bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion
Authors: Broaddus William C. , Prabhu Sujit S. , Gillies George T. , Neal Jeffrey , Conrad William S. , Chen Zhi-Jian , Fillmore Helen , Young Harold F.
Published: June 2009

Object.High-flow microinfusion is a novel technique for delivery of compounds directly into brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into brain parenchyma represents an additional potential application of this technique not previously described. In this report the authors sought to examine the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) for this reason.

Methods.An 18-mer35S-PS-ODN (Mrapproximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was analyzed to determine the radioactivity and stability of the35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 ± 210.5 nCi/g. This represents a tissue concentration of 19.2 ± 0.84 µM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The35S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 1% (50 ± 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, but stabilized at a lower CSF content of 0.2% (1 ± 0.1 nCi) thereafter. The volume of distribution was 105 ± 7.9 mm3at 1 hour, representing a volume of distribution/volume of infusion ratio of 5.2. The volume of distribution increased to 443 ± 62.3 mm3at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 µM to 3.2 µM. Undegraded 18-mer was observed throughout the 48-hour period by means of 20% polyacrylamide/7 M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity and minimal structural changes in tissue were observed on histological investigation.

Conclusions.The authors found that PS-ODNs can be safely delivered in high concentrations to wide areas of rat brain by using high-flow microinfusion and are stable even after 48 hours in situ.
Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma
Authors: Leblanc Richard , Bekhor Sabah , Melanson Denis , Carpenter Stirling
Published: June 2009

✓ Choroid plexus papillomas can metastasize to the subarachnoid space, but extensive metastasis has only been reported when the tumors are malignant. The authors report a case of diffuse, extensive metastasis to the craniospinal leptomeninges from a benign fourth ventricular choroid plexus papilloma in an adult.

This 19-year-old woman presented with a 2-year history of headache, blurred vision, diplopia, and ataxia. Magnetic resonance imaging of the brain and spinal cord revealed obstructive hydrocephalus caused by a 4-cm, partially calcified, inhomogeneously enhancing tumor of the fourth ventricle that was displacing the pons, medulla oblongata, and cerebellum. Innumerable cystic lesions of varying size were also seen in the cranial and spinal leptomeninges. Histological examination of the resected fourth ventricular tumor and of a few of the leptomeningeal lesions revealed a benign choroid plexus papilloma and leptomeningeal choroid plexus cysts. This singular case of diffuse and extensive metastasis to the craniospinal leptomeninges from a histologically benign fourth ventricular papilloma adds to the available information about the biological potential of these tumors and expands the differential diagnosis of posterior fossa lesions with subarachnoid metastasis.
Intradural retroclival chordoma without bone involvement: no tumor regrowth 5 years after operation
Authors: Nishigaya Kazuyuki , Kaneko Masami , Ohashi Yasuhiro , Nukui Hideaki
Published: June 2009

✓ Chordomas are most commonly located in the extradural region. A 56-year-old man presented with a large chondroid chordoma located totally within the intradural retroclival region. The tumor was resected via the petrosal approach. Five years after subtotal removal, the residual tumor showed no sign of regrowth despite the fact that radiation therapy had not been used. The patient was free of symptoms except for moderate, conductive hearing loss in his right ear. The position of the intradural tumor could be preoperatively diagnosed by neuroimaging and, thus, the petrosal approach was selected. Primary intradural extraosseous chordomas are very rare and difficult to differentiate from ecchordoses physaliphorae on the basis of histological and radiological features; however, MIB-1 staining may be useful.
Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients
Authors: Cecil Kim M. , Hills Everett C. , Sandel M. Elizabeth , Smith Douglas H. , McIntosh Tracy K. , Mannon Lois J. , Sinson Grant P. , Bagley Linda J. , Grossman Robert I. , Lenkinski Robert E.
Published: June 2009

Object. This study was conducted to determine whether proton magnetic resonance spectroscopy (MRS) is a sensitive method for detecting diffuse axonal injury, which is a primary sequela of traumatic brain injury (TBI). Diffuse axonal injury is characterized by selective damage to white matter tracts that is caused in part by the severe inertial strain created by rotational acceleration and deceleration, which is often associated with motor vehicle accidents. This axonal injury is typically difficult to detect by using conventional imaging techniques because it is microscopic in nature. The splenium was selected because it is a site vulnerable to shearing forces that produce diffuse axonal injury.

