-early re-bleeding is highest for patients with poor grades. Securing ruptured aneurysms by surgery or coil placement on an emergency basis for all patients with SAH has a strong rational argument.
Giant prolactinomas: clinical management and long-term follow up
Authors: Shrivastava Raj K. , Arginteanu Marc S. , King Wesley A. , Post Kalmon D.
Published: May 2009

Object. Giant prolactinomas are rare tumors whose treatment and outcome has only been addressed in isolated case reports. The authors document the long-term follow-up findings and clinical outcome in a group of patients with giant prolactinomas.

Methods. This study is a retrospective chart and clinical review of more than 2000 cases of pituitary tumors treated at the authors' institution, of which 10 met the criteria for inclusion (prolactin level > 1000 ng/ml, diameter > 4 cm on neuroimaging studies, and clinical signs of hyperprolactinemia/mass effect). The average follow-up duration was 6.7 years after initial treatment with either bromocriptine or transsphenoidal resection. In more than 90% of the patients in this series the disease was controlled by medical treatment with bromocriptine alone; the other 10% required early surgery via transsphenoidal resection. All patients had improvement in visual symptoms. All tumors had extrasellar components, five of which exhibited frank invasion of the cavernous sinus. Tumor volume on magnetic resonance imaging was decreased on average by 69%; this occurred at a faster rate and in larger amounts when treated with bromocriptine than has been reported in the literature for macroprolactinomas.

Conclusions. According to long-term follow-up findings, giant prolactinomas are exquisitely responsive to dopamine agonist therapy. In giant prolactinomas the prolactin level does not correlate with size. The main indication for early surgery is intratumoral hematoma, whereas our main indications for late surgery are cerebrospinal fluid leakage caused by medical treatment, or an increasing prolactin level despite medical therapy. Checking prolactin levels in suspicious sellar and/or suprasellar lesions may be diagnostic and prevent unnecessary surgery.
Long-term functional outcome after selective posterior rhizotomy
Authors: Mittal Sandeep , Farmer Jean-Pierre , Al-Atassi Borhan , Gibis Joanne , Kennedy Eileen , Galli Carlo , Courchesnes Guylaine , Poulin Chantal , Cantin Marie-André , Benaroch Thierry E.
Published: May 2009

Object. Selective posterior rhizotomy (SPR) is a well-recognized treatment for children with spastic cerebral palsy (CP). Few investigators have used quantitative outcome measures to assess the surgical results beyond 3 years. The authors analyzed data obtained from the McGill Rhizotomy Database to determine the long-term functional outcome of children who had undergone selective dorsal rhizotomy accompanied by intraoperative electrophysiological monitoring.

Methods. The study population was composed of children with spastic CP who underwent SPR and were evaluated by a multidisciplinary team preoperatively, and at 6 months and 1 year postoperatively. Quantitative standardized assessments of lower-limb spasticity, passive range of motion, muscle strength, and ambulatory function were obtained. Of the 93 patients who met the entry criteria for the study, 71 completed the 3-year and 50 completed the 5-year assessments, respectively. Statistical analysis demonstrated significant improvements in spasticity, range of motion, and functional muscle strength at 1 year after SPR. The preoperative, 1-, 3-, and 5-year values for the global score of the Gross Motor Function Measure were 64.6, 70.8, 80, and 85.6, respectively. The greatest improvement occurred in the dimensions reflecting lower-extremity motor function, where the mean change was 10.1% at 1 year, 19.9% at 3 years, and 34.4% at the 5-year follow-up review in comparison with the baseline value. This was associated with a lasting improvement in alignment and postural stability during developmental positions, as well as increased ability to perform difficult transitional movements.

Conclusions. The results of this study support the presence of significant improvements in lower-limb functional motor outcome 1 year after SPR, and the improvements persist at 3 and 5 years. The authors conclude that SPR in conjunction with intraoperative stimulation is valuable for permanently alleviating lower-limb spasticity while augmenting motor function.
Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningiomas
Authors: Mason Warren P. , Gentili Fred , Macdonald David R. , Hariharan Subramanian , Cruz Charlene R. , Abrey Lauren E.
Published: May 2009

Object. The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas.

Methods. Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31–75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy.

All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8–151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively; the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression.

