bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of proliferative activity and size in acoustic neuroma: implications for timing of surgery
Authors: Bedavanija Anan , Brieger Jürgen , Lehr Hans-Anton , Maurer Jan , Mann Wolf J.
Published: May 2009

Object. Acoustic neuroma is the most frequent benign tumor of the cerebellopontine angle, and surgery is still the most common form of treatment. To gain better insight into the dysregulated mechanisms causing growth of acoustic neuroma, the authors studied the proliferative activity of 34 consecutive samples by analyzing immunohistochemical staining with Ki-67 and proliferating cell nuclear antigen (PCNA), and apoptosis based on the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling. Data from these analyses were correlated with clinical parameters (that is, tumor size, duration of symptoms, and patient age).

Methods. Apoptotic cells were found in none of the tumors. Proliferation measured on staining with Ki-67 and PCNA correlated with tumor size, but not with patient age or duration of symptoms. The authors demonstrated that tumors 18 mm or smaller in diameter have lower proliferation indices and growth rates, compared with tumors larger than 18 mm with high proliferative indices and growth rates. Additionally, they observed that these more aggressive, larger tumors occur mostly in patients younger than 50 years of age.

Conclusions. Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.
Consistency of interictal and ictal onset localization using magnetoencephalography in patients with partial epilepsy
Authors: Tang Lilly , Mantle Mary , Ferrari Paul , Schiffbauer Hagen , Rowley Howard A. , Barbaro Nicholas M. , Berger Mitchel S. , Roberts Timothy P. L.
Published: May 2009

Object. The aim of this study was to evaluate the spatial accuracy of interictal magnetoencephalography (MEG) in localizing the primary epileptogenic focus in comparison with alternative MEG-derived estimates such as ictal onset recording or sensory mapping of the periphery where seizures manifest.

Methods. During this retrospective study of 12 patients with epilepsy who had undergone successful magnetic source (MS) imaging with the aid of a dual 37-channel biomagnetometer as well as simultaneous MEG/electroencephalography (EEG) recordings, ictal events were observed in five patients and quantitative comparisons of interictal spike and ictal seizure onset source localizations were made. In the eight patients who had presented with sensorimotor seizure, source localization of cortical sites concordant with seizure foci was determined using somatosensory functional mapping, and the results were quantitatively compared with interictal spike source localizations.

Interictal spike sources demonstrated on MEG localized to the same region as the corresponding ictal event or somatosensory source localizations. The mean distance between the ictal foci and interictal spike sources was 1.1 ± 0.3 cm. Results of functional somatosensory mapping in patients with sensorimotor seizures demonstrated that seizure sources consistently colocalized with interictal MEG spike sources, with a mean distance of 1.5 ± 0.4 cm. No systematic directional bias was observed. Interictal sources tended to be tightly clustered, and the mean ellipsoid volume, defined by one standard deviation of the source spatial coordinates, was 1 cm3.

Conclusions. Interictal spike localizations on MEG were concordant with ictal and, where relevant, functional somatosensory mapping localizations. These findings support the interpretation of interictal spikes on MEG as a useful and effective noninvasive method for localizing primary seizure foci.
Morphological assessment of the development of multinucleated giant cells in glioma by using mitosis-specific phosphorylated antibodies
Authors: Maeda Kenkou , Mizuno Masaaki , Wakabayashi Toshihiko , Takasu Syuntarou , Nagasaka Tetsurou , Inagaki Masaki , Yoshida Jun
Published: May 2009

Object. The nature and origin of multinucleated giant cells in glioma have not been made clear. To investigate the phosphorylation of intermediate filaments, the authors studied multinucleated giant cells in vitro and in vivo by using mitosis-specific phosphorylated antibodies.

Methods. Cultured human glioma cells were immunostained with monoclonal antibodies (mAbs) 4A4, KT13, and TM71, which recognized the phosphorylation of vimentin at Ser55, glial fibrillary acidic protein at Ser13, and vimentin at Ser71, respectively. Subsequently, the nature of multinucleated giant cells was investigated using laser scanning confocal microscopy. In addition, paraffin-embedded tissue sections obtained in three patients with giant cell glioblastoma were also investigated.

Multinucleated giant cells were immunoreacted with the mAb 4A4 and not with KT13 and TM71 in vitro and in vivo. In addition, the authors obtained these results in multinucleated giant cells under natural conditions, without drug treatments.

Conclusions. Findings in this investigation indicated that multinucleated giant cells are those remaining in mitosis between metaphase and telophase, undergoing neither fusion nor degeneration.
Cytidinediphosphocholine treatment to decrease traumatic brain injury—induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats
Authors: Dempsey Robert J. , Raghavendra Rao Vemuganti L.
Published: May 2009

Object. In previous studies at their laboratory the authors showed that cytidinediphosphocholine (CDP-choline), an intermediate of phosphatidylcholine synthesis, decreases edema formation and blood—brain barrier disruption following traumatic brain injury (TBI). In the present study the authors investigate whether CDP-choline protects hippocampal neurons after controlled cortical impact (CCI)—induced TBI in adult rats.

Methods. After adult male Sprague—Dawley rats had been anesthetized with halothane, a moderate-grade TBI was induced with the aid of a CCI device set at a velocity of 3 m/second, creating a 2-mm deformation. Sham-operated rats, which underwent craniectomy without impact served as controls. The CDP-choline (100, 200, and 400 mg/kg body weight) or saline was injected into the animals twice (once immediately postinjury and once 6 hours postinjury). Seven days after the injury, the rats were neurologically evaluated and killed, and the number of hippocampal neurons was estimated by examining thionine-stained brain sections.

By 7 days postinjury, there was a significant amount of neuronal death in the ipsilateral hippocampus in the CA2 (by 53 ± 7%, p < 0.05) and CA3 (by 59 ± 9%, p < 0.05) regions and a contusion (volume 34 ± 8 mm3) in the ipsilateral cortex compared with sham-operated control animals. Rats subjected to TBI also displayed severe neurological deficit at 7 days postinjury. Treating rats with CDP-choline (200 and 400 mg/kg, intraperitoneally) significantly prevented TBI-induced neuronal loss in the hippocampus, decreased cortical contusion volume, and improved neurological recovery.

Conclusions. Treatment with CDP-choline decreased brain damage following TBI.
Stereotactic transplantation of a dopamine-producing capsule into the striatum for treatment of Parkinson disease: a preclinical primate study
Authors: Yoshida Hideyuki , Date Isao , Shingo Tetsuro , Fujiwara Kenjiro , Kobayashi Kazuki , Miyoshi Yasuyuki , Ohmoto Takashi
Published: May 2009

Object. The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal models encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; this technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials.

Methods. Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules after removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell—grafted groups.

Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells.

Conclusions. These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.
Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy—parkinsonism
Authors: Visser-Vandewalle Veerle , Temel Yasin , Colle Henry , van der Linden Chris
Published: May 2009

✓ The aim of this study was to investigate the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in patients with a subtype of multiple system atrophy (MSA) in which levodopa-unresponsive MSA parkinsonism (MSA-P) is predominant.

After a local anesthetic was administered, electrodes were stereotactically implanted bilaterally into the STN in four patients with MSA-P and predominantly akinetorigid symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated preoperatively, at 1 month, and at long-term follow up.

At 1 month the median decrease in the UPDRS III motor score was 22 on the 56-point scale (decreases of 16, 13, 29, and 15 points compared with baseline for Cases 1, 2, 3, and 4, respectively). This was mainly due to an improvement in rigidity and akinesia. The median decrease in the UPDRS II score was 11 on the 52-point scale (respective decreases of 5, 7, 13, and 9 points). At 2 years (mean follow up 27 months) there was a median decrease in the UPDRS III score of 12 (respective decreases of 18, 13, 21, and 9 points), and in the UPDRS II score of 5 (with respective decreases of 2, 2, 17, and 2), both compared with the stimulation off state.

At long-term follow up there was an increase in the individual Schwab and England scores of 10 to 15% in the stimulation on compared with the stimulation off condition.

There was a beneficial effect of STN HFS in these four patients on both a short-term and a long-term basis. A larger prospective study is justified.
Thalamic deep brain stimulation for disabling tremor after excision of a midbrain cavernous angioma
Authors: Samadani Uzma , Umemura Atsushi , Jaggi Jurg L. , Colcher Amy , Zager Eric L. , Baltuch Gordon H.
Published: May 2009

✓ Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor.

A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing.

The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.
Hydrocephalus due to idiopathic stenosis of the foramina of Magendie and Luschka
Authors: Karachi Carine , Le Guérinel Caroline , Brugières Pierre , Melon Eliane , Decq Philippe
Published: May 2009

✓ Idiopathic stenosis of the foramina of Magendie and Luschka is a rare cause of obstructive hydrocephalus involving the four ventricles. Like other causes of noncommunicating hydrocephalus, it can be treated with endoscopic third ventriculostomy (ETV).

Three patients who were 21, 53, and 68 years of age presented with either headaches (isolated or associated with raised intracranial pressure) or vertigo, or a combination of gait disorders, sphincter disorders, and disorders of higher functions. In each case, magnetic resonance (MR) imaging demonstrated hydrocephalus involving the four ventricles (mean transverse diameter of third ventricle 14.15 mm; mean sagittal diameter of fourth ventricle 23.13 mm; and mean ventricular volume 123.92 ml) with no signs of a Chiari Type I malformation (normal posterior fossa dimensions, no herniation of cerebellar tonsils). The diagnosis of obstruction was confirmed using ventriculography (in two patients) and/or MR flow images (in two patients). All patients presented with marked dilation of the foramen of Luschka that herniated into the cisterna pontis. All patients were treated using ETV.

No complications were observed. All three patients became asymptomatic during the weeks following the surgical procedure and remained stable at a mean follow-up interval of 36 months. Postoperative MR images demonstrated regression of the hydrocephalus (mean transverse diameter of third ventricle 7.01 mm; mean sagittal diameter of fourth ventricle 16.6 mm; and mean ventricular volume 79.95 ml), resolution of dilation of the foramen of Luschka, and good patency of the ventriculostomy (flow sequences).

These results confirm the existence of hydrocephalus caused by idiopathic fourth ventricle outflow obstruction without an associated Chiari Type I malformation, and the efficacy of ETV for this rare indication.
Arteriovenous malformation in the trigeminal nerve
Authors: Maher Cormac O. , Atkinson John L. D. , Lane John I.
Published: May 2009

✓ The authors report on an arteriovenous malformation (AVM) within the trigeminal nerve in an otherwise healthy 76-year-old man who presented with the sudden onset of headache and ataxia. The AVM was totally resected via a lateral sub-occipital approach to the cerebellopontine angle. Dural arteriovenous fistulas and AVMs of the dorsal root entry zone and adjacent brainstem that compress the trigeminal nerve have been previously described. To the authors' knowledge, this is the first reported case of an angiographically, surgically, and pathologically proven AVM arising from within the trigeminal nerve itself.
Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study
Authors: Magnoni Sandra , Ghisoni Laura , Locatelli Marco , Caimi Mariangela , Colombo Angelo , Valeriani Valerio , Stocchetti Nino
Published: May 2009

Object. The authors investigated the effects of hyperoxia on brain tissue PO2 and on glucose metabolism in cerebral and adipose tissue after traumatic brain injury (TBI).

Methods. After 3 hours of ventilation with pure O2, 18 tests were performed on different days in eight comatose patients with TBI. Lactate, pyruvate, glucose, glutamate, and brain tissue PO2 were measured in the cerebral extracellular fluid (ECF) by using microdialysis. Analytes were also measured in the ECF of abdominal adipose tissue.

After 3 hours of increase in the fraction of inspired O2, brain tissue PO2 rose from the baseline value of 32.7 ± 18 to 122.6 ± 45.2 mm Hg (p < 0.0001), whereas brain lactate dropped from its baseline (3.21 ± 2.77 mmol/L), reaching its lowest value (2.90 ± 2.58 mmol/L) after 3 hours of hyperoxia (p < 0.01). Pyruvate dropped as well, from 153 ± 56 to 141 ± 56 µmol/L (p < 0.05), so the lactate/pyruvate ratio did not change. No significant changes were observed in glucose and glutamate. The arteriovenous difference in O2 content dropped, although not significantly, from a baseline of 4.52 ± 1.22 to 4.15 ± 0.76 ml/100 ml. The mean concentration of lactate in adipose tissue fell significantly as well (p < 0.01), but the lactate/pyruvate ratio did not change.

Conclusions. Hyperoxia slightly reduced lactate levels in brain tissue after TBI. The estimated redox status of the cells, however, did not change and cerebral O2 extraction seemed to be reduced. These data indicate that oxidation of glucose was not improved by hyperoxia in cerebral and adipose tissue, and might even be impaired.
Anemia, testosterone, and pituitary adenoma in men
Authors: Ellegala Dilantha B. , Alden Tord D. , Couture Daniel E. , Vance Mary L. , Maartens Nicholas F. , Laws Edward R.
Published: May 2009

Object. Older men with clinically nonfunctioning pituitary tumors have been noted to be anemic, to have hypopituitarism, and to have low serum levels of testosterone. The authors hypothesized that men with pituitary adenomas and hypogonadism have a physiologically related decrease in hematocrit.

Methods. A retrospective analysis was conducted of 216 patients older than 50 years of age who harbored pituitary adenomas. In 100 men serum testosterone levels and a complete blood (cell) count (CBC) were obtained before treatment; a CBC was also acquired in a series of women with pituitary adenomas. Using clinical laboratory standards, anemia was defined as a hematocrit less than 40% in men and less than 35% in women.

Thirty-one (46.3%) of 67 men with low serum concentrations of testosterone were anemic. In men with low levels of testosterone, the average hematocrit was 39.9%, compared with 45.6% for men with normal testosterone levels (p < 0.001). Men with macroadenomas were most likely to have both anemia and a low serum concentration of testosterone. Anemia was associated with a low level of testosterone, adjusting for tumor size (odds ratio 19, 95% confidence interval 4.86–77.03). Of patients with anemia, 84% were men and 16% were women (p < 0.001). The prevalence of anemia in women was low and was not correlated with tumor size. Men receiving testosterone replacement therapy had a significantly higher hematocrit value than men with low or normal testosterone levels.

Conclusions. These findings support a direct relationship between serum testosterone levels and hematopoiesis in men, and demonstrate that hematopoiesis is compromised in men who have low concentrations of testosterone due to a pituitary adenoma.
Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage
Authors: Treggiari Miriam M. , Walder Bernhard , Suter Peter M. , Romand Jacques-André
Published: May 2009

Object. There is uncertainty about the efficacy of hypertension, hypervolemia, and hemodilution (triple-H) therapy in reducing the occurrence of delayed ischemic neurological deficits (DINDs) and death after subarachnoid hemorrhage. The authors therefore conducted a systematic review to evaluate the efficacy of triple-H prevention in decreasing the rate of clinical vasospasm, DINDs, and death.

Methods. The authors systematically reviewed studies identified based on a MEDLINE, EMBASE, and COCHRANE Register search of articles published between 1966 and 2001, and reference lists of identified articles. An independent assessment of each study's methodological quality, population, intervention, and outcomes (rates of symptomatic vasospasm, DINDs, and death) was performed. Summary relative risk estimates were calculated for the main outcomes using fixed- or random-effect models, as appropriate.

Only four prospective, comparative studies with a total of 488 patients were identified. The median internal validity score was 0.5 (range 0–2); the median external validity score was 3 (range 2–6). Compared with no prevention, triple-H therapy was associated with a reduced risk of symptomatic vasospasm (relative risk [RR] 0.45, 95% confidence interval [CI] 0.32–0.65), but not DIND (RR 0.54, 95% CI 0.2–1.49). The risk of death was higher (RR 0.68, 95% CI 0.53–0.87). Sensitivity analyses including only randomized, controlled trials showed no evidence of statistically significant results for these major end points.

Conclusions. The paucity of information and important limitations in the design of the studies analyzed preclude evaluation of the efficacy of triple-H prevention and formulation of any recommendations regarding its use for the prevention of cerebral vasospasm.
Edema after intracerebral hemorrhage: correlations with coagulation parameters and treatment
Authors: Sansing Lauren H. , Kaznatcheeva Elena A. , Perkins Candice J. , Komaroff Eugene , Gutman Frederick B. , Newman George C.
Published: May 2009

Object. Development of edema is known to contribute to poor outcome after spontaneous intracerebral hemorrhage (ICH). Recent research has identified thrombin as a key mediator in the development of edema in animal models; however, little has been published correlating the coagulation cascade and edema in humans.

Methods. In this retrospective clinical study of 80 patients with spontaneous supratentorial ICH, the authors sought to identify factors associated with edema development and outcome, including lesion imaging parameters, anticoagulant use, international normalized ratio and platelet count on hospital admission, and treatment with mannitol and steroid medications. A multivariate model was used to identify edema volume, use of mannitol, elevated blood glucose, and the presence of intraventricular hemorrhage as predictors of poor outcome at the time patients were discharged from the hospital. The authors developed a quadratic model for predicting edema volume against time by using a random coefficients model, and found that edema peaks between Days 5 and 6 after onset of ICH. The volume of the hemorrhage and the platelet count correlated significantly with edema volume within the first 24 hours post-ICH in the multiple regression analysis (p < 0.0001, r2 = 0.75). Edema growth during the first 5 days post-ICH also correlated with the platelet count, with an increasing platelet count associated with an increasing growth of edema (p = 0.0013).

Conclusions. The authors propose that factors released from activated platelets at the site of hemorrhage, for example vascular endothelial growth factor, may interact with thrombin to increase vascular permeability and contribute to the development of edema.
Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible?
Authors: Tsuyuguchi Naohiro , Sunada Ichiro , Iwai Yoshiyasu , Yamanaka Kazuhiro , Tanaka Kiyoaki , Takami Toshihiro , Otsuka Yumiko , Sakamoto Shinichi , Ohata Kenji , Goto Takeo , Hara Mitsuhiro
Published: May 2009

Object. In this study the authors examined how to differentiate radiation necrosis from recurrent metastatic brain tumor following stereotactic radiosurgery by using positron emission tomography (PET) with l-[methyl-11C]methionine (MET).

Methods. In 21 adult patients with suspected recurrent metastatic brain tumor or radiation injury, MET-PET scans were obtained. These patients had previously undergone stereotactic radiosurgery and subsequent contrast-enhanced magnetic resonance (MR) examinations before nuclear medicine imaging. Positron emission tomography images were obtained as a static scan of 10 minutes performed 20 minutes after injection of 370 MBq of MET. On MET-PET scans, the portion of the tumor with the highest accumulation of MET was selected as the region of interest (ROI), and the ratio of tumor tissue to normal tissue (T/N) was defined as the mean counts of radioisotope per pixel in the tumor divided by the mean counts per pixel in normal gray matter. The standardized uptake value (SUV) was calculated using the same ROI in the tumor. The accuracy of the MET-PET scan was evaluated by correlating findings with results of subsequent histological analysis (11 cases) or, in cases in which surgery or biopsy was not performed, with subsequent clinical course and MR imaging findings (10 cases).

Histological examinations performed in 11 cases showed viable tumor cells with necrosis in nine and necrosis with no viable tumor cells in two. Another 10 cases were characterized as radiation necrosis because the patients exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR images after 5 months. The mean T/N was 1.15 in the radiation necrosis group (12 cases) and 1.62 in the tumor recurrence group (nine cases). The mean SUV was 1.78 in the necrosis group and 2.5 in the recurrence group. There were statistically significant differences between the recurrence and necrosis groups in T/N and SUV. Furthermore, the borderline T/N value was 1.42 according to a 2 × 2 factorial table (high T/N or low T/N, recurrence or necrosis). From this result, the sensitivity and specificity of MET-PET scanning in detecting tumor recurrence were determined to be 77.8 and 100%, respectively.

Conclusions. The use of MET-PET scanning is a sensitive and accurate technique for differentiating between metastatic brain tumor recurrence and radiation necrosis following stereotactic radiosurgery. This study reveals important information for creating strategies to treat postradiation reactions.
Trauma-induced tumorigenesis of cells implanted into the rat spinal cord
Authors: Hasegawa Koichi , Grumet Martin
Published: May 2009

Object. Findings in several clinical cases have suggested a correlation between tumor formation and previous injury to the central nervous system (CNS); however, the relationship between trauma and tumorigenesis has not been investigated well experimentally. In this study the authors provide evidence correlating tumorigenesis with trauma in the rat spinal cord.

Methods. A glial cell line, C6R-G/H, which expresses green fluorescent protein (GFP) and hygromycin phosphotransferase (HPT), was implanted into normal and injured rat spinal cords. In all rats in which the cells were implanted into an injured site, locomotor function deteriorated and histological analysis demonstrated glioblastoma multiforme by 6 weeks; tumorigenesis was correlated with a loss of both GFP expression and resistance to hygromycin treatment. In contrast, no evidence of tumor formation was found at 6 weeks in rats in which the cells were implanted into healthy tissue. When C6R-G/H cells were treated with contused spinal cord extract in culture before implantation, they lost GFP expression and hygromycin resistance, and later formed tumors after implantation into normal spinal cord.

Conclusions. The findings of this study indicate that trauma can induce tumorigenesis. Implantation of C6R-G/H cells into traumatized spinal cords resulted in their transformation, which was signaled by loss of GFP expression and hygromycin resistance accompanied by tumor formation. Exposure to extracts derived from injured spinal cord produced similar transformation and gene expression changes, as well as tumor formation after such cells were implanted into normal cords. Care, therefore, should be taken when cells are implanted into an injured CNS because of potential mutagenesis due to trauma-induced factors.
Amyloid β accumulation in axons after traumatic brain injury in humans
Authors: Smith Douglas H. , Chen Xiao-han , Iwata Akira , Graham David I.
Published: May 2009

Object. Although plaques composed of amyloid β (Aβ) have been found shortly after traumatic brain injury (TBI) in humans, the source for this Aβ has not been identified. In the present study, the authors explored the potential relationship between Aβ accumulation in damaged axons and associated Aβ plaque formation.

Methods. The authors performed an immunohistochemical analysis of paraffin-embedded sections of brain from 12 patients who died after TBI and from two control patients by using antibodies selective for Aβ peptides, amyloid precursor protein (APP), and neurofilament (NF) proteins. In nine brain-injured patients, extensive colocalizations of Aβ, APP, and NF protein were found in swollen axons. Many of these immunoreactive axonal profiles were present close to Aβ plaques or were surrounded by Aβ staining, which spread out into the tissue. Immunoreactive profiles were not found in the brains of the control patients.

Conclusions. The results of this study indicate that damaged axons can serve as a large reservoir of Aβ, which may contribute to Aβ plaque formation after TBI in humans.
Functional motor neurons differentiating from mouse multipotent spinal cord precursor cells in culture and after transplantation into transected sciatic nerve
Authors: MacDonald Stephen C. , Fleetwood Ian G. , Hochman Shawn , Dodd Janice G. , Cheng Gavin K. W. , Jordan Larry M. , Brownstone Robert M.
Published: May 2009

Object. One of the current challenges in neurobiology is to ensure that neural precursor cells differentiate into specific neuron types, so that they can be used for transplantation purposes in patients with neuron loss. The goal of this study was to determine if spinal cord precursor cells could differentiate into motor neurons both in culture and following transplantation into a transected sciatic nerve.

Methods. In cultures with trophic factors, neurons differentiate from embryonic precursor cells and express motor neuronal markers such as choline acetyltransferase (ChAT), Islet-1, and REG2. Reverse transcription—polymerase chain reaction analysis has also demonstrated the expression of Islet-1 in differentiated cultures. A coculture preparation of neurospheres and skeletal myocytes was used to show the formation of neuromuscular connections between precursor cell—derived neurons and myocytes both immunohistochemically and electrophysiologically. Following various survival intervals, precursor cells transplanted distal to a transection of the sciatic nerve differentiated into neurons expressing the motor neuron markers ChAT and the α11.2 (class C, L-type) voltage-sensitive Ca++ channel subunit. These cells extended axons into the muscle, where they formed cholinergic terminals.

Conclusions. These results demonstrate that motor neurons can differentiate from spinal cord neural precursor cells grown in culture as well as following transplantation into a transected peripheral nerve.
Treatment of patients with intractable obsessive—compulsive disorder with anterior capsular stimulation
Authors: Anderson Douglas , Ahmed Azam
Published: May 2009

✓ Obsessive—compulsive disorder (OCD) is a common, chronic, disabling anxiety disorder characterized by recurrent obsessive thoughts and uncontrolled repetitive acts. Although many patients respond to various pharmacological treatments, there is a cohort of patients with intractable or refractory disease. The authors present the case of a patient with intractable OCD who was treated with bilateral electrical stimulators, which were stereotactically placed in the anterior limbs of the internal capsules.

Following psychiatric consultation and 10 years of empirical medication regimens for OCD, a woman was referred for neurosurgical evaluation. After informed consent had been obtained from the patient, the authors placed bilateral stimulator leads in the anterior limbs of the internal capsules. The stereotactic coordinates were based on data in pertinent current literature. The stimulation parameters, which are presented in this paper, were set at 2 weeks and reviewed at 6 weeks and 3 months postoperatively. No changes were required. Postoperative analysis included evaluation by the patient's referring psychiatrist, a second independent psychiatrist, and pre- and postoperative administration of the Yale—Brown Obsessive Compulsive Scale. A marked improvement was noted in this patient's OCD symptomatology and general psychosocial function.

Previous documentation of patient responses to psychosurgical procedures for intractable or refractory OCD has been met with little enthusiasm, presumably because of the invasiveness and irreversibility of the surgery. In this report the authors suggest that deep brain stimulation of appropriate targets may be an effective and safe treatment for certain patients with OCD and a potentially reversible treatment for those patients who do not obtain therapeutic benefit.
Amusia following resection of a Heschl gyrus glioma
Authors: Russell Stephen M. , Golfinos John G.
Published: May 2009

✓ The incidence and character of neurological deficits following resection of glial neoplasms localized to the Heschl gyrus are currently unknown. In this series, the authors report the clinical presentation, management, and postoperative course of three patients with right hemisphere Heschl gyrus gliomas, one of whom developed difficulty with music production and comprehension postoperatively.

Resection of right hemisphere Heschl gyrus gliomas can result in deficits involving music comprehension. Preliminary evidence suggests that when these deficits occur, they may be transient in nature.
Rapid development of Chiari I malformation in an infant with Seckel syndrome and craniosynostosis
Authors: Hopkins Timothy E. , Haines Stephen J.
Published: May 2009

✓ To illustrate the rapidity with which a child can develop a severe, symptomatic Chiari I malformation, the authors present the case of a 3-month-old infant with Seckel syndrome (microcephaly, micrognathia, craniosynostosis, and multiple other abnormalities) and posterior sagittal and bilateral lambdoid synostosis. The infant underwent magnetic resonance (MR) imaging shortly after birth; the initial image demonstrated the cerebellar tonsils in the posterior fossa, with no herniation. He subsequently developed severe apneic episodes and bradycardia; repeated MR imaging at 3 months demonstrated severe tonsillar herniation with compression of the brainstem. The child underwent posterior fossa remodeling surgery, including release of the posterior sagittal and lambdoid sutures and decompression of the Chiari I malformation. The patient's apnea gradually improved; however, he died of complications of pneumonia and sepsis several weeks later.

The authors identified from the literature 21 patients in whom there was a documented MR image or other neuroimage that did not reveal evidence of a Chiari I malformation, followed by a subsequent study with clear documentation of the presence of Chiari I malformation. The interval between the initial study and the development of the tonsillar herniation ranged from 11 days to 18.5 years. In most cases, a lumbar cerebrospinal fluid (CSF) diversion had been performed. This patient developed a severely symptomatic Chiari I malformation during a 3-month period. These reports illustrate that the Chiari I malformation can develop rapidly in the face of increased intracranial pressure, craniosynostosis, and spinal CSF diversion.
Vascularized temporalis muscle flap for the treatment of otorrhea
Authors: Tender Gabriel C. , Kutz Scott , Awasthi Deepak , Rigby Peter
Published: May 2009

✓ The surgical treatment for cerebral spinal fluid (CSF) fistulas provides closure of the bone and dural defects and prevents the recurrence of brain herniation and CSF fistula. The two main approaches used are the transmastoid and middle fossa ones. The authors review the results of performing a modified middle fossa approach with a vascularized temporalis muscle flap to create a barrier between the repaired dural and bone defects.

Fifteen consecutive cases of CSF fistulas treated at the authors' institution were retrospectively reviewed. All patients presented with otorrhea. Eleven patients had previously undergone ear surgery. A middle fossa approach was followed in all cases. The authors used a thin but watertight and vascularly preserved temporalis muscle flap that had been dissected from the medial side of the temporalis muscle and was laid intracranially on the floor of the middle fossa, between the repaired dura mater and petrous bone. The median follow-up period was 2.5 years. None of the patients experienced recurrence of otorrhea or meningitis. There was no complication related to the intracranial temporalis muscle flap (for example, seizures or increased intracranial pressure caused by muscle swelling). One patient developed hydrocephalus, which resolved after the placement of a ventriculoperitoneal shunt 2 months later.

The thin, vascularized muscle flap created an excellent barrier against the recurrence of CSF fistulas and also avoided the risk of increased intracranial pressure caused by muscle swelling. This technique is particularly useful in refractory cases.
Third ventriculostomy for internal hydrocephalus complicated by unrecognized subdural hygroma and hematoma: a case report of a patient treated by Dr. Walter Dandy
Authors: King Robert B. , Davis Richard L. , Collins George H.
Published: May 2009

✓ The authors review the case of a patient treated by Dr. Walter Dandy. When the patient was a young child he underwent two right transtemporal third ventriculostomies during which he sustained an unrecognized contralateral subdural hygroma and a chronic subdural hematoma with a mild infantile hemiparesis. He was able to complete high school, albeit at a slower pace than usual. As an adult he held several limited employment positions, lived at home for several decades, and was later cared for at a nursing home for a short time. The patient died when he was 66 years of age.
Repeated operations for infiltrative low-grade gliomas without intervening therapy
Authors: Schmidt Meic H. , Berger Mitchel S. , Lamborn Kathleen R. , Aldape Ken , McDermott Michael W. , Prados Michael D. , Chang Susan M.
Published: May 2009

Object. Progression of infiltrative low-grade gliomas (LGGs) has been reported previously. The limitations of such studies include diverse histological grading systems, intervening therapy, and the lack of histological confirmation of malignant tumor progression. The aim of this study was to determine tumor progression in adult patients with an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation, but no other intervening therapy. The authors examined factors that may be associated with tumor progression.

Methods. The authors retrospectively reviewed a database of 300 patients with the initial diagnosis of LGG and who had been treated at their institution between 1990 and 2000. One hundred four of these patients had undergone a second surgery. Patients with infiltrative LGGs who had undergone two surgical procedures at least 3 months apart without intervening therapy were selected; the authors identified 40 patients who fit these criteria. Clinical, neuroimaging, and pathological data were centrally reviewed.

There were 29 men and 11 women in the study, whose median age was 35.5 years (range 23–48 years). At the time of the second surgery, 50% of patients had experienced tumor progression. Patients whose tumors had progressed had a longer median time to repeated operation (49 compared with 22.5 months). Patients who had undergone gross-total resection, as demonstrated on postoperative magnetic resonance images, had a median time to repeated operation of 49 compared with 25 and 24 months in patients who underwent subtotal resection and biopsy, respectively (p = 0.02). The extent of resection did not influence the likelihood of tumor progression (p > 0.3).

Conclusions. Fifty percent of patients with initially diagnosed infiltrative LGGs had tumor progression at the time of a repeated operation. A gross-total resection was associated with an increased time to repeated surgery. There was no statistically significant effect of gross-total resection as a predictor of tumor progression.
Independent predictors of recurrence of chronic subdural hematoma: results of multivariate analysis performed using a logistic regression model
Authors: Yamamoto Hiromichi , Hirashima Yutaka , Hamada Hideo , Hayashi Nakamasa , Origasa Hideki , Endo Shunro
Published: May 2009

Object. The authors attempted to determine independent predictors that contribute to the recurrence of chronic subdural hematoma (CSDH).

Methods. A total of 105 consecutive patients who underwent surgery for CSDH were included in this study. Eleven patients underwent a repeated operation because the CSDH recurred. Univariate and multivariate analyses were performed to assess the relationships among various variables and CSDH recurrence. Finally, four variables were found to be independently associated with the recurrence of CSDH: 1) absence of a multiplicity of hematoma cavities on CT scans; 2) presence of a history of seizure; 3) width of the hematoma; and 4) absence of a history of diabetes mellitus (DM).

Conclusions. As previously reported, the width of the hematoma is related to the incidence of CSDH recurrence. In this study, the lack of a multiplicity of hematoma cavities was the favorite predictor of CSDH recurrence. In addition, histories of seizure and no past DM are closely related to the incidence of CSDH recurrence.
Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Authors: McGirt Matthew J. , Mavropoulos John C. , McGirt Laura Y. , Alexander Michael J. , Friedman Allan H. , Laskowitz Daniel T. , Lynch John R.
Published: May 2009

Object. The identification of patients at an increased risk for cerebral vasospasm after subarachnoid hemorrhage (SAH) may allow for more aggressive treatment and improved patient outcomes. Note, however, that blood clot size on admission remains the only factor consistently demonstrated to increase the risk of cerebral vasospasm after SAH. The goal of this study was to assess whether clinical, radiographic, or serological variables could be used to identify patients at an increased risk for cerebral vasospasm.

Methods. A retrospective review was conducted in all patients with aneurysmal or spontaneous nonaneurysmal SAH who were admitted to the authors' institution between 1995 and 2001. Underlying vascular diseases (hypertension or chronic diabetes mellitus), Hunt and Hess and Fisher grades, patient age, aneurysm location, craniotomy compared with endovascular aneurysm stabilization, medications on admission, postoperative steroid agent use, and the occurrence of fever, hydrocephalus, or leukocytosis were assessed as predictors of vasospasm.

Two hundred twenty-four patients were treated for SAH during the review period. One hundred one patients (45%) developed symptomatic vasospasm. Peak vasospasm occurred 5.8 ± 3 days after SAH. There were four independent predictors of vasospasm: Fisher Grade 3 SAH (odds ratio [OR] 7.5, 95% confidence interval [CI] 3.5–15.8), peak serum leukocyte count (OR 1.09, 95% CI 1.02–1.16), rupture of a posterior cerebral artery (PCA) aneurysm (OR 0.05, 95% CI 0.01–0.41), and spontaneous nonaneurysmal SAH (OR 0.14, 95% CI 0.04–0.45). A serum leukocyte count greater than 15 × 109/L was independently associated with a 3.3-fold increase in the likelihood of developing vasospasm (OR 3.33, 95% CI 1.74–6.38).

Conclusions. During this 7-year period, spontaneous nonaneurysmal SAH and ruptured PCA aneurysms decreased the odds of developing vasospasm sevenfold and 20-fold, respectively. The presence of Fisher Grade 3 SAH on admission or a peak leukocyte count greater than 15 × 109/L increased the odds of vasospasm sevenfold and threefold, respectively. Monitoring of the serum leukocyte count may allow for early diagnosis and treatment of vasospasm.
Subarachnoid hemorrhage without evident cause on initial angiography studies: diagnostic yield of subsequent angiography and other neuroimaging tests
Authors: Topcuoglu Mehmet A. , Ogilvy Christopher S. , Carter Bob S. , Buonanno Ferdinando S. , Koroshetz Walter J. , Singhal Aneesh B.
Published: May 2009

Object. The aim of this study was to assess the diagnostic yield of imaging tests performed in patients in whom the cause of subarachnoid hemorrhage (SAH) had not been demonstrated on initial angiography.

Methods. By reviewing medical records of 806 patients with SAH who had been admitted during a 6.5-year period, the authors identified 86 in whom initial transfemoral catheter angiography failed to reveal the cause of SAH. Clinical and radiological data were analyzed to determine the diagnostic yield of subsequent catheter angiography, computerized tomography (CT) angiography, magnetic resonance (MR) angiography, and MR imaging of the brain and spine for various subtypes of SAH (bleeding not visualized on CT studies [CT-negative SAH], perimesencephalic SAH, and nonperimesencephalic SAH).

Of 41 patients with nonperimesencephalic SAH, 36, 32, and 21 underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in 23 patients (18 with Gd and 15 with susceptibility contrast sequences), and spine MR imaging in 17. Of 36 patients with perimesencephalic SAH, 31, 23, and 17 underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in 18 patients (17 with Gd and 11 with susceptibility contrast sequences), and spine MR imaging in 14. Of nine patients with SAH not visualized on CT scanning, three, one, and six underwent repeated catheter angiography, CT angiography, and MR angiography, respectively; brain MR imaging was performed in eight patients (five with Gd and three with susceptibility contrast sequences), and spine MR imaging in seven. The cause of SAH could be determined in only four patients, all with nonperimesencephalic SAH. The only test that yielded a diagnosis was catheter angiography (three aneurysms on the second and one on the third angiography, all surgically secured). Diffusion-weighted MR imaging demonstrated small, deep infarcts in five patients.

Conclusions. Repeated catheter angiography remains the most sensitive test to determine the cause of SAH that is not demonstrated on initial angiography, particularly in the subtype of nonperimesencephalic SAH. Newer, noninvasive imaging techniques provide little diagnostic yield.