Methods. The authors used proton MRS to evaluate the splenium, the posterior commissure of the corpus callosum, in normal control volunteers and in patients with TBI. Proton MRS provided an index of neuronal and axonal viability by measuring levels of N-acetyl aspartate (NAA).

Conclusions. A majority of mildly brain injured patients, as well as those more severely injured, showed diminished NAA/creatine (Cr) levels in the splenium compared with normal control volunteers. The patients displaying lowered NAA/Cr in the splenium were also likely to exhibit lowered NAA/Cr in lobar white matter. Also, the levels of NAA/Cr in the splenium of normal volunteers were higher compared with those found in lobar white matter. Decreases in NAA/Cr levels in the splenium may be a marker for diffuse injury. A proton MRS examination may be particularly useful in evaluating mildly injured patients with unexplained neurological and cognitive deficits. It is concluded that MRS is a sensitive tool in detecting axonal injury.
The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients
Authors: Kampfl Andreas , Franz Gerhard , Aichner Franz , Pfausler Bettina , Haring Hans-Peter , Felber Stefan , Luz Gabriele , Schocke Michael , Schmutzhard Erich
Published: June 2009

Object. In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state.

Methods. Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain.

The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups.

Conclusions. The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.
Hearing preservation in patients undergoing vestibular schwannoma surgery: comparison of middle fossa and retrosigmoid approaches
Authors: Irving Richard M. , Jackler Robert K. , Pitts Lawrence H.
Published: June 2009

Object. The goal of this retrospective study was to evaluate hearing preservation after surgery for vestibular schwannoma in which the middle fossa (MF) or retrosigmoid (RS) approaches were used. Hearing preservation in vestibular schwannoma surgery can be achieved by using either the MR or RS approach. Comparative outcome data between these approaches are lacking, and, as a result, selection has generally been determined by the surgeon's preference.

Methods. The authors have compared removal of small vestibular schwannomas via MF and RS approaches with regard to hearing preservation and facial nerve function. The study group was composed of consecutively treated patients with vestibular schwannoma, 48 of whom underwent operation via an MF approach and 50 of whom underwent the same number of RS operations. Tumors were divided into size-matched groups. Hearing results were recorded according to the American Academy of Otolaryngology—Head and Neck Surgery criteria, and facial nerve outcome was recorded as the House—Brackmann grade. Overall, 26 (52%) of the patients treated via the MF approach achieved a Class B or better hearing result compared with seven (14%) of the RS group. Some hearing was preserved in 32 (64%) of the patients in the MF group and in 17 (34%) of the RS group. The results obtained by using the MF approach were superior for intracanalicular tumors (p = 0.009, t-test), and for tumors with a cerebellopontine angle (CPA) component measuring 0.1 to 1 cm (p = 0.006, t-test). For tumors in the CPA that were 1.1 to 2 cm in size, our data were inconclusive because of the small sample size. Facial weakness was seen more frequently after MF surgery in the early postoperative period, but results were equal at 1 year.

Conclusions. The results of this study have demonstrated a more favorable hearing outcome for patients with intracanalicular tumors and tumors extending up to 1 cm into the CPA that were removed via the MF when compared with the RS approach.
Modified approach for the selective treatment of temporal lobe epilepsy: transsylvian—transcisternal mesial en bloc resection
Authors: Vajkoczy Peter , Krakow Karsten , Stodieck Stefan , Pohlmann-Eden Bernd , Schmiedek Peter
Published: June 2009

Object. The authors propose a novel surgical approach for amygdalohippocampectomy (AH) in patients with temporal lobe epilepsy. Via a transsylvian—transcisternal route, the parahippocampal gyrus is directly exposed from its medial aspect, thus allowing a standardized en bloc resection of the temporomesial epileptogenic structures—the amygdala, anterior hippocampus, parahippocampal gyrus, and subiculum. Additional anatomical studies have been performed for standardization of this approach.

