Development of an adjustable patient-specific rigid guide to improve the accuracy of external ventricular catheter placement.

OBJECTIVE: The most common method for external ventricular drain (EVD) placement is the freehand approach, which has reported inaccuracy rates of 12.3%-44.9%, especially in the case of altered ventricular anatomy. Current assistive devices require added time or equipment or do not account for shifted ventricles. To improve the accuracy of emergent EVD placement in the setting of altered ventricular anatomy, the authors designed a patient-specific EVD (PS-EVD) guide. METHODS: The PS-EVD guide has a tripod base and a series of differently angled inserts that lock in place at multiple rotational positions, allowing for numerous insertion angles. For testing, the authors designed a 3D-printed phantom skull with a gelatin brain analog containing ventricles simulating normal and altered ventricular anatomy. Low-resolution CT scans of the phantom were used to calculate the insertion angle in relation to the standard perpendicular entry. The corresponding insert at the correct rotational position within the base unit was positioned over the entry point on the phantom, and the catheter was inserted. Accuracy was evaluated with repeat CT scans. RESULTS: With normal ventricular anatomy, as well as abnormally shifted ventricles, proper use of the PS-EVD guide led to accurate catheter insertion into the ventricle in trials, as confirmed on coronal and sagittal CT images, including cases in which a perpendicular trajectory, such as with the Ghajar guide, was insufficient. CONCLUSIONS: The PS-EVD guide allows consistent and accurate EVD placement in phantom skulls with both normal and altered ventricular anatomy. Further trials comparing this device to the freehand approach are required.

Dear Program Director: An Evaluation of Implicit Bias in Letters of Recommendation for Neurosurgery Residency.

BACKGROUND AND OBJECTIVES: Despite comprising half of medical students, women represent only 29.6% of neurosurgery applicants and 17% of residents, suggesting a "leak" in the career pipeline for women neurosurgeons. Surveys persistently show that neurosurgery programs identify United States Medical Licensing Examination (USMLE®) Step 1 score and letters of recommendation (LORs) as the most important factors in selecting applicants to interview. A previous study in neurosurgery found no differences in LORs. However, multiple studies in other specialties have demonstrated implicit gender bias in LORs, which may influence resident selection. Our objective is to evaluate neurosurgery residency LORs for evidence of implicit gender bias. METHODS: Retrospective analysis of LORs for interviewed neurosurgery applicants at a single institution during the 2014 to 2020 National Residency Matching Program (NRMP®) match cycles. Letters were evaluated using Linguistic Inquiry & Word Count (LIWC) software (Pennebaker Conglomerates), and additional applicant data were obtained from candidate applications. LIWC (Pennebaker Conglomerates) output data included custom dictionary categories and terms that were analyzed using Prism 10 and Rstudio. RESULTS: Two hundred eighteen applications were reviewed for a total of 827 letters. LIWC (Pennebaker Conglomerates) analysis showed significant differences in word count (331 vs 297, difference = 34, 95% CI: 9-61, P = .008). LORs for applicants who were men were more likely to mention Alpha Omega Alpha Honor Medical Society (1.17 vs 0.778, difference = 0.4, 95% CI: 0.13-0.67, P = .023). USMLE® Step 1 scores were significantly lower for women (241 vs 247, difference = 6, 95% CI: 2-10, P = .004). There was no significant difference between letters for men and women for all categories evaluated in the linguistic evaluation. CONCLUSION: LORs are vital to the neurosurgical residency application process. The data exhibit some differences between the men and women applicants but few differences in their LORs, consistent with the results of the previous neurosurgical study.

A Vascular Quartet: Scalp Arteriovenous Malformation, Sinus Pericranii, Dural Arteriovenous Fistula, and Arteriovenous Brain Malformation in a Single Patient.

