Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

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.

Fever, Cognitive Decline, and Multifocal T2 Hyperintensities on Brain MRI: A Case Report of Cytokine Release Syndrome.

Cytokine release syndrome (CRS) is a systemic inflammatory response characterized by fever, constitutional symptoms, and multiorgan dysfunction. While most commonly associated with immunotherapy, CRS can also be incited by infections or drugs. This case details the presentation and evaluation of a 71-year-old woman with a history of primary myelofibrosis and breast cancer who presented with acute onset of altered mental status. Initial vital signs were notable for severe hypertension, tachycardia, and fever. The patient was alert and oriented only to self, with little verbal output, and spontaneously moving all extremities. The patient had a submandibular gland abscess that had been diagnosed prior to presentation via a computed tomography scan of the neck. A comprehensive analysis, including blood tests, cerebrospinal fluid (CSF) analysis, electroencephalogram (EEG), and neuroimaging, was performed. Severe leukocytosis was noted and brain MRI demonstrated scattered areas of diffusion restriction and diffuse T2 white matter hyperintensities. Serial imaging demonstrated the progression of T2 hyperintensities. Ultimately, CRS was the most likely diagnosis. In this case, the inciting event was likely an infectious etiology, suspected to be the submandibular gland abscess that was present at the time of admission. It is vital to have a high index of suspicion for CRS in patients with recent infection, drug exposure, or immune dysregulation.

Clinical Reasoning: A 32-Year-Old Woman With Tunnel Vision and Back Pain.

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.

Pearls & Oy-sters: Cerebral Venous Congestion Associated With Cognitive Decline Treated by Jugular Release.

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.

Pearls & Oy-sters: Vertical Diplopia and Ocular Torsion: Peripheral vs Central Localization.

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 towards the shoulder), the eyes roll in the opposite direction as part of the torsional vestibulo-ocular reflex known as the ocular counter-roll (OCR). 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 cause 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 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 (OCT), and video-oculography are used to measure torsional eye position.

Correlation of Pre-Race Anxiety Using the Generalized Anxiety Disorder 2-Item Scale.

An estimated 40 million adults in the United States have been diagnosed with an anxiety disorder, making it the most common psychiatric disorder in the country. Although the data are conflicting and limited, engaging in or increasing exercise has been proposed for the management of anxiety and other mental health disorders. The purpose of this study was to determine if there is a correlation between pre-race anxiety and running experience, sex, body mass index, age, and mental health history using the validated Generalized Anxiety Disorder 2-Item screening tool for anxiety. This study was a prospective trial of 403 adult runners who were scheduled to participate in a 5 K, 10 K, half marathon, or full marathon race. Each participant completed a survey consisting of epidemiologic variables and the Generalized Anxiety Disorder 2-Item screening tool. Results revealed that the runners with more experience and increased mileage demonstrated a decrease in reported worrying on a daily to near-daily basis; whether this finding correlates with a decreased risk of developing an anxiety disorder has yet to be determined. Based on our findings, exercise as a prescription for the treatment and possibly prevention of anxiety should be considered.

Impact of RapidAI mobile application on treatment times in patients with large vessel occlusion.

BACKGROUND: Current efforts to reduce door to groin puncture time (DGPT) aim to optimize clinical outcomes in stroke patients with large vessel occlusions (LVOs). The RapidAI mobile application (Rapid Mobile App) provides quick access to perfusion and vessel imaging in patients with LVOs. We hypothesize that utilization of RapidAI mobile application can significantly reduce treatment times in stroke care by accelerating the process of mobilizing stroke clinicians and interventionalists. METHODS: We analyzed patients presenting with LVOs between June 2019 and October 2020. Thirty-one patients were treated between June 2019 and March 2020 (pre-app group). Thirty-three patients presented between March 2