Methods. From 1990 to 1996, 32 patients presenting with medically intractable mesial temporal lobe epilepsy underwent AH via the transsylvian—transcisternal approach. Preoperative computerized tomography and magnetic resonance imaging revealed temporomesial lesions in 16 patients. Histopathological examination revealed cavernous malformations in seven patients, low-grade astrocytomas in four, hamartomas in three, and gangliogliomas in two patients. Specimens obtained in patients with no lesions were diagnosed as hippocampal sclerosis in all cases. No patient experienced permanent morbidity. Nine percent of the patients developed a temporary partial oculomotor nerve palsy. Only one patient developed a postoperative visual field deficit with a contralateral quadrantanopsia. With respect to seizure outcome, all patients benefited from surgery. At follow-up evaluation (mean 26.4 months), 80% of the patients were free from seizures (Engel Class I). Eight patients in this group were no longer receiving medication. Seventeen percent had experienced only one to several seizures since surgery (Engel Class II) and 3% reported a worthwhile improvement (Engel Class III).

Conclusions. In contrast to previously described standard techniques for AH, the transsylvian—transcisternal approach presented in this study offers improved anatomical orientation and intraoperative control over the mesial temporal lobe and preserves the lateral as well as the laterobasal temporal lobe.
Clinical application of functional magnetic resonance imaging in presurgical identification of the central sulcus
Authors: Pujol Jesús , Conesa Gerardo , Deus Joan , López-Obarrio Luis , Isamat Fabián , Capdevila Antoni
Published: June 2009

Object. The authors sought to evaluate the advantages and limitations of functional magnetic resonance (fMR) imaging when it was used regularly in the clinical context to identify the central sulcus.

Methods. A 1.5-tesla MR system comprising a spoiled gradient recalled acquisition in the steady-state functional sequence and a cross-hand cancellation analysis method were used to evaluate 50 surgical candidates with centrally located space-occupying lesions in the brain. Three-dimensional (3-D) models of the patient's head and brain showing the relative position of the tumor and the eloquent cortex were obtained in each case. A selective and reproducible focal activation was found, indicating the probable central sulcus position in 41 patients (82%). Direct cortical stimulation confirmed the fMR findings in 100% of 22 intraoperatively assessed patients. Failure to identify the central sulcus occurred in 18% of cases and was mainly a consequence of intrinsic damage in the primary sensorimotor region that resulted in severe hand paresis.

Conclusions. Although specific factors were identified that contributed to reduced sensitivity of fMR imaging in the clinical context, the present study supports functional assessment and 3-D representation of specific surgical situations as generally feasible in common practice.
Abscess formation within a parasagittal meningioma
Authors: Eisenberg Mark B. , Lopez Rolando , Stanek Albert E.
Published: June 2009

✓ The authors present the case of a 78-year-old woman who developed right lower-extremity paralysis after a focal seizure. Neuroradiological studies revealed a small parasagittal meningioma, which at the time of resection was found to contain a bacterial intratumoral abscess secondary to Proteus mirabilis. This is only the second reported case of intratumoral abscess formation in a meningioma and the first such occurrence to be reported in an otherwise healthy, immunocompetent individual.
Spinal epidural vascular malformation presenting in association with a spontaneously resolved acute epidural hematoma
Authors: Miyagi Yasushi , Miyazono Masayuki , Kamikaseda Kazufumi
Published: June 2009

✓ A 16-year-old boy developed acute neck pain and severe quadriparesis after mild rotatory movement of his neck. Magnetic resonance imaging revealed a cervical epidural hematoma that resolved spontaneously within a few days. Vertebral angiography demonstrated a small vascular malformation in the upper cervical epidural space. The vascular mass on the dural surface was totally resected and confirmed to be an arteriovenous malformation. This case represents the importance of including routine angiography in designing therapeutic strategy for cases of spinal epidural hematoma with spontaneous resolution.
Tumor devascularization by intratumoral ethanol injection during surgery
Authors: Lonser Russell R. , Heiss John D. , Oldfield Edward H.
Published: June 2009

✓ Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection.

Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.
Gait before and 10 years after rhizotomy in children with cerebral palsy spasticity
Authors: Subramanian Nivedita , Vaughan Christopher L. , Peter Jonathan C. , Arens Leila J.
Published: June 2009

Object.Selective dorsal rhizotomy is a neurosurgical procedure performed for the relief of spasticity in children with cerebral palsy, but its long-term functional efficacy is still unknown. The authors sought to address this issue by means of an objective, prospective study in which quantitative gait analysis was used.