Conclusions. Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.
A novel fibroblast growth factor receptor 2 mutation in Crouzon syndrome associated with Chiari Type I malformation and syringomyelia
Authors: Fujisawa Hironori , Hasegawa Mitsuhiro , Kida Shinya , Yamashita Junkoh
Published: May 2009

Object. It has been reported that due to premature synostosis of the lambdoid suture in the first 24 months of life, more than 70% of patients with Crouzon syndrome concurrently suffer from chronic tonsillar herniation (Chiari Type I malformation) and some (20%) associated syringomyelia. The goal of the present study was to examine mutations in the fibroblast growth factor receptor (FGFR) genes in Crouzon syndrome and its related conditions.

Methods. Five patients were studied: three with Crouzon syndrome (one sporadic and two familial), one with sporadic Chiari I with syringomyelia, and one with unilateral lambdoid synostosis. Deoxyribonucleic acid was screened for FGFR1–3 mutations by using single-strand conformational polymorphism and subsequent direct sequencing.

Two types of missense mutations were detected in the FGFR2 gene, Cys342Trp (1205, TGC → TGG) in a patient with sporadic Crouzon syndrome and Tyr281Cys (1021, TAC → TGC) in two siblings (brother and sister) with familial Crouzon syndrome, respectively. The former has been reported only in sporadic cases but the latter has not previously been identified. A polymorphism in the FGFR3 gene, Asn294Asn (882, AAT → AAC), was also detected in three patients. No mutation was found in the patient with sporadic Chiari I with syringomyelia.

Conclusions. The FGFR2 missense mutation was detected in Crouzon syndrome but not in sporadic Chiari I with syringomyelia or lambdoid synostosis. A novel FGFR2 mutation, Tyr281Cys, was found in familial Crouzon syndrome with Chiari I and syringomyelia. It may be informative to look for this in patients with Crouzon syndrome and associated syringomyelia.
Expression of members of the calcium-binding S-100 protein family in a rat model of cerebral basilar artery vasospasm
Authors: Lefranc Florence , Golzarian Jafar , Chevalier Catherine , Dewitte Olivier , Pochet Roland , Heizman Claus , Decaestecker Christine , Brotchi Jacques , Salmon Isabelle , Kiss Robert
Published: May 2009

Object. The aim of this study was to investigate the role of S-100 proteins in the onset of vasospasm induced by subarachnoid hemorrhage (SAH), which leads to severe neurological morbidity and death. It has recently been argued that modifications in the levels of expression of some intracellular signaling elements controlling the organization of the actin cytoskeleton (including the rho A small guanosine triphosphatase and its related kinases) play significant roles in the induction of smooth-muscle cell contraction, a calcium-dependent process that is pathognomonic of SAH-induced vasospasm at the molecular level. Several members of the calcium-binding S-100 protein family are known to exercise significant control over the organization of the actin cytoskeleton.

Methods. The levels of expression of S-100 proteins in SAH-induced vasospasm have never been investigated. The authors therefore used a double-hemorrhage rat model of SAH-induced vasospasm to determine whether the levels of expression of S-100B, S-100A1, S-100A2, S-100A4, and S-100A6 proteins on immunohistochemical studies were significantly modified in this pathological condition. Quantitative determination of immunohistochemically confirmed expression of S-100 proteins (accomplished with the aid of computer-assisted microscopy) revealed that SAH-induced vasospasm is accompanied by a very significant increase in S-100B, S-100A2, and, to a lesser extent, in S-100A4 and S-100A6 expression, whereas this condition is not accompanied by significant modifications to S-100A1 expression.

Conclusions. Such significant modifications in the levels of expression of different members of the S-100 protein family in SAH-induced vasospasm could relate to the various roles played by this specific class of calcium-binding proteins at the level of actin cytoskeleton organization. These modifications in S-100 protein expression seem relatively specific to SAH-induced vasospasm, because heparin-induced epilepsy-like symptoms were accompanied by dramatically distinct profiles of S-100 protein expression.
Epileptiform activity extinguished by amygdala infusion of the neurotoxin ibotenate in a rat model of temporal lobe epilepsy
Authors: Pace John R. , Lonser Russell R. , Kirkby R. Duncan , Jeffries Neal , Rogawski Michael A. , Oldfield Edward H.
Published: May 2009

Object. The long-term antiseizure effects of local convection-enhanced infusion of the excitotoxin ibotenate were examined in a rat model of temporal lobe epilepsy.

