bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of benefit of endoscopic ventriculoperitoneal shunt insertion: a multicenter randomized trial
Authors: Kestle John R. W. , Drake James M. , Cochrane D. Douglas , Milner Ruth , Walker Marion L. , Abbott Rick , Boop Frederick A. , _ _
Published: May 2009

Object. Endoscopically assisted ventricular catheter placement has been reported to reduce shunt failure in uncontrolled series. The authors investigated the efficacy of this procedure in a prospective multicenter randomized trial.

Methods. Children younger than 18 years old who were scheduled for their first ventriculoperitoneal (VP) shunt placement were randomized to undergo endoscopic or nonendoscopic insertion of a ventricular catheter. Eligibility and primary outcome (shunt failure) were decided in a blinded fashion. An intention-to-treat analysis was performed. The sample size offered 80% power to detect a 10 to 15% absolute reduction in the 1-year shunt failure rate.

The authors studied 393 patients from 16 pediatric neurosurgery centers between May 1996 and November 1999. Median patient age at shunt insertion was 89 days. The baseline characteristics of patients within each group were similar: 54% of patients treated with endoscopy were male and 55% of patients treated without endoscopy were male; 30% of patients treated with and 26% of those without endoscopy had myelomeningocele; a differential pressure valve was used in 51% of patients with and 49% of those treated without endoscopy; a Delta valve was inserted in 38% of patients in each group; and a Sigma valve was placed in 9% of patients treated with and 12% of those treated without endoscopy. Median surgical time lasted 40 minutes in the group treated with and 35 minutes in the group treated without endoscopy. Ventricular catheters, which during surgery were thought to be situated away from the choroid plexus, were demonstrated to be in it on postoperative imaging in 67% of patients who had undergone endoscopic insertion and 61% of those who had undergone nonendoscopic shunt placements. The incidence of shunt failure at 1 year was 42% in the endoscopic insertion group and 34% in the nonendoscopic group. The time to first shunt failure was not different between the two groups (log rank = 2.92, p = 0.09).

Conclusions. Endoscopic insertion of the initial VP shunt in children suffering from hydrocephalus did not reduce the incidence of shunt failure.
Long-term intrathecal baclofen therapy for severe spasticity of cerebral origin
Authors: Albright A. Leland , Gilmartin Richard , Swift Dale , Krach Linda E. , Ivanhoe Cindy B. , McLaughlin John F.
Published: May 2009

Object. The goal of this study was to ascertain the long-term effectiveness and safety of intrathecal baclofen (ITB) in the treatment of spasticity of cerebral origin in children and young adults.

Methods. A prospective, multicenter study was conducted in 68 patients who had been enrolled in the initial evaluation of ITB therapy and were willing to participate in long-term surveillance. Seventy-three percent of the patients were younger than 16 years of age at the time of study entry. The patients were examined at least every 3 months and were observed for an average of 70 months. At each follow-up visit, spasticity in the upper and lower extremities was evaluated by applying Ashworth scores. All adverse events and complications were recorded on standardized data forms.

Spasticity in both upper and lower extremities decreased significantly (p < 0.005) and remained decreased up to 10 years. The dosage of ITB increased from a mean of 157 (µg/day 3 months after pump insertion to 300 (µg/day at 2 years postimplantation, and remained relatively stable thereafter. There were no significant differences in ITB dosage in children of different ages. Adverse events potentially related to ITB therapy occurred in 50% of patients within 2 months after pump insertion and in 50% of patients thereafter; hypotonia and lethargy were the two most common adverse events. The most common complications of surgery were catheter-related problems (31%), seromas (24%), and cerebrospinal fluid leaks (15%).

Conclusions. Intrathecal baclofen provides effective long-term treatment of spasticity of cerebral origin and its effects do not appear to diminish with time. This therapy is frequently associated with adverse side effects that usually can be alleviated by adjustments in dosage.
Brachial plexus injury: factors affecting functional outcome in spinal accessory nerve transfer for the restoration of elbow flexion
Authors: Samii Amir , Carvalho Gustavo Adolpho , Samii Madjid
Published: May 2009

Object. Between 1994 and 1998, 44 nerve transfers were performed using a graft between a branch of the accessory nerve and musculocutaneous nerve to restore the flexion of the arm in patients with traumatic brachial plexus injuries. A retrospective study was conducted, including statistical evaluation of the following pre- and intraoperative parameters in 39 patients: 1) time interval between injury and surgery; and 2) length of the nerve graft used to connect the accessory and musculocutaneous nerves.

Methods. The postoperative follow-up interval ranged from 23 to 84 months, with a mean ± standard deviation of 36 ± 13 months. Reinnervation of the biceps muscle was achieved in 72% of the patients. Reinnervation of the musculocutaneous nerve was demonstrated in 86% of the patients who had undergone surgery within the first 6 months after injury, in 65% of the patients who had undergone surgery between 7 and 12 months after injury, and in only 50% of the patients who had undergone surgery 12 months after injury. A statistical comparison of the different preoperative time intervals (0–6 months compared with 7–12 months) showed a significantly better outcome in patients treated with early surgery (p < 0.05). An analysis of the impact of the length of the interposed nerve grafts revealed a statistically significant better outcome in patients with grafts 12 cm or shorter compared with that in patients with grafts longer than 12 cm (p < 0.005).

