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Patients with nmoyamoya disease (MMD) who present primarily with ischemic stroke are known to have greater rates of perioperative strokes as compared with those who present with nonstroke symptoms. The optimal timing for revascularization for these patients remains unclear.From 1994 to 2015, 91 patients with MMD presented with signs and symptoms of an acute ischemic stroke with diffusion restriction correlate on magnetic resonance imaging, and these patients were subdivided into those who underwent early revascularization (90 days from last stroke), versus those who underwent delayed revascularization (≥90 days after last stroke), based on evidence that most neurological recovery after stroke occurs during the first three months. Perioperative and long-term outcomes were compared between the 2 surgical cohorts.In total, 27 patients underwent early revascularization, and 64 patients underwent delayed revascularization. Patients who underwent early revascularization had a statistically greater rate of perioperative stroke (P = 0.04) and perioperative mortality (P = 0.03), and overall complication rate (P = 0.049). At last follow-up of 5.2 ± 4.3 years, patients who underwent delayed revascularization had a lower mortality rate (P = 0.01) and a lower overall postoperative stroke incidence (P = 0.002). As a function of time, patients with MMD undergoing delayed revascularization had a statistically higher length of stroke-free survival (P = 0.005).Patients with MMD who present with ischemic stroke are more likely to have perioperative strokes, overall perioperative complications, worse long-term mortality rates, and lower rates of stroke-free survival if revascularization surgery occurred within 90 days of last stroke.

OBJECTIVE Pediatric intracranial aneurysms are rare. Most large series in the last 15 years reported on an average of only 39 patients. The authors sought to report their institutional experience with pediatric intracranial aneurysms from 1991 to 2021 and to compare pediatric patient and aneurysm characteristics with those of a contemporaneous adult cohort. METHODS Pediatric (≤ 18 years of age) and adult patients with one or more intracranial aneurysms were identified in a prospective database. Standard epidemiological features and outcomes of each pediatric patient were retrospectively recorded. These results were compared with those of adult aneurysm patients managed at a single institution over the same time period. RESULTS From a total of 4500 patients with 5150 intracranial aneurysms admitted over 30 years, there were 47 children with 53 aneurysms and 4453 adults with 5097 aneurysms; 53.2% of children and 36.4% of adults presented with a subarachnoid hemorrhage (SAH). Pediatric aneurysms were significantly more common in males, more likely giant (≥ 25 mm), and most frequently located in the middle cerebral artery. Overall, 85.1% of the pediatric patients had a modified Rankin Scale score ≤ 2 at the last follow-up (with a mean follow-up of 65.9 months), and the pediatric mortality rate was 10.6%; all 5 patients who died had an SAH. The recurrence rate of treated aneurysms was 6.7% (1/15) in the endovascular group but 0% (0/31) in the microsurgical group. No de novo aneurysms occurred in children (mean follow-up 5.5 years). CONCLUSIONS Pediatric intracranial aneurysms are significantly different from adult aneurysms in terms of sex, presentation, location, size, and outcomes. Future prospective studies will better characterize long-term aneurysm recurrence, rebleeds, and de novo aneurysm occurrences. The authors currently favor microsurgical over endovascular treatment for pediatric aneurysms.

Introduction Hemangioblastomas typically present throughout the neuroaxis, particularly within the cerebellum and spinal cord. A rare case of cystic hemangioblastoma within the quadrigeminal cistern is described. Case Report A 18-year-old female presented with 3 weeks of worsening headaches and vomiting. Workup revealed multiple contrast enhancing lesions throughout the neuroaxis concerning for hemangioblastoma, with the largest cystic mass within the quadrigeminal cistern causing brainstem compression and hydrocephalus. The patient experienced an acute neurologic decompensation likely due to brainstem compression and hydrocephalus, which was temporized by cyst drainage and endoscopic third ventriculostomy. After neurological stabilization and Von Hippel Lindau disease workup, she underwent a suboccipital craniotomy and resection of the hemangioblastoma via a transcystic approach. Intraoperatively, the trochlear nerve was identified and preserved. Conclusion Operative approaches to the quadrigeminal cistern typically include the infratentorial supracerebellar approach and the occipital transtentorial approach. Here, we describe a safe and efficacious transcystic approach to a quadrigeminal cistern hemangioblastoma.

Trigeminal neuralgia (TN) has been described in the literature as one of the most debilitating presentations of orofacial pain. This review summarizes over 150 years of collective clinical experience in the medical and surgical treatment of TN. Fundamentally, TN remains a clinical diagnosis that must be distinguished from other types of trigeminal neuropathic pain and/or facial pain associated with other neuralgias or headache syndromes. What is increasingly clear is that there is no catch-all medical or surgical intervention that is effective for all patients with trigeminal neuralgia, likely reflective of the fact that TN is likely a heterogenous group of disorders that jointly manifests in facial pain. The first-line treatment for TN remains anticonvulsant medical therapy. Patients who fail this have a range of surgical options available to them. In general, microvascular decompression is a safe and effective procedure with immediate and durable outcomes. Patients who are unable to tolerate general anesthesia or whose medical comorbidities preclude a suboccipital craniectomy may benefit from percutaneous methodologies including glycerol or radiofrequency ablation, or both. For patients with bleeding diathesis due to blood thinning medications who are ineligible for invasive procedures, or for those who are unwilling to undergo open surgical procedures, radiosurgery may be an excellent option—provided the patient understands that maximum pain relief will take on the order of months to achieve. Finally, peripheral neurectomies continue to provide an inexpensive and resource-sparing alternative to pain relief for patients in locations with limited economic and medical resources. Ultimately, elucidation of the molecular mechanisms underlying trigeminal neuralgia will pave the way for novel, more effective and less invasive therapies.