Methods. A single injection of kainate, an epileptogenic excitatory amino acid, into the left amygdala elicited chronic spontaneous recurrent seizure activity for at least 36 days after the injection. Two weeks after the injection, infusion of ibotenate, a nonepileptogenic excitatory amino acid that is an axon-sparing neuronal cell toxin, into the left amygdala and piriform lobe induced immediate and permanent extinction of electrical and behavioral seizure activity.

Conclusions. Lesioning of an epileptic focus by convective distribution of ibotenate can produce an enduring suppression of seizure activity, indicating a chemical neurosurgical approach for epilepsy therapy.
Galenic dural arteriovenous fistula: unusual clinical presentation and successful endovascular therapy
Authors: Weigele John B. , Chaloupka John C. , Lesley Walter S.
Published: May 2009

✓ The authors report a case in which the clinical and neuroimaging findings were initially considered diagnostic of a brainstem glioma. Angiography revealed a deep venous system (galenic) dural arteriovenous fistula causing brainstem interstitial edema. Successful endovascular surgery resulted in complete clinical recovery of the patient and resolution of the structural abnormalities that had been observed on magnetic resonance images. The neuroimaging and therapeutic significance of this case are discussed.
A graft-versus-tumor effect in a patient with ependymoma who received an allogenic bone marrow transplant for therapy-related leukemia
Authors: Tanaka Minoru , Shibui Soichiro , Kobayashi Yukio , Nomura Kazuhiro , Nakanishi Yukihiro
Published: May 2009

✓ Graft-versus-leukemia effect is an immune-mediated antitumor phenomenon associated with allogenic bone marrow transplants (BMTs) for hematological malignancies, and recent findings have indicated that a similar effect could occur in some solid tumors such as breast cancers. The authors report on a 42-year-old man with a recurrent ependymoma who received an allogenic BMT for therapy-related leukemia. After transplantation, the patient developed chronic graft-versus-host disease, which was controlled with steroid agents. Interestingly, the recurrent ependymoma regressed steadily over the next 21 months posttransplant, until the tumor became almost undetectable on magnetic resonance images. This case indicates that the graft-versus-tumor effect, mediated by cytotoxic T cells, may be able to target intraparenchymal neuroepithelial tumors, despite the brain's generally recognized status as an immunoprivileged organ.
Intracranial-to-intracranial vascular anastomosis created using a microanastomotic device for the treatment of distal middle cerebral artery aneurysms
Authors: Newell David W. , Schuster James M. , Avellino Anthony M.
Published: May 2009

✓ The use of a microanastomotic device for direct connection of intracranial vessels can be helpful to facilitate removal of distally located middle cerebral artery (MCA) aneurysms. The authors report on two patients who presented for treatment with large aneurysms distally located on the MCA. The aneurysms were completely excised and the proximal and distal portions of the parent vessel were connected in an end-to-end fashion by using a microanastomotic device. The time required to crossclamp the vessel for excision of the aneurysm and primary anastomosis was 10 minutes in one case and 15 minutes in the other. The short crossclamp time and high-quality anastomosis afforded by this device may be useful in the treatment of these difficult lesions and the prevention of cerebral ischemia.
Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm
Authors: Witwer Brian P. , Moftakhar Roham , Hasan Khader M. , Deshmukh Praveen , Haughton Victor , Field Aaron , Arfanakis Konstantinos , Noyes Jane , Moritz Chad H. , Meyerand M. Elizabeth , Rowley Howard A. , Alexander Andrew L. , Badie Behnam
Published: May 2009

Object. Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms.

Methods. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case.

Conclusions. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.
Subarachnoid hemorrhage caused by a dissecting aneurysm of the internal carotid artery
Authors: Ohkuma Hiroki , Nakano Takahiro , Manabe Hiroshi , Suzuki Shigeharu
Published: May 2009

Object. Subarachnoid hemorrhage (SAH) caused by the rupture of a dissecting aneurysm of the internal carotid artery (ICA) has been considered rare. Based on data from cooperatively collected cases, the clinical features of patients with dissecting aneurysms of the ICA who presented with SAH were examined.