Conclusions. Together, these results demonstrated that outcome in patients who undergo accessory to musculocutaneous nerve neurotization for restoration of elbow flexion following brachial plexus injury is greatly dependent on the time interval between trauma and surgery and on the length of the nerve graft used.
Salvage retreatment after failure of radiosurgery in patients with arteriovenous malformations
Authors: Foote Kelly D. , Friedman William A. , Ellis Thomas L. , Bova Frank J. , Buatti John M. , Meeks Sanford L.
Published: May 2009

Object. The goal of this study was to evaluate the outcomes of patients who underwent repeated radiosurgery to treat a residual intracranial arteriovenous malformation (AVM) after an initial radiosurgical treatment failure.

Methods. The authors reviewed the cases of 52 patients who underwent repeated radiosurgery for residual AVM at the University of Florida between December 1991 and June 1998. In each case, residual arteriovenous shunting persisted longer than 36 months after the initial treatment; the mean interval between the first and second treatment was 41 months. Each AVM nidus was measured at the time of the original treatment and again at the time of retreatment, and the dosimetric parameters of the two treatments were compared. After retreatment, patients were followed up and their outcomes were evaluated according to a standard posttreatment protocol for radiosurgery for AVMs.

The mean original lesion volume was 13.8 cm3 and the mean volume at retreatment was 4.7 cm3, for an average volume reduction of 66% after the initial treatment failure. Only two AVMs (3.8%) failed to demonstrate size reduction after the primary treatment. The median doses on initial and repeated treatment were 12.5 and 15 Gy, respectively. Five patients were lost to follow up and five refused neuroimaging follow up. One patient died of a hemorrhage shortly after retreatment. Of the remaining 41 patients, 24 had evidence of cure, 15 on angiographic studies and nine on magnetic resonance (MR) images. Seventeen had evidence of treatment failure, 10 on angiographic studies and seven on MR images. By angiographic criteria alone, the cure rate after retreatment was 60%, whereas according to angiographic and MR imaging results, the cure rate was 59%.

Conclusions. Although initial radiosurgical treatment failed to obliterate the AVM in these 52 patients, it did produce a substantial therapeutic effect (volume reduction). This size reduction commonly allowed higher doses to be delivered during radiosurgical retreatment. The results show rates of angiographically confirmed cure comparable to primary treatment and a low incidence of complications, indicating that salvage radiosurgical retreatment is a safe and effective therapy in cases of failed AVM radiosurgery.
Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats
Authors: Özgenel Güzin Yeşim , Filiz Gülaydan
Published: May 2009

Object. Peripheral nerve repair surgery is still replete with challenges. Despite technical improvements in microsurgery, classic methods of nerve repair have failed to provide satisfactory results. The purpose of this study was to investigate the effects of amniotic fluid from humans on peripheral nerve scarring and regeneration in rats.

Methods. Forty adult Sprague—Dawley rats were used in this study. After the right sciatic nerve in each rat was transected and repaired using an epineural suture procedure, the nerves were divided into two groups according to the solution applied around the repair site: experimental group, 0.3 ml human amniotic fluid (HAF); and control group, 0.3 ml saline. Macroscopic and histological evaluations of peripheral nerve scarring were performed 4 weeks postsurgery. Nerves treated with HAF demonstrated a significant reduction in the amount of scar tissue surrounding the repair site (p < 0.05). No evidence of a reaction against HAF was noted. Functional nerve regeneration was measured once every 2 weeks by using a sciatic function index until 12 weeks postsurgery. Functional recovery in nerves treated with amniotic fluid occurred significantly faster than that in nerves treated with saline (p < 0.05). Peripheral nerve regeneration was evaluated histomorphologically at 12 weeks postsurgery. Nerves treated with amniotic fluid showed significant improvement with respect to the indices of fiber maturation (p < 0.05).

Conclusions. Preliminary data show that HAF enhances peripheral nerve regeneration. The preventive effect of HAF on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.
Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of cyclin-dependent kinase inhibitors, and autophagy
Authors: Yao Kevin C. , Komata Tadashi , Kondo Yasuko , Kanzawa Takao , Kondo Seiji , Germano Isabelle M.
Published: May 2009

Object. Ionizing radiation is the gold-standard adjuvant treatment for glioblastoma multiforme (GBM), the most aggressive primary brain tumor. The mechanisms underlying neoplastic glial cell growth inhibition after administration of ionizing radiation, however, remain largely unknown. In this report, the authors characterize the response of GBM cells to ionizing radiation and elucidate factors that correlate with the radiosensitivity of these tumors.

Methods. Six human GBM cell lines were subjected to increasing doses of radiation. Each demonstrated a dose-dependent suppression of cell proliferation. In the most radiosensitive cell line, the authors demonstrated a transient increase in the expression of the cyclin-dependent kinase inhibitors (CDKIs) p21 and p27, which corresponded with a G1 cell-cycle arrest. In contrast, the most radioresistant cell line demonstrated a decrease in p21 and p27 expression levels, which correlated with a failure to arrest. Apoptosis did not occur in any cell line following irradiation. Instead, autophagic cell changes were observed following administration of radiation, regardless of the relative radiosensitivity of the cell line.