Methods.Eleven children with spastic diplegia (mean age at initial surgery 7.8 years) were evaluated preoperatively in 1985 and then at 1, 3, and at least 10 years after surgery. For comparison, 12 age-matched healthy individuals were also studied. Retroreflective targets were placed over the hip, knee, and ankle joints, and each individual's gait was videotaped. The video data were subsequently entered into a computer for extraction and analysis of the gait parameters. An analysis of variance yielded a significant time effect (p < 0.05), and post hoc comparisons revealed differences before and after surgery and with respect to the healthy volunteers. The knee and hip ranges of motion (59° and 44°, respectively, for healthy volunteers) were significantly restricted in children with spastic diplegia prior to surgery (41° and 41°, respectively), but were within normal limits after 10 years (52° and 45°, respectively). The knee and hip midrange values (31° and 3°, respectively, for healthy volunteers), indicative of posture, were significantly elevated preoperatively (42° and 15°) and increased sharply at 1 year (56° and 18°), but by 10 years they had decreased to within normal limits (36° and 9°). Step length and velocity improved postoperatively but were not within the normal range after 10 years. Ten years after surgery these patients not only had increased ranges of motion, but also used that movement at approximately a normal midrange point.

Conclusions.Selective dorsal rhizotomy is an effective method for alleviating spasticity. Furthermore, the authors provide evidence to show that lasting functional benefits, as measured by improved gait, can also be obtained.
Spasticity and strength changes as a function of selective dorsal rhizotomy
Authors: Engsberg Jack R. , Olree Kenneth S. , Ross Sandy A. , Park T. S.
Published: June 2009

Object.The goal of this investigation was to quantify changes in hamstring muscle spasticity and strength in children with cerebral palsy (CP) as a function of their having undergone a selective dorsal rhizotomy.

Methods.Nineteen children with CP (CP group) and six children with able bodies (AB group) underwent testing with a dynamometer. For the spasticity measure, the dynamometer measured the resistive torque of the hamstring muscles during passive knee extension at four different speeds. Torque—angle data were processed to calculate the work done by the machine to extend the knee for each speed. Linear regression was used to calculate the slope of the line of best fit for the work—velocity data. The slope simultaneously encompassed three key elements associated with spasticity (velocity, resistance, and stretch) and was considered the measure of spasticity. For the strength test, the dynamometer moved the leg from full knee extension to flexion while a maximum concentric contraction of the hamstring muscles was performed. Torque—angle data were processed to calculate the work done on the machine by the child. Hamstring spasticity values for the CP group were significantly greater than similar values for the AB group prior to surgery; however, they were not significantly different after surgery. Hamstring strength values for the CP group remained significantly less than those for the AB group after surgery, but were significantly increased relative to their presurgery values.

Conclusions.The results of spasticity testing in the present investigation agreed with those of previous studies, indicating a reduction in spasticity for the CP group. The results of strength testing did not agree with those in the previous literature; a significant increase in strength was observed for the CP group.
Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease
Authors: Vitek Jerrold L. , Bakay Roy A. E. , Hashimoto Takao , Kaneoke Yoshiki , Mewes Klaus , Zhang Jian Yu , Rye David , Starr Philip , Baron Mark , Turner Robert , Delong Mahlon R.
Published: June 2009

Object. The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy.

Methods. Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by “form fitting” the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies.

Conclusions. These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.
Gamma knife radiosurgery for thalamotomy in parkinsonian tremor: a five-year experience
Authors: Duma Christopher M. , Jacques Deane B. , Kopyov Oleg V. , Mark Rufus J. , Copcutt Brian , Farokhi Halle K.
Published: June 2009

Object. Certain patients, for example, elderly high-risk surgical patients, may be unfit for radiofrequency thalamotomy to treat parkinsonian tremor. Some patients, when given the opportunity, may choose to avoid an invasive surgical procedure. The authors retrospectively reviewed their experience using gamma knife radiosurgery for thalamotomies in this patient subpopulation: 1) to determine the efficacy of the procedure; 2) to see if there is a dose—response relationship; 3) to review radiological findings of radiosurgical lesioning; and 4) to assess the risks of complications.

