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The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial.To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas.Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts.There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P.001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%).Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.

Determining the appropriate surgical indications for obtunded octogenarians with traumatic acute subdural hematoma (aSDH) has been challenging. We sought to determine which easily available data would be useful adjuncts to assist in early and quick decision-making.We performed a single-center, retrospective review of patients aged ≥80 years with confirmed traumatic aSDH who had undergone emergent surgery. The clinical measurements included the Karnofsky performance scale score, Charlson comorbidity index, Glasgow coma scale (GCS), and abbreviated injury score. The radiographic measurements included the Rotterdam computed tomography score, aSDH thickness, midline shift, and optic nerve sheath diameter (ONSD). The neurologic outcomes were defined using the extended Glasgow outcome scale-extended (GOS-E) at hospital discharge and 3-month follow-up. The Pearson correlation coefficient was used to compare the ONSD with all clinical, radiographic, and outcome variables. Multivariate logistic regression was used to assess the relationship between the discharge and 3-month GOS-E scores between all clinical and radiographic variables.A total of 17 patients met the inclusion criteria. The mean age was 82.5 ± 1.6 years (range, 80-85 years), and the mean GCS score was 11.2 ± 4.1 (range, 4-15). The mean discharge and 3-month GOS-E scores were 3.4 ± 2.6 (range, 1-8) and 2.3 ± 2.1 (range, 1-7), respectively. We found significant negative correlations between the ONSD and the GCS score (r = -0.62; P0.01) and the ONSD and discharge GOS-E score (r = -0.49; P = 0.05). Multivariate analysis revealed a significant association between the abbreviated injury score and the discharge GOS-E score (P = 0.05).Octogenarians sustaining aSDH and requiring emergent surgery have poor outcomes. More data are needed to determine whether the ONSD can be a useful adjunct tool to predict the efficacy of emergent surgery.

Gamma knife radiosurgery (GKRS) is often performed to treat brain metastases (BrMs). Widely referenced guidelines have suggested post-treatment imaging studies at 3-month intervals. However, clinicians frequently obtain magnetic resonance imaging (MRI) studies at3 months after GKRS.We performed a retrospective medical record review study to assess the utility of early (3 months) MRI after GKRS in patients with BrMs.A total of 415 GKRS procedures were performed. For 325 patients, early MRI studies were obtained. A total of 31 patients had new or worsened neurological symptoms. The early MRI studies showed adverse findings in 25 patients (78%), which in 23 (72%) had resulted in a change in treatment. For 294 patients, no new or worsened neurological symptoms were found on early MRI studies. Of these 294 patients, 86 (29%) had ≥1 adverse finding on MRI, and 60 (20%) had a change in management as a result. However, no rapidly growing tumors or other emergent adverse findings were seen.Early MRI (within 3 months) after post GKRS will frequently show adverse findings even in asymptomatic patients, more often in patients aged65 years and patients with multiple treated BrMs. However, according to the nature of the adverse findings observed in our retrospective study, it is unlikely that the clinical outcomes would have been affected if the post-GKRS MRI studies had been deferred to 3 months after treatment. Our data support deferring post-GKRS MRI to 3 months after treatment in the absence of new neurological signs or symptoms.

BACKGROUND Primary decompressive craniectomy (DC) is commonly performed for patients with traumatic brain injury (TBI). Some, but not all patients, will benefit from invasive monitoring of intracranial pressure (ICP) after surgery. We intended to identify risk factors for elevated ICP after primary DC to treat TBI. METHODS A retrospective chart review study identified all patients at our institution who underwent primary DC for TBI during the study period and who had ICP monitors placed at the time of surgery. Various preoperative and intraoperative variables were assessed for correlation with the presence of postoperative elevated ICP. RESULTS Postoperative elevated ICP occurred in 36% of patients after DC. In univariate analysis, Glasgow Coma Scale

The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas. This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits. There were 72 patients (22 males, mean age 59.53 years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5 months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits. Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up.