Conclusions. These findings elucidate some of the molecular responses of GBMs to irradiation and suggest novel targets for future therapy.
Neuroprotection by the stable nitroxide 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia
Authors: Hu Guohan , Lyeth Bruce G. , Zhao Xueren , Mitchell James B. , Watson Joe C.
Published: May 2009

Object. Nitroxides mimic superoxide dismutase (SOD) biochemically and may prevent free radical oxidative injury in settings in which endogenous SOD is overwhelmed. The authors have previously shown the efficacy of a nitroxide, Tempol, in reducing stroke infarct size. Of the nitroxides, 3-carbamoyl-proxyl (3-CP) is especially promising for clinical use, because it does not cause hypotension in animals. Its efficacy in brain ischemia, however, is untested. The goal of this study was to ascertain whether 3-CP would reduce brain damage in a rat ischemia—reperfusion model.

Methods. The authors performed a blinded, dose—response study of the effect of different amounts of 3-CP (1, 10, and 100 mg/kg) on infarct size at 24 hours after focal ischemia and reperfusion. The 3-CP was given intravenously during reperfusion, which followed 1 hour of reversible ischemia induced by a thread placed intraluminally in the middle cerebral artery of rats. Brain infarcts, measured with 2,3,5-triphenyltetrazolium chloride staining in six 3-CP groups, were compared with those measured in controls (animals given an equal volume of saline).

Edema-corrected infarct sizes (mean ± standard deviation) were as follows: 146 ± 64 mm3 in controls; 107 ± 18 mm3 in rats given 1 mg/kg 3-CP; 40 ± 20 mm3 in those given 10 mg/kg 3-CP; and 44 ± 17 mm3 in those given 100 mg/kg 3-CP. A statistically significant reduction in infarct size was achieved in the 10- and 100-mg/kg 3-CP—treated groups (p < 0.01). A reduction in infarct size was also seen in the 1 mg/kg 3-CP—treated group, but this did not reach statistical significance. The authors observed no effects of 3-CP on blood pressure or brain temperature.

Conclusions. Given at reperfusion, 3-CP significantly decreases brain infarct size at doses of 10 and 100 mg/kg without causing hypotension. The authors found that 3-CP is well suited for further laboratory and clinical use in brain ischemia and reperfusion.
Reduced brain infarct volume and improved neurological outcome by inhibition of the NR2B subunit of NMDA receptors by using CP101, 606-27 alone and in combination with rt-PA in a thromboembolic stroke model in rats
Authors: Yang Yi , Li Qiu , Yang Tao , Hussain Munawar , Shuaib Ashfaq
Published: May 2009

Object. A novel postsynaptic antagonist of N-methyl-d-aspartate (NMDA) receptors, CP-101,606-27 may attenuate the effects of focal ischemia. In current experiments, the authors investigated its neuroprotective effect alone and in combination with recombinant tissue plasminogen activator (rt-PA) in thromboembolic focal cerebral ischemia in rats.

Methods. Forty-eight male Wistar rats underwent embolization of the right middle cerebral artery to produce focal cerebral ischemia. After random division into six groups (eight rats in each group), animals received: vehicle; low-dose (LD) CP-101,606-27, 14.4 mg/kg; high-dose (HD) CP-101,606-27, 28.8 mg/kg; rt-PA, 10 mg/kg; low-dose combination (LDC) CP-101,606-27, 14.4 mg/kg plus rt-PA, 10 mg/kg; or high-dose combination (HDC) CP-101,606-27, 28.8 mg/kg plus rt-PA, 10 mg/kg) 2 hours after induction of embolic stroke. Animals were killed 48 hours after the onset of focal ischemia. Brain infarction volume, neurobehavioral outcome, poststroke seizure activity, poststroke mortality, and intracranial hemorrhage incidence were observed and evaluated. Compared with vehicle-treated animals (39.4 ± 8.6%) 2 hours posttreatment with CP-101,606-27 or rt-PA or in combination a significant reduction in the percentage of brain infarct volume was seen (LD CP-101,606-27: 20.8 ± 14.3%, p < 0.05; HD CP-101,606-27: 10.9 ± 3.2%, p < 0.001; rt-PA: 21.1 ± 7.3%, p < 0.05; LDC, 18.6 ± 11.5%, p < 0.05; and HDC: 15.2 ± 10.1%, p < 0.05; compared with control: 39.4 ± 8.6%). Combination of CP-101,606-27 with rt-PA did not show a significantly enhanced neuroprotective effect. Except for the control and LDC treatment groups, neurobehavioral outcome was significantly improved 24 hours after embolic stroke in animals in all other active therapeutic groups receiving CP-101,606-27 or rt-PA or in combination. The authors also observed that treatment with HD CP-101,606-27 decreased poststroke seizure activity.

