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Objective. Clinical adoption of innovative EEG technology is contingent on the non-inferiority of the new devices relative to conventional ones. We present the four key results from testing the signal quality of Zeto's WR 19 EEG system against a conventional EEG system conducted on patients in a clinical setting. Methods. We performed 30 min simultaneous recordings using the Zeto WR 19 (zEEG) and a conventional clinical EEG system (cEEG) in a cohort of 15 patients. We compared the signal quality between the two EEG systems by computing time domain statistics, waveform correlation, spectral density, signal-to-noise ratio and signal stability. Results. All statistical comparisons resulted in signal quality non-inferior relative to cEEG. (i) Time domain statistics, including the Hjorth parameters, showed equivalence between the two systems, except for a significant reduction of sensitivity to electric noise in zEEG relative to cEEG. (ii) The point-by-point waveform correlation between the two systems was acceptable (r > 0.6; P < 0.001). (iii) Each of the 15 datasets showed a high spectral correlation (r > 0.99; P < 0.001) and overlapping spectral density across all electrode positions, indicating no systematic signal distortion. (iv) The mean signal-to-noise ratio (SNR) of the zEEG system exceeded that of the cEEG by 4.82 dB, equivalent to a 16% improvement. (v) The signal stability was maintained through the recordings. Conclusion. In terms of signal quality, the zEEG system is non-inferior to conventional clinical EEG systems with respect to all relevant technical parameters that determine EEG readability and interpretability. Zeto's WR 19 wireless dry electrode system has signal quality in the clinical EEG space at least equivalent to traditional cEEG recordings., (Creative Commons Attribution license.)

Background: Spontaneous skull base cerebrospinal fluid leaks (CSFLs) are associated with increased intracranial pressure in idiopathic intracranial hypertension (IIH) and hypothesized to relate to skull base erosions due to increased CSF pressure. Given the increasing recognition of internal jugular venous stenosis (IJVS) as a cause of intracranial hypertension (IH), we evaluated the relationship between spinal CSFL and venous causes of IH., Methods: The spinal CSFL database at a single institution was assessed to identify 12 consecutive spontaneous, non-traumatic spinal CSFL patients with CTV data. Exclusion criteria included documented IIH and iatrogenic CSFL. Demographics, clinical parameters, imaging characteristics, and IJV manometry results were recorded. Internal jugular venous stenosis was graded as: none (0-10%), mild (10-50%), moderate (50-80%), severe (>80-99%), and occluded (100%). Twelve consecutive patients who presented with cerebrovascular accidents without CSFL, matched by age and sex, were similarly analyzed as a control group. STROBE guidelines were used in reporting results., Results: All CSFL patients had IJVS (83.3% bilateral, 33.3% severe) compared to 41.7% of the control group (33.3% bilateral, 16.7% severe-occluded); p  = 0.04. All CSFL patients with available venogram manometry data had at least unilateral IJV gradients. Most patients presented with modified Rankin score (mRS) of 1 (66.7%), but in those with higher mRS, medical and/or surgical interventions were associated with decreased morbidity., Conclusion: Spontaneous spinal CSFL was associated with IJVS in patients not meeting IIH criteria. Persistently high CSF pressure resulting in CSFL may cause opening pressure to be falsely normal or low. Internal jugular venous stenosis may be a viable target in recurrent CSFL management and improve morbidity., Competing Interests: Author contributionsFH and CP contributed to the design of the research and collection of data. SM contributed to the collection of data, analysis of the results, and writing of the manuscript, with input/contribution from KF, MA, LG, WS, ML, and FH. Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurological long Covid (NLC) is a major post-acute sequela of SARS-CoV-2 infection, affecting up to 10% of infected patients. The clinical presentation of patients with NLC is varied, but general NLC symptoms have been noted to closely mimic symptoms of cerebral venous outflow disorders (CVD). Here we review key literature and discuss evidence supporting this comparison. We also aimed to describe the similarity between CVD symptomatology and neuro-NLC symptoms from two perspectives: a Twitter-distributed survey for long covid sufferers to estimate nature and frequency of neurological symptoms, and through a small cohort of patients with long covid who underwent CVD work up per our standard workflow. Over 700 patients responded, and we argue that there is a close symptom overlap with those of CVD. CVD workup in a series of 6 patients with neurological long COVID symptoms showed jugular vein stenosis by CT venography and varying degrees of increased intracranial pressure. Finally, we discuss the potential pathogenic association between vascular inflammation, associated with COVID-19 infection, venous outflow congestion, and its potential involvement in NLC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

