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.

Direct V3 Vertebral Artery Access for Embolization of Partially Thrombosed Fusiform Basilar Trunk Aneurysm: Technical Case Instruction.

BACKGROUND AND IMPORTANCE: Fusiform vertebrobasilar aneurysms carry significant morbidity. Endovascular strategies are preferred; however, unsafe or unfeasible access can call for innovative strategies. CLINICAL PRESENTATION: An octogenarian patient with an enlarging fusiform proximal basilar artery aneurysm causing a sixth nerve palsy was found to have multiple anatomic features that precluded a transradial or transfemoral endovascular approach. She was thus treated with direct microsurgical access of the V3 segment of the vertebral artery for subsequent coil embolization and flow diversion. CONCLUSION: This case introduces a novel combined microsurgical and endovascular strategy for treating a complex partially thrombosed fusiform basilar artery aneurysm. This approach should be reserved only for patients where conventional endovascular access is dangerous or unfeasible.

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.

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.

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.

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.

A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window.

Recording human brain activity is crucial for understanding normal and aberrant brain function. However, available recording methods are either highly invasive or have relatively low sensitivity. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging. However, fUSI cannot be performed through adult human skull. Here, we use a polymeric skull replacement material to create an acoustic window allowing ultrasound to monitor brain activity in fully intact adult humans. We design the window through experiments in phantoms and rodents, then implement it in a participant undergoing reconstructive skull surgery. Subsequently, we demonstrate fully non-invasive mapping and decoding of cortical responses to finger movement, marking the first instance of high-resolution (200 µm) and large-scale (50 mmx38 mm) brain imaging through a permanent acoustic window.

Combined open revascularization and endovascular treatment of complex intracranial aneurysms: case series.

Background and purpose: The treatment of complex intracranial aneurysms can be challenging with stand-alone open or endovascular techniques, particularly after rupture. A combined open and endovascular strategy can potentially limit the risk of extensive dissections with open-only techniques, and allow for aggressive definitive endovascular treatments with minimized downstream ischemic risk. Materials and methods: Retrospective, single-institution review of consecutive patients undergoing combined open revascularization and endovascular embolization/occlusion for complex intracranial aneurysms from 1/2016 to 6/2022. Results: Ten patients (4 male [40%]; mean age 51.9 ± 8.7 years) underwent combined open revascularization and endovascular treatment of intracranial aneurysms. The majority of aneurysms, 9/10 (90%), were ruptured and 8/10 (80%) were fusiform in morphology. Aneurysms of the posterior circulation represented 8/10 (80%) of the cases (vertebral artery [VA] involving the posterior inferior cerebellar artery [PICA] origin, proximal PICA or anterior inferior cerebellar artery/PICA complex, or proximal posterior cerebral artery). Revascularization strategies included intracranial-to-intracranial (IC-IC; 7/10 [70%]) and extracranial-to-intracranial (EC-IC; 3/10 [30%]) constructs, with 100% postoperative patency. Initial endovascular procedures (consisting of aneurysm/vessel sacrifice in 9/10 patients) were performed early after surgery (0.7 ± 1.5 days). In one patient, secondary endovascular vessel sacrifice was performed after an initial sub-occlusive embolization. Treatment related strokes were diagnosed in 3/10 patients (30%), largely from involved or nearby perforators. All bypasses with follow-up were patent (median 14.0, range 4-72 months). Good outcomes (defined as a Glasgow Outcomes Scale ≥4 and modified Rankin Scale ≤2) occurred in 6/10 patients (60%). Conclusion: A variety of complex aneurysms not amenable to stand-alone open or endovascular techniques can be successfully treated with combined open and endovascular approaches. Recognition and preservation of perforators is critical to treatment success.

Surgical Outcomes Following Vestibular Schwannoma Resection in Patients over the Age of Sixty-five.

Objective Vestibular schwannoma (VS) are benign, often slow growing neoplasms. Some institutions opt for radiosurgery in symptomatic patients of advanced age versus surgical resection. The aim of the study is to analyze surgical outcomes of VS in patients over the age of 65 who were either not candidates for or refused radiosurgery. Methods This includes retrospective analysis of VS patients between 1988 and 2020. Demographics, tumor characteristics, surgical records, and clinical outcomes were recorded. Patient preference for surgery over radiosurgery was recorded in the event that patients were offered both. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor growth was defined by increase in size of >2 mm. Results In total, 64 patients were included of average age 72.4 years (65-84 years). Average maximum tumor diameter was 29 mm (13-55 mm). Forty-five patients were offered surgery or GKRS, and chose surgery commonly due to radiation aversion (48.4%). Gross total resection was achieved in 39.1% ( n = 25), near total 32.8% ( n = 21), and subtotal 28.1% ( n = 18). Average hospitalization was 5 days [2-17] with 75% ( n = 48) discharged home. Postoperative HB scores were good (HB1-2) in 43.8%, moderate (HB3-4) in 32.8%, and poor (HB5-6) in 23.4%. HB scores improved to good in 51.6%, moderate in 31.3%, and remained poor in 17.1%, marking a rate of facial nerve improvement of 10.9%. Tumor control was achieved in 95.3% of cases at an average follow-up time of 37.8 months. Conclusion VS resection can be safely performed in patients over the age of 65. Advanced age should not preclude a symptomatic VS patient from being considered for surgical resection.

