Cilostazol for the management of moyamoya disease: a systematic review of the early evidence, efficacy, safety, and future directions.

Surgical revascularization remains the standard treatment for symptomatic moyamoya disease (MMD). As with any major surgical treatment, revascularization is associated with risks and limitations, denoting the need for noninvasive treatments to improve ischemic symptoms and prevent strokes. Cilostazol is a selective phosphodiesterase III inhibitor with antiplatelet, antithrombotic, and vasodilatory effects commonly used in peripheral vascular disease. Clinical studies assessing the efficacy of cilostazol in the management of stroke and MMD were recently reported, although a comprehensive assessment of the overall evidence is lacking. A systematic scoping review was conducted to assess the early evidence on cilostazol administration in patients with MMD. The inclusion criteria encompassed original human studies primarily focused on cilostazol's safety, efficacy, or utilization in managing MMD patients. A search of the PubMed database was conducted in June 2023, yielding 5 peer-reviewed publications that satisfied the inclusion criteria and were subjected to narrative synthesis. Risk of bias assessment was not applicable due to the scoping nature of this review. East Asian studies demonstrate increasing rates of cilostazol prescriptions for patients with MMD. In a large population-based study, cilostazol was compared to other antiplatelet medications and yielded the largest decrease in mortality among patients with newly diagnosed MMD. Other studies reported significant improvements in cerebral blood flow and cognitive function, which were deemed to be independent of one another. There are limited data on the safety profile of cilostazol in the MMD population, although the evidence derived from various studies performed in the general stroke population can likely provide insights into its potential utility in MMD patients. Cilostazol targets several critical pathways involved in the pathophysiology of MMD. The evidence corroborates the potential benefits of cilostazol for the management of MMD, although these findings should be interpreted with caution due to the small number of studies and lack of randomized trials. Subgroups of patients need to be identified who can safely undergo medical management in lieu of revascularization surgery or to improve surgical outcomes. Additional studies are needed to assess the efficacy and safety of cilostazol therapy, especially in Western populations.

Semiautomatic cerebrovascular territory mapping based on dynamic ASL MR angiography without vessel-encoded labeling.

PURPOSE: Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time-resolved 4D magnetic resonance angiography (MRA). METHODS: Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA-derived arterial arrival time maps of intracranial vessels. RESULTS: Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA-based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. CONCLUSION: The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user-defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies.

Quantification of intracranial arterial blood flow using noncontrast enhanced 4D dynamic MR angiography.

PURPOSE: Noncontrast enhanced dynamic magnetic resonance angiography delineates the pattern of dynamic blood flow of the cerebral vasculature. A model-free solution was proposed to quantify arterial blood flow (aBF) by using the monotonic property of the residual function. THEORY AND METHODS: Analytical simulations and in-vivo studies were performed to evaluate the performance of the proposed method by comparing the aBF values generated from the proposed and conventional singular value decomposition methods. The aBF values were compared with blood flow velocity measured by 2D phase contrast MRI, and compared between balanced steady-state free precession-based radial and spoiled GRE-based Cartesian acquisitions. Hemodynamic parametric maps were generated in 1 patient with arteriovenous malformation. RESULTS: The proposed method generates reliable aBF measurement at different signal-to-noise ratio levels, whereas overestimation/underestimation of aBF was observed when a high/low threshold was applied in the singular value decomposition method. Average aBF in large vascular branches was 214.4 and 214.5 mL/mL/min with radial and Cartesian acquisitions, respectively. Significant correlations were found between aBF and blood flow velocity measured by phase contrast MRI (P = 0.0008), and between Cartesian and radial acquisitions (P < 0.0001). Altered hemodynamics were observed at the lesion site of the arteriovenous malformation patient. CONCLUSION: A robust analytical solution was proposed for quantifying aBF. This model-free method is robust to noise, and its clinical value in the diagnosis of cerebrovascular disorders awaits further evaluation.

Role of botulinum neurotoxin-A in cerebral revascularization graft vasospasm prevention: current state of knowledge.

Graft stenosis and occlusion remain formidable complications in cerebral revascularization procedures, which can lead to significant morbidity and mortality. Graft vasospasm can result in early postoperative graft stenosis and occlusion and is believed to be at least partially mediated through adrenergic pathways. Despite various published treatment protocols, there is no single effective spasmolytic agent. Multiple factors, including anatomical and physiological variability in revascularization conduits, patient age, and comorbidities, have been associated with graft vasospasm pathogenesis and response to spasmolytics. The ideal spasmolytic agent thus likely needs to target multiple pathways to exert a generalizable therapeutic effect. Botulinum toxin (BTX)-A is a powerful neurotoxin widely used in clinical practice for the treatment of a variety of spastic conditions. Although its commonly described paradigm of cholinergic neural transmission blockade has been widely accepted, evidence for other mechanisms of action including inhibition of adrenergic transmission have been described in animal studies. Recently, the first pilot study demonstrating clinical use of BTX-A for cerebral revascularization graft spasm prevention has been reported. In this review, the mechanistic basis and potential future clinical role of BTX-A in graft vasospasm prevention is discussed.