Conclusions. The data in this study suggested that postischemia treatment with CP-101,606-27 is neuroprotective in the current stroke model; however, the authors also note that although rt-PA may offer modest protection when used alone, combination with CP-101,606-27 did not appear to enhance its effects.
Disappearance of self-mutilation in a patient with Lesch—Nyhan syndrome after bilateral chronic stimulation of the globus pallidus internus
Authors: Taira Takaomi , Kobayashi Tomonori , Hori Tomokatsu
Published: May 2009

✓ Lesch—Nyhan syndrome (LNS) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. Patients with this syndrome are characterized by hyperuricemia, self-mutilation, developmental retardation, and movement disorders such as spasticity and dystonia. The authors performed bilateral chronic stimulation of the globus pallidus internus for control of dystonic movements in a 19-year-old man with LNS. His self-mutilating behavior unexpectedly disappeared after chronic stimulation. This is the first case of LNS that has been successfully treated with deep brain stimulation. The findings indicate that neurobehavioral features of this syndrome are either mediated in the basal ganglia pathways or secondary to the dystonia.
Brown tumors of the skull base
Authors: Al-Gahtany Mubarak , Cusimano Michael , Singer William , Bilbao Juan , Kovacs Kalman , Marotta Thomas
Published: May 2009

✓ The natural history of brown tumor of the skull base, a rare and benign condition, has not been adequately documented, particularly after nonsurgical treatment and over a long follow-up period. The authors report a case of brown tumor of the ethmoidal sinus, documenting its clinical, neuroimaging, and pathological features with long-term follow-up results, and review previous reports on this disorder.
Delayed stenosis following placement of a polyethylene terephthalate endograft in the cervical carotid artery
Authors: Smith Tony P. , Alexander Michael J. , Enterline David S.
Published: May 2009

✓ Three patients with carotid artery (CA) pseudoaneurysms were treated using four polyethylene terephthalate endografts (Wallgraft endoprostheses). Two patients received a single graft and one patient with bilateral pseudoaneurysms received two grafts. Complete occlusion of the pseudoaneurysm with patency of the arterial lumen was achieved following endograft placement in all patients. The clinical follow-up interval ranged from 12 to 18 months and included angiography or ultrasonography studies or both. One patient experienced neurological symptoms, and in-graft stenosis ranging from 50 to 100% occurred in three of the four grafts. Although the Wallgraft endoprosthesis produced good initial results for the treatment of cervical CA pseudoaneurysms, as demonstrated on radiography, it was associated with a high rate of stenosis or occlusion in all three patients.
Improvement in brainstem auditory evoked potentials after suboccipital decompression in patients with Chiari I malformations
Authors: Anderson Richard C. E. , Emerson Ronald G. , Dowling Kathryn C. , Feldstein Neil A.
Published: May 2009

Object. The optimal treatment for patients with symptoms related to Chiari I malformation remains controversial. Although a suboccipital decompression with duraplasty is most commonly performed, there may be a subset of patients who improve in response to bone decompression alone. In an initial attempt to identify such patients, we performed a continuous study of intraoperative brainstem auditory evoked potentials (BAEPs) in patients undergoing a standard decompression with duraplasty and compared conduction times at three different time points: 1) baseline while the patient is supine (before positioning); 2) immediately after opening of the bone and release of the atlantooccipital membrane (that is, the dural band); and 3) after opening of the dura mater.

Methods. Eleven children and young adults (mean age 9.8 years) with symptoms related to Chiari I malformation underwent suboccipital decompression and duraplasty with intraoperative monitoring of BAEPs and somatosensory evoked potentials (SSEPs). Six patients (55%) had associated syringomyelia.

At baseline, the I to V interpeak latency (IPL) for both sides (total 21 BAEPs) was 4.19 ± 0.22 msec (mean ± standard deviation). After complete bone decompression and before the dura mater was opened, the I to V IPL decreased to 4.03 ± 0.25 msec (p = 0.0005). When the dura was opened, however, no further decrease in the I to V IPL was detected (4.03 ± 0.25 msec; p = 0.6). The SSEPs remained stable throughout the procedure.

Conclusions. In children and young adults undergoing suboccipital decompression with duraplasty for Chiari I malformation, the vast majority of improvement in conduction through the brainstem occurs after bone decompression and division of the atlantooccipital membrane, rather than after opening of the dura. Additional studies are needed to establish whether the improvement seen with BAEP monitoring during bone decompression will predict long-term clinical improvement in these patients.
Localization of language function in children: results of electrical stimulation mapping
Authors: Ojemann Steven G. , Berger Mitchel S. , Lettich Ettore , Ojemann George A.
Published: May 2009

Object. The authors examined the localization of language sites and the frequency of naming errors at these sites in a population of children undergoing electrical stimulation mapping during surgeries in which epileptic foci and dominant hemisphere neoplasms were resected. The frequency with which essential language sites were found (that is, “the frequency of language sites”) in children was compared with that of a population of adults who had undergone this procedure, to assess the relationship of age to the distribution of essential areas for language.

Methods. The results of electrical stimulation mapping to determine sites of naming and speech arrest in 26 children ranging in ages from 4 to 16 years are presented in this report. Mapping was performed in the intraoperative setting in eight patients and in the extraoperative setting, by stimulation across a subdural grid, in 18 patients. The frequency and distribution of essential language areas were analyzed in populations of different ages and according to the method used to obtain the map.

Considerable variability was found in the localization of language sites. When the language site distribution in pediatric patients was compared with the language site distribution found previously in a population of patients older than 16 years of age, a relative paucity of language sites was found in all perisylvian cortices in the younger age group. This relationship was also found within the group of patients 16 years of age and younger, when segregated into two groups: those patients 8 years of age or younger, and those patients between 9 and 16 years of age. These findings are relevant to theories of the intrahemispheric organization of the cortex devoted to language function.