A Novel Bypass Technique to Prevent Vexing Spinal Cord Ischemia in Endovascular Thoracoabdominal Aortic Intervention.

BACKGROUND: Spinal cord ischemia remains a devastating complication when treating patients with complex thoracoabdominal aortic aneurysms using fenestrated endovascular aortic repair. This approach is progressively deployed. However, to date, no strategy has been identified to reduce the feared risk of spinal cord ischemia. OBJECTIVE: To introduce a novel bypass technique using a customized composite graft to create a direct extra-anatomic revascularization before fenestrated endovascular aortic repair in patients with high-risk of spinal cord ischemia. METHODS: To demonstrate this novel concept, we present here a clinical case that reports the strategy of this novel concept in detail. An 83-year-old man with medical history of endovascular repair of an abdominal aortic aneurysm and thoracic aorta presented with a type IA endoleak, located along the posterior superior aspect of the aortic stent graft adjacent to the lumbar arteries. A multidisciplinary plan was developed, which included a novel bypass from the profunda femoris to the left L1 radicular artery before fenestrated endovascular aortic repair to prevent spinal cord ischemia. RESULTS: The patient successfully receives the novel extra-anatomic revascularization bypass before fenestrated endovascular aortic repair. During the first implementation of this strategy, no intraoperative difficulties and postoperative complications were observed. CONCLUSION: This case demonstrates a novel surgical technique before fenestrated endovascular aortic repair for prevention of spinal cord ischemia. In addition, this concept provides a promising direction to not only complement the existing surgical techniques but also to generate more future innovations.

Rethinking Cerebral Bypass Surgery.

Despite the evolution of indications, cerebral bypass remains an important treatment for selected patients with moyamoya disease, steno-occlusive cerebrovascular disease, complex aneurysms, and tumors. Ongoing advancements in patient selection and recent strategic, technical, and technological innovations are facilitating more tailored constructs with lower complication rates and continue to reshape the field. The consolidation of cerebral bypass to specialized centers will likely continue as the complexity of both the pathologies requiring treatment and the revascularization constructs performed increases.

Cerebral Bypass Using the Descending Branch of the Lateral Circumflex Femoral Artery: A Case Series.

BACKGROUND: When performing extracranial to intracranial (EC-IC) and intracranial to intracranial (IC-IC) bypass, the choice of donor vessel and interposition graft depends on several factors: vessel size and accessibility, desired blood flow augmentation, revascularization site anatomy, and pathology. The descending branch of the lateral circumflex femoral artery (DLCFA) is an attractive conduit for cerebrovascular bypass. OBJECTIVE: To present our institutional experience using DLCFA grafts for cerebral revascularization. METHODS: Retrospective review of perioperative data and outcomes for patients undergoing cerebrovascular bypass surgery using a DLCFA graft from 2016 to 2019. RESULTS: Twenty consecutive patients underwent EC-IC bypass using a DLCFA interposition graft. Bypass indications included 13 (65%) intracranial aneurysms, 4 (20%) medically refractory atherosclerotic large artery occlusions (internal carotid artery or middle cerebral artery), 2 (10%) internal carotid artery dissections, and 1 (5%) patient with moyamoya disease. Most commonly, a donor superior temporal artery was bypassed to a recipient middle cerebral artery (14 of 20; 70%). Two cases demonstrated graft spasm. Graft occlusion occurred in one patient and was asymptomatic. Perioperative bypass surgery-related ischemia occurred in 3 patients: 1 patient with insufficient bypass flow, 1 patient with graft stenosis because of an adventitial band, and 1 patient with focal status epilepticus in the bypassed territory resulting in cortical ischemia. One donor site hematoma occurred. The median (range) modified Rankin scale (mRS) score on follow-up was 1.5 (1-4) at 7.8 (1-27) months, with most patients achieving good functional outcomes (mRS ≤2). CONCLUSION: The DLCFA is a versatile graft for cerebral revascularization surgery, demonstrating good outcomes with minimal graft harvest site morbidity and an acceptable graft patency rate.