The incidence of new onset visual disturbances in emergency departments across the country is frequent. A detailed history of events and thoughtful physical examination may produce a diagnosis; however, atypical cases may require further diagnostic testing to explain symptoms. We present a case of presumed increased intracranial pressure with atypical findings on diagnostic testing, which allowed our team to explore a broader differential diagnosis. This clinical reasoning article will benefit students, residents, and attendings alike to continue to uncover etiologies for symptoms of increased intracranial pressure and review differential diagnoses in similar presentations., (© 2022 American Academy of Neurology.)

Cognitive dysfunction is often multifaceted and can be seen across all age groups in medicine. The combination of cognitive decline and increased intracranial pressure may suggest possible anatomical abnormalities. We present a case report from our academic center that describes a young man with new cognitive fatigue and brain fog in the setting of increased venous pressure that resolved with surgical intervention at a site of jugular vein stenosis. We discuss current hypotheses from basic and clinical research related to pathophysiology underlying venous vascular congestion and associated neurologic disorders. Further research is warranted to elucidate the underlying mechanisms of venous congestion and cognition to better identify therapies and improve quality of life for patients., (© 2022 American Academy of Neurology.)

We describe a case with torsional deviation of the eyes from a brainstem lesion. Torsional eye movement refers to changes in the position of the eyes in the roll plane around the visual axis. When the head is tilted laterally (that is, rolled toward the shoulder), the eyes roll in the opposite direction as part of the torsional vestibulo-ocular reflex known as the ocular counter-roll. Pathologies that affect the otolith-ocular pathway can lead to a torsional deviation of the eyes as part of the ocular tilt reaction (OTR) that also causes vertical deviation of the eyes (skew deviation) and head tilt. Lesions caudal to the pontomedullary junction (such as the labyrinth, eighth cranial nerve, or vestibular nucleus) result in an OTR with ipsiversive torsional deviation, whereas lesions rostral to the junction result in an OTR with contraversive torsional deviation. Furthermore, torsional deviation of the eyes in the OTR is conjugate (incyclotorsion in the higher eye and excyclotorsion in the lower eye), whereas torsional deviation from ocular palsy in peripheral lesions is disconjugate (e.g., exyclotorsion only in the higher eye with superior oblique palsy). Therefore, the pattern of torsional eye deviation can be helpful in localizing the lesion. Several techniques including fundus photography, double Maddox rod testing, optical coherence tomography, and video-oculography are used to measure torsional eye position., (© 2022 American Academy of Neurology.)

The diagnosis of epilepsy is primarily based on the history and the verbal description of the events in question. Smartphone videos are increasingly used to assist in the diagnosis. The purpose of this study is to evaluate their value for the diagnosis of seizures. We prospectively collected smartphone videos from patients who presented to our epilepsy center over two years. The video-based diagnosis was then compared to the eventual diagnosis based on video-electroencephalographic (EEG) monitoring with recorded episodes. Video-EEG studies and smartphone videos were reviewed by two separate physicians, each blinded to the other's interpretation. Fifty-four patients were included in the final analysis (mean age = 34.7 years, SD = 17 years). Data (either smartphone video or video-EEG monitoring) were inconclusive in 18 patients. Of the 36 patients with conclusive data, 34 (94%) were in agreement. Smartphone video interpretation can be a useful adjunctive tool in the diagnosis of seizure-like events., (© 2021 International League Against Epilepsy.)

Introduction: The availability of ambulatory EEG-video monitoring gives an alternative to traditional inpatient EEG-video, but its yield and diagnostic value are not well known. This study evaluates the yield of ambulatory EEG-video for the diagnosis of epilepsy., Methods: We retrospectively reviewed the ambulatory EEG-video monitoring data from 200 consecutive and unselected patients aged 12 years and older performed by a single company (RSC Diagnostic Services) between January 2018 and May 2018. Studies were processed by two senior certified long-term monitoring EEG technologists and interpreted by neurologists., Results: Of the 200 patients, 130 (65%) were women, mean age was 45 years. Mean duration of studies were 76.6 hours (range 23-175 hours). There were 110 studies (55%) with events recorded and 101 (92%) were captured on video. Epileptic events accounted for 17.8% (18/101) of the events captured and 9% (18/200) of our total cohort. Nonepileptic diagnosis accounted for 38% of the total number of patients in study (76/200)., Conclusion: Ambulatory EEG-video monitoring may be a useful alternative to inpatient epilepsy monitoring unit, particularly with high clinical suspicion for nonepileptic events.