EC-IC bypass for cerebral revascularization following skull base tumor resection: Current practices and innovations.

Complex skull base tumors can involve critical vessels of the head and neck. To achieve a gross total resection, vessel sacrifice may be necessary. In cases where vessel sacrifice will cause symptomatic cerebral ischemia, surgical revascularization is required. The purpose of this paper is to review cerebral revascularization for skull base tumors, the indications for these procedures, outcomes, advances, and future directions.

Combined Direct and Indirect Cerebral Revascularization Using Local and Flow-Through Flaps.

BACKGROUND: Extracranial-intracranial bypass is indicated in ischemic disease such as moyamoya, certain intracranial aneurysms, and other complex neurovascular diseases. In this article, we present our series of local and flow-through flaps for cerebral revascularization as an additional tool to provide direct and indirect revascularization and/or soft tissue coverage. METHODS: A retrospective review of a prospectively maintained database was performed identifying nine patients. Ten direct arterial bypass procedures with nine indirect revascularization and/or soft tissue reconstruction were performed. RESULTS: Indications for arterial bypass included intracranial aneurysm (n = 2) and moyamoya disease (n = 8). Indications for soft tissue transfer included infected cranioplasty (one) and indirect cerebral revascularization (eight). Four flow-through flaps and five pedicled flaps were used including a flow-through radial forearm fasciocutaneous flap (one), flow-through radial forearm fascial flaps (three), and pedicled temporoparietal fascial (TPF) flaps with distal end anastomosis (five). The superficial temporal vessels (seven) and facial vessels (two) were used as the vascular inflow. Arterial bypass was established into the middle cerebral artery (six) and anterior communicating artery (three). There were no intraoperative complications. All flaps survived with no donor-site complications. In one case of flow-through TPF flap, the direct graft failed, but the indirect flap remained vascularized. CONCLUSION: Local and flow-through flaps can improve combined direct and indirect revascularization and provide soft tissue reconstruction. Minimal morbidity has been encountered in early outcomes though long-term results remain under investigation for these combined neurosurgery and plastic surgery procedures. LEVEL OF EVIDENCE: The level of evidence is IV.

Selective embolization of ruptured feeding artery aneurysm followed by resection of arteriovenous malformation.

This is the case of a man in his 40s who suffered sudden collapse into a deep coma as a result of a ruptured arteriovenous malformation (AVM) feeding artery aneurysm within the lateral ventricle. The ruptured aneurysm was successfully treated with Onyx embolization of the feeding pedicle. The AVM and the feeding artery aneurysm were then removed via a transcallosal approach. This case highlights the utility of interrogating the AVM with microcatheterization of the feeding pedicles in order to define the exact anatomical features necessary for treatment planning. It also reviews the anatomy of the choroidal fissure. The video can be found here: https://youtu.be/UeqFzhTRU1Q .

Surgical management of skull base tumors.

AIM: To present a review of the contemporary surgical management of skull base tumors. BACKGROUND: Over the last two decades, the treatment of skull base tumors has evolved from observation, to partial resection combined with other therapy modalities, to gross total resection and no adjuvant treatment with good surgical results and excellent clinical outcomes. MATERIALS AND METHODS: The literature review of current surgical strategies and management of skull base tumors was performed and complemented with the experience of Barrow Neurological Institute. RESULTS: Skull base tumors include meningiomas, pituitary tumors, sellar/parasellar tumors, vestibular and trigeminal schwannomas, esthesioneuroblastomas, chordomas, chondrosarcomas, and metastases. Surgical approaches include the modified orbitozygomatic, pterional, middle fossa, retrosigmoid, far lateral craniotomy, midline suboccipital craniotomy, and a combination of these approaches. The selection of an appropriate surgical approach depends on the characteristics of the patient and the tumor, as well as the experience of the neurosurgeon. CONCLUSION: Modern microsurgical techniques, diagnostic imaging, intraoperative neuronavigation, and endoscopic technology have remarkably changed the concept of skull base surgery. These refinements have extended the boundaries of tumor resection with minimal morbidity.

Update on transient cardiac standstill in cerebrovascular surgery.