Methods. Radiosurgical nucleus ventralis intermedius thalamotomy using the gamma knife unit was performed to make 38 lesions in 24 men and 10 women (median age 73 years, range 58–87 years) over a 5-year period. A median radiation dose of 130 Gy (range 100–165 Gy) was delivered to 38 nuclei (four patients underwent bilateral thalamotomy) using a single 4-mm collimator following classic anatomical landmarks. Twenty-nine lesions were made in the left nucleus ventralis intermedius thalamus for right-sided tremor. Patients were followed for a median of 28 months (range 6–58 months). Independent neurological evaluation of tremor based on the change in the Unified Parkinson's Disease Rating Scale tremor score was correlated with subjective patient evaluation. Comparison was made between a subgroup of patients in whom “low-dose” lesions were made (range 110–135 Gy, mean 120 Gy) and those in whom “high-dose” lesions were made (range 140–165 Gy, mean 160 Gy) for purposes of dose—response information.

Four thalamotomies (10.5%) failed, four (10.5%) produced mild improvement, 11 (29%) produced good improvement, and 10 (26%) produced excellent relief of tremor. In nine thalamotomies (24%) the tremor was eliminated completely. The median time to onset of improvement was 2 months (range 1 week–8 months). Concordance between an independent neurologist's evaluation and that of the patient was statistically significant (p < 0.001). Two patients who underwent unilateral thalamotomy experienced bilateral improvement in their tremor. There were no neurological complications. There was better tremor reduction in the high-dose group than in the low-dose group (p < 0.04).

Conclusions. Although less effective than other stereotactic techniques, gamma knife radiosurgery for thalamotomy offers tremor control with minimal risk to patients unsuited for open surgery.
Neuroprotective effects of NPS 846, a novel N-methyl-d-aspartate receptor antagonist, after closed head trauma in rats
Authors: Gurevich Boris , Artru Alan A. , Lam Arthur M. , Mueller Alan L. , Merkind Vladimir , Talmor Daniel , Katchko Ludmila , Shapira Yoram
Published: June 2009

Object. The authors sought to determine whether 3,3-bis (3-fluorophenyl) propylamine (NPS 846), a novel noncompetitive N-methyl-d-aspartate receptor antagonist, alters outcome after closed head trauma in rats.

Methods. The experimental variables were: presence or absence of closed head trauma, treatment with NPS 846 or no treatment, and time at which the rats were killed (24 or 48 hours). The NPS 846 (1 mg/kg) was administered intraperitoneally at 1 and 3 hours after closed head trauma or sham operation. Outcome measures were the neurological severity score (NSS), ischemic tissue volume, hemorrhagic necrosis volume, and specific gravity, water content, and concentrations of calcium, sodium, potassium, and magnesium in brain tissue. The following closed head trauma—induced changes in the injured hemisphere (expressed as the mean ± the standard deviation) were reversed by NPS 846: decreased specific gravity of 1.035 ± 0.006 at 24 hours was increased to 1.042 ± 0.004; the decreased potassium level of 0.583 ± 0.231 mg/L at 48 hours and at 24 hours was increased to 2.442 ± 0.860 mg/L; the increased water content of 84.7 ± 2.6% at 24 hours was decreased to 79.8 ± 2%; the increased calcium level of 0.592 ± 0.210 mg/L at 24 hours was decreased to 0.048 ± 0.029 mg/L; and the increased sodium level of 2.035 ± 0.649 mg/L was decreased to 0.631 ± 0.102 mg/L. Administration of NPS 846 also lowered the NSS (improved neurological status) at 48 hours (7 ± 3) and caused no significant changes in ischemic tissue or hemorrhagic necrosis volumes in the injured hemisphere at 24 or 48 hours.

Conclusions. In this model of closed head trauma, NPS 846 improved neurological outcome, delayed the onset of brain edema, and improved brain tissue ion homeostasis.
Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage
Authors: Germanò Antonino , Imperatore Claudia , d'Avella Domenico , Costa Giovanni , Tomasello Francesco
Published: June 2009

Object. The radical scavenger (±)-N,N′-propylenedinicotinamide (AVS) was shown recently to ameliorate delayed neurological deficits resulting from ischemia in patients who have had an aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of AVS administration after experimental SAH on 1) behavioral deficits; 2) angiographically confirmed basilar artery (BA) spasm; and 3) blood-brain barrier (BBB) permeability changes.