Conclusions. The differences found between groups of younger and older patients in the frequencies of sites where stimulation produces naming errors was identified suggests the possibility that, with advancing age, maturational processes contribute new foci of cortex essential for language.
Clinical experience with the use of a shunt with an adjustable valve in children with hydrocephalus
Authors: Zemack Göran , Bellner Johan , Siesjö Peter , Strömblad Lars-Göran , Romner Bertil
Published: May 2009

Object. The goal of this study was to assess the value of making adjustments in the opening pressure of a shunt valve and to determine shunt survival in children and young adults in whom an adjustable valve was used to manage cerebrospinal fluid drainage.

Methods. The authors conducted a single-center retrospective study of 158 children and young adults who had received 199 Codman Hakim programmable valves (noninvasively adjustable to settings in the range of 30–200 mm H2O). The mean age at which the patients underwent shunt implantation was 4.4 years (median 0.4 years, maximum 18 years); 94 patients were younger than 2 years of age, including 14 patients with a gestational age younger than 38 weeks at the time of implantation. In 84 (53.2%) of the 158 patients, valve pressure adjustment was required at least once (mean 1.3 times, maximum 16 times). Among the 202 adjustments made in patients the reason for adjustment was underdrainage in 74 adjustments (36.6%) and overdrainage in 119 (58.9%). The clinical status of the patient improved after 121 (69.1%) of 175 adjustments and after 58 (73.4%) of 79 minor adjustments (less than or equal to ± 20 mm H2O). The shunt infection rate was 13 (10.9%) of 119 patients. Shunt survival was 60.5% at 1 year, 47.1% at 2 years, and 43.9% at 3 years of follow-up review.

Conclusions. Adjustment of the valve's opening pressure further improves outcome in pediatric patients.
Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement
Authors: Terada Tomoaki , Tsuura Mitsuharu , Matsumoto Hiroyuki , Masuo Osamu , Tsumoto Tomoyuki , Yamaga Hiroo , Itakura Toru
Published: May 2009

Object. The effects of percutaneous transluminal angioplasty (PTA) and stent placement for stenosis of the petrous or cavernous portion of the internal carotid artery (ICA) were compared.

Methods. Twenty-four patients with symptomatic, greater than 60% stenosis of the petrous or cavernous portion of the ICA were treated using PTA or stent placement; 15 were treated with PTA and nine with stent insertion. Initial and follow-up results (> 3 months posttreatment) were compared in each group.

Stenotic portions of the ICA were successfully opened in 13 of 15 patients in the PTA group, and in all nine patients in the stent-treated group. In one case in the PTA group stent delivery was attempted; however, the device could not pass through the vessel's tortuous curve, and PTA alone was performed in this case. Postoperatively, the mean stenotic ratio decreased from 72.1 to 29.6% in the PTA group, and from 75.6 to 2.2% in the stent-treated group. In four patients in the PTA group, stenoses greater than 50% were demonstrated on follow-up angiography performed at 3 to 6 months after PTA. In the stent-treated group, no restenosis was encountered, although in one case acute occlusion of the stent occurred; the device was recanalized with PTA and infusion of tissue plasminogen activator. This case was the only one of the 24 in which any neurological deficits related to the endovascular procedure occurred. Stent placement brought a greater gain in diameter than did PTA at the initial and late follow-up period; this gain was statistically significant.

Conclusions. Stent placement is more effective than PTA for stenosis of the petrous or cavernous portion of the ICA from the viewpoint of initial and late gain in diameter.
Regulation of aquaporin-4 in a traumatic brain injury model in rats
Authors: Sun Ming-Chieh , Honey Christopher R. , Berk Caglar , Wong Norman L. M. , Tsui Joseph K. C.
Published: May 2009

Object. Aquaporin-4 (AQP4) plays a significant role in the regulation of brain water homeostasis. In this study the authors investigated the regulation of AQP4 following a focal cortical contusion injury in rats.

Methods. Thirty-three adult male Wistar rats received a focal cortical contusion of the parietal cortex. An additional nine rats underwent a craniectomy, but no trauma was inflicted (sham injury). Animals were killed 1, 4, and 24 hours later. The rat brains were examined for water content by comparing the wet and dry weights of each hemisphere. Aquaporin-4 messenger (m)RNA was measured by reverse transcription—polymerase chain reaction. A ratio of AQP4 mRNA expression in the lesioned hemisphere compared with that in the contralateral control hemisphere was calculated for each animal at the injury site (parietal cortex) and at sites adjacent to (occipital cortex) and distant from the injury (frontal pole cortex).

Brain edema was significantly increased at the injury site. The expression of AQP4 mRNA was significantly increased at the injury site, significantly decreased adjacent to the injury site, and not significantly different at a site distant from the injury. The magnitude of AQP4 mRNA upregulation at the injured parietal cortex correlated with the degree of downregulation in the adjacent occipital cortex.