Transient cardiac standstill is a complementary procedure used with microsurgery to treat patients with particularly complex aneurysms, such as large or giant cerebral aneurysms. These procedures allow the aneurysms to be decompressed while maintaining a bloodless field and increased surgical exposure. Deep hypothermia combined with circulatory arrest provides cerebroprotection with optimal surgical conditions. However, its disadvantage is the relatively high risk of the procedure, which requires extensive expertise and infrastructure. Thus, its use is typically limited to patients with complex posterior circulation aneurysms. Adenosine-induced transient asystole is an easily applied technique in a variety of clinical situations. Its use requires minimal advanced preparation and no complex logistical coordination with other subspecialties. However, patient-specific dose-response relationships must be determined by exposure, so the relationship may not be known in an emergent situation. Persistent hypotension is a potentially major complication. Rapid ventricular pacing (RVP) has recently been reintroduced into cerebrovascular surgery. It is more predictable than adenosine in response time and, thus, can be used during unanticipated complications, such as aneurysmal rupture. It also induces a shorter period of hypotension compared with adenosine. However, RVP is more invasive and more complex from an anesthesia standpoint. Vascular neurosurgeons should be familiar with these techniques and know their applications and limitations.

Left retrosigmoid craniotomy for cavernous malformation of the middle cerebellar peduncle.

We present a 25-year-old female with a history of multiple intracranial cavernous malformations complaining of vertigo. Imaging is significant for increasing size of a lesion in her left cerebellar peduncle. Given the proximity to the lateral border of the cerebellar peduncle, a retrosigmoid approach was chosen. After performing a craniotomy that exposed the transverse-sigmoid sinus junction, the dura was open and reflected. The arachnoid was sharply opened and cerebrospinal fluid was aspirated to allow the cerebellum to fall away from the petrous bone. The cerebellopontine fissure was then opened to visualize the lateral wall of the cerebellar peduncle. The cavernous malformation was entered and resected. The video can be found here: http://youtu.be/P7mpVbaCiJE .

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

OBJECT: Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. METHODS: A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. RESULTS: Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. CONCLUSIONS: Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

Contemporary management of spinal AVFs and AVMs: lessons learned from 110 cases.

OBJECT: Spinal arteriovenous fistulas (AVFs) and arteriovenous malformations (AVMs) are rare, complex spinal vascular lesions that are challenging to manage. Recently, understanding of these lesions has increased thanks to neuroimaging technology. Published reports of surgical results and clinical outcome are limited to small series. The authors present a large contemporary series of patients with spinal AVFs and AVMs who were treated at Barrow Neurological Institute in Phoenix, Arizona. METHODS: Retrospective detailed review of a prospective vascular database was performed for all patients with spinal AVFs and AVMs treated between 2000 and 2013. Patient demographic data, AVF and AVM characteristics, surgical results, clinical outcomes, complications, and long-term follow-up were reviewed. RESULTS: Between 2000 and 2013, 110 patients (57 male and 53 female) underwent obliteration of spinal AVFs and AVMs. The mean age at presentation was 42.3 years (range 18 months-81 years). There were 44 patients with AVFs and 66 with AVMs. The AVM group included 27 intramedullary, 21 conus medullaris, 12 metameric, and 6 extradural. The most common location was thoracic spine (61%), followed by cervical (22.7%), lumbar (14.5%), and sacral (1.8%). The most common presenting signs and symptoms included paresis/paralysis (75.5%), paresthesias (60%), pain (51.8%), bowel/bladder dysfunction (41.8%), and myelopathy (36.4%). Evidence of rupture was seen in 26.4% of patients. Perioperative embolization was performed in 42% of patients. Resection was performed in 95 patients (86.4%). Embolization alone was the only treatment in 14 patients (12.7%). One patient was treated with radiosurgery alone. Angiographically verified AVF and AVM obliteration was achieved in 92 patients (83.6%). At a mean follow-up duration of 30.5 months (range 1-205 months), 43 patients (97.7%) with AVFs and 57 (86.4%) with AVMs remained functionally independent (McCormick Scale scores ≤ 2). Perioperative complications were seen in 8 patients (7%). No deaths occurred. Temporary neurological deficits were observed in 27 patients (24.5%). These temporary deficits recovered 6-8 weeks after treatment. Recurrence was identified in 6 patients (13.6%) with AVFs and 10 (15.2%) with AVMs. CONCLUSIONS: Spinal AVFs and AVMs are complex lesions that should be considered for surgical obliteration. Over the last several decades the authors have changed surgical strategies and management to achieve better clinical outcomes. Transient neurological deficit postoperatively is a risk associated with intervention; however, clinical outcomes appear to exceed the natural history based on patients' ability to recover during the follow-up period. Due to the recurrence rate associated with these lesions, long-term follow-up is required.

