The history of neurosurgery at the University of Rochester.

The Department of Neurosurgery at the University of Rochester has a long legacy of excellent patient care and innovation in the neurosciences. The department's founder, Dr. William Van Wagenen, was a direct pupil of Harvey Cushing and the first president of the Harvey Cushing Society. His successor, Dr. Frank P. Smith, was also a leader in organized neurosurgery and helped to permanently memorialize his mentor with an endowed fellowship that today is one of the most prestigious training awards in neurosurgery. The first 2 chiefs are honored every year by the department with memorial invited lectureships in their names. The department is home to a thriving multidisciplinary research program that fulfills the lifelong vision of its founder, Dr. Van Wagenen.

Perforation of the right cardiac ventricular wall by polymethylmethacrylate after lumbar kyphoplasty.

The authors report the case of a 74-year-old woman who underwent an L-2 vertebral kyphoplasty. The patient experienced delayed postoperative hemodynamic deterioration that may have been caused by embolization of polymethylmethacrylate (PMMA) cement through the right cardiac ventricular wall. Cardiac and pulmonary embolization of bone cement can develop as a complication of vertebral kyphoplasty. Surgeons should be alert to this potentially life-threatening condition when performing this increasingly popular form of spine procedure.

Stereotactic radiosurgery for glioblastoma: retrospective analysis.

PURPOSE: This retrospective study was done to better understand the conditions for which stereotactic radiosurgery (SRS) for glioblastoma may be efficacious. METHODS: Between 2000 and 2007, 33 patients with a pathological diagnosis of glioblastoma received SRS with the Novalis Shaped Beam Radiosurgery system. Eighteen patients (54%) underwent salvage SRS for recurrence while 15 (45%) patients received upfront SRS following standard fractionated RT for newly diagnosed glioblastoma. RESULTS: There were no RTOG grade >2 acute side effects. The median survival after SRS was 6.7 months (range 1.4 - 74.7). There was no significant difference in overall survival (from the time of initial diagnosis) with respect to the timing of SRS (p = 0.2). There was significantly better progression free survival in patients treated with SRS as consolidation versus at the time of recurrence (p = 0.04). The majority of patients failed within or at the margin of the SRS treatment volume (21/26 evaluable for recurrence). CONCLUSION: SRS is well tolerated in the treatment of glioblastoma. As there was no difference in survival whether SRS is delivered upfront or at recurrence, the treatment for each patient should be individualized. Future studies are needed to identify patients most likely to respond to SRS.

Increased STAT-3 and synchronous activation of Raf-1-MEK-1-MAPK, and phosphatidylinositol 3-Kinase-Akt-mTOR pathways in atypical and anaplastic meningiomas.

The intracellular events promoting meningioma cell proliferation in high grade tumors are not established. In this study we compared 45 WHO grade I and 35 grade II or III meningiomas by Western blot or immunohistochemistry for phosphorylation/activation of the MEK-1-MAPK, PI3 K-Akt-mTOR-PRAS40 and STAT3 pathways. By Western blot, STAT3 activation was detected in 75% of grade I compared to 100% of grade II and III meningiomas. By immunohistochemistry p-STAT3 was detected in 28% of grade I compared to 65 or 66% of grade II and III meningiomas, respectively. Phosphorylated MEK-1 and p-MAPK were activated in nearly all grade I, II and III tumors. Phosphorylated Akt was also detected in the majority of meningiomas of each grade although downstream pathway component activation was less widespread. These findings suggest that there is increased STAT3 activation in WHO grade II and III meningiomas compared with grade I tumors. Moreover, each of the three major growth regulatory pathways is concomitantly activated in higher grade meningiomas.

Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor.

Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.

Axial loading during MR imaging can influence treatment decision for symptomatic spinal stenosis.

BACKGROUND AND PURPOSE: Previous studies have shown that axial loading can narrow the spinal canal. However, the clinical significance is unclear. The purpose of this study was to determine whether the narrowing of the spinal canal with axial loading during MR imaging could influence treatment decision for spinal stenosis. METHODS: Two hundred patients with clinical symptoms of spinal stenosis underwent routine MR imaging and then immediately underwent axially loaded MR imaging. We selected 20 of these patients because they had narrowing of the spinal canal shown on the axially loaded images. Three experienced neurosurgeons evaluated these 20 patients based on clinical information and routine MR images. The same neurosurgeons were then asked for second treatment decisions based on the same clinical information but with axially loaded MR images. RESULTS: Axial loading during MR imaging of the lumbar spine can influence neurosurgeons in their treatment decisions for symptomatic spinal stenosis. For this selected group of patients, all three neurosurgeons changed their treatment decision from conservative management to decompressive surgery for five patients when shown the axially loaded MR images. For two other patients, two neurosurgeons changed their treatment decisions, and for three additional patients, one neurosurgeon changed his treatment decision, all based on the axially loaded MR images. Treatment was not changed from surgical to medical management for any of the patients when shown the axially loaded images. CONCLUSION: In selected patients with spinal stenosis and apparent narrowing of the spinal canal shown by axially loaded MR imaging, the additional information gained from this technique can influence experienced neurosurgeons in their treatment decisions.

Low-dose radiosurgery for benign intracranial lesions.

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.