We present a case of a 51-year-old female who presented for evaluation of a large scalp mass found to have a different quartet of vascular malformations- a persistent scalp arteriovenous malformation (sAVM) with sinus pericranii, an inoperable intracranial SM-V brain arteriovenous malformation (bAVM), and a Cognard I dural arteriovenous fistula (dAVF). This is the first reported instance with four distinct vascular pathologies. We review the etiologies of multiple vascular abnormalities in the cerebral circulation that could contribute to this patient's findings and review strategies for treatment. We conducted a retrospective review of the clinical and angiographic records for a single adult female patient, including a management approach and an in-depth literature review. Given the high baseline vascularity of these complex lesions, surgery was not considered the initial therapy. We focused primarily on the sAVM with a staged embolization involving both transarterial and transvenous approaches. Transarterial coil embolizes 5 feeding artery branches of the right external carotid artery, followed by transvenous coil embolization into the common venous pouch accessed through the transosseous sinus pericranii via the SSS, dramatically reduced the size and filling of the large sAVM and eliminated a significant source of hypertensive venous outflow. Serial endovascular treatments of her sAVM led to a significant reduction in size and pulsatility, and the pain from tenderness to palpation was concurrently decreased. Despite multiple treatments, serial angiographic evaluations of her scalp lesion showed continued new development of collaterals. Ultimately the patient elected to forego further treatment for her sAVM. To our knowledge, there has not been another report of a single adult patient with a quartet of vascular malformations in the literature. Treatment paradigms for sAVMs are limited to case reports and small series; however, we purport that the most successful therapeutic approaches are multimodal and likely should incorporate surgical resection when feasible. We emphasize the caution required for patients with multiple other underlying intracranial vascular malformations. The altered intracranial flow dynamics can drastically hinder the success of a unimodal approach involving endovascular therapy alone.

Transcondylar Approach for Resection of Medullary Cavernous Malformation: 2-Dimensional Operative Video.

Cavernous malformations located within the brainstem present with a high rate of neurological symptoms and carry a more aggressive course in both pediatric and adult populations.1,2 Cavernomas within the medulla are the rarest form, representing only 5% of all brainstem lesions.3 Repeated hemorrhage of brainstem cavernomas is associated with significant and cumulative neurological deficits and thus requires treatment.4 Microsurgical resection has become the optimal mode of treatment with the aim of resecting the live malformation and not merely the multiaged, organized hematoma.4 This is best achieved by approaching the cavernoma at the location where it projects to the surface and entering the lesion through a safe brainstem anatomic zone. For ventrally located lesions in the medulla, a transcondylar skull base approach provides a direct trajectory to the entry zone through a short surgical distance without the need to manipulate or retract neurovascular structures.5-8 Neuronavigation and intraoperative neurophysiological monitoring of somatosensory evoked potential, motor, and lower cranial nerves are adjuncts to increase patient safety. Radiosurgery for the treatment of brainstem cavernous malformations has been proposed; however, it demonstrates high risk and variable and often poor response rates.9 We present a surgical video demonstrating the transcondylar approach and resection of a medullary cavernoma in a 54-yr-old woman who has had multiple known prior hemorrhages and presented with a new onset of facial numbness and weakness, ataxia, and left body sensory loss. The patient consented to surgery and to photograph publication. Images at 1:28, 1:43 (left), 2:02 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997,5 with permission. Images at 1:43 (right) from Arnautovic et al,8 with permission from JNSPG.

Petrosal Approach for Giant Retrochiasmatic Craniopharyngioma: 2-Dimensional Operative Video.

Microsurgical resection of craniopharyngiomas poses significant challenges, which are amplified with tumors in the retrochiasmatic location and larger size. Traditional pterional trans-sylvian, subfrontal translamia terminalis, or interhemispheric approaches provide narrow surgical corridors with obstructed visualization of the tumor by the prefixed chiasm and slit optic carotid window.1-5 The superior extension of the tumor compressing the hypothalamus and third ventricle are likewise inaccessible. Dissection through these approaches requires crossing and manipulation of the already compromised optic apparatus with surgical instruments. Finally, the basilar artery and its perforating branches are often adherent to the posterior aspect of the tumor, and are invisible. Endonasal endoscopic techniques have been utilized as a surgical approach that accesses the tumor without crossing the optic apparatus; however, these approaches have a significant risk of cerebrospinal fluid leakage and require dissection of the basilar artery and hypothalamus from long distances with lengthy instruments.6-9 Frequently, the surgeon achieves only partial removal. The petrosal approach is ideal for tumors in the retrochiasmatic location.10-13 Advantages include unhindered access to the retrochiasmatic space without crossing the optic nerve and chiasm. The angle of approach allows visualization superiorly to the hypothalamus. Additionally, the approach shortens the distance to the tumor, allowing for delicate bimanual dissection of the tumor, especially at the basilar artery and hypothalamic interfaces. This video demonstrates three cases of retrochiasmatic craniopharyngioma resection through the petrosal approach, highlighting these advantages to optimize patient outcome. The patients and guardians consented for the surgery, photography, and publication of the patient's image. Figures from Al-Mefty et al11 used with permission from the Journal of Neurosurgery Publishing Group. Additional figures republished from Al-Mefty et al.12 "The petrosal approach for the resection of retrochiasmatic craniopharyngiomas," Neurosurgery, 2008, volume 62, issue 5 Suppl 2 (ONS), ONS331-ONS336, by permission of the Congress of Neurological Surgeons.

Utility of skull X-rays in identifying recurrence of coiled cerebral aneurysms.

OBJECTIVE: A high rate of cerebral aneurysm recurrence following endovascular coiling has prompted the use of digital subtraction angiography (DSA) for interval follow-up. However, the utility of skull x-rays as an alternative screening method for aneurysm recurrence is unproperly characterized. METHODS: Retrospective review of a prospective registry of ruptured and unruptured cerebral aneurysms. Anteroposterior and lateral skull x-rays were obtained immediately at the end of the procedure and at 6-month follow-up. Aneurysm recurrence was defined by comparing post-procedure and 6-month DSA imaging. A true positive was defined as a change in coil mass morphology on at least one projection with aneurysm recurrence on DSA, and a true negative defined as a stable coil mass on both projections and no recurrence on DSA. Receiver operating characteristic area under the curve (AUC) statistics was used to assess the performance of skull x-rays in identifying aneurysm recurrence. RESULTS: A total of 118 cerebral aneurysms were evaluated with DSA imaging and skull x-rays. A change in coil mass morphology on one projection of skull x-rays correctly detected all true recurrences with a sensitivity of 100% (95% confidence interval [CI], 91-100%). Skull x-rays failed to identify a stable aneurysm coil mass in 15 cases, with a specificity of 79% (68-88%). Skull x-rays performed with AUC 0.8958 (95% CI, 0.8490-0.9431) in identifying aneurysm recurrence. CONCLUSIONS: The findings of our study suggest that skull x-rays may represent a lowcost, non-invasive screening tool to rule out aneurysm recurrence, which can potentially aid in decreasing the utilization of DSA in the follow-up of patients with coiled cerebral aneurysms.

Changes in Procoagulant Blood Biomarkers After Mechanical Thrombectomy.

OBJECTIVES: There is limited knowledge of the relationship between mechanical thrombectomy (MT) and endothelial inflammation in large-vessel occlusion (LVO) acute ischemic stroke (AIS). Intimal arterial damage releases tissue factor, a precipitant of the clotting cascade and thrombosis. We report changes in blood coagulation markers after MT treated with and without tissue plasminogen activator for AIS. MATERIALS AND METHODS: Cases of LVO-AIS treated with MT were included. Blood coagulation marker levels were measured within 10 h of stroke onset as a baseline and then 48 h later. Assayed biomarkers included: tissue factor procoagulant activity (TFPCA), factor VII (FVII), activated factor VII (FVIIa), factor VIII (FVIII), d-dimer, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1), and tissue factor pathway inhibitor (TFPI). Biomarker levels of MT with tissue plasminogen activator (TPA) or without (non-TPA) are reported. RESULTS: Biomarker levels from five patients with LVO-AIS treated with MT (three non-TPA, two TPA) were included. In non-TPA cases, TFPCA and PAI-1 increased while FVII, FVIIa, TAT, d-dimer, and TFPI decreased from baseline to 48 h. In TPA cases, TFPCA, FVIIa, d-dimer, TFPI, and PAI-1 decreased while FVIII increased from baseline to 48 h. CONCLUSIONS: TFPCA increased after MT in non-TPA but decreased in TPA treated patients. This finding suggests that MT is associated with elevated inflammation and procoagulation which may be reduced with TPA treatment. With further validation, the increase in TFPCA levels could help guide anticoagulant management of patients with MT without TPA.

Use of single versus multiple vasodilator agents in the treatment of cerebral vasospasm: is more better than less?