Introduction: The endovascular stent-assisted coiling approach for the treatment of cerebral aneurysms is evolving rapidly with the availability of new stent devices. It remains unknown how each type of stent affects the safety and efficacy of the stent-coiling procedure., Methods: This study compared the outcomes of endovascular coiling of cerebral aneurysms using Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS) stents. Patient characteristics, treatment details and angiographic results using the Raymond-Roy grade scale (RRGS), and procedural complications were analyzed in our study., Results: Our study included 659 patients with 670 cerebral aneurysms treated with stent-assisted coiling (NEU, n=182; EP, n=158; LVIS, n=330) that were retrospectively collected from six academic centers. Patient characteristics included mean age 56.3±12.1 years old, female prevalence 73.9%, and aneurysm rupture on initial presentation of 18.8%. We found differences in complete occlusion on baseline imaging, defined as RRGS I, among the three stents: LVIS 64.4%, 210/326; NEU 56.2%, 95/169; EP 47.6%, 68/143; P=0.008. The difference of complete occlusion on 10.5 months (mean) and 8 months (median) angiographic follow-up remained significant: LVIS 84%, 251/299; NEU 78%, 117/150; EP 67%, 83/123; P=0.004. There were 7% (47/670) intra-procedural complications and 11.5% (73/632) post-procedural-related complications in our cohort. Furthermore, procedure-related complications were higher in the braided-stents vs laser-cut, P=0.002., Conclusions: There was a great variability in techniques and choice of stent type for stent-assisted coiling among the participating centers. The type of stent was associated with immediate and long-term angiographic outcomes. Randomized prospective trials comparing the different types of stents are warranted., Competing Interests: Competing interests: Mokin: reports consultant: Cerebrotech, Canon Medical, Imperative Care; stock options – Serenity Medical, Inc. Fiorella: reports grants, non-financial support, and other from Penumbra; non-financial support and other from Cerenovous and Medtronic; grants and non-financial support from Siemens and Microvention; and stock in Vascular Simulations and Neurogami. Rai: reports other from Penumbra; and non-financial support from Microvention and Stryker. Mocco: reports other from Penumbra, Cerebrotech, Rebound Therapeutics, TSP, Lazarus Effect, Medina, Pulsar Vascular, and Blockade. DeLeacy: reports other and non-financial support from Penumbra; and non-financial support from Cerenovus and Siemens. Turner: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. Guilherme Dabus is a consultant for Medtronic, Microvention, and Penumbra and a shareholder in Surpass/Stryker, InNeuroCo, and Medina/Medtronic. Chaudry: reports other, grants, and non-financial support from Penumbra and Pulsar Vascular; grants and non-financial support from Medtronic, Microvention, and Codman; non-financial support and other from Blockade and non-financial support from Siemens. Turk: reports other, grants, and non-financial support from Penumbra and Pulsar Vascular; grants and non-financial support from Codman, Microvention, and Medtronic; non-financial support and other from Blockade; and non-financial support from Siemens., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: The first pass effect (FPE; achieving complete recanalization with a single thrombectomy device pass) has been shown to be associated with higher rates of good clinical outcomes in patients with acute ischemic stroke. Here, we investigate clinical and radiographic factors associated with FPE in a large U.S. post-marketing registry (TRACK, Trevo Stent-Retriever Acute Stroke). Methods: We analyzed the TRACK database (multicenter registry of 634 patients from 23 centers from March 2013 through August 2015), which 609 patients were included in the final analysis. FPE was defined as a single pass/use of device, TICI 2c/3 recanalization, and no use of rescue therapy. Analysis of individual patient data from TRACK were performed to analyze clinical and radiographic characteristics associated with FPE as well-compared clinical outcomes defined as modified Rankin Scale (mRS) score at 30 and 90 days from hospital discharge to the non-FPE group. Results: The rate of FPE in TRACK was 23% (140/609). There was no association between patient demographics and FPE, including age ( p = 0.36), sex ( p = 0.50), race ( p = 0.50), location of occlusion ( p = 0.26), baseline NIHSS ( p = 0.62), or past medical history. There was no difference in the use of a balloon-guide catheter or general anesthesia (49 and 57% with FPE vs. 47 and 64%, p = 0.63 and p = 0.14, respectively). Clinical outcomes were significantly associated with FPE; 63 vs. 44% in non-FPE patients achieved mRS 0-2 at 90 days ( p = 0.0004). Conclusion: Our study showed that achieving complete recanalization with a single thrombectomy pass using the Trevo device was highly beneficial. The most common clinical factors that are used to determine eligibility for endovascular therapy, such as NIHSS severity, location of occlusion or patient age were not predictive of the ability to achieve FPE., (Copyright © 2020 Mokin, Primiani, Castonguay, Nogueira, Haussen, English, Satti, Chen, Farid, Borders, Veznedaroglu, Binning, Puri, Vora, Budzik, Dabus, Linfante, Janardhan, Alshekhlee, Abraham, Edgell, Taqi, Khoury, Majjhoo, Kabbani, Froehler, Finch, Ansari, Novakovic, Nguyen and Zaidat.)