Methods. Data from 18 patients with dissecting aneurysms of the ICA who presented with SAH diagnosed on the basis of clinical signs, neuroradiological findings, and intraoperative findings from 41 institutions were collected during a 5-year period between 1995 and 1999. The authors found that 0.3% of all cases of SAH and 3.1% of cases of SAH of unverified cause were attributable to a dissecting aneurysm of the ICA. Eleven patients (61%) were middle-aged women, and eight patients (44%) had hypertension. Rebleeding before admission was demonstrated in 13 patients (72%), and intraoperative bleeding was exhibited in half of the patients who underwent surgery during the acute stage. Postoperative growth of an aneurysm bulge or recurrent SAH was seen in five of 10 patients who had undergone wrapping or clipping of the aneurysm bulge in the acute phase. Trapping with or without bypass, which resulted in no postoperative recurrence, was performed in three patients in the acute stage and in two patients in the chronic stage. Twelve patients (67%) had a poor prognosis, primarily attributed to intraoperative bleeding and postoperative recurrence.

Conclusions. Generally, dissecting aneurysms of the ICA are not thought of as frequent causes of SAH. Nonetheless, the presence of these aneurysms should be considered when dealing with SAH because they have a susceptibility to bleeding that can lead to a poor prognosis. Careful surgical planning is necessary to decrease intraoperative bleeding and to avoid postoperative recurrence.
Ventricular volume change in childhood
Authors: Xenos Chris , Sgouros Spyros , Natarajan Kalyan
Published: May 2009

Object. The aim of this study was to construct a model of age-related changes in ventricular volume in a group of normal children ages 1 month to 15 years, which could be used for comparative studies of cerebrospinal fluid circulation disorders and cerebral atrophy developmental syndromes.

Methods. A magnetic resonance imaging—based segmentation technique was used to measure ventricular volumes in normal children; each volume was then plotted against the child's age. In addition, intracranial volumes were measured and the ratio of ventricular to intracranial volume was calculated and plotted against age.

The study group included 71 normal children, 39 boys and 32 girls, whose ages ranged from 1 month to 15.3 years (mean 84.9 months, median 79 months). The mean ventricular volume was 21.3 cm3 for the whole group, 22.7 cm3 in boys and 19.6 cm3 in girls (p = 0.062, according to t-tests). The mean ventricular volume at 12 months for the whole group was 17 cm3 (20 cm3 in boys and 15 cm3 in girls), representing 65% of the volume achieved by 15 years of age (87% in boys and 53% in girls). The volume increased by a factor of 1.53, to 26 cm3 (23 cm3 in males and 28 cm3 in females, increase factors of 1.15 and 1.86, respectively) at 15 years of age. The change in ventricular volume with age is not linear, but follows a segmental pattern. These age periods were defined as: 0 to 3, 4 to 6, 7 to 10, and 11 to 16 years. A statistical difference based on sex was only demonstrated in the first 6 years of life. The mean ventricular volume for the first 6-year period was 22.4 cm3 in boys and 15.7 cm3 in girls, and the difference was significant for the two sexes (linear regression analysis for age and sex, significant according to analysis of variance regression at 0.007, p = 0.108 for age, p = 0.012 for sex). Thereafter, there was no significant difference in ventricular volume between boys and girls with further growth. The ratio of ventricular volume to intracranial volume was 0.0175 for the whole group, 0.017 in boys and 0.018 in girls (p = 0.272, according to t-tests). At 12 months of age the ratio was 0.019; it stabilized to 0.015 at 8 years of age, and increased to 0.018 at 15 years of age. No statistical difference based on sex was demonstrated with growth.

Conclusions. The ventricular volume in normal children increases with age by a factor of 1.5; the increase is in a nonlinear segmental pattern. Boys have significantly higher ventricular volumes only in the first 6 years of life. The ventricular/intracranial volume ratio remains stable throughout childhood.
Age-related changes in the proportion of intracranial cerebrospinal fluid space measured using volumetric computerized tomography scanning
Authors: Wanifuchi Hiroshi , Shimizu Takashi , Maruyama Takashi
Published: May 2009

Object. The purpose of this study was to establish a standard curve to demonstrate normal age-related changes in the proportion of intracranial cerebrospinal fluid (CSF) space in intracranial volume (ICV) during each decade of life.

Methods. Using volumetric computerized tomography (CT) scanning and computer-guided volume measurement software, ICV and cerebral parenchymal volume (CPV) for each decade of life were measured and the intracranial CSF ratio was calculated by the following formula: percentage of CSF = (ICV − CPV)/ICV × 100%. The standard curve for age-related changes in normal percentages of intracranial CSF was obtained.