Background Delayed subdural fluid collections can occur after Ommaya reservoir placement and can cause neurological symptoms and interfere with treatment. We performed a retrospective chart review in order to study risk factors for delayed subdural fluid collections and clinical outcomes. Methods Retrospective chart review was performed for patients undergoing ommaya reservoir placement between 2010-2019 at our institution. Results Out of 53 patients who had Ommaya reservoir placement during the study period, 11 developed delayed subdural fluid collections (21%). HIV infection was the only statistically significant risk factor (p=0.001, Fisher exact test). Thrombocytopenia, ventricle size, use of the reservoir, and suboptimal catheter placement were not associated with development of delayed subdural fluid collections. 2 patients, both HIV positive, required surgical evacuation. Conclusions Delayed subdural fluid collections occur in a significant minority of patients after Ommaya reservoir placement, and some patients require surgical intervention. HIV infection is associated with a higher risk of development of delayed subdural fluid collections. This patient subpopulation may benefit from closer monitoring or adjustment of management protocols.

Patients who present with traumatic brain injury (TBI) combined with blunt cerebrovascular injuries (BCVI) are difficult to manage, in part because treatment for each entity may exacerbate the other. It is necessary to develop a treatment paradigm that ensures maximum benefit while mitigating the opposing risks. A cohort of 150 patients from 2015 to present, with either internal carotid artery (ICA) and/or vertebral artery (VA) dissections or pseudoaneurysms, was cross-referenced with those who had sustained TBI. Of the 38 patients identified with both TBI and BCVI, 25 suffered ICA injuries, 10 had VA injuries and 3 had combined ICA/VA injuries. Unilateral BCVI occurred in 30 patients, while 8 had bilateral BCVI. Two patients required surgical intervention for TBI, and 5 patients required endovascular intervention for BCVI. Positive emboli detection studies (EDS) on transcranial dopplers (TCD) were demonstrated in 19 patients, with 9 patients having radiographic evidence of stroke. Anti-platelet therapy was initiated in 32 patients, and anti-coagulation in 10 patients, without new or worsening intracranial hemorrhages (ICH). Overall, 76% of patients were able to be discharged home or to rehabilitation, with good recovery demonstrated in 73% of the patients who had appropriate follow-up. In the setting of concurrent TBI and BCVI, use of anti-platelet/coagulation to prevent stroke can be safe if monitored closely. Here we describe a treatment paradigm which weighs the risk and benefits of therapies based on severity of ICH and stroke prevention, which tended to result in good disposition and recovery.

Normal pressure hydrocephalus (NPH) is generally treated with ventriculoperitoneal shunts (VPS), with improved symptoms in the majority of patients. We performed a retrospective chart review study in order to describe patterns of, and risk factors for, delayed symptom progression after initially successful VPS placement. 69 consecutive patients underwent VPS placement for NPH, and were followed for a minimum of 12 months postoperatively. 55 patients (80%) had objective improvement in their NPH symptoms after surgery. Of these, 27 patients (49%) developed delayed deterioration of at least one of their NPH symptoms, at a mean of 28.3 months postoperatively (range, 3–77). 1 of the 27 patients was found to have shunt malfunction; 19 had specific clinical or imaging evidence of shunt function. 6/19 patients had transient improvement in their symptoms (lasting 30 days or more) after adjustment of their programmable shunt valves (32%), although symptoms in all of these patients later worsened. During a mean follow up period of 44.4 months (range, 15–87), 12 patients (44%) received other neurological diagnoses felt to at least partially explain their symptoms. Increased patient age was associated with likelihood of delayed symptom progression. We conclude that delayed symptom progression is common after VPS placement for NPH, including after initial symptom improvement; that symptom progression can often be temporarily palliated by shunt valve pressure adjustment; and that older patients are more likely to experience delayed symptom progression. We suggest that patients and their families be counselled accordingly before surgery.

Objective We sought to determine whether a set of simple criteria can identify patients in the neuroscience intensive care unit (NICU) at high risk of poor outcome and delivery of nonbeneficial care early in the course of their illness. Secondarily, factors affecting limitation of care protocols were assessed. Methods We prospectively identified patients who were admitted to the NICU with partial loss of brainstem reflexes persisting for >24 hours due to an intrinsic lesion of the brain (trauma, stroke, hemorrhage, etc.). Results The study included 102 patients. Seventy-two of them died after a mean of 16 days (median: 8 days), and 23 remained comatose, locked-in, or in a vegetative state. Four were conscious and following commands, while 3 were minimally conscious, episodically obeying simple commands. Three out of 4 conscious patients were young males with traumatic brain injuries. Patients who remained full code spent a mean of 22.2 days in the NICU, compared with 10.4 for those who had withdrawal of care (P = 0.022) and 11.9 for patients who received a do-not-resuscitate order (P = 0.045). Time to death did not differ significantly between the groups. Overall, institution of various limitations of care protocols correlated positively with older age (odds ratio [OR] = 1.07, P = 0.0008), being treated on the neurology service (OR = 4.4, P = 0.043), and having health insurance (OR = 5.4, P = 0.03). Conclusions We identified simple criteria that can be used to identify patients in the NICU setting for whom continued aggressive care is likely nonbeneficial. Our analysis revealed demographic, social, and economic factors correlating with proxies' willingness to consider limitation of care.