Background: Accurate assessment of the frequency of large vessel occlusion (LVO) is important to determine needs for neurointerventionists and thrombectomy-capable stroke facilities. Current estimates vary from 13% to 52%, depending on acute ischemic stroke (AIS) definition and methods for AIS and LVO determination. We sought to estimate LVO prevalence among confirmed and suspected AIS patients at 2 comprehensive US stroke centers using a broad occlusion site definition: internal carotid artery (ICA), first and second segments of the middle cerebral artery (MCA M1,M2), the anterior cerebral artery, vertebral artery, basilar artery, or the proximal posterior cerebral artery., Methods: We analyzed prospectively maintained stroke databases of patients presenting to the centers between January and December 2017. ICD-10 coding was used to determine the number of patients discharged with an AIS diagnosis. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) was reviewed to determine LVO presence and site. Percentages of patients with LVO among the confirmed AIS population were reported., Results: Among 2245 patients with an AIS discharge diagnosis, 418 (18.6%:95% confidence interval [CI] 17.3%-20.0%) had LVO documented on CTA or MRA. Most common occlusion site was M1 (n=139 [33.3%]), followed by M2 (n=114 [27.3%]), ICA (n=69[16.5%]), and tandem ICA-MCA lesions (n=44 [10.5%]). Presentation National Institutes of Health Stroke Scale scores were significantly different for different occlusion sites (P=.02)., Conclusions: The LVO prevalence in our large series of consecutive AIS patients was 18.6% (95% CI 17.3%-20.0%). Despite the use of a broad definition, this estimate is less than that reported in most previous studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Intracranial aneurysms located in the distal vessels are rare and remain a challenge to treat through surgical or endovascular interventions., Objective: To describe a multicenter approach with flow diversion using the pipeline embolization device (PED) for treatment of distal intracranial aneurysms., Methods: Cases of distal intracranial aneurysms defined as starting on or beyond the A2 anterior cerebral artery, M2 middle cerebral artery, and P2 posterior cerebral artery segments were included in the final analysis., Results: 65 patients with distal aneurysms treated with the PED were analyzed. Median aneurysm size at the largest diameter was 7.0 mm, 60% were of a saccular morphology, and 9/65 (13.8%) patients presented in the setting of acute rupture. Angiographic follow-up data were available for 53 patients, with a median follow-up time of 6 months: 44/53 (83%) aneurysms showed complete obliteration, 7/53 (13.2%) showed reduced filling, and 2/53 (3%) showed persistent filling. There was no association between patient characteristics, including aneurysm size (P=0.36), parent vessel diameter (P=0.27), location (P=0.81), morphology (P=0.63), ruptured status on admission (P=0.57), or evidence of angiographic occlusion at the end of the embolization procedure (P=0.49). Clinical outcome data were available for 60/65 patients: 95% (57/60) had good clinical outcome (modified Rankin Scale score of 0-2) at 3 months., Conclusions: This large multicenter study of patients with A2, M2, and P2 distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The two most common approaches to thrombectomy of emergent large vessel occlusion (direct aspiration and primary stent retriever thrombectomy) have been extensively studied; however, the detailed benefit and risk comparison is largely unknown., Objective: To conduct a systematic review and meta-analysis to compare radiographic and clinical outcomes between the use of primary stent retrievers and direct aspiration in management of acute ischemic stroke., Methods: PubMed database was searched for studies between September 1, 2012 and December 31, 2017 with acute ischemic stroke patients., Results: We identified 64 studies with 6875 patients in the primary stent retriever group and 25 studies with 2252 patients in the aspiration group. Primary aspiration alone, without the need of rescue stent retriever devices within the aspiration cohort, was performed in 65% of 2252 patients. There was no difference in the distribution of emergent large vessel occlusion based on occlusion site, age, baseline National Institutes of Health Stroke Scale, or the use of intravenous tPA (P = .19, .051, .23, and .093, respectively). Successful recanalization rates, defined as thrombolysis in cerebral Infarction 2b/3, were significantly higher in the aspiration group than the primary stent retriever group (89% versus 80%, P < .0001). No significant difference in good clinical outcome, defined as modified Rankin scale 0-2 (aspiration 52% versus stent 48%, P = .13), symptomatic intracerebral hemorrhage (aspiration 5.6% versus stent 7.2%, P = .07), and mortality at 3 months (aspiration 15% versus stent 19%, P = .10)., Conclusions: Both aspiration-first (including the subsequent use of stent retriever) and primary stent retriever thrombectomy approaches are equally effective in achieving good clinical outcomes. Our study suggests that direct aspiration with or without subsequent use of stent retriever is a safe and effective alternative to primary stent retriever in acute ischemic stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Repetitive behaviors are seemingly purposeless patterns of behavior that vary little in form and are characteristic of many neurodevelopmental, psychiatric, and neurologic disorders. Our work has identified an association between hypofunctioning of the indirect basal ganglia pathway and the expression of repetitive behavior in the deer mouse model. In this study, we targeted indirect pathway cells of the striatum with single drugs and drug combinations that bind to dopamine D 2 , adenosine A 2A , and glutamate mGlu 5 receptors. These receptors function both individually and as receptor heteromers. We found that only the triple drug cocktail (L-741,626+CGS21680+CDPPB) that was designed to increase striatal indirect basal ganglia pathway cell function reduced repetitive behavior in adult male deer mice. No single drug or double drug combinations were effective at selectively reducing repetitive behavior. We found this triple drug cocktail reduced repetitive behavior in both short-acting and long-acting formulations and was effective throughout 7 days of daily administration. Conversely, another triple drug cocktail (quinpirole+SCH58261+MTEP) that was designed to further reduce striatal indirect basal ganglia pathway cell function caused a significant increase in repetitive behavior. Significant and behaviorally selective effects on repetitive behavior were only achieved with the triple drug cocktails that included doses of L-741,626 and quinpirole that have