Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Management of Low-Grade Gliomas and Radiation Necrosis: A Single-Institution Case Series

Background: Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). Objective: To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. Methods: The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan-Meier analyses comprised overall survival (OS) and progression-free survival (PFS). Results: Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm(3) and 26.7 (27.9) cm(3), respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. Conclusions: LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions

Clinical Trials of Microsurgery for Cerebral Aneurysms: Past and Future

BACKGROUND: New findings and research regarding the microsurgical treatment of intracerebral aneurysms (IAs) continue to advance even in the era of endovascular therapies. Research in the past 2 decades has continued to revolve around the question of whether open surgery or endovascular treatment is preferable. The answer remains both complex and in flux. OBJECTIVE: This review focuses on microsurgery, reflects on the research decisions of previous landmark studies, and proposes future study designs that may further our understanding of IAs and how best to treat them. RESULTS: The future of IA research may include a combination of pragmatic trials, artificial intelligence integrated tools, and mining of large data sets, in addition to the publication of high-quality single-center studies. CONCLUSIONS: The future will likely emphasize testing innovative techniques, looking at granular patient data, and considering every patient encounter as a potential source of knowledge, creating a system in which data are updated daily because each patient interaction contributes to answering important research questions

Double-Barrel Superficial Temporal Artery-M2 Middle Cerebral Artery Bypass and Creation of a Middle Communicating Artery via M2-M2 End-to-End Reimplantation for Trapping of a Dolichoectatic Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video.

Large dolichoectatic aneurysms of middle cerebral artery (MCA) trifurcations are rare and often require trapping and revascularization of the region with a bypass.1-9 This video describes the treatment of an MCA trifurcation aneurysm by clip trapping and double-barrel superficial temporal artery (STA) to M2-MCA bypass followed by M2-M2 end-to-end reimplantation to create a middle communicating artery (MCoA). The patient, a 60-yr-old woman, presented with headache, a history of smoking, and a family history of ruptured aneurysms. Angiography demonstrated a 1.7-cm dolichoectatic aneurysm of the MCA trifurcation. While the natural history of these lesions is unclear, the aneurysm size and family history of aneurysmal subarachnoid hemorrhage were factors in proceeding with treatment. Informed written consent was obtained from the patient and her family.  The STA branches were harvested microsurgically, a pterional craniotomy was performed, and the aneurysm was exposed through a transsylvian approach. The two STA branches were anastomosed end-to-side to the middle and inferior trunks of the MCA. Due to the significant mismatch between the donor and recipient vessel calibers, we were concerned that the donors might provide insufficient flow in isolation. Therefore, we decided to transect both M2 trunks from the aneurysm, proximal to the inflow of the bypass, and reimplant them end-to-end. This reimplantation created an MCoA, allowing the two donor arteries to supply the new communication between the inferior and middle trunks, redistributing blood flow through the MCoA according to cerebral demand.  Bypass patency and aneurysm obliteration were confirmed on postoperative angiography. At the 6-mo follow-up, the patient\u27s modified Rankin Scale (mRS) score was 0. The MCoA is a novel construct that, like natural communicating arteries, redistributes flow in response to shifting demand, without the need for additional ischemia time during the bypass. Used with permission from Barrow Neurological Institute, Phoenix, Arizona

Spetzler-Martin Grade III Arteriovenous Malformations: A Comparison of Modified and Supplemented Spetzler-Martin Grading Systems

BACKGROUND: The modified Spetzler-Martin (SM) grading system proposes that grade III arteriovenous malformation (AVM) subtypes are associated with variable microsurgical risks, with small AVMs (III-) having lower risk and medium/eloquent AVMs (III+) having higher risk. Adding patient age and AVM bleeding status and compactness to the SM grade produces a score - the supplemented SM (Supp-SM) grade - to more accurately assess preoperative risk. OBJECTIVE: To compare the predictive power of the modified SM and Supp-SM grades for risk assessment in patients with grade III AVMs. METHODS: Patients with SM grade III AVMs treated between 2011 and 2018 were retrospectively reviewed. Good outcomes were defined as modified Rankin Scale (mRS) scores ≤ 2 or unchanged/improved mRS scores (pre- vs postsurgery). RESULTS: Of 102 patients with SM grade III AVMs, 59% had grade III- and 24% had grade III+ AVMs. Supp SM grade 6 and grade 7 AVMs accounted for 44% and 24%, respectively. Overall, 33% of patients worsened but outcomes did not significantly differ by SM III subtype. Neurological outcomes were associated with Supp-SM grade, with proportions of patients with worsening increasing from 0% with Supp-SM grade 4 AVMs to 54% with Supp-SM grade 7 AVMs. Analyses of factors associated with neurological worsening identified age \u3e 60 yr and Supp-SM grade 7 as significant. CONCLUSION: Supp-SM grades were more predictive of microsurgical outcomes than modified SM grades for grade III AVMs, with a hard cutoff for acceptable surgical risk at Supp-SM grade 6. Supp-SM grading is a better decision-making tool than subtyping with the modified SM scale