Racial and socioeconomic disparities in access to mechanical revascularization procedures for acute ischemic stroke.

BACKGROUND: Mechanical revascularization procedures performed for treatment of acute ischemic stroke have increased in recent years. Data suggest association between operative volume and mortality rates. Understanding procedural allocation and patient access patterns is critical. Few studies have examined these demographics. METHODS: Data were collected from the 2008 Nationwide Inpatient Sample database. Patients hospitalized with ischemic stroke and the subset of individuals who underwent mechanical thrombectomy were characterized by race, payer source, population density, and median wealth of the patient's zip code. Demographic data among patients undergoing mechanical thrombectomy procedures were examined. Stroke admission demographics were analyzed according to thrombectomy volume at admitting centers and patient demographics assessed according to the thrombectomy volume at treating centers. RESULTS: Significant allocation differences with respect to frequency of mechanical thrombectomy procedures among stroke patients existed according to race, expected payer, population density, and wealth of the patient's zip code (P < .0001). White, Hispanic, and Asian/Pacific Islander patients received endovascular treatment at higher rates than black and Native American patients. Compared with the white stroke patients, black (P < .001), Hispanic (P < .001), Asian/Pacific Islander (P < .001), and Native American stroke patients (P < .001) all demonstrated decreased frequency of admission to hospitals performing mechanical thrombectomy procedures at high volumes. Among treated patients, blacks (P = .0876), Hispanics (P = .0335), and Asian/Pacific Islanders (P < .001) demonstrated decreased frequency in mechanical thrombectomy procedures performed at high-volume centers when compared with whites. While present, socioeconomic disparities were not as consistent or pronounced as racial differences. CONCLUSIONS: We demonstrate variances in endovascular acute stroke treatment allocation according to racial and socioeconomic factors in 2008. Efforts should be made to monitor and address potential disparities in treatment utilization.

Three-Vessel Anastomosis for Direct Multiterritory Cerebral Revascularization: Case Series.

BACKGROUND AND OBJECTIVE: Cerebral revascularization of multiple territories traditionally requires multiple constructs, serial anastomoses, or a combination of direct and indirect approaches. A novel 3-vessel anastomosis technique allows for direct, simultaneous multiterritory cerebral revascularization using a single interposition graft. We herein present our experience with this approach. METHODS: Retrospective review of perioperative data and outcomes for patients undergoing multiterritory cerebral revascularization using a 3-vessel anastomosis from 2019 to 2023. RESULTS: Five patients met inclusion criteria (median age 53 years [range 12-73]). Three patients with complex middle cerebral artery aneurysms (1 ruptured) were treated with proximal ligation or partial/complete clip trapping and multiterritory external carotid artery-M2-M2 revascularization using a saphenous vein interposition graft. Two patients with moyamoya disease, prior strokes, and predominately bilateral anterior cerebral artery hypoperfusion were treated with proximal superficial temporal artery-A3-A3 revascularization using a radial artery or radial artery fascial flow-through free flap graft. No patients experienced significant surgery-related ischemia. Bypass patency was 100%. One patient had new strokes from vasospasm after subarachnoid hemorrhage. One patient required a revision surgery for subdural hematoma evacuation and radial artery fascial flow-through free flap debridement, without affecting bypass patency or neurologic outcome. On hospital discharge, median Glasgow Outcome Scale and modified Rankin Scale scores were 4 (range 3-5) and 2 (range 0-5), respectively. On follow-up, 1 patient died from medical complications of their presenting stroke; Glasgow Outcome Scale and modified Rankin Scale scores were otherwise stable or improved. CONCLUSION: The 3-vessel anastomosis technique can be considered for simultaneous revascularization of multiple intracranial territories.

Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window.

Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game "connect the dots" task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 µm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.

Open Surgical Treatment of Middle Cerebral Artery Aneurysms: A Single-Center Series in the Endovascular Era.

OBJECTIVE: We review the outcomes of open surgical treatment of middle cerebral artery aneurysms (MCAAs) at a single center, focusing on aneurysm obliteration rates and functional outcomes at the most recent follow-up. These findings can be used for future comparisons of surgical outcomes with MCAAs. METHODS: We retrospectively reviewed cases from a prospectively maintained database of patients receiving open surgical treatment for ruptured or unruptured MCAAs between July 2014 and December 2022. We utilized patients' modified Rankin Scale (mRS) score and Glasgow Outcome Scale score as functional outcome measures. Means, standard deviations, medians, and interquartile ranges were calculated, and a student's t test or its nonparametric equivalent was used to compare subgroups. RESULTS: One hundred fifty patients (114 women, 76%; mean age 55.0 ± 14.7 years) with a total of 156 MCAAs comprised 152 cases; 85 (56%) ruptured and 71 (46%) unruptured. Bypass was performed in 34 cases (22.4%); 18 ruptured (51.4%) and 16 unruptured (48.6%). Intraoperative rupture occurred in 5 (5%) ruptured and 1 (2%) unruptured cases. Onwe hundred forty-five patients (95.4%) had aneurysm obliteration with initial surgery, with 98.4% of patients having complete occlusion at 40.2± 65.5 weeks of follow-up. Intrahospital mortality occurred in 7 (6.9%) ruptured versus 1 (2.0%) unruptured case. Fifty-two (51.5%) of the ruptured compared to 43 (86%) unruptured patients were discharged home, with the remaining patients requiring inpatient rehabilitation or long-term hospitalization. The ruptured group had a mean hospital stay of 18.4 ± 10.5 days versus. 5.7 ± 6.0 days for unruptured. Length of stay, discharge mRS/ Glasgow Outcome Scale, and mRS at 4-6 weeks favored unruptured cases (P < 0.0001-0.0336). Mean change in mRS from presentation to last follow-up favored ruptured cases (-0.7 ± 1.2 vs. -0.04 ± 1.2, P = 0.0215). CONCLUSIONS: Open surgery remains a safe and definitive treatment option for MCAAs in the endovascular era.

A compact and cost-effective laser-powered speckle visibility spectroscopy (SVS) device for measuring cerebral blood flow.

In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF non-invasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. This study aims to introduce a compact speckle visibility spectroscopy (SVS) device designed for non-invasive CBF measurements, offering cost-effectiveness and scalability while tracking CBF with remarkable sensitivity and temporal resolution. The wearable hardware has a modular design approach consisting solely of a laser diode as the source and a meticulously selected board camera as the detector. They both can be easily placed on a subject's head to measure CBF with no additional optical elements. The SVS device can achieve a sampling rate of 80 Hz with minimal susceptibility to external disturbances. The device also achieves better SNR compared with traditional fiber-based SVS devices, capturing about 70 times more signal and showing superior stability and reproducibility. It is designed to be paired and distributed in multiple configurations around the head, and measure signals that exceed the quality of prior optical CBF measurement techniques. Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing non-invasive cerebral monitoring technologies.

Compact and cost-effective laser-powered speckle contrast optical spectroscopy fiber-free device for measuring cerebral blood flow.

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution. Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz. Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head. Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies.

Neurotropism of SARS-CoV-2: A Pathological Examination of Neurosurgical Specimens.

BACKGROUND AND OBJECTIVES: Neurological manifestations may occur in more than 80% of patients hospitalized with COVID-19 infection, including severe disruptions of the central nervous system (CNS), such as strokes, encephalitis, or seizures. Although the primary pathophysiological mechanism for the effects of COVID-19 in CNS remains unknown, evidence exists for both direct injury from neuroinvasion and indirect effects from disruptions in systemic inflammatory and coagulation pathways. In this study, we analyzed CNS tissue from living patients to better understand these processes. METHODS: With institutional review board approval and patient consent, samples that would be otherwise discarded from patients with active or recent (within 6 days of surgery) COVID-19 infection undergoing neurosurgical intervention were collected and tested for the presence of SARS-CoV-2 using immunohistochemistry, in situ hybridization, electron microscopy, and reverse transcription polymerase chain reaction. RESULTS: Five patients with perioperative mild-to-moderate COVID-19 infection met inclusion criteria (2 male, 3 female; mean age 38.8 ± 13.5 years). Neurosurgical diagnoses included a glioblastoma, a ruptured arteriovenous malformation, a ruptured posterior inferior cerebellar artery aneurysm, a middle cerebral artery occlusion, and a hemorrhagic pontine cavernous malformation. Samples analyzed included the frontal lobe cortex, olfactory nerve, arteriovenous malformation/temporal lobe parenchyma, middle cerebral artery, cerebellum, and cavernous malformation/brainstem parenchyma. Testing for the presence of SARS-CoV-2 was negative in all samples. CONCLUSION: The CNS is likely not a significant viral reservoir during mild-to-moderate COVID-19 infection, although direct neuroinvasion is not definitively excluded. Additional testing to help elucidate the relative contributions of direct and indirect pathways for CNS injury from COVID is warranted.