off-target effects (e.g., dopamine D 3 receptors). These data further a role for decreased indirect basal ganglia pathway activation in repetitive behavior and suggest that targeting these receptors and/or heteromeric complexes on the indirect pathway neurons of the striatum may offer pharmacotherapeutic benefit for individuals with repetitive behavior disorders., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Blood blister aneurysms (BBA) are a rare subset of intracranial aneurysms that represent a therapeutic challenge from both a surgical and endovascular perspective., Objective: To report multicenter experience with flow diversion exclusively for BBA, located at non-branching segments along the anteromedial wall of the supraclinoidal internal carotid artery (ICA)., Methods: Consecutive cases of BBA located at non-branching segments along the anteromedial wall of the supraclinoidal ICA treated with flow diversion were included in the final analysis., Results: 49 patients with 51 BBA of the ICA treated with devices to achieve the flow diversion effect were identified. 43 patients with 45 BBA of the ICA were treated with the pipeline embolization device and were included in the final analysis. Angiographic follow-up data were available for 30 patients (32 aneurysms in total); 87.5% of aneurysms (28/32) showed complete obliteration, 9.4% (3/32) showed reduced filling, and 3.1% (1/32) persistent filling. There was no difference between the size of aneurysm (≤2 mm vs >2 mm) or the use of adjunct coiling and complete occlusion of the aneurysm on follow-up (P=0.354 and P=0.865, respectively). Clinical follow-up data were available for 38 of 43 patients. 68% of patients (26/38) had a good clinical outcome (modified Rankin scale score of 0-2) at 3 months. There were 7 (16%) immediate procedural and 2 (5%) delayed complications, with 1 case of fatal delayed re-rupture after the initial treatment., Conclusions: Our data support the use of a flow diversion technique as a safe and effective therapeutic modality for BBA of the supraclinoid ICA., Competing Interests: Competing interests: ASA: consultant for Covidien, Johnson and Johnson, Siemens, Stryker, and Terumo; grants from Siemens and Terumo. BWB: personal fees from Penumbra Inc, Stryker, Medtronic, Route 92 Medical, and Pulsar. MIC: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. GD: consultant for Proctor; speakers bureau for Medtronic and Microvention; shareholder in Medina Medical, InNeuroCo, and Stryker/Surpass. LE: consultant for Stryker Neurovascular, Microvention, and Codman Neurovascular. RH: consultant for Covidien, Stryker, Codman, and MicroVention. PK: consultant for Stryker Neurovascular, Covidien, and MicroVention. EIL: shareholder/ownership interests in Intratech Medical Ltd, Blockade Medical LLC, and Medina Medical; principal investigator in Covidien US SWIFT PRIME Trials; honoraria for training and lecturing from Covidien; consultant for Pulsar, Medina Medical, and Blockade Medical; other financial support from Abbott for carotid training for physicians. IL: consultant and speaker bureau for Covidien, Codman, and Stryker. DKL: consultant for Covidien and Stryker; shareholder/ownership in Penumbra and Blockade Medical; advisory board for Siemens; principal investigator for Liberty Trial (Penumbra). VMP: consultant for Medtronic, Stryker, Penumbra, and BALT; research grant from Philips. MM: consultant for Toshiba (Canon) Medical. ASP: consultant for Medtronic Neurovascular and Stryker Neurovascular; research grants from Medtronic Neurovascular and Stryker Neurovascular. AJR: consultant for Stryker, MicroVention, and Covidien/ev3. AHS: grants from National Institutes of Health/NINDS/NIBIB, University at Buffalo–none related to present study; financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical, Blockade Medical, and Lazarus Effect; consultant for Codman & Shurtleff Inc, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting, Penumbra, Stryker, Pulsar Vascular, MicroVention, Lazarus Effect, and Blockade Medical; speakers bureau for Codman & Shurtleff Inc; National Steering Committee for Penumbra Inc 3D Separator Trial, Covidien SWIFT PRIME trial, and MicroVention FRED trial; advisory boards for Codman & Shurtleff and Covidien Neurovascular; honoraria from Abbott Vascular, Codman & Shurtleff, and Penumbra Inc. AST: consultant for Stryker, Codman, Penumbra, and Microvention; research grants (not related to the present study) from Stryker, Codman, Micorvention, Penumbra, and Covidien; financial interests in Medina Medical, Lazarus Effect, Pulsar Vascular, and Blockade Medical. RDT: consultant for Penumbra, Medtronic, Microvention, Codman, Pulsar Vascular, Q’Apel, Rebound Medical, and Blockade Medical. AKW: consultant for Stryker Neurovascular; research grants from Philips Healthcare, and Wyss Institute; speaker for Harvard Postgraduate Course and Miami Cardiovascular Institute. BGW: consultant for Stryker and Medtronic., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Understanding how many patients are eligible for endovascular therapy can help develop more effective stroke systems of care., Objective: To determine the proportion of patients eligible for endovascular therapy., Methods: In this single center retrospective cohort study, we identified patients with acute ischemic stroke from large vessel occlusion (LVO) from January 2014 to December 2015. Selection criteria including LVO location, Alberta stroke program early computed tomography score (ASPECTS) range, hospital arrival time, and the use of intravenous thrombolysis were applied to calculate proportions of patients eligible for endovascular therapy., Results: Of 989 patients with acute ischemic stroke, LVO was identified in 224 (23%) cases. Eighty-four percent of patients admitted within 6 h, 75% of patients admitted within 6 to 12 h, and 77% of patients with M1 and internal carotid artery occlusions admitted within 12 to 24 h had favorable ASPECTS for thrombectomy, defined as ASPECTS ≥ 6. Severity of NIHSS (National Institutes of Health Stroke Scale) was predictive of favorable ASPECTS (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.04-0.74; P = .014 for NIHSS > 10 and OR 0.30, 95% CI 0.12-0.80; P = .014 for NIHSS > 20), whereas time of hospital arrival was not (OR 1.73, 95% CI 0.76-4.03; P = .26). Using all class I, Level of Evidence A American Heart Association guidelines criteria, 4% of patients with acute ischemic stroke were eligible for endovascular therapy. Up to 20% of patients were eligible for endovascular therapy with less restrictive criteria (Class IIb; Level of Evidence C)., Conclusion: Depending on the sets of selection criteria, between 4% (the most restrictive criteria) and 20% (the least restrictive criteria) of patients with LVO are potentially eligible for endovascular therapy.