A Review of Medical and Surgical Options for the Treatment of Facial Pain.

Facial pain is a common medical complaint that is easily misdiagnosed. As a result, this pain often goes mistreated. Despite this, there are a variety of pharmacologic, surgical, and neuromodulatory options for the treatment of facial pain. In this review, the authors detail the forms of facial pain and their treatment options. They discuss the common medications used in the first-line treatment of facial pain and the second-line surgical and neuromodulatory options available to patients when pharmacologic options fail.

Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy.

The hippocampus is the most common seizure focus in people. In the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models, but it is unknown whether this also holds true in humans. To address this question, we used immunofluorescence on control healthy hippocampus and surgical resections from mesial temporal lobe epilepsy (MTLE), plus neural stem-cell cultures and multi-electrode recordings of ex vivo hippocampal slices. We found that a longer duration of epilepsy is associated with a sharp decline in neuronal production and persistent numbers in astrogenesis. Further, immature neurons in MTLE are mostly inactive, and are not observed in cases with local epileptiform-like activity. However, immature astroglia are present in every MTLE case and their location and activity are dependent on epileptiform-like activity. Immature astroglia, rather than newborn neurons, therefore represent a potential target to continually modulate adult human neuronal hyperactivity.

Massively parallel functional photoacoustic computed tomography of the human brain.

Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging of the human brain requires bulky equipment for the generation of magnetic fields. Photoacoustic computed tomography obviates the need for magnetic fields by using light and sound to measure deoxyhaemoglobin and oxyhaemoglobin concentrations to then quantify oxygen saturation and blood volumes. Yet, the available imaging speeds, fields of view (FOV), sensitivities and penetration depths have been insufficient for functional imaging of the human brain. Here, we show that massively parallel ultrasonic transducers arranged hemispherically around the human head can produce tomographic images of the brain with a 10-cm-diameter FOV and spatial and temporal resolutions of 350 µm and 2 s, respectively. In patients who had a hemicraniectomy, a comparison of functional photoacoustic computed tomography and 7 T BOLD functional magnetic resonance imaging showed a strong spatial correspondence in the same FOV and a high temporal correlation between BOLD signals and photoacoustic signals, with the latter enabling faster detection of functional activation. Our findings establish the use of photoacoustic computed tomography for human brain imaging.

Neuroprotective effect of minocycline against acute brain injury in clinical practice: A systematic review.

Acute brain injury is a leading cause of morbidity and mortality worldwide. The term is inclusive of traumatic brain injury, cerebral ischemia, subarachnoid hemorrhage, and intracerebral hemorrhage. Current pharmacologic treatments have had minimal effect on improving neurological outcomes leading to a significant interest in the development neuroprotective agents. Minocycline is a second-generation tetracycline with high blood brain barrier penetrance due to its lipophilic properties. It functions across multiple molecular pathways involved in secondary-injury cascades following acute brain injury. Animal model studies suggest that minocycline might lead to improved neurologic outcomes, but few such trials exist in humans. Clinical investigations have been limited to small randomized trials in ischemic stroke patients which have not demonstrated a clear advantage in neurologic outcomes, but also have not been sufficiently powered to draw definitive conclusions. The potential neuroprotective effect of minocycline in the setting of traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage have all been limited to pilot studies with phase II/III investigations pending. The authors aim to synthesize what is currently known about minocycline as a neuroprotective agent against acute brain injury in humans.

Cerebrovascular bypass for ruptured aneurysms: A case series.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) unfavorable for endovascular or traditional open surgical techniques, surgical revascularization strategies comprise one of remaining limited options. There is nonetheless a paucity of data on the safety and efficacy of bypass in aSAH. In this study, we aimed to investigate complications and outcomes in a cohort of patients with aSAH treated with bypass. A prospective single-surgeon database of consecutive patients treated for aSAH between 2013 and 2018 was retrospectively analyzed. Complications and functional status at discharge were recorded and analyzed for the patients that underwent bypass surgery. Forty patients with aSAH were treated with bypass surgery (23 extracranial-intracranial; 17 intracranial-intracranial). All-cause perioperative mortality was 13% (6 patients). At discharge and at mean 14-month follow up, respectively, 16/40 (40%) and 16/25 (64%) of patients achieved a Glasgow Outcome Score of 4-5. All-cause, in-hospital complications occurred in 28 patients (70%), of which any ischemic complication occurred in 20 patients (50%), 7 (18%) being open surgical complications. This work represents the largest modern series of bypass for aSAH to date. In cases of aSAH unfavorable for endovascular intervention or traditional open surgical techniques, bypass remains a viable option in this complex group of patients.