Object The aim of this study is to identify pre-operative clinical and/or radiological predictors of clinical failure of decompressive hemicraniectomy (DH) in the setting of malignant hemispheric infarction. These predictors could guide the decision for adjunctive internal brain decompression (e.g. strokectomy) at the time of the initial DH. Methods Retrospective chart review of all patients with malignant hemispheric infarction who underwent DH at our institution, from November 2008 to January 2013. Demographics, pre- and post-operative clinical characteristics and neuroimaging data were reviewed. The surgical outcome after DH was evaluated and clinical failure was defined as follows: lack of post-operative resolution of basal cistern effacement, and/or failure to achieve a post-operative decrease in midline shift by at least 50%, and/or post-operative neurological deterioration felt to be due to persistent mass effect, with or without a second, salvage operation (strokectomy). Results Out of 26 patients included in the study, 7 were considered to have clinical failure of their DH. Preoperative clinical and imaging variables were similar in the two groups, except that the presence of a nonreactive pupil immediately before surgery was associated clinical failure of the DH (p = 0.0015). Patients in the clinical failure group had a lower postoperative GCS motor score and a strong but not statistically significant trend towards less favorable functional outcome (GOS 1–3). Conclusions The presence of a nonreactive pupil before surgery is associated with clinical failure of DH, and should be taken into account when deciding whether to perform strokectomy at the time of DH.

Objective Diagnosing tumor progression and pseudoprogression remains challenging for many clinicians. Accurate recognition of these findings remains paramount given necessity of prompt treatment. However, no consensus has been reached on the optimal technique to discriminate tumor progression. We sought to investigate the role of magnetic resonance perfusion (MRP) to evaluate tumor progression in glioma patients. Methods An institutional retrospective review of glioma patients undergoing MRP with concurrent clinical follow up visit was performed. MRP was evaluated in its ability to predict tumor progression, defined clinically or radiographically, at concurrent clinical visit and at follow up visit. The data was then analyzed based on glioma grade and subtype. Resusts A total of 337 scans and associated clinical visits were reviewed from 64 patients. Sensitivity, specificity, positive and negative predictive value were reported for each tumor subtype and grade. The sensitivity and specificity for high-grade glioma were 60.8% and 87.8% respectively, compared to low-grade glioma which were 85.7% and 89.0% respectively. The value of MRP to assess future tumor progression within 90 days was 46.9% (sensitivity) and 85.0% (specificity). Conclusion Based on our retrospective review, we concluded that adjunct imaging modalities such as MRP are necessary to help diagnose clinical disease progression. However, there is no clear role for stand-alone surveillance MRP imaging in glioma patients especially to predict future tumor progression. It is best used as an adjunctive measure in patients in whom progression is suspected either clinically or radiographically.