Methods. These parameters were measured by 1) using a battery of well-characterized chronic assessment tasks over a 5-day observation period; 2) assessing in vivo the mean vessel diameter 2 days after SAH; and 3) evaluating the extravasation of protein-bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after SAH. Groups of eight to 10 rats received injections of 400 µl of autologous blood into the cisterna magna. Within 5 minutes after the surgical procedures were completed the rats were treated with an intravenously administered continuous infusion of saline (Group III) or AVS (1 mg/kg/minutes, Group IV). Results were compared with those in sham-operated animals treated with intravenously administered saline (Group I) or AVS (Group II). The AVS-treated rats had significantly improved balance beam scores on Days 1 to 2 (p < 0.05), shorter beam traverse times on Day 1 (p < 0.05), and better beam walking performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in terms of SAH-related changes in body weight. Treatment with AVS also attenuated the SAH-induced BA spasm (p < 0.05) and decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices, and in the subcortical and cerebellar gray matter and brainstem (p < 0.01).

Conclusions. These results demonstrate useful antivasospastic and brain-protective actions of AVS after induction of experimental SAH and provide support for observations of beneficial effects of AVS made in the clinical setting.
Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line—derived neurotrophic factor
Authors: Mehta Vivek , Hong Murray , Spears Julian , Mendez Ivar
Published: June 2009

Object.The goal of this study was to investigate the ability of fetal dopaminergic neurons to improve complex sensorimotor behavior.

Methods.The authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The cells were exposed to glial cell line—derived neurotrophic factor (GDNF) prior to transplantation into rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed to GDNF demonstrated significant improvement in contralateral forelimb function and showed improvement in rotational behavior faster than animals that received cells not exposed to GDNF. Increasing the number of implanted cells to 800,000 exposed to GDNF did not result in any additional improvement in functional recovery.

Conclusions.As neural grafting procedures in the nervous system evolve and genetically engineered cells or stem cells replace fetal tissue, crucial questions about cell number and trophic regulation will need to be addressed. This study demonstrates that grafting of 400,000 cells exposed to GDNF before transplantation has a beneficial effect in the restoration of complex sensorimotor behavior.
Multiple schwannomas: schwannomatosis or neurofibromatosis type 2?
Authors: Seppälä Matti Tapio , Sainio Markku Alarik , Haltia Matti Jouko Johannes , Kinnunen Jaakko Jyri , Setälä Kirsi Hannele , Jääskeläinen Juha Erik
Published: June 2009

Object. The aim of this study was to clarify the clinical outcome of schwannomatosis, a rare condition characterized by multiple nonvestibular schwannomas in the absence of meningiomas, intraspinal ependymomas, and other clinical signs of neurofibromatosis type 2 (NF2).

Methods. Nine patients with schwannomatosis treated at one institution are presented and their clinical course during a median follow-up time of 9.9 years is discussed. The patients were typically middle-aged at the time of their first operation (median 43.5 years), none had a positive family history of schwannomatosis or NF2, and none showed cutaneous or ocular signs of NF2. On histopathological examination the tumors from the patients with schwannomatosis showed a lobular appearance and frequent Verocay bodies, signs indicating NF2, more often than 20 sporadic schwannomas that were investigated as controls. Two patients died of unrelated causes at 3.2 and 9.9 years, respectively, of follow up. Magnetic resonance images of the head and spine were obtained in seven patients at the end of the follow-up period. New spinal schwannomas were detected in one patient and a residual schwannoma in three. No germline mutations of the NF2 gene were found in these seven patients. Two additional patients originally included in the schwannomatosis group who were 8.6 and 11.7 years old at initial surgery had NF2. One was diagnosed at follow-up review and the other developed a fulminant disease that led to death in 4 years.

Conclusions. The clinical course, long-term outcome, and genetic mechanism of schwannomatosis differ from that of NF2.
Improvement of cerebral oxygenation patterns and metabolic validation of superselective intraarterial infusion of papaverine for the treatment of cerebral vasospasm
Authors: Fandino Javier , Kaku Yasuhiko , Schuknecht Bernhard , Valavanis Anton , Yonekawa Yasuhiro
Published: June 2009

Object. The purpose of the present study was to assess cerebral oxygenation patterns and brain lactate concentration changes before, during, and after intraarterial infusion of papaverine with or without balloon angioplasty in patients with symptomatic vasospasm.