Conclusions. Data from this study demonstrate that an upregulation of AQP4 occurs at the site of traumatic brain injury and that a downregulation of this molecule occurs adjacent to the site of injury. Understanding the physiology of AQP4 and its regulation following brain injury may allow for the development of novel treatments for cerebral edema that accompanies head injury.
Camptothecin analogs in malignant gliomas: comparative analysis and characterization
Authors: Sampath Prakash , Amundson Eric , Wall Monroe E. , Tyler Betty M. , Wani Mansukh C. , Alderson Lloyd M. , Colvin Michael , Brem Henry , Weingart Jon D.
Published: May 2009

Object. The authors compared and characterized several new classes of camptothecin (CPT) analogs (a total of 22 drugs) directed against human and murine glioma cell lines in vitro, trying to identify CPT analogs that can be used for local therapy in future clinical trials. Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I. Moreover, CPT and its analogs have shown promising antitumor activity against both systemic and intracranial neoplasms. Because the CPTs have poor bioavailability and are unable to cross the blood—brain barrier, they may best be delivered to the central nervous system by polymers. The authors have previously shown that local delivery of Na-CPT by implantable polymers prolongs survival in a rat intracranial glioma model. In recent years, a number of newly synthesized CPT analogs have been developed that exhibit more potency and stability than Na-CPT.

Methods. Cytotoxicities of the drugs were tested using modified clonogenic and monotetrazolium assays in three glioma cell lines. A potassium chloride—sodium dodecyl sulfate coprecipitation assay was used to determine the frequency of drug-stabilized cleavable complexes. Of the CPT analogs analyzed, the 10,11-methylenedioxy (MD) class consistently demonstrated the greatest cytotoxicity. Three of these analogs, 10,11-MD-20(RS)-CPT, 10,11-MD-20(S)-CPT-glycinate ester (Gly).HCl, and 9-amino-10,11-MD-20(S)-CPT-Gly, exhibit significantly greater antiproliferative activities than CPT, Na-CPT, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against all three glioma cell lines. In addition, the 10,11-MD20(RS)-CPT analog induces more cleavable complexes than Na-CPT at every concentration.

Conclusions. The increased potency and greater stability of CPT analogs hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. The greater cytotoxicity of 10,11-MD CPTs in comparison with other CPT analogs as well as CPT, BCNU, or Na-CPT, may present an ideal candidate drug class for development against both primary and metastatic brain tumors.
Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging
Authors: Nguyen Tung T. , Pannu Yashdip S. , Sung Cynthia , Dedrick Robert L. , Walbridge Stuart , Brechbiel Martin W. , Garmestani Kayhan , Beitzel Markus , Yordanov Alexander T. , Oldfield Edward H.
Published: May 2009

Object. Convection-enhanced delivery (CED), the delivery and distribution of drugs by the slow bulk movement of fluid in the extracellular space, allows delivery of therapeutic agents to large volumes of the brain at relatively uniform concentrations. This mode of drug delivery offers great potential for the treatment of many neurological disorders, including brain tumors, neurodegenerative diseases, and seizure disorders. An analysis of the treatment efficacy and toxicity of this approach requires confirmation that the infusion is distributed to the targeted region and that the drug concentrations are in the therapeutic range.

Methods. To confirm accurate delivery of therapeutic agents during CED and to monitor the extent of infusion in real time, albumin-linked surrogate tracers that are visible on images obtained using noninvasive techniques (iopanoic acid [IPA] for computerized tomography [CT] and Gd—diethylenetriamine pentaacetic acid for magnetic resonance [MR] imaging) were developed and investigated for their usefulness as surrogate tracers during convective distribution of a macromolecule. The authors infused albumin-linked tracers into the cerebral hemispheres of monkeys and measured the volumes of distribution by using CT and MR imaging. The distribution volumes measured by imaging were compared with tissue volumes measured using quantitative autoradiography with [14C]bovine serum albumin coinfused with the surrogate tracer. For in vivo determination of tracer concentration, the authors examined the correlation between the concentration of the tracer in brain homogenate standards and CT Hounsfield units. They also investigated the long-term effects of the surrogate tracer for CT scanning, IPA-albumin, on animal behavior, the histological characteristics of the tissue, and parenchymal toxicity after cerebral infusion.

Conclusions. Distribution of a macromolecule to clinically significant volumes in the brain is possible using convection. The spatial dimensions of the tissue distribution can be accurately defined in vivo during infusion by using surrogate tracers and conventional imaging techniques, and it is expected that it will be possible to determine local concentrations of surrogate tracers in voxels of tissue in vivo by using CT scanning. Use of imaging surrogate tracers is a practical, safe, and essential tool for establishing treatment volumes during high-flow interstitial microinfusion of the central nervous system.
Neurogenic motor evoked potentials: role in brachial plexus surgery
Authors: Burkholder Lee M. , Houlden David A. , Midha Rajiv , Weiss Erin , Vennettilli Marco
Published: May 2009