Little is known regarding the neurocognitive impact of temporal lobe tumor resection. To clarify subacute surgery-related changes in neurocognitive functioning (NCF) in patients with left (LTL) and right (RTL) temporal lobe glioma. Patients with glioma in the LTL (n = 45) or RTL (n = 19) completed comprehensive pre- and postsurgical neuropsychological assessments. NCF was analyzed with 2-way mixed design repeated-measures analysis of variance, with hemisphere (LTL or RTL) as an independent between-subjects factor and pre- and postoperative NCF as a within-subjects factor. About 60% of patients with LTL glioma and 40% with RTL lesions exhibited significant worsening on at least 1 NCF test. Domains most commonly impacted included verbal memory and executive functioning. Patients with LTL tumor showed greater decline than patients with RTL tumor on verbal memory and confrontation naming tests. Nonetheless, over one-third of patients with RTL lesions also showed verbal memory decline. In patients with temporal lobe glioma, NCF decline in the subacute postoperative period is common. As expected, patients with LTL tumor show more frequent and severe decline than patients with RTL tumor, particularly on verbally mediated measures. However, a considerable proportion of patients with RTL tumor also exhibit decline across various domains, even those typically associated with left hemisphere structures, such as verbal memory. While patients with RTL lesions may show even greater decline in visuospatial memory, this domain was not assessed. Nonetheless, neuropsychological assessment can identify acquired deficits and help facilitate early intervention in patients with temporal lobe glioma. ANOVA, analyses of varianceCOWA, Controlled Oral Word AssociationCTB Comp, Clinical Trial Battery CompositeFLAIR, fluid-attenuated inversion recoveryHVLT-R, Hopkins Verbal Learning Test-RevisedHVLT-R DR, HVLT-R delayed recallHVLT-R Rec, HVLT-R delayed recognitionHVLT-R TR, HVLT-R total recallLTL, left temporal lobeNCF, neurocognitive functioningRTL, right temporal lobeSD, standard deviationTMTA, Trail Making Test Part ATMTB, Trail Making Test Part B.

Object. In this paper the authors describe the indications for and the results and complications of repeated transsphenoidal surgery (RTSS) to treat recurrent or residual pituitary adenoma. Methods. A retrospective review was conducted of 96 consecutive patients who underwent RTSS to treat recurrent or residual pituitary adenoma. Ninety-six patients underwent RTSS: 42 to treat a recurrent or residual pituitary mass and 54 to treat a recurrent or persistent hormone hypersecretion. There was no case of perioperative death and there was a 1% incidence of major complications. Postoperative endocrinological deficiencies were uncommon unless planned total hypophysectomy was performed to treat Cushing disease. Clinical remission occurred in 93% of patients undergoing RTSS to treat a tumor mass, and 15% of patients initially experienced remission only to face a relapse after a mean of 32 months. Endocrinological remission occurred in 57% of patients undergoing RTSS to treat hormone hypersecretion; most of these patients had Cushing disease. Thirty-five percent of patients with an initial endocrinological remission experienced a relapse of their symptoms after a mean of 31 months (thus, 37% of patients achieved sustained endocrinological remission). We failed to identify factors that accurately predicted initial symptom remission or delayed relapse following RTSS. Ten patients in our series eventually underwent a third transsphenoidal surgery without major complications. Conclusions. Repeated transsphenoidal surgery is a more effective treatment for recurrent or residual mass than it is for hormone hypersecretion and has acceptable rates of morbidity and mortality. If hypophysectomy is not performed, endocrinological deficiencies are unlikely following RTSS.

Object. The aim of this study was to identify the optimal surgical goals and techniques for managing symptomatic Rathke cleft cysts (RCCs). Methods. The authors conducted a retrospective study of 62 consecutive patients who had undergone surgery for RCCs. Postoperative follow up was a mean of 28 months. Fifty-six patients underwent transsphenoidal cyst decompression and biopsy procedures, and six underwent cyst wall resection. Postoperatively, symptoms improved in 91% of patients with headaches and 92% of patients with visual deficits. Decompression and biopsy were associated with a 10% incidence of new anterior pituitary hormone deficiencies and a 6% incidence of new permanent diabetes insipidus; the incidence of new hormone deficiencies was significantly higher in the few patients who had undergone cyst wall resection. The incidence of relapse, defined as cyst regrowth with either recurrent symptoms or chiasmal compression, was 16%. Resection of the cyst wall was associated with a trend toward a decreased risk of relapse. Sellar packing, sellar floor reconstruction, and irrigation with absolute ethanol did not affect the likelihood of relapse. Squamous metaplasia and inflammation increased the risk of relapse. Residual cyst demonstrated on postoperative magnetic resonance imaging was associated with an increased risk of subsequent asymptomatic cyst regrowth. Seven patients (11%) underwent repeated operation with symptomatic improvement and minimal morbidity; only one patient relapsed following a second surgery. Conclusions. Decompression and biopsy procedures in the treatment of RCCs lead to improvement in signs and symptoms, with low morbidity rates. Repeated operations will be required in as many as 16% of patients but are also associated with symptomatic improvement, low morbidity, and durable remission. Decompression and biopsy may represent the optimal surgical management of RCC.