Efficacy and Safety of Primary Stereotactic Radiosurgery in Patients With Intraventricular Meningiomas

Purpose: Primary stereotactic radiosurgery for intraventricular meningiomas remains controversial owing to the potential for life-threatening peritumoral edema and lack of long-term follow-up data. We review the literature and present the largest series to assess efficacy and safety of primary stereotactic radiosurgery. Methods and materials: A systematic review of the literature for primary stereotactic radiosurgery for intraventricular meningiomas was conducted. The retrospective series presented here comprised 33 patients who received primary stereotactic radiosurgery between 1999 and 2015 for a radiologically detected intraventricular meningioma. Demographic, diagnostic, and therapeutic data were extracted from medical records, imaging, and treatment-planning systems. Both standalone and pooled analysis were performed. Results: The mean patient age was 53 years, and 24 patients (73%) were female. The median Karnofsky performance status pretreatment was 80 (range, 60-100). The majority of lesions were located in the lateral ventricles (n = 32; 97%). The mean tumor volume was 8.7 cm3 (range, 0.6-44.55 cm3). The mean delivered dose was 1390.9 cGy. Complete imaging follow-up data were available for 21 patients (64%). Of those, 14 (67%) showed partial or marginal response, 7 (33%) had stable disease, and no patient progressed per Response Assessment in Neuro-Oncology criteria. On last follow-up, 32 patients (97%) had significant improvement in performance status and a decrease in pretreatment symptoms. No high-grade Common Terminology Criteria for Adverse Events (version 5.0) toxicity was observed with the dose range employed. Conclusions: Primary stereotactic radiosurgery for intraventricular meningiomas shows excellent treatment efficacy and low toxicity in patients with a long follow-up period. The best therapeutic algorithm remains to be established leveraging further clinical investigation

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

Objective: Qualitative and quantitative analyses of blood flow in normal and pathologic brain and spinal cord microvasculature were performed using confocal laser endomicroscopy (CLE). Methods: Blood flow in cortical, dural, and spinal cord microvasculature was assessed in vivo in swine. We assessed microvasculature under normal conditions and after vessel occlusion, brain injury due to cold or surgical trauma, and cardiac arrest. Tumor-associated microvasculature was assessed in vivo and ex vivo in 20 patients with gliomas. Results: We observed erythrocyte flow in vessels 5-500 µm in diameter. Thrombosis, flow arrest and redistribution, flow velocity changes, agglutination, and cells rolling were assessed in normal and injured brain tissue. Microvasculature in in vivo CLE images of gliomas was classified as normal in 68% and abnormal in 32% of vessels on the basis of morphological appearance. Dural lymphatic channels were discriminated from blood vessels. Microvasculature CLE imaging was possible for up to 30 minutes after a 1 mg/kg intravenous dose of fluorescein. Conclusions: CLE imaging allows assessment of cerebral and tumor microvasculature and blood flow alterations with subcellular resolution intraoperative imaging demonstrating precise details of real-time cell movements. Research and clinical scenarios may benefit from this novel intraoperative in vivo microscopic fluorescence imaging modality

The astrocyte network in the ventral nerve cord neuropil of the Drosophila third-instar larva

Understanding neuronal function at the local and circuit level requires understanding astrocyte function. We have provided a detailed analysis of astrocyte morphology and territory in the Drosophila third-instar ventral nerve cord where there already exists considerable understanding of the neuronal network. Astrocyte shape varies more than previously reported; many have bilaterally symmetrical partners, many have a high percentage of their arborization in adjacent segments, and many have branches that follow structural features. Taken together, our data are consistent with, but not fully explained by, a model of a developmental growth process dominated by competitive or repulsive interactions between astrocytes. Our data suggest that the model should also include cell-autonomous aspects, as well as the use of structural features for growth. Variation in location of arborization territory for identified astrocytes was great enough that a standardized scheme of neuropil division among the six astrocytes that populate each hemi-segment is not possible at the third instar. The arborizations of the astrocytes can extend across neuronal functional domains. The ventral astrocyte in particular, whose territory can extend well into the proprioceptive region of the neuropil, has no obvious branching pattern that correlates with domains of particular sensory modalities, suggesting that the astrocyte would respond to neuronal activity in any of the sensory modalities, perhaps integrating across them. This study sets the stage for future studies that will generate a robust, functionally oriented connectome that includes both partners in neuronal circuits-the neurons and the glial cells, providing the foundation necessary for studies to elucidate neuron-glia interactions in this neuropil.NSF, Division of Integrative Organismal SystemsNational Science Foundation (NSF) [IOS1353739]; State of Arizona: University of Arizona12 month embargo; published online: 7 January 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Neuroanatomic Studies of Albert L. Rhoton Jr. in Historical Context: An Analysis of Origin, Evolution, and Application

The incorporation of perspective into art and science revolutionized the study of the brain. Beginning in about 1504, Leonardo da Vinci began to model the ventricles of the brain in three dimensions. A few years later, Andreus Vesalius illustrated radically novel brain dissections. Thomas Willis\u27 work, Cerebri Anatome (1664), illustrated by Christopher Wren, remarkably showed the brain undersurface. Later, in the early 1800s, Charles Bell\u27s accurate images of neural structures changed surgery. In the 1960s, Albert L. Rhoton Jr. (1932–2016) began to earn his place among the preeminent neuroanatomists by focusing his lens on microanatomy to harness a knowledge of microneurosurgery, master microneurologic anatomy, and use it to improve the care of his patients. Although his biography and works are well known, no analysis has been conducted to identify the progression, impact, and trends in the totality of his publications, and no study has assessed his work in a historical context compared with the contributions of other celebrated anatomists. We analyzed 414 of 508 works authored by Rhoton; these studies were analyzed according to subjects discussed, including anatomic region, surgical approaches, subjects covered, anatomic methods used, forms of multimedia, and subspecialty. Rhoton taught detailed neuroanatomy from a surgical perspective using meticulous techniques that evolved as the technical demands of neurosurgery advanced, inspiring students and contemporaries. His work aligns him with renowned figures in neuroanatomy, arguably establishing him historically as the most influential anatomist of the neurosurgical era

Nancy Davis Reagan, First Lady with a neurosurgical legacy

Various well-known people associated with the history of the presidency of the United States have experienced neurological disease or injury, especially trauma to the head or spine. Nancy Reagan, however, as the wife of President Ronald Reagan and First Lady, would leave a significant and lasting mark on the progress of neurosurgical science and education. Recognized for endeavors against drug abuse, Alzheimer\u27s disease, and polio, her interest in neurosurgical research is less well known. Nancy\u27s father Loyal Davis was a remarkable neurosurgeon and educator of extraordinary influence. When Barrow Neurological Institute (BNI) founder John Green experienced complications after an illness, Davis served as BNI director during 1966-1967. After Davis\u27s death in 1982, Robert Spetzler, who had been a student of Davis at Northwestern University Medical School and was then BNI director, convinced Green, despite his misgivings, to support a neurosurgical laboratory recognizing Davis. In 1988, Nancy Reagan, then First Lady, dedicated the Loyal and Edith Davis Neurosurgical Research Laboratory. At the dedication, she remarked on her years growing up in the home of a pioneering neurosurgeon and remarked that my father believed deeply in the importance of research to develop new methods for treating patients. Green and Spetzler\u27s unified efforts honored the extraordinary career of Davis in a manner he would have appreciated, were supported by a First Lady with deep involvement in politics and philanthropy dedicated to promoting advances in medicine, and are part of neurosurgery\u27s unique heritage

Rupture risk and outcomes of giant aneurysms in pediatric patients: a multi-institutional case series and systematic review

OBJECTIVE: Giant aneurysms in pediatric patients are vascular lesions that can cause significant neurological morbidity and mortality. Their rarity has precluded large cohort studies to inform their management. The objective of this study was to understand the clinical course and outcomes of giant aneurysms in pediatric patients. METHODS: The authors performed a multi-institutional cohort study of cases from Boston Children\u27s Hospital and Barrow Neurological Institute, as well as a systematic review and pooled cohort analysis of previously reported cases using descriptive statistics and multivariate regression modeling. RESULTS: Fifteen patients were included in the multi-institutional cohort, and an additional 88 patients were included from 14 series, yielding 103 patients within the pooled cohort. Among the pooled cohort, the most common aneurysm locations were in the middle cerebral artery (36%), internal carotid artery (27%), vertebral artery (11%), and vertebrobasilar junction (8%). Within 69 cases containing radiographic data in the analysis, 38% of aneurysms were saccular. Twenty-eight cases presented with aneurysm rupture (28%), including 0% of cavernous carotid aneurysms, 26% of other anterior circulation aneurysms, and 44% of posterior circulation aneurysms (p = 0.003). In multivariate analysis, posterior circulation location (OR 2.66, 95% CI 1.03-6.86) and younger age (OR 0.90 per year, 95% CI 0.81-1.00) were associated with aneurysm rupture presentation. Most cases were treated (97%) rather than observed (3%). The mortality rate was 3% for unruptured aneurysms and 18% for ruptured aneurysms. A favorable neurological outcome occurred in 80% of unruptured aneurysm cases and 54% of ruptured cases. In multivariate analysis, unruptured aneurysm presentation (OR 3.74, 95% CI 1.24-11.29) and endovascular treatment modality (OR 5.05, 95% CI 1.56-16.29) were associated with a favorable outcome. CONCLUSIONS: Giant aneurysms are rare entities in pediatric patients that are unlikely to be discovered incidentally and usually merit treatment. Most patients survive with good neurological outcome, even in ruptured aneurysm cases. These data reveal that posterior circulation location and younger age are risk factors that correlate with an increased risk of aneurysm rupture