Rod J. Oskouian

Incidence of symptomatic hemorrhage after stereotactic electrode placement

OBJECT Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition. METHODS Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits. RESULTS The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home. CONCLUSIONS The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases.

OBJECT This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis. METHODS A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2-115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75-35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery. RESULTS The mean radiographic follow-up duration was 14 months (median 10 months, range 4-37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p=0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p=0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40-100). CONCLUSION Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Stereotactic radiosurgery for pituitary adenomas: a review of the literature.

AbstractObjective: Pituitary adenomas are very common neoplasms and represent between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research is to define accurately the efficacy, safety, and role of radiosurgery for treatment of pituitary adenomas. Methods: Medical literature databases from 1965 to 2003 were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was evaluated for the number of patients, radiosurgical parameters (e.g. tumor margin dose), length of follow-up, tumor growth control rate, complications, and rate of hormonal normalization in the case of functioning adenomas. Results: A total of 34 published studies including 1567 patients were reviewed. Radiosurgery offers a tumor growth control rate of ead differences in endocrinological criteria utilized for post-radiosurgical assessment. Thus far, the risks of radiation induced neoplasia and cerebral vasculopathy associated with radiosurgery appear to be lower than for fractionated radiation therapy. The incidence of other serious complications following radiosurgery is quite low. Conclusions: Although surgical resection typically is the primary treatment modality, stereotactic radiosurgery offers safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Refinements in the radiosurgical technique will likely lead to improved outcomes.

Radiographic restoration of lumbar alignment after transforaminal lumbar interbody fusion.

OBJECTIVERestoration of lumbar lordosis is a critical factor in long-term success after lumbar fusions. Transforaminal lumbar interbody fusion (TLIF) is a popular surgical technique in the lumbar spine, but few data exist on change in spinal alignment after the procedure. METHODSEighty patients who underwent TLIF surgery were retrospectively reviewed (minimum follow-up period, 2 years). Standing x-rays were assessed for changes in focal and segmental kyphosis, and restoration of lumbar lordosis. Improvement in spondylolisthesis, sagittal balance, and scoliosis were also assessed. Fusion was assessed as well. RESULTSEighty operations were performed at 107 levels. Mean presenting lumbar Cobb angle measurement (L1–S1) was 36.3 ± 4.5 degrees (range, 12–77 degrees). Forty patients (50%) had sagittal imbalance. Mean postoperative Cobb angle (L1–S1) was 55.1 ± 6.6. Thirty-three of 36 patients with segmental kyphosis (92%) had restoration of lordosis. Improvement in alignment was most prominent at the surgical level (mean increase in lordosis, 20.2 ± 4.2 degrees). The improvement in lumbar lordosis among patients undergoing multilevel TLIFs (27.3 ± 3.4 degrees) was significantly higher compared with patients undergoing single-level operations (17.4 ± 4.4) (Students t test, P = 0.0004). Thirty of the 40 patients with sagittal imbalance (75%) achieved immediate restoration of normal sagittal balance. The ability to restore normal sagittal balance was correlated with a sagittal imbalance of less than 10 cm (P = 0.0001). Spondylolisthesis was completely corrected at the TLIF site in 90 of 99 levels (91%). Three patients (4%) required reoperation, 2 for implant disengagement and 1 for worsening kyphoscoliosis above the original surgical levels. Two of the 80 patients had pseudoarthrosis; hence, the rate of pseudoarthrosis was 2.5%. CONCLUSIONThe TLIF operation is highly effective in improving spinal alignment in patients with degenerative spinal disorders when the appropriate surgical technique is implemented.

Mouse spinal cord compression injury is reduced by either activation of the adenosine A2A receptor on bone marrow–derived cells or deletion of the A2A receptor on non-bone marrow–derived cells

Activation of the adenosine A(2A) receptor (A(2A)R) at the time of reperfusion has been shown to reduce ischemia-reperfusion injury in peripheral tissues and spinal cord. In this study we show that treating mice with the A(2A)R agonist, 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester for four days beginning before or just after the onset of reperfusion after compression-induced spinal cord injury rapidly (within 1 day) and persistently (>42 days) reduces locomotor dysfunction and spinal cord demyelination. Protection is abolished in knockout/wild type bone marrow chimera mice selectively lacking the A(2A)R only on bone marrow-derived cells but retaining receptors on other tissues including blood vessels. Paradoxically, reduced spinal cord injury is also noted in A(2A)R -/- mice, and in wild type/knockout bone marrow chimera mice selectively lacking the A(2A)R on non-bone marrow-derived cells, or in mice treated with the A(2A) antagonist, 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol. The greatest protection is seen in knockout/wild type bone marrow chimera mice treated with 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester, i.e. by activating the A(2A)R in mice expressing the receptor only in bone marrow-derived cells. The data suggest that inflammatory bone marrow-derived cells are the primary targets of A(2A) agonist-mediated protection. We conclude that A(2A) agonists or other interventions that inhibit inflammation during and after spinal cord ischemia may be effective in reducing spinal cord injury in patients, but excessive or prolonged stimulation of the A(2A)R may be counterproductive. It may be possible to devise strategies to produce optimal spinal cord protection by exploiting temporal differences in A(2A)R-mediated responses.

Endovascular management of unruptured intracranial aneurysms

Endovascular coil embolisation is increasingly used to treat unruptured intracranial aneurysms (UIA). Endovascular coil embolisation of UIA is associated with a 5–10% risk of morbidity and nearly zero mortality from the procedure. Complete or near complete occlusion is usually achieved in >90% of cases, and endovascular therapy seems to reduce the risk of future rupture significantly. Specific selection criteria for endovascular embolisation and novel approaches to endovascular treatment of aneurysms are discussed. Endovascular therapy appears to be a safe and effective treatment for selected UIA. Treatment failure rates will probably decrease with greater experience and advances in techniques and devices. Further study with long term follow up, however, is still necessary to characterise the efficacy, durability, and cost efficiency of endovascular treatment of UIA.

Endoscopic thoracic microdiscectomy

OBJECT The purpose of this investigation was to evaluate surgical and neurological outcomes in thoracic disc surgery in a prospective fashion. METHODS Quantifiable outcome data such as operating time, blood loss, duration of chest tube drainage, narcotic drug use, length of hospital stay (LOS), and long-term follow up of neurological function and pain-related symptoms were collected prospectively. In patients with myelopathy there was an improvement of two Frankel grades in the thoracoscopic discectomy group and one Frankel grade in the patients treated with thoracotomy; however, patients in the thoracotomy group were significantly worse preoperatively. None of the patients experienced worsened pain, and pain related to radiculopathy was improved by 75% in the thoracoscopic group. CONCLUSIONS Thoracoscopic discectomy yields acceptable surgical results and has several distinct advantages, with reduced postoperative pain, morbidity, and LOS.

Vascular injury and transsphenoidal surgery.

Vascular complications can and do arise from transsphenoidal surgery and, when they occur, they have a high incidence of mortality and serious morbidity. The anatomic substrate for such complications is discussed, along with technical aspects of surgery and other methods for the avoidance of vascular complications.

Cell cycle times of short-term cultures of brain cancers as predictors of survival.

Tumour cytokinetics estimated in vivo as potential doubling times (Tpot values) have been found to range in a variety of human cancers from 2 days to several weeks and are often related to clinical outcome. We have previously developed a method to estimate culture cycle times of short-term cultures of surgical material for several tumour types and found, surprisingly, that their range was similar to that reported for Tpot values. As Tpot is recognised as important prognostic variable in cancer, we wished to determine whether culture cycle times had clinical significance. Brain tumour material obtained at surgery from 70 patients with glioblastoma, medulloblastoma, astrocytoma, oligodendroglioma and metastatic melanoma was cultured for 7 days on 96-well plates, coated with agarose to prevent proliferation of fibroblasts. Culture cycle times were estimated from relative 3H-thymidine incorporation in the presence and absence of cell division. Patients were divided into two groups on the basis of culture cycle times of ⩽10 days and >10 days and patient survival was compared. For patients with brain cancers of all types, median survival for the ⩽10-day and >10-day groups were 5.1 and 12.5 months, respectively (P=0.0009). For 42 patients with glioblastoma, the corresponding values were 6.5 and 9.0 months, respectively (P=0.03). Lower grade gliomas had longer median culture cycle times (16 days) than those of medulloblastomas (9.9 days), glioblastomas (9.8 days) or melanomas (6.7 days). We conclude that culture cycle times determined using short-term cultures of surgical material from brain tumours correlate with patient survival. Tumour cells thus appear to preserve important cytokinetic characteristics when transferred to culture.

Molecular Biology of Unreresectable Meningiomas: Implications for New Treatments and Review of the Literature

Even though meningiomas are most often benign tumors, they can be locally invasive and can develop in locations that prevent surgical treatment. The molecular and biologic factors underlying meningioma development are only now beginning to be understood. Genetic factors such as mutations in the neurofibromatosis-2 gene and in chromosomes 1, 9, and 10 play important roles in meningioma development and may be responsible for atypical tumors in some cases. Cellular factors such as telomerase activation and tyrosine kinase receptor mutations may also play an important role. Finally, autocrine and paracrine factors including epidermal growth factor receptor, platelet-derived growth factor-1, and fibroblast growth factor have been implicated in the development of some tumors. Although the relationship between the various factors implicated in tumor development is unknown, understanding these factors will be critical in the treatment of malignant or surgically inaccessible tumors.