Neurosurgeons are often involved in the care of patients with cerebral venous sinus thrombosis (CVST). Medical management of CVST includes appropriate diagnostic imaging studies, evaluation for potentially treatable causes of thrombosis, and control of increased intracranial pressure with m

Object Frameless image-guided stereotaxy is often used in the resection of high-grade gliomas. The authors of several studies, however, have suggested that brain shift may occur intraoperatively and result in inaccurate resection. To determine the usefulness of frameless stereotactic image-guided surgery of high-grade gliomas, the authors correlated factors predictive of brain shift, such as tumor size, periventricular location, and patient age (as an indicator of brain atrophy) with the extent of resection. Methods Inclusion criteria included the following: 1) stereotactic volumetric craniotomy for resection of tumor; 2) histologically proven high-grade glioma; 3) preoperative magnetic resonance (MR) imaging demonstration of an enhancing portion of tumor; 4) postoperative MR imaging within 48 hours to assess the extent of resection; and 5) preoperative intention to perform gross-total resection of the enhancing tumor. Fifty-four patients met these criteria between September 1997 and November 2002. Accurate resection was considered to be indicated by a lack of nodular enhancement on postoperative Gd-enhanced MR images obtained within 48 hours of surgery. Frameless stereotactic image-guided surgery resulted in the successful resection of 46 (85%) of 54 high-grade gliomas. Accurate resection was significantly more likely with tumors less than 30 ml in volume than with those greater than 30 ml (93 and 58%, respectively [p < 0.05]). In addition, small periventricular tumors were associated with significant less successful resection compared with nonperiventricular tumor (77 and 96%, respectively [p = 0.5]). Patient age did not affect the likelihood of successful resection. Conclusions Frameless image-guided stereotactic techniques can be reliably used for accurate resection of high-grade gliomas when the tumor is less than 30 ml in volume and not adjacent to the ventricular system. In cases involving tumors larger in volume or located near the ventricles, intraoperative ultrasonography or MR imaging updates should be considered.

Magnetic resonance imaging (MRI) or computerized tomography (CT) is routinely performed after resection of brain metastases (BrM), regardless of whether there are specific clinical concerns about residual tumor or potential complications. Routine imaging studies contribute a significant amount to the cost of medical care, and their yield and utility are unknown. An IRB-approved retrospective chart review study was performed to analyze all craniotomies for BrM performed at our institution from 2005 to 2012. Descriptive statistics were used to quantify the yield of postoperative imaging. 218 consecutive patients underwent 226 craniotomies for BrM. In 21 cases, new or worsened neurologic deficits occurred after surgery (9.0 %), and 19 of the 21 underwent postoperative imaging. 9 of the 19 patients (47 %) had significant findings on postoperative imaging, and 2 patients required reoperation. 201 patients had no new neurologic deficits (91 %), and 23 of these patients had no postoperative imaging. Of the 178 remaining patients, 160 underwent postoperative MRI and 18 underwent postoperative CT. 9 patients (5.1 %) had unexpected adverse imaging findings; 6 had small stroke, 1 had a subdural hemorrhage and 2 had possible or definite venous sinus occlusion. None of the imaging findings led to changes in management. 182 patients underwent imaging appropriate to detect residual tumor (177 gadolinium enhanced MRI and 5 contrast enhanced CT). Of these patients, 16 were known to have small residual tumors based on intraoperative findings. Of the remaining 166 patients felt to have had gross total tumor resection, 9 (5.4 %) were found to have a small amount of residual tumor on postoperative imaging; no patient had a change in treatment plan as a result. Routine postoperative imaging in patients undergoing craniotomy for BrM has a very low yield and may not be appropriate in the absence of new neurologic deficits, or specific clinical concerns about large amounts of residual tumor or intraoperative complications.

Surgical evacuation of nontraumatic, supratentorial intracerebral hemorrhage (SICH) is uncommonly performed, and outcomes are generally poor. On the basis of published experimental data and the authors' anecdotal observations, a retrospective chart review study was performed to test the hypothesis that large decompressive craniectomies (DCs), compared with craniotomies, would improve clinical outcomes after surgical evacuation of SICH. For patients with putaminal SICH, DC was associated with a statistically significant improvement in midline shift, compared with craniotomy. Decompressive craniectomies also resulted in a strong trend toward decreased likelihood of poor neurological outcome (modified Rankin Scale score > 3). For patients with lobar SICH, no associations were found between DC or craniotomy and clinical outcomes. For patients selected to undergo surgical evacuation of putaminal SICH, a DC in addition to surgical evacuation of the hematoma might improve outcome.