Background: Patients with strokes from M2 segment middle cerebral artery (MCA) occlusion have been underrepresented in recent randomized trials of endovascular therapy., Objective: To better understand the clinical, imaging, and procedural predictors of successful recanalization and clinical outcomes in this population of patients., Methods: We performed a multicenter retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics., Results: One hundred and seventeen patients were included in analysis (median admission National Institutes of Health stroke scale [NIHSS] score 15, mean age 67.0 ± 14.5, 42% females). Good clinical outcome at 3 months (modified Rankin scale [mRS] ≤ 2) was achieved in 56% of patients. Treatment beyond 6 h of symptoms onset (P = .69, OR 0.80, 95% CI 0.38-1.73) and age over 80 (P = .47, OR 0.65, 95% CI 0.25-1.70) were not predictive of poor outcome. NIHSS > 15 was a strong predictor of clinical outcome, based on mRS distribution at 3 months (P = .0085, OR 0.35, 95% CI 0.16-0.74). Direct aspiration and primary stent retriever thrombectomy approaches showed similar radiographic and clinical success rates., Conclusion: Advanced age and time to treatment beyond 6 h from symptom onset were not predictive of clinical outcome with thrombectomy. NIHSS score above 15 was a strong predictor of outcome. Direct aspiration and primary stent retriever thrombectomy showed similar efficacy., (Copyright © 2017 by the Congress of Neurological Surgeons)