✓ Peripheral nerve graft repair after severe brachial plexus injury is futile if there is degeneration of motor fibers in the proximal nerve stump to which the graft must be attached. Traditional intraoperative neurophysiological assessment methods like nerve action potential (NAP) and somatosensory evoked potential (SSEP) monitoring have been used to evaluate proximal nerve stump integrity, but these methods do not allow evaluation of the integrity of motor fibers back to the anterior horn cell. Consequently, the authors used transcranial electrical stimulation and recorded neurogenic motor evoked potentials (MEPs) directly from the brachial plexus in a patient undergoing surgical repair of a complete upper brachial plexus injury (Erb palsy) to assess the functional continuity of motor fibers. In addition, selected elements of the brachial plexus were directly stimulated, and NAPs were recorded. Finally, SSEPs were recorded from the scalp after stimulation of selected elements of the brachial plexus. Neurogenic MEPs were present from the medial cord of the brachial plexus, but not the middle or upper trunk; NAPs were present from the lateral and posterior cords after middle trunk stimulation, but absent after upper trunk stimulation; and SSEPs were present after medial cord stimulation but absent after stimulation of the upper and middle trunks. For the first time, neurogenic MEPs were coupled with NAPs and SSEPs to evaluate successfully the functional status of motor fibers back to the anterior horn cell for accurate localization of the lesion sites.
Recombinant activated factor VII for cerebral injury—induced coagulopathy in pediatric patients
Authors: Morenski John David , Tobias Joseph D. , Jimenez David F.
Published: May 2009

✓ Brain injury remains one of the leading causes of death and disability in children. Appropriate therapy involves aggressive management of intracranial pressure (ICP) and cerebral perfusion pressure, which often requires placement of an intraparenchymal ICP monitor or intraventricular catheter. These potentially life-saving interventions require normal coagulation function; however, several factors may lead to coagulopathy in the head-injured patient. Standard therapies, which often include multiple doses of fresh frozen plasma (FFP), have a number of drawbacks when used in the pediatric population. The use of FFP requires time to type and crossmatch, thaw, and administer. It imposes a significant volume load on a child in whom cerebral edema remains a problem. Success in using recombinant activated factor VII (rFVIIa) in the hemophiliac population suggests an alternative therapy.

Three patients suffered severe coagulopathy after cerebral injury. One patient received rFVIIa after repeated doses of FFP had failed to correct the coagulopathy; the other two patients received rFVIIa as the initial therapy. Treatment with rFVIIa consisted of a bolus of 90 µg/kg. Recombinant activated factor VII rapidly corrected the patients' coagulopathies, which allowed placement of intraparenchymal fiberoptic lines and intraventricular catheters to monitor ICP. The patients suffered no complication from the placement of ICP monitoring devices, as demonstrated on computerized tomography scans obtained within 24 hours after placement.

Brain injury—induced coagulopathy may lead to significant secondary injury and delays the invasive monitoring necessary for the aggressive management of intracranial hypertension. Fresh frozen plasma takes time to administer, may require repeated doses of significant volume for the pediatric patient, and may ultimately fail. Preliminary data indicated that rFVIIa provides a rapid and successful correction of coagulopathy in the head-injured patient.
Selective loss of Purkinje cells in transverse and sigmoid dural arteriovenous fistulas
Authors: Tominaga Teiji , Shamoto Hiroshi , Shimizu Hiroaki , Watanabe Mika , Yoshimoto Takashi
Published: May 2009

✓ The histological changes that occur in brain tissue have rarely been documented in patients with dural arteriovenous fistulas (AVFs). In this study the authors report on two patients with dural AVFs in the transverse—sigmoid sinus who presented with subarachnoid hemorrhage or progressive dementia. Histological studies of the cerebellar cortices showed a selective loss of Purkinje cells, indicating an ischemic insult caused by venous hypertension. Admission N-isopropyl-p-123I-iodoamphetamine single-photon emission computerized tomography scans demonstrated a decrease in cerebral blood flow, including flow through the cerebellum. Venous hypertension caused by transverse—sigmoid sinus dural AVFs provokes an ischemic condition severe enough to cause selective neuronal damage in the cerebellum.
Intraparenchymal schwannoma of the medulla oblongata
Authors: Lin Jiangkai , Feng Hua , Li Fei , Zhao Bingmei , Guo Qiaonan
Published: May 2009

✓ A 48-year-old man presented with a rare intraparenchymal schwannoma of the medulla oblongata. After he underwent gamma knife surgery, the patient's condition deteriorated and the mass, which at the time was thought to be a glioma, became larger on magnetic resonance images. The mass was resected through a suboccipital craniectomy via the transcerebellomedullary fissure approach. The tumor, which was moderately firm but distinct from the surrounding parenchyma, was removed totally. Postoperative histological and immunohistochemical examinations confirmed the diagnosis of a benign schwannoma. Brainstem schwannomas can be cured by microneurosurgery. It is important to distinguish these tumors from glioma. The main theories on the cause(s) of this lesion are briefly reviewed.
“Real” three-dimensional constructive interference in steady-state imaging to discern microneurosurgical anatomy
Authors: Kakizawa Yukinari , Hongo Kazuhiro , Takasawa Hisayoshi , Miyairi Yosuke , Sato Atsushi , Tanaka Yuichiro , Kobayashi Shigeaki
Published: May 2009