Objectives Our practice has transitioned from using fat autograft to acellular dermal matrix (AlloDerm, LifeCell Corp, Woodlands, Texas, USA). We present the largest series to our knowledge of AlloDerm for sellar floor repair after transsphenoidal approach to pituitary adenoma and compare rates of postoperative cerebrospinal fluid (CSF) leak with an earlier cohort of patients whose CSF leaks were repaired with fat autograft. Design This is a retrospective cohort study comparing sellar repair with fat autograft versus inlay Alloderm between the years 2003 and 2012. The primary end point was postoperative CSF leak. Results A total of 429 patients (368 primary; 83 revision operations) without intraoperative lumbar drainage were included. A total of 18 postoperative CSF leaks were observed (3.9%). Intraoperative CSF leak occurred in 160 cases (35.5%). Among this subset of patients with intraoperative CSF leak, 95 underwent repair with AlloDerm and 46 underwent repair with fat autograft, with postoperative CSF leak rates of 8.4% and 15.2%, respectively (p = 0.34, chi-square test); 19 patients underwent repair with other techniques or no repair at all, with postoperative leak rate of 0%. Conclusions AlloDerm is an effective alternative to fat autograft in cases of low-flow CSF leak following transsphenoidal resection of pituitary adenoma.

Background/Aims: A significant minority of stereotactic biopsies (SBs) of brain lesions is nondiagnostic, yet there are no optimal strategies for preventing nondiagnostic SB (NDSB) and for managing patients after NDSB. We performed this study in order to identify risk factors for NDSB, to determine how diagnoses are eventually reached in these patients, and to ascertain whether NDSB affects clinical outcomes. Methods: Retrospective chart review of patients at our institution who underwent SB of brain lesions. Results: Twenty-four out of 100 SBs were nondiagnostic. NDSB was less likely in contrast-enhancing brain lesions in immunocompetent patients, with larger lesions and in the setting of diagnostic findings on intraoperative frozen section analysis. Of 16 patients with adequate postoperative follow-up, a diagnosis was eventually reached in 11, via further review of the pathology, retrieval of additional tissue specimens or additional noninvasive testing. Survival times for patients with NDSB and eventual tumor diagnoses were within expected ranges for patients with similar tumors. Three of the 5 patients who never received a final diagnosis enjoyed prolonged survival without progressive symptoms. Conclusions: Surgeons should consider taking additional specimens in the case of nondiagnostic intraoperative frozen section during SB. If a tumor is suspected and final pathology is nondiagnostic, outside review of the slides may be helpful, and sampling further tissue should be considered. For diseases other than tumors, the diagnosis will generally be made without a repeat biopsy. The delays in diagnosis resulting from NDSB do not appear to affect survival, at least in patients eventually found to have brain tumors.

The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations.Charts of MEN 2A patients enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were reviewed retrospectively. Statistical analysis was performed using SAS software (SAS Institute, Inc, Cary, NC).RET mutation data and pheochromocytoma data were compiled for 323 patients. Overall, penetrance of pheochromocytoma occurred in 102 of 323 patients (32%). Bilateral pheochromocytomas were observed in 67 patients (66%). The following codon-specific expression of pheochromocytoma was observed: 1 of 24 patients expressed codon 609 (4%), 0 of 5 patients expressed codon 611 (0%), 23 of 105 patients expressed codon 618 (22%), 4 of 45 patients expressed codon 620 (9%), and 74 of 149 patients expressed codon 634 (50%) (P.001). An association between pheochromocytoma expression and amino acid substitutions at codon 618 was observed as follows: 0 of 7 patients with C618F, 5 of 21 patients with C618G (24%), 11 of 27 patients with C618R (41%), 7 of 41 patients with C618S (17%), and 0 of 9 patients with C618Y (P = .04.) In our cohort, no deaths were attributable to PC with a median follow-up of 9 years.The penetrance of PC varies between MEN 2A RET codon mutations. Furthermore, we observed variable expression with different amino acid substitutions at the same codon. These results may help guide screening and therapy for MEN 2A patients.