BACKGROUND: Patients with cerebral vasospasm caused by aneurysmal subarachnoid hemorrhage (aSAH) are often treated with intra-arterial (IA) vasodilator infusion. However, the optimal drug regimen is yet to be elucidated. METHODS: A retrospective review of patients with aSAH and cerebral vasospasm treated with IA vasodilator infusion was performed. Patients in group 1 (2008-2011) were treated with a single agent, either nicardipine or verapamil, and patients in group 2 (2010-2016) were treated with a regimen of nitroglycerin, verapamil, and nicardipine. The post-infusion improvement ratio (PIIR) was compared between groups. Adjusted multivariate logistic regression models were utilized to determine whether patients treated with multiple vasodilators had an improved functional outcome, defined by the modified Rankin Scale, at discharge and 90-day follow-up. RESULTS: Among 116 patients from group 1 (N = 47) and group 2 (N = 69), the median age was 54.5 years [IQR, 46-53 years] and 78% were female. Use of multiple-agent therapy resulted in a 24.36% improvement in vessel diameter over single-agent therapy (median PIIR: group 1, 10.5% [IQR, 5.3-21.1%] vs group 2, 34.9% [IQR, 21.4-66.0%]; p < 0.0001). In the adjusted multivariate logistic regression, the use of multiple-agent therapy was associated with a better functional outcome at discharge (OR 0.15, 95% CI [0.04-0.55]; p < 0.01) and at 90-day follow-up (OR 0.20, 95% CI [0.05-0.77]; p < 0.05) when compared to single-agent therapy. CONCLUSION: In this study, we found that patients treated for cerebral vasospasm with IA infusion of multiple vasodilators had an increased vessel response and better functional outcomes compared to those treated with a single agent.

The Role of Anesthesia during Intra-Arterial Mechanical Thrombectomy for theTreatment of Acute Ischemic Stroke.

Background Type of sedation (conscious sedation (CS) or general anesthesia (GA)) during Intra-arterial mechanical thrombectomy (IAMT) for treatment of acute ischemic stroke may affect patient outcomes. Previous studies suggested that CS cohorts have a higher probability of good outcome than GA cohorts. However, CS cohorts had lower initial NIH stroke scores (NIHSS). This study offers an investigation into outcomes after IAMT based on sedation type. Methods Patients at our institution who underwent IAMT for treatment of acute ischemic stroke caused by anterior circulation occlusion between 2013-2015 were included in the study. Primary endpoint was functional outcome on the modified Rankin Scale (mRS) at 90 days post-IAMT. Secondary endpoints included NIHSS at 48 hours post-IAMT, time from CT scan to puncture and from puncture to initial recanalization, recanalization as defined by the Thrombolysis in Cerebral Ischemia (TICI) score, intensive care and hospital length of stay, and all-cause in-hospital mortality. Results Thirty nine patients were included in analysis; 17 received GA and 22 received CS. Cohorts were similar in baseline characteristics, including NIHSS. The 90-day mRS was not significantly different between cohorts, as was the case for most secondary endpoints. Successful recanalization was higher in both groups than previously reported and a significantly higher TICI 3 recanalization rate was achieved in the GA cohort. Conclusions We show that equal outcomes are possible with either CS or GA if initial NIHSS is comparable. It seems reasonable for neuro-interventionalists to continue practicing using their personal preference for sedation. However, prospective randomized trials are still needed.

Neuroprotective Effects of Nasopharyngeal Perfluorochemical Cooling in a Rat Model of Subarachnoid Hemorrhage.

OBJECTIVE: Subarachnoid hemorrhage (SAH) frequently results in severe morbidity, even mortality. Hypothermia is known to have a neuroprotective effect in ischemic injuries. The aim of this study was to determine whether nasopharyngeal (NP) perfluorochemical (PFC) cooling could be used in a rat model of SAH model for neuroprotection. METHODS: SAH was induced in 16 male Sprague-Dawley rats by cisterna magna injection of 0.3 mL autologous blood. Vital signs, temperatures, cerebral blood flow (CBF), and brain histology were assessed. Brain cooling was performed on the treatment group using the NP-PFC method starting from 20 minutes after SAH. RESULTS: No SAH-related deaths were observed in either group. SAH caused an immediate decrease in mean arterial pressure (17.0% ± 4.90% below baseline values). SAH induction caused a significant and rapid decrease in CBF from baseline (approximately -65%, ranging from -32% to -85%) in both hemispheres. In the left hemisphere, cooling facilitated the return of CBF to baseline values within 20 minutes of treatment with further increase in CBF that stabilized by the 2 hours after injury time point. Quantitative immunohistochemistry showed that there were significantly more NeuN-positive cells in the cortex and significantly fewer IBA-1-positive microglia and glial fibrillary acidic protein-positive astrocytes cells in both cortex and hippocampus in the animals that received NP-PFC cooling compared with no treatment, reflecting preserved neuronal integrity and reduced inflammation. CONCLUSIONS: The data from this study indicate that local hypothermia by NP-PFC cooling supports return of CBF and neuronal integrity and suppresses the inflammatory response in SAH, suggestive of a promising neuroprotective approach in management of SAH.

Endoscope-assisted repair of CSF otorrhea and temporal lobe encephaloceles via keyhole craniotomy.

OBJECTIVE Temporal lobe encephaloceles and cerebrospinal fluid otorrhea from temporal bone defects that involve the tegmen tympani and mastoideum are generally repaired using middle fossa craniotomy, mastoidectomy, or combined approaches. Standard middle fossa craniotomy exposes patients to dural retraction, which can lead to postoperative neurological complications. Endoscopic and minimally invasive techniques have been used in other surgeries to minimize brain retraction, and so these methods were applied to repair the lateral skull base. The goal of this study was to determine if the use of endoscopic visualization through a middle fossa keyhole craniotomy could effectively repair tegmen defects. METHODS The authors conducted a retrospective review of 6 cases of endoscope-assisted middle fossa repairs of tegmen dehiscences at a tertiary care medical center within an 18-month period. RESULTS All cases were successfully treated using a keyhole craniotomy with endoscopic visualization and minimal retraction. Surgical times did not increase. There were no major postoperative complications, recurrences of encephaloceles, or cerebrospinal fluid otorrhea in these patients. CONCLUSIONS Endoscopic visualization allows for smaller incisions and craniotomies and less risk of brain retraction injury without compromising repair integrity during temporal encephalocele and tegmen repairs.

Bilateral persistent primitive hypoglossal arteries associated with unilateral symptomatic carotid thromboembolism.

We report the fifth case of bilateral persistent primitive hypoglossal arteries in the literature. This is also the first such case to be demonstrated on computerized tomography angiogram (CTA) and the first case to be associated with a symptomatic carotid thrombus. The sub-occlusive thrombus was distal to the take-off of the dominant persistent hypoglossal artery (PHA) from the internal carotid artery, thus sparing involvement of posterior circulation. Timely identification of the internal carotid artery thromboembolism in the setting of a PHA is important to allow for thrombectomy. Any intervention was not done in this case as the patient was out of the window and at an additional risk of inducing intracranial thromboembolism. Symptomatic carotid stenosis at the PHA take-off is typically treated with endovascular angioplasty and stenting due to the typically high level of the bifurcation in the neck.

Nervus Intermedius Symptoms following Surgical or Radiation Therapy for Vestibular Schwannoma.

OBJECTIVES: This study compares the functional outcomes of nevus intermedius impairment following surgery, radiation, or observation for the treatment of vestibular schwannoma. STUDY DESIGN: Retrospective cohort study. SETTINGS: Tertiary care medical center. SUBJECTS AND METHODS: We retrospectively examined 141 charts of patients with a vestibular schwannoma seen in the Dartmouth-Hitchcock Acoustic Neuroma Clinic between 2012 and 2014. Seventy-one patients underwent intervention (including radiation) as their primary treatment, and 70 were treated with observation. As part of routine care, patients were interviewed at clinic visits and with a questionnaire assessing nervus intermedius impairment. RESULTS: At presentation, 25 patients (19%) reported nervus intermedius impairment. Most common disturbances were xerophthalmia (dry eyes, 13%) and dysgeusia (taste alteration, 7.6%). Postintervention, 35 patients (53%) had ≥1 symptoms of nervus intermedius dysfunction, which is increased in comparison with patients in the observation group (17 patients, 26.5%, P < .05). Twelve intervention patients had symptoms resolve postoperatively, making no long-term difference between the observation and intervention groups (P = .20). Motor function of the facial nerve postoperatively is correlated with nervus intermedius symptoms. Surgical approaches were compared with radiation therapy, and no significant difference in nervus intermedius outcomes was found. CONCLUSION: This study demonstrates the clinical importance of monitoring nervus intermedius symptoms, since a high percentage of all patients undergoing intervention will be symptomatic during management. Patients with motor dysfunction are at a higher risk of developing nervus intermedius sequelae and need close follow-up. Although impairment is common, many symptoms will improve over time with no long-term difference between intervention patients and those under observation.

Cranio-orbito-zygomatic approach for a previously coiled/recurrent giant MCA aneurysm in a hybrid angio/OR suite.

We present surgical clipping of a giant middle cerebral artery aneurysm. The patient is a 64-year-old woman who suffered subarachnoid hemorrhage in 2005. She was treated with coiling of the aneurysm at an outside institution. She presented to our clinic with headaches and was found on angiography to have giant recurrence of the aneurysm. To allow adequate exposure for clipping, we performed the surgery through a cranio-orbito-zygomatic (COZ) skull base approach, which is demonstrated. The surgery was performed in an operating room/angiography hybrid suite allowing for high quality intraoperative angiography. The technique and room flow are also demonstrated. The video can be found here: http://youtu.be/eePcyOMi85M.

Medial acoustic neuromas: clinical and surgical implications.

OBJECT: Medial acoustic neuroma is a rare entity that confers a distinct clinical syndrome. It is scarcely discussed in the literature and is associated with adverse features. This study evaluates the clinical and imaging features, pertinent surgical challenges, and treatment outcome in a large series of this variant. The authors postulate that the particular pathological anatomy with its arachnoidal rearrangement has a profound implication on the surgical technique and outcome. METHODS: The authors conducted a retrospective analysis of 52 cases involving 33 women and 19 men who underwent resection of medial acoustic neuromas performed by the senior author (O.A.) over a 20-year period (1993-2013). Clinical, radiological, and operative records were reviewed, with a specific focus on the neurological outcomes and facial nerve function and hearing preservation. Intraoperative findings were analyzed with respect to the effect of arachnoidal arrangement on the surgeon's ability to resect the lesion and the impact on postoperative function. RESULTS: The average tumor size was 34.5 mm (maximum diameter), with over 90% of tumors being 25 mm or larger and 71% being cystic. Cerebellar, trigeminal nerve, and facial nerve dysfunction were common preoperative findings. Hydrocephalus was present in 11 patients. Distinguishing intraoperative findings included marked tumor adherence to the brainstem and frequent hypervascularity, which prompted intracapsular dissection resulting in enhancement on postoperative MRI in 18 cases, with only 3 demonstrating growth on follow-up. There was no mortality or major postoperative neurological deficit. Cerebrospinal fluid leak was encountered in 7 patients, with 4 requiring surgical repair. Among 45 patients who had intact preoperative facial function, only 1 had permanent facial nerve paralysis on extended follow-up. Of the patients with preoperative Grade I-II facial function, 87% continued to have Grade I-II function on follow-up. Of 10 patients who had Class A hearing preoperatively, 5 continued to have Class A or B hearing after surgery. CONCLUSIONS: Medial acoustic neuromas represent a rare subgroup whose site of origin and growth patterns produce a distinct clinical presentation and present specific operative challenges. They reach giant size and are frequently cystic and hypervascular. Their origin and growth pattern lead to arachnoidal rearrangement with marked adherence against the brainstem, which is critical in the surgical management. Excellent surgical outcome is achievable with a high rate of facial nerve function and attainable hearing preservation. These results suggest that similar or better results may be achieved in less complex tumors.

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

BACKGROUND: The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE: To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS: ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS: Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION: ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

Postoperative stereotactic radiosurgery without whole-brain radiation therapy for brain metastases: potential role of preoperative tumor size.

PURPOSE: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). METHODS AND MATERIALS: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or "distant" recurrence (DR) in the brain, for time to WBRT, and for OS. RESULTS: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. CONCLUSIONS: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.

Association of a higher density of specialist neuroscience providers with fewer deaths from stroke in the United States population.

OBJECT: Stroke is a leading cause of death and disability. Given that neurologists and neurosurgeons have special expertise in this area, the authors hypothesized that the density of neuroscience providers is associated with reduced mortality rates from stroke across US counties. METHODS: This is a retrospective review of the Area Resource File 2009-2010, a national county-level health information database maintained by the US Department of Health and Human Services. The primary outcome variable was the 3-year (2004-2006) average in cerebrovascular disease deaths per million population for each county. The primary independent variable was the combined density of neurosurgeons and neurologists per million population in the year 2006. Multiple regression analysis was performed, adjusting for density of general practitioners (GPs), urbanicity of the county, and socioeconomic status of the residents of the county. RESULTS: In the 3141 counties analyzed, the median number of annual stroke deaths was 586 (interquartile range [IQR] 449-754), the median number of neuroscience providers was 0 (IQR 0-26), and the median number of GPs was 274 (IQR 175-410) per million population. On multivariate adjusted analysis, each increase of 1 neuroscience provider was associated with 0.38 fewer deaths from stroke per year (p < 0.001) per million population. Rural location (p < 0.001) and increased density of GPs (p < 0.001) were associated with increases in stroke-related mortality. CONCLUSIONS: Higher density of specialist neuroscience providers is associated with fewer deaths from stroke. This suggests that the availability of specialists is an important factor in survival after stroke, and underlines the importance of promoting specialist education and practice throughout the country.

Multimodal actions of neural stem cells in a mouse model of ALS: a meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by the unremitting degeneration of motor neurons. Multiple processes involving motor neurons and other cell types have been implicated in its pathogenesis. Neural stem cells (NSCs) perform multiple actions within the nervous system to fulfill their functions of organogenesis and homeostasis. We test the hypothesis that transplanted, undifferentiated multipotent migratory NSCs may help to ameliorate an array of pathological mechanisms in the SOD1(G93A) transgenic mouse model of ALS. On the basis of a meta-analysis of 11 independent studies performed by a consortium of ALS investigators, we propose that transplanted NSCs (both mouse and human) can slow both the onset and the progression of clinical signs and prolong survival in ALS mice, particularly if regions sustaining vital functions such as respiration are rendered chimeric. The beneficial effects of transplanted NSCs seem to be mediated by a number of actions including their ability to produce trophic factors, preserve neuromuscular function, and reduce astrogliosis and inflammation. We conclude that the widespread, pleiotropic, modulatory actions exerted by transplanted NSCs may represent an accessible therapeutic application of stem cells for treating ALS and other untreatable degenerative diseases.

Computed tomography angiography: improving diagnostic yield and cost effectiveness in the initial evaluation of spontaneous nonsubarachnoid intracerebral hemorrhage.

OBJECT: Computed tomography angiography (CTA) is increasingly used as a screening tool in the investigation of spontaneous intracerebral hemorrhage (ICH). However, CTA carries additional costs and risks, necessitating its judicious use. The authors hypothesized that subsets of patients with nontraumatic, nonsubarachnoid ICH are unlikely to benefit from CTA as part of the diagnostic workup and that particular patient risk factors may be used to increase the yield of CTA in the detection of vascular sources. METHODS: The authors performed a retrospective analysis of 1376 patients admitted to Dartmouth-Hitchcock Medical Center with ICH over an 8-year period. Patients with subarachnoid hemorrhage, hemorrhagic conversion of ischemic infarcts, trauma, and known prior malignancy were excluded from the analysis, resulting in 257 patients for final analysis. Records were reviewed for medical risk factors, hemorrhage location, and correlation of CTA findings with final diagnosis. Multiple logistic regression analysis was used to investigate the combined effects of baseline variables of interest. Model selection was conducted using the stepwise method with p = 0.10 as the significance level for variable entry and p = 0.05 the significance level for variable retention. RESULTS: Computed tomography angiography studies detected vascular pathology in 34 patients (13.2%). Patient characteristics that were associated with a significantly higher likelihood of identifying a structural vascular lesion as the source of hemorrhage included patient age younger than 65 years (OR = 16.36, p = 0.0039), female sex (OR = 14.9, p = 0.0126), nonsmokers (OR = 103.8, p = 0.0008), patients with intraventricular hemorrhage (OR = 9.42, p = 0.0379), and patients without hypertension (OR = 515.78, p < 0.0001). Patients who were older than 65 years of age, with a history of hypertension, and hemorrhage located in the cerebellum or basal ganglia were never found to have an identified structural source of hemorrhage on CTA. CONCLUSIONS: Patient characteristics and risk factors are important considerations when ordering diagnostic tests in the workup of nonsubarachnoid, nontraumatic spontaneous ICH. Although CTA is an accurate diagnostic examination, it can usually be omitted in the workup of patients with the described characteristics. The use of this algorithm has the potential to increase the yield, and thus the safety and cost effectiveness, of this diagnostic tool.