Purpose of Review: Cerebral cavernous malformations (CCMs) are common vascular abnormalities often discovered on imaging as an incidental finding. The most common clinical presentations of CCMs include seizure, headache, focal neurological deficits, and intracranial hemorrhage. This article discusses the most recent guidelines including imaging diagnostic criteria and radiographic standards of CCMs and reviews the utility of currently available imaging techniques., Recent Findings: Gradient echo T2*-weighted imaging and susceptibility-weighted imaging are the recommended imaging protocols for evaluation of suspected CCMs. Diffusion tensor imaging-based tractography provides visualization of the eloquent white matter tracks in the brain. This imaging is increasingly used in clinical practice to assist in selecting the optimal surgical approach, especially for brainstem lesions. Quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion are presently considered experimental. Its proposed value might prove helpful in the future to monitor disease activity and response to treatments. The choice of imaging modality of CCMs depends on the goals the clinician expects to achieve, such as establishing the initial diagnosis, follow-up and monitoring disease activity, preoperative, intraoperative, and postoperative evaluation, or research and experimental work on patients with CCM.

Background: Vessel perforation during stent retriever thrombectomy is a rare complication; typically only single instances have been reported., Objective: To report on a series of patients whose stent retriever thrombectomy was complicated by intraprocedural vessel perforation and discuss its potential mechanisms, rescue treatment strategies, and clinical significance., Methods: Cases with intraprocedural vessel perforation, where a stent retriever was used either as a primary treatment approach or as a part of a direct aspiration first pass technique (ADAPT), were included in the final analysis. Clinical data, procedural details, radiographic and clinical outcomes were collected from nine participating centers., Results: Intraprocedural vessel perforation during stent retriever thrombectomy occurred in 16 (1.0%) of 1599 cases. 63% of intraprocedural perforations occurred at distal locations. Endovascular rescue techniques (most commonly, intracranial balloon occlusion for tamponade) were attempted in 50% of cases. Procedure was aborted without any rescue attempts in 44% of cases. Mortality during hospitalization and at 3 months was 56% and 63%, respectively. 25% of patients achieved good functional outcome at 3 months after the procedure., Conclusions: Intraprocedural perforations during stent retriever thrombectomy were rare, but when they occurred were associated with high mortality. Perforations most commonly occurred at distal occlusion sites and were often characterized by difficulty traversing the occlusion with a microcatheter or microwire, or while withdrawing the stent retriever. Nevertheless, 25% of patients had a favorable functional outcome, suggesting that in some patients with this complication good neurological recovery is achievable., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood., Methods: A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved., Results: We find that in both rat and mouse brains, DJ-1 knockout results in an age-dependent accumulation of hexokinase 1 in the cytosol, away from its usual location at the mitochondria, with subsequent activation of the polyol pathway of glucose metabolism in vivo. Both in the brain and in cultured cells, DJ-1 deficiency is associated with accumulation of the phosphatase PTEN that antagonizes the kinase AKT. In cells, addition of an inhibitor of AKT (MK2206) or addition of a peptide to dissociate association of hexokinases from mitochondria both inhibit the PINK1/parkin pathway, which works to maintain mitochondrial integrity., Conclusion: Hexokinases are an important link between three major genetic causes of early onset Parkinson's disease. Because aging is associated with deregulated nutrient sensing, these results help explain why DJ-1 is associated with age-dependent disease.