Conclusions. Based on this standard curve, the percentage of intracranial CSF rapidly increased after the sixth decade, seeming to reflect the brain atrophy that accompanies increased age.
Enhancement of macrophage cytotoxicity against murine gliomas by interferon beta increase in nitric oxide production in response to glioma-derived soluble factors
Authors: Kito Tomohiro , Kuroda Etsushi , Yokota Akira , Yamashita Uki
Published: May 2009

Object. In previous studies interferon-β (IFNβ) has been shown to suppress tumor growth. In this report, the antitumor effect of macrophages stimulated with IFNβ is investigated in murine gliomas in vitro.

Methods. The authors examined the cytotoxic activity of IFNβ-stimulated peritoneal macrophages in glioma cells labeled with [3H]thymidine. The addition of IFNβ enhanced cytotoxic activity in gliomas as well as the nitric oxide (NO) production of macrophages in cocultures. Addition of NG-monomethyl-l-arginine (l-NMMA) and l-N6-(1-iminoethyl)-lysine, but not d-NMMA (an inactive analog of l-NMMA), blocked this cytotoxic activity. The addition of IFNβ had no direct effect on the growth of glioma cells. Because NO was not produced from macrophages treated with IFNβ alone and IFNβ-induced cytotoxic activity did not need cell-to-cell contact, the authors suspected that gliomas produce some soluble factors that act as cofactors for IFNβ-induced cytotoxic activity. Macrophages stimulated with IFNβ in the presence of glioma culture supernatants showed higher cytotoxicity against glioma cells than macrophages stimulated with IFNβ alone. Furthermore, NO was markedly produced by IFNβ-stimulated macrophages in the presence of glial culture supernatants.

Conclusions. These data indicate that the antiglioma activity of IFNβ through macrophages is due to NO produced by macrophages and that glioma-derived soluble factors play a role as an essential cofactor in this activity.
Aberrant G protein signaling in nervous system tumors
Authors: Woods Stacey A. , Marmor Eric , Feldkamp Matthias , LAU NELSON , Apicelli Anthony J. , Boss Gerry , Gutmann David H. , Guha Abhijit
Published: May 2009

Object. Guanosine triphosphate (GTP)—binding proteins, also known as G proteins, play important roles in the regulation of cell growth and differentiation by transmitting intracellular signals from cell surface receptors. In this paper, the authors review G protein signaling in general and its aberrations in four human nervous system tumors.

Methods. In the nervous system, four tumor types have been associated with aberrant G protein signaling. The first tumor type includes astrocytomas, which have increased levels of the activated form of the small G protein, p21-ras, without primary oncogenic p21-ras mutations. The likely source for increased p21-ras activity in sporadically occurring astrocytomas is overexpressed or constitutively activated growth factor receptors, whereas in neurofibromatosis Type 1 (NF1)—associated astrocytomas, the source is a loss of expression of neurofibromin, a major inactivator of p21-ras (ras—GTPase activating protein [GAP]). The second type of tumor associated with aberrant G protein signaling includes sporadic and NF1-associated neurofibromas and malignant peripheral nerve sheath tumors, which also have increased p21-ras activity due to a loss of neurofibromin expression. The third tumor type includes subependymal giant cell astrocytomas as part of the tuberous sclerosis complex (TSC). These tumors display a loss of tuberin expression due to germline mutations in the TSC2 gene. Tuberin functions as an inactivator of the small G protein rap1B (rap1-GAP) and, hence, loss of its expression could lead to increased rap1B activity. In addition to TSC-associated tumors, the authors demonstrate that the majority of sporadically occurring astrocytomas display either loss of tuberin or overexpression of rap1B. This suggests that increased rap1B activity, which can augment p21-ras—mediated signals, also contributes to G protein—mediated aberrant signaling in sporadically occurring astrocytomas. The fourth tumor type includes a significant subset of pituitary adenomas that show constitutive activation of the Gα subunit of the large heterotrimeric Gs protein, which is involved in hormone receptor signaling. The net result of this aberrant activation is increased cyclic adenosine monophosphate and mitogenic tumor-promoting signals.

Conclusions. The authors' review of G protein signaling and aberrations in this process is made with the long-term view that increased understanding of relevant signaling pathways will eventually lead to novel biological targeted therapies against these tumors.