Several East Asian studies have examined the role of revascularization in the context of hemorrhagic moyamoya disease (MMD) and found a decrease in postoperative rehemorrhage rates. To date, no data exist comparing revascularization with conservative management in North American patients with hemorrhagic MMD.To compare the clinical outcomes of conservative management vs surgical revascularization for North American patients with hemorrhagic MMD and investigate the effect of revascularization timing.We retrospectively studied the mortality and stroke-free survival of patients with MMD presenting with hemorrhagic stroke between 1994 and 2015.The diagnosis of hemorrhagic MMD was established in 38 patients. Seventeen patients were managed conservatively, and 21 were surgically revascularized. Twelve patients underwent revascularization within 6 months of hemorrhage, and 9 underwent surgery in a delayed fashion. Six conservatively managed patients (35.3%) died within the follow-up period compared with 0 (0%) surgically revascularized patients, P = .004. Conservatively managed patients also experienced an increased number of postoperative strokes, P = .037, and shorter stroke-free survival compared with patients undergoing revascularization, P = .047. On multivariate analysis, increased age, worse baseline modified Rankin score, and conservative management were independently associated with worse neurological outcomes, P.05. Early revascularization was associated with higher rates of postoperative seizures, P = .033, and wound complications, P = .031, compared with those who underwent delayed surgery.Conservative management in a North American patient cohort was associated with greater mortality and worsened neurological outcomes compared with those undergoing revascularization. Early revascularization was associated with higher rates of postoperative seizures and wound complications, although these risks must be balanced against the risk of rehemorrhage.

Summary The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.

Cortical layer 1 (L1) interneurons have been proposed as a hub for attentional modulation of underlying cortex, but the transformations that this circuit implements are not known. We combined genetically targeted voltage imaging with optogenetic activation and silencing to study the mechanisms underlying sensory processing in mouse barrel cortex L1. Whisker stimuli evoked precisely timed single spikes in L1 interneurons, followed by strong lateral inhibition. A mild aversive stimulus activated cholinergic inputs and evoked a bimodal distribution of spiking responses in L1. A simple conductance-based model that only contained lateral inhibition within L1 recapitulated the sensory responses and the winner-takes-all cholinergic responses, and the model correctly predicted that the network would function as a spatial and temporal high-pass filter for excitatory inputs. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo and suggest an intuitive picture for how L1 transforms sensory and modulatory inputs. Video Abstract: [Figure presented] By simultaneously combining genetically targeted voltage imaging with optogenetic modulation of neuronal activity, Fan et al. demonstrate that all-optical electrophysiology in awake animals can be a powerful tool for revealing hidden principles of neural circuit function.

The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved high signal to noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise that present analysis challenges, namely light scattering, out-of-focus sources, motion, and blood flow. We present a novel signal extraction methodology, Spike-Guided Penalized Matrix Decomposition-Nonnegative Matrix Factorization (SGPMD-NMF), which resolves supra- and sub-threshold voltages with high fidelity, even in the presence of correlated noise. The method incorporates biophysical constraints (shared soma profiles for spiking and subthreshold dynamics) and optical constraints (smoother spatial profiles from defocused vs. in-focus sources) to cleave signal from background. We validated the pipeline using simulated and composite datasets with realistic noise properties. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon, mouse cortex expressing SomArchon or Voltron, and zebrafish spine expressing zArchon1.

The stability of neural dynamics arises through a tight coupling of excitatory (E) and inhibitory (I) signals. Genetically encoded voltage indicators (GEVIs) can report both spikes and subthreshold dynamics in vivo, but voltage only reveals the combined effects of E and I synaptic inputs, not their separate contributions individually. Here we combine optical recording of membrane voltage with simultaneous optogenetic manipulation to probe E and I individually in barrel cortex Layer 1 (L1) neurons in awake mice. Our studies reveal how the L1 microcircuit integrates thalamocortical excitation, lateral inhibition and top-down neuromodulatory inputs. We develop a simple computational model of the L1 microcircuit which captures the main features of our data. Together, these results suggest a model for computation in L1 interneurons consistent with their hypothesized role in attentional gating of the underlying cortex. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo.One Sentence SummaryAll-optical electrophysiology revealed the function in awake mice of an inhibitory microcircuit in barrel cortex Layer 1.

A technology that simultaneously records membrane potential from multiple neurons in behaving animals will have a transformative effect on neuroscience research1,2. Genetically encoded voltage indicators are a promising tool for these purposes; however, these have so far been limited to single-cell recordings with a marginal signal-to-noise ratio in vivo3–5. Here we developed improved near-infrared voltage indicators, high-speed microscopes and targeted gene expression schemes that enabled simultaneous in vivo recordings of supra- and subthreshold voltage dynamics in multiple neurons in the hippocampus of behaving mice. The reporters revealed subcellular details of back-propagating action potentials and correlations in subthreshold voltage between multiple cells. In combination with stimulation using optogenetics, the reporters revealed changes in neuronal excitability that were dependent on the behavioural state, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behaviour. A combination of improved near-infrared voltage indicators, high-speed microscopes and targeted gene expression schemes enabled simultaneous in vivo optogenetic control and recording of voltage dynamics in multiple neurons in the hippocampus of behaving mice.