Methods. A total of 23 vascular territories were successfully treated in 10 patients. In three patients balloon angioplasty was performed before the papaverine infusion. Continuous monitoring of jugular bulb vein oxygen saturation with a fiberoptic catheter and blood sampling allowed the assessment of the cerebral arteriovenous oxygen and lactate differences. A significant and rapid improvement in jugular bulb oxygen saturation was observed in all cases, with critical values reflecting an improvement in cerebral oxygenation after endovascular treatment of vasospasm (p = 0.005). Lactate concentration in the jugular bulb normalized within 4 hours in all patients who had evidence of brain lactic acidosis before superselective intraarterial infusion of papaverine. Recurrence of abnormal metabolic and oxygenation patterns were observed in one case in which an optimal hypertension and hypervolemic therapy could not be achieved after the procedure.

Conclusions. Improvement in cerebral oxygenation as well as prevention of cerebral lactic acidosis can be successfully achieved after intraarterial infusion of papaverine. Normalization of the oxygen supply after endovascular treatment has to be supported by optimal and well-monitored hypertension and hypervolemic hemodilution.
Local cerebral blood flow autoregulation following “asymptomatic” cerebral venous occlusion in the rat
Authors: Nakase Hiroyuki , Nagata Kiyoshi , Otsuka Hiroyuki , Sakaki Toshisuke , Kempski Oliver
Published: June 2009

Object. Maintenance of cerebral blood flow (CBF) autoregulation in the brain is of major importance for patient outcome in various clinical conditions. The authors assessed local autoregulation after “asymptomatic” cortical vein occlusion.

Methods. In Wistar rats, a single cortical vein was occluded photochemically by using rose bengal and fiberoptic illumination. In rats with bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension. Local CBF at each pressure level was assessed by performing laser Doppler (LD) scanning at 25 (5 × 5) locations within bilateral cranial windows. In this manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm Hg in both right and left hemispheres in Group A (five rats), in which the animals received illumination without rose bengal and had no venous occlusion. Of the 11 rats that underwent vein occlusion, three developed severe reductions in local CBF and/or a growing venous thrombus and were distinguished as Group C (symptomatic; three rats); from previous work we know that those animals are bound to experience venous infarction. The remaining rats formed Group B (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the left hemisphere without occlusion, whereas, in the right cortex with the occluded vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly ischemic range than that in the opposite normal hemisphere.

Conclusions. The results of the present study suggest that cerebral venous circulation disorders are manifested via additional pathways, that is, from a partially impaired local autoregulation in the vicinity of the occluded vein, even under conditions in which the vein occlusion itself does not cause brain damage. Care should be taken in the control of blood pressure in patients with this pathological condition.
Ninety-degree rotation of the thoracic spinal thecal sac
Authors: Tuli Sagun K. , Hurlbert R. John , Mikulis David , Fleming J. F. Ross
Published: June 2009

✓ This 44-year-old man presented with a 4-year history of progressive spastic weakness of his legs. He was found to have epidural lipomatosis behind the thoracic spinal cord, and the nerve roots exited from the posterior and anterior midline planes of the dura, indicating a 90° rotation of the thoracic cord. Magnetic resonance images clearly demonstrated the segmental thoracic nerve roots exiting from the dorsal midline of the dura, a finding confirmed at surgery. The authors found only one previously published case of rotation of the spinal cord.

Directed mechanical stress caused by deformation of the rotated spinal cord, rather than compression from adipose tissue, is proposed as the mechanism of the myelopathy. The extent, location, and thickness of the associated extradural adipose tissue is suggestive of epidural lipomatosis. The lipomatous tissue might have been an epiphenomenon and cord rotation an isolated congenital anomaly. Alternatively, asymmetrical growth of epidural fat may have exerted torque, rotating the thecal sac.
Suprasellar tension pneumocyst after transsphenoidal surgery
Authors: Brown Lewis J.
Published: June 2009

✓ Tension pneumocephalus is an uncommon occurrence after transsphenoidal surgery. The author presents an unusual case of postoperative visual deterioration related to expanding air within a suprasellar tumor cavity.
Use of ligamentum nuchae graft for dural closure in posterior fossa surgery
Authors: Kosnik Edward J.
Published: June 2009