Background and Purpose: The ASPECTS (Alberta Stroke Program Early CT Score) is a quantitate score that measures the extent of early ischemic changes. Our aim was to investigate how measurement of ASPECTS using Hounsfield unit (HU) values on initial noncontrast head computerized tomography (CT) correlates with the extent of final infarct on follow-up imaging., Methods: Cases of acute stroke from the middle cerebral artery M1 occlusion in which complete recanalization (TICI [Thrombolysis in Cerebral Infarction] 3) was achieved were included for analysis. Using HU ratio (HU affected/HU control hemisphere) and HU difference (HU control-HU affected hemisphere) values, ASPECTS was measured on initial CT imaging and correlated with final ASPECTS at 24 hours. The study cohort consisted of 41 patients with acute stroke from the M1 occlusion. The mean time from stroke symptoms onset to baseline head CT imaging was 264 minutes and from CT to TICI 3 recanalization was 142 minutes., Results: HU ratio within the 0.94 to 0.96 ranges showed the highest correlation coefficient and lowest mean and median errors with the final ASPECTS. The difference of 2.0 HU between the 2 hemispheres demonstrated the higher correlation coefficient ( r =0.71; P <0.0001) and the lowest mean and median absolute errors (1.4 and 1, respectively)., Conclusions: We established a simple algorithm for rapid and accurate assessment of ASPECTS on baseline CT imaging to predict the extent of final stroke in patients with emergent large vessel occlusion who undergo endovascular revascularization., (© 2017 American Heart Association, Inc.)

Early onset Parkinson's disease can be caused by variants in the PINK1, Parkin, and DJ-1 genes. Since their initial discoveries, hundreds of variants have been found in these genes that are associated with a Parkinsonian phenotype. This review will briefly discuss the functions of the protein products of the three genes, then focus on the effects that disease associated variants have on these functions. We will also discuss how experimental findings can help decide whether individual variants are pathogenic or not., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade., Hypothesis: Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging., Methods: We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years) and Aging (21+ years)., Results: We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band., Conclusions: Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging.

Mutations in the DJ-1 gene cause autosomal recessive parkinsonism in humans. Several mouse models of DJ-1 deficiency have been developed, but they do not have dopaminergic neuron cell death in the substantia nigra pars compacta (SNpc). Mitochondrial DNA (mtDNA) damage occurs frequently in the aged human SNpc but not in the mouse SNpc. We hypothesized that the reason DJ-1-deficient mice do not have dopaminergic cell death is due to an absence of mtDNA damage. We tested this hypothesis by crossing DJ-1-deficient mice with mice that have similar amounts of mtDNA damage in their SNpc as aged humans (Polg mutator mice). At 1 year of age, we counted the amount of SNpc dopaminergic neurons in the mouse brains using both colorimetric and fluorescent staining followed by unbiased stereology. No evidence of dopaminergic cell death was observed in DJ-1-deficient mice with the Polg mutator mutation. Furthermore, we did not observe any difference in dopaminergic terminal immunostaining in the striatum of these mice. Finally, we did not observe any changes in the amount of GFAP-positive astrocytes in the SNpc of these mice, indicative of a lack of astrogliosis. Altogether, our findings demonstrate the DJ-1-deficient mice, Polg mutator mice, and DJ-1-deficient Polg mutator mice have intact nigrastriatal pathways. Thus, the lack of mtDNA damage in the mouse SNpc does not underlie the absence of dopaminergic cell death in DJ-1-deficient mice.

Background: Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases., Hypothesis: Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades., Methods: We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes., Results: Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1., Conclusions: Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate throughout the lifespan underlie different phenotypic processes during Aging compared to Development.

Background: The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades., Hypothesis: AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging., Methods: The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism., Results: Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci., Conclusions: Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.