✓ Three-dimensional (3D) neuroimages are generally considered useful for neurosurgical practice. Nevertheless, neuroimaging modalities such as 3D digital subtraction angiography and 3D computerized tomography angiography are still insufficient because the resulting images fail to delineate neural structures. Complex neurosurgical procedures are mostly performed in the cerebrospinal fluid (CSF) space of the basal cistern, where vessels and neural structures are present along with the lesion. The magnetic resonance (MR) imaging—derived 3D constructive interference in steady-state (CISS) imaging displays the margin between the CSF and neural structures, vessels, and dura mater in detail, in a two-dimensional fashion. The authors know that volume-rendered 3D CISS images would be more useful for surgery than conventional ones. Although the usefulness of “virtual MR image endoscopy” was reported previously, the endoscopic view is different from the operative field because of the perspective being emphasized. Therefore, to simulate surgical views, the authors made 3D neuroimages from a 3D CISS MR sequence by using an advanced computer workstation. After generating volume images, a cutting method was used in the desired plane to visualize the lesion with reference to a multiplanar reformatted image. The authors call these “real” 3D CISS images, and they are more comparable to the operative field. This newly developed method of producing a real 3D CISS image was used in 30 cases and contributed to the understanding of the relationship between a lesion and surrounding structures before attempting neurosurgical procedures, with minimal invasiveness to the patient.
Aneurysm clips
Authors: Louw Deon F. , Kaibara Taro , Sutherland Garnette R.
Published: May 2009

✓ This communication outlines the development of aneurysm clips, from those originally used by Walter Dandy to those in use today. The history is rich, with many contributions from neurosurgical pioneers and innovators. As a result, the modern neurosurgeon has a wide selection of biocompatible aneurysm clips from which to choose, clips that have known closing pressures and various sizes and shapes, as well as a selection of clip applicators that do not obstruct the surgical field.
The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings
Authors: Lin Julian , Hanigan William C. , Tarantino Michael , Wang John
Published: May 2009

Object. In this report the authors describe the use of the hemostatic agent recombinant activated factor VII (rFVIIa) in the perioperative treatment of hemorrhages in the central nervous system that are associated with warfarin therapy.

Methods. Two patients sustained hemorrhages within the spinal canal, and the other two had acute intracranial subdural hematomas. All patients had normal platelet counts, activated partial thromboplastin times, and fibrinogen levels, and all received fresh frozen plasma in conjunction with rFVIIa. The initial international normalized ratios (INRs) ranged from 1.9 to 5.6. Each dose of rFVIIa was 1200 µg, ranging from 16 to 22 µg/kg of body weight. Two patients received two perioperative doses of rFVIIa; the others required just one dose before surgery. The INR normalized within 2 hours of administration of rFVIIa in all patients. There were no thromboembolic complications, and surgical blood loss was less than 100 ml for all operations.

Conclusions. This clinical experience indicates that rFVIIa may be safe and effective as the initial hemostatic agent for rapid reversal of orally administered anticoagulation medications in patients who require urgent neurosurgical intervention.
Deep arteriovenous malformations of the basal ganglia and thalamus: natural history
Authors: Fleetwood Ian G. , Marcellus Mary L. , Levy Richard P. , Marks Michael P. , Steinberg Gary K.
Published: May 2009

Object. Patients with arteriovenous malformations (AVMs) in a deep location and with deep venous drainage are thought to be at higher risk for hemorrhage than those with AVMs in other locations. Despite this, the natural history of AVMs of the basal ganglia and thalamus has not been well studied.

Methods. The authors retrospectively evaluated a cohort of 96 patients with AVMs in the basal ganglia and thalamus with respect to the tendency of these lesions to hemorrhage between the time of detection and their eventual successful management.

The 96 patients studied had a mean age of 22.7 years at diagnosis, and 51% were male. Intracranial hemorrhage (ICH) was the event leading to clinical detection in 69 patients (71.9%), and 85.5% of these patients were left with hemiparesis. After diagnosis, 25 patients bled a total of 49 times. The cumulative clinical follow up after detection but before surgical management was 500.2 patient-years. The risk of hemorrhage after detection of an AVM of the basal ganglia or thalamus was 9.8% per patient-year.

Conclusions. The rate of ICH in patients with AVMs of the basal ganglia or thalamus (9.8%/year) is much higher than the rate in patients with AVMs in other locations (2–4%/year). The risk of incurring a neurological deficit with each hemorrhagic event is high. Treatment of these patients at specialized centers is recommended to prevent neurological injury from a spontaneous ICH.
Deep brain stimulation for movement disorders: morbidity and mortality in 109 patients
Authors: Umemura Atsushi , Jaggi Jurg L. , Hurtig Howard I. , Siderowf Andrew D. , Colcher Amy , Stern Matthew B. , Baltuch Gordon H.
Published: May 2009

Object. Deep brain stimulation (DBS) has been advocated as a more highly effective and less morbidity-producing alternative to ablative stereotactic surgery in the treatment of medically intractable movement disorders. Nevertheless, the exact incidence of morbidity and mortality associated with the procedure is not well known. In this study the authors reviewed the surgical morbidity and mortality rates in a large series of DBS operations.

Methods. The authors retrospectively analyzed surgical complications in their consecutive series of 179 DBS implantations in 109 patients performed by a single surgical team at one center between July 1998 and April 2002. The mean follow-up period was 20 months.

There were 16 serious adverse events related to surgery in 14 patients (12.8%). There were two perioperative deaths (1.8%), one caused by pulmonary embolism and the second due to aspiration pneumonia. The other adverse events were two pulmonary embolisms, two subcortical hemorrhages, two chronic subdural hematomas, one venous infarction, one seizure, four infections, one cerebrospinal fluid leak, and one skin erosion. The incidence of permanent sequelae was 4.6% (five of 109 patients). The incidence of device-related complications, such as infection or skin erosion, was also 4.6% (five of 109 patients).

Conclusions. There is a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders.