Persistent communicating hydrocephalus in adult tuberous sclerosis patients: a possible therapeutic role for everolimus.

Subependymal giant cell tumor (SGCT) is a benign intraventricular tumor, usually located near the foramen of Monro. It is almost always associated with tuberous sclerosis complex (TSC). SGCTs may obstruct cerebrospinal fluid (CSF) pathways. Rarely, they may secrete a protein-rich exudate, causing communicating hydrocephalus. Surgery is indicated for symptomatic lesions or growing asymptomatic lesions. The operative approach to SGCT has shifted from simple shunt placement to a more aggressive approach, leading to early attempts at gross total resection. Recently, the mTOR inhibitor everolimus has been approved for treating SGCT. In this article, we present two cases of recurrent shunt malfunctions in adult TSC patients with protein-secreting SGCTs. We describe the complexity of treating such patients with an emphasis on the role mTOR inhibitors may have in their management. We also review the literature on surgical management of SGCT-related hydrocephalus.

Cord compression due to extradural thoracic nerve root hemangioblastoma.

Hemangioblastomas (HGBs) are benign tumors that occur sporadically or as part of von Hippel-Lindau (VHL) disease. 6-8% of spinal HGBs are extramedullary in location, and basically referred to as HGB of the spinal nerve root. Purely extradural (ED) location is the rarest form of these tumors. We report a case of a non-VHL patient with large thoracic ED HGB, who presented with myelopathy due to cord compression. We emphasize the importance of correct pre-operative diagnosis as well as pre-operative embolization in order to reach the goal of complete tumor resection with minimal complications. We also review the relevant literature and summarize the few case reports of this unique tumor.

Novel surgical approach in the management of longitudinal pathologies within the spinal canal: the split laminotomy and "archbone" technique: alternative to multilevel laminectomy or laminotomy.

Multilevel laminectomy to open the spinal canal carries the risk of spinal deformities and instability. With the aim of preserving and reconstructing the posterior structures the authors developed a novel, minimally invasive, multilevel spinous process splitting and distracting laminotomy approach with or without complementary corticocancellous iliac crest or PEEK cage "archbone" grafting. The technique allows exploration of the spinal canal and the removal of intramedullary pathologies. Moderate enlargement of the spinal canal with preservation of the majority of posterior structures is also possible, so that muscle attachments remain intact and postoperative complications are substantially reduced.This surgical approach, while fulfilling the requirements of previous laminotomy techniques, helps to prevent damage to the crucial posterior stabilizers of the spine. In contrast to conventional spinal canal approaches, preservation of the majority of posterior structures is possible, leaving muscle attachments on the spinous processes and laminae completely intact.Furthermore, the procedure for exposure and decompression of the spinal canal is a suitable method for all spinal segments, the cervical, thoracic, and the lumbar spine in all age groups.

Risk factors for development of significant chronic subdural hematoma following conservative treatment of acute subdural hemorrhage.

OBJECTIVE: One of the complications of untreated acute subdural hemorrhage (aSDH) is the late development of chronic subdural hematomas (cSDH). cSDH may cause major neurologic deficits, requiring their surgical evacuation. The aim of our work was to find risk factors for the development of significant cSDH requiring surgery following conservative treatment of trauma-related aSDH. METHODS: In a retrospective manner, we analyzed the data of 95 adult patients admitted with a non-surgical, traumatic aSDH. The patients were divided into two groups. The first group contained 52 patients who did not, on follow-up, develop cSDH requiring surgery. The second group contained 43 patients who ended up with a significant cSDH, based on clinical and radiological criteria, requiring surgical evacuation. Data acquisition and comparison between the two groups was performed by analyzing the patients' charts for diverse medical conditions and other trauma-related parameters. RESULTS: The operation rate was significantly higher in patients with medical history of ischemic heart disease (IHD) or hypertension (66.7% vs. 38%, p = 0.019 and 56.9% vs. 20%, p < 0.01, respectively), with a 4-fold increase in the risk for developing surgical cSDH in patients with IHD and a 6-fold increase in the risk in patients with hypertension (odds ratio 4.2 [95% CI for odds, 1.3-13.1] and 5.9 [95% C.I for odds, 1.6-21.5], respectively). Among 21 patients, 20 (95%) patients, who were either on more than 1 anti-aggregant agents (AAA), used Clopidrogrel, or took anti-coagulant drug were in the operative group (OG). A larger initial thickness of the aSDH was statistically significant in the OG as compared to the non-OG (8.9 mm ± 4.6 vs. 5.5 mm ± 2.1, p < 0.001). CONCLUSION: Head-trauma patients with a medical history of IHD or hypertension, patients on more than one AAA or anti-coagulant agents and patients with worse initial CT scan parameters are at risk of developing significant cSDH requiring surgery after conservative treatment of aSDH and consequently should have closer follow-up.

Endoscopic transnasal cerebrospinal fluid leak repair: a 10 year experience.

BACKGROUND: Endoscopic techniques have gained popularity for the repair of anterior skull base defects. OBJECTIVE: To describe the 10 year experience with endoscopic surgical repair of cerebrospinal fluid (CSF) rhinorrhea in a tertiary medical center. METHODS: The files of all patients who underwent endoscopic transnasal CSF leak repair in our institution between 1996 and 2006 were reviewed. RESULTS: Twenty-four patients were identified: 16 women and 7 men with a mean age of 48 years and one child aged 9.5 years. The leak was trauma-induced in 17 patients and occurred spontaneously in the other 7. The defect was localized by preoperative computed tomography or CT/cysternography in 86% of cases. A fascia lata graft was the dominant choice for defect closure, and it was combined with a conchal or septal flap, fat, periosteum, or fibrin glue in 15 patients. The success rate was 83% after the first closure attempt and 91% after the second. Two patients required a craniotomy at the third attempt. Mean hospitalization time was 6.7 days. There were two minor complications. Two patients were lost to follow-up; none of the others had a recurrence during 2 years of follow-up. CONCLUSIONS: The endoscopic transnasal technique for the repair of CSF rhinorrhea is associated with a high success rate and low morbidity, and it should be considered for the majority of cases. Repeated attempts may improve success.

Outcome of untreated meningiomas.

BACKGROUND: Nowadays meningiomas are frequently detected incidentally. Their natural history has not yet been established because it is difficult to predict the growth pattern. Therefore, the management, after the radiological diagnosis, is still controversial. OBJECTIVES: To evaluate the clinical outcome and growth rate of conservatively treated meningiomas at our tertiary center, identify prognostic factors of tumor growth, and suggest guidelines based on the available data and our experience. METHODS: We reviewed the clinical records of 56 patients with 63 untreated meningiomas. Most were diagniosed incidentally. Clinical features and imaging findings at diagnosis and during follow-up were compared between growing and non-growing tumors. Potential patient- and tumor-related predictive factors for growth were analyzed. RESULTS: The study group included 46 women (52 meningiomas) and 10 men (11 meningiomas) aged 39-83 years. Mean tumor size was 18 +/- 11 mm (range 3-70 mm) at diagnosis and 22 +/- 11 mm (range 8-70 mm) at last follow-up; mean follow-up time was 65 +/- 34 months (range 15-152 months). During follow-up 24 tumors (38%) grew ata rate of 4 mm per year; none became symptomatic. Only two prognostic factors were statistically significantly associated with low growth rate: older age and tumor calcifications. CONCLUSIONS: Given our finding of a low growth incidence of meningiomas in the elderly, we support conservative management in patients aged 70 years or older. Calcifications into the meningioma are also indicative of slow growth, suggesting a conservative strategy. Surgery is recommended in younger patients in whom tumor growth occurs more often and a longer follow-up is necessary.

Epidemiology of gliomas in Israel: a nationwide study.

BACKGROUND: Glial brain tumors span a wide range of neoplasms with distinct clinical and histopathological features. This report presents the descriptive epidemiology of glial tumors by histological subtype and tumor behavior. METHODS: The study population included all incident cases of glial tumors diagnosed in Israel during March 2001 to July 2003. Age-standardized incidence rates (ASR) were calculated using the world population as a standard. RESULTS: A total of 548 tumors were diagnosed, of which 520 had histological confirmation. The ASR of all adult (>20 years) glial tumors was 5.82/100,000 (7.11 for males; 4.75 for females, p < 0.001). The majority of tumors (78%) were classified as high grade; astrocytic tumors were the most frequent (85%), with glioblastoma multiforme accounting for 70% of them. A significant positive association was shown between age at diagnosis and grade. The highest ASR was seen for Europe- and-American-born, followed by Israeli, Asian and African-born individuals (6.78, 5.86, 4.94 and 3.84/100,000, respectively). CONCLUSIONS: In general, these results describing data of incident cases of pathologically validated glial tumors are consistent with previous reports. To enhance our understanding of these diseases, epidemiological studies should rely on well-defined histological tumor types, incorporating comprehensive information which will allow comparability between different groups of patients.

Hearing preservation using combined monitoring of extra-tympanic electrocochleography and auditory brainstem responses during acoustic neuroma surgery.

The aim of this study was to evaluate the efficacy of an intraoperative monitoring hearing preservation strategy that includes simultaneous recordings of an auditory brainstem response (ABR) and non-invasive electrocochleography (ECochG). The combined ABR and tympanic membrane (TM) ECochG testing was performed in 74 patients undergoing acoustic neuroma (AN) surgery. In addition, EMG recordings were conducted to monitor the facial nerve function. Hearing was preserved in 19 of the 30 patients with residual hearing prior to surgery (63%), and facial nerve function was maintained in 89% of the patients. In most cases, the presence of both auditory brainstem and TM-ECochG responses at the end of surgery was associated with preservation of postoperative functional hearing; however, eight patients had a TM-ECochG response with a complete loss of the ABR, pointing to deafferentation of the auditory nerve. Tumour size and preoperative hearing thresholds significantly affected the postoperative hearing. The TM-ECochG response yielded large reproducible responses, which, in some patients, was the only way to monitor the auditory function. This auditory monitoring approach offers a valuable auditory tool that helps to improve the hearing preservation during AN surgery.

Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop.

Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies.

Visual disability rates in a ten-year cohort of patients with anterior visual pathway meningiomas.

PURPOSE: To examine the visual outcome of anterior visual pathway meningioma (AVPM) patients followed for at least one year. METHODS: Data were collected on demographics, clinical course and management. Visual disability was classified at the first and last examination as follows: I--no visual disability; II--mild visual defect in one eye; III--mild visual defect in both eyes; IV--loss of driver's license; V--legally blind. RESULTS: Eight-one AVPM patients had their tumor originate in the clinoid process in 23 (28%), sphenoid-wing area in 18 (22%), cavernous sinus in 15 (19%), tuberculum sellae in 8 (10%), and mixed in 17 (21%). On last examination, 46 patients (57%) had good visual acuity in one or both eyes (Class I or II) and 17 (21%) were mildly affected in both eyes. The rate of Class IV disability was 16%, and Class V disability was 6%. CONCLUSIONS: Attention needs to be addressed to the considerable proportion of patients with AVPM (22% in this study) who may lose their driver's license or become legally blind. Occupational therapists should play an important role in the multidisciplinary management of those patients to help them adapt to their new physical and social situation. IMPLICATIONS FOR REHABILITATION: Anterior visual pathway meningiomas (AVPMs) are commonly not life-threatening but they can lead to profound visual disability, especially when the tumor originates in the tuberculum sellae and cavernous sinus. Particular attention should be paid to visual acuity and visual field deficits, as these can profoundly affect the patient's quality of life including ability to drive and activities of daily living. The interdisciplinary management of patients with AVPM should include the neurosurgeon, neuro-ophthalmologist and occupational therapist. Also, early intervention by the occupational therapist can help patients adapt to their current physical and social situation and return to everyday tasks more rapidly.

[Cushing disease: long-term follow-up after transsphenoidal surgery].

BACKGROUND: Cushing's syndrome due to an ACTH-secreting pituitary tumor is associated with serious morbidity and mortality. As there is no definitive medical treatment, surgical removal of the tumor via the transsphenoidal route remains the first choice. Postoperative hypocortisolemia is recognized as the best indicator of cure. OBJECTIVE: To report the postoperative outcome and long-term follow-up of patients with surgically treated Cushing disease at the Rabin Medical Center. METHODS: We reviewed the medical records of 27 patients with Cushing disease operated on between the period 1990 and 2003. The same experienced surgeon performed all surgeries. RESULTS: Cushing disease accounted for 15% of all pituitary surgeries in our center. The mean age was 46 years, and the female to male ratio was 25:2. Macroadenomas were found in 19% of cases, and a negative MRI in another 19%. The cure rate was 70% overall and 80% when only microadenomas were considered. There were no major perioperative complications. Four out of 8 surgical failures were re-operated, and three achieved cure. After a mean follow-up period of 5.9 years, there was only one recurrence. CONCLUSION: Our results are in accordance with those reported by others and confirm that in the hands of an experienced neurosurgeon, pituitary surgery constitutes an effective treatment for Cushing disease.

Visual outcome in meningiomas around anterior visual pathways treated with linear accelerator fractionated stereotactic radiotherapy.

PURPOSE: Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. PATIENTS AND METHODS: We included all patients with AVP meningiomas followed up at our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. RESULTS: Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). CONCLUSIONS: Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.

Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial.

OBJECTIVE: To establish the safety of intravenous dexanabinol in severe head injury. DESIGN: Prospective, randomized, double-blind, placebo- (vehicle) controlled, multicenter, escalating dose study of a single administration of drug (48 or 150 mg) or vehicle (1 or 3 mL). SETTING: All Israeli neurosurgical intensive care units (a total of six units). PATIENTS: Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure, cerebral perfusion pressure, blood pressure, and heart rate were measured continuously in the intensive care unit. Adverse medical events were recorded and clinical outcome was assessed by the Glasgow outcome scale throughout a 6-month follow-up period. A highly significant reduction in the percentage of time with intracranial pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm Hg was observed in the drug-treated group. The nature and incidence of adverse medical events were similar in the two groups. The percentage of patients achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14% higher in the drug-treated group at 3 and 6 months, respectively. Statistical analysis of these differences by a logistic model using dose, entry Glasgow coma scale score, and computed tomograph as covariates yielded p values for the effect of treatment of .03 and .14 at 3 and 6 months, respectively. CONCLUSIONS: Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.

Non-resectable slow-growing meningiomas treated by hydroxyurea.

PURPOSE: To test the benefit of hydroxyurea in the treatment of recurrent and non-resectable slow-growing meningiomas. METHODS: Twelve patients with regrowing non-malignant meningiomas, were enrolled for a protocol of 2 years with continuous chemotherapy with hydroxyurea, 20 mg/kg/day. Response to treatment was evaluated both clinically and by diagnostic imaging using computed tomography (CT) and 201-Thallium single photon emission CT. One minimal response was documented by CT, accompanied by clinical stabilization. Nine patients showed progressive disease, at least by one imaging procedure, with a median time to progression of 13 months (range 4-24). Two other patients were not available for response due to early removal from the study, following abrupt manifestation of grades 3-4 hematological toxicity. CONCLUSION: In this series hydroxyurea has not shown effectiveness in the treatment of non-resectable slow-growing meningiomas: neither for achieving response, nor for arresting disease progression.