Object For gene therapy strategies currently in clinical trials, viral vectors are used to deliver transgenes directly to normal and tumor cells within the central nervous system (CNS). The use of viral vectors is limited by several factors. The aim of this study was to assess whether embryonic stem cell (ESC)–derived astrocytes expressing a doxycycline-inducible transgene can be used as a vector for gene therapy. Methods The authors generated a pure population of ESC-derived astrocytes carrying a transgene, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), inserted in the chromosome under the control of a highly regulated doxycycline-inducible expression system. Fully differentiated ESC-derived astrocytes were stereotactically transplanted in the mouse brain, and then cell migration and transgene expression were studied. Results The ESC-derived astrocytes started to migrate from the transplant site 48 hours after the procedure. They were found to have migrated throughout the brain tissue by 6 weeks. Transplanted ESC-derived astrocytes expressed the TRAIL transgene after doxycycline induction throughout the duration of the experiment. Teratoma formation was not observed in long-term experiments (12 weeks). Conclusions These data show that ESC-derived astrocytes can be used as delivery vectors for CNS tumors. This technique might have a major impact on the treatment of patients with malignant gliomas and a wide spectrum of other neurological diseases.

Background Despite near complete penetrance and frequent early evaluation of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia 2 (MEN 2) variants, a significant minority of patients are evaluated later in life. Methods With the aim of characterizing the expression of hereditary MTC in an older cohort, MEN 2 patients from our institutional database who were evaluated after age 50 years were identified, and clinical data were reviewed. Results Thirty-nine patients (36 MEN 2A, 3 FMTC, and no MEN 2B) who were evaluated after age 50 years were identified; they represented 9% of all MEN 2 patients who were enrolled in our program. Most of the patients (79%) had abnormal screening examinations, and the AJCC staging was significantly higher in this cohort compared with younger patients. Overall, 43% of the patients had normal calcitonin levels after operation. There were 3 observed MTC-related deaths, all from distant metastases; the overall survival rate was 86% at 5 years and 74% at 10 years. The distribution of RET mutations in this cohort was similar to younger patients. Conclusions These results suggest the presence of modifiers of MTC expression. Despite the tendency of older patients with hereditary MTC to have advanced stage disease at evaluation, they have high rates of biochemical cure, and the overall survival is excellent.

Background Intraoperative brain shift may cause inaccuracy of stereotactic image guidance on the basis of preoperatively acquired imaging data. The purpose of our study was to determine whether factors predicting brain shift affect the success of image-guided resection of malignant brain tumors. Methods We retrospectively studied 54 patients who underwent image-guided resections of histopathologically confirmed malignant brain tumors (9 metastases, 45 high-grade gliomas). Precautions were taken during surgery to minimize brain shift, but intraoperative imaging was not performed. The following factors predictive of intraoperative brain shift were assessed: tumor size, periventricular location, patient age, prior surgery or radiation therapy, patient positioning, use of mannitol, and length of operative time. Postoperative magnetic resonance imaging was obtained in all cases within 48 hours of surgery to assess extent of resection. Results Perioperative mortality was 0% in our series; perioperative morbidity was 3 of 54 patients (5.5%); 1 patient required reoperation for a hematoma, and 2 had transient neurological deficits. Successful resection was accomplished in 93% of tumors less than 30 cm 3 compared with 63.6% of tumors greater than 30 cm 3 ( P = .026, Fisher exact test). This difference was more pronounced for patients with malignant gliomas. However, other factors predictive of intraoperative brain shift were not associated with unsuccessful resection. Conclusions Intraoperative brain shift does not significantly affect the likelihood of successful resection of malignant brain tumors smaller than 30 cm 3 . Larger tumors are less likely to be successfully resected, although factors other than brain shift can contribute to unsuccessful resection.

SUMMARY Respiratory changes following transurethral resection of the prostate were studied in 26 men. Right-to-left pulmonary shunt determinations were made in ten patients, and total lung volume and weight determinations were made in the remainder. Nine of ten showed postoperative decrease in pulmonary shunt. The tenth showed no change. Total lung volume, functional residual capacity, inspiratory capacity, and body weight measurements showed no consistent change after transurethral resection. The significance of a large right-to-left shunt preoperatively, and its apparent decrease after surgery are discussed.