✓ The technique of harvesting the ligamentum nuchae and its use in posterior fossa surgery are discussed. By using this technique the author has avoided postoperative cerebrospinal fluid leakage in more than 200 procedures.
Posterior ventricular catheter burr-hole localizer
Authors: Garell P. Charles , Mirsky Roman , Noh M. Daniel , Loftus Christopher M. , Hitchon Patrick W. , Grady M. Sean , Dacey Ralph G. , Howard Matthew A.
Published: June 2009

✓ Proper ventricular catheter placements are associated with improved shunt performance. When placing ventricular catheters via the posterior approach, the surgeon must determine an optimum trajectory and then pass a catheter along that trajectory. The incidence of optimal posterior catheter placements is increased by using a posterior catheter guide (PCG); however, errors may still occur because of poor selection of a posterior burr-hole site. In this report an easy-to-use posterior burr-hole localizer (Localizer) is described that defines the optimum burr-hole location based on geometric relationships involving the ear and supraorbital rims.

The basic design principle of the Localizer was formulated and tested by using neuronavigational imaging tools to examine normal adult ventricular anatomy in relation to surface landmarks and by reviewing imaging studies obtained in 50 adult patients with hydrocephalus. Subsequently, the Localizer was used in 28 consecutive patients scheduled to undergo shunt surgery performed by using the PCG. In all cases the catheter entered the ventricle on the first pass and postoperative imaging studies demonstrated successful placement in the ipsilateral anterior horn. There were no catheter-related complications. These early results indicate that the Localizer and PCG devices may be safe and effective when used in combination for placement of posterior ventricular catheters.
Arthur A. Ward, Jr.
Authors: Winn H. Richard
Published: June 2009

✓ Arthur A. Ward, Jr., the former Professor and founding Chairman of the Department of Neurological Surgery at the University of Washington, died on December 23, 1997. He was a former member (1963–1973) and Chairman (1971–1973) of the Editorial Board of the Journal of Neurosurgery.
Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report
Authors: Rodas Raul A. , Fenstermaker Robert A. , McKeever Paul E. , Blaivas Mila , Dickinson Lawrence D. , Papadopoulos Stephen M. , Hoff Julian T. , Hopkins L. Nelson , Duffy-Fronckowiak Mary , Greenberg Harry S.
Published: June 2009

Object. Thrombotic complications (deep vein thrombosis and/or pulmonary embolization [DVT/PE]) occur in 18 to 50% of patients harboring brain tumors who undergo neurosurgical procedures. Such patients are at risk for DVT/PE because of immobility, paresis, hypovolemia, and lengthy surgery. The present study was undertaken to see whether tumor patients at highest risk for DVT/PE could be identified so that augmentation of prophylactic measures might be used to reduce the incidence of thrombotic complications.

Methods. The authors conducted a retrospective analysis of 488 patients enrolled in their brain tumor registries between 1988 and 1995, identifying 57 patients (12%) with recorded symptomatic DVT, PE, or both postoperatively. In 24 of these 57 cases histological specimens were retrievable for review, allowing an in-depth analysis. Forty-five patients were lost to follow-up review, and the remaining 386 patients had no record of systemic thrombosis. Slides of pathological specimens were retrievable in 50 cases in which there was no DVT/PE. From these 50 cases, 25 were selected at random to represent the control group by a blinded observer. Seventeen (71%) of the 24 brain tumor specimens obtained in patients with DVT/PE stained positively for intraluminal thrombosis (ILT) after hematoxylin and eosin had been applied. The odds ratio associated with the presence of ILT was 17.8, with a confidence interval ranging from 4 to 79.3. No evidence of ILT was found in 22 patients (88%) within the control group (p < 0.0001, Fisher's exact test). Other factors that may predispose patients with brain tumors to DVT/PE—limb paresis, extent of tumor removal, and duration of the surgery—were also analyzed and found not to be statistically significant. Therefore, these factors were not the basis for differences seen between the study and control groups.

Conclusions. These preliminary observations suggest that the presence of ILT within malignant glioma or glioblastoma tumor vessels may represent a marker of tumor-induced hypercoagulability.
Cranioplasty performed with a new osteoconductive, osteoinducing hydroxyapatite-derived material
Authors: Pompili Alfredo , Caroli Fabrizio , Carpanese Livio , Caterino Mauro , Raus Laura , Sestili Giancarlo , Occhipinti Emanuele
Published: June 2009

Object.Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used.

Methods.The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone—derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed.

The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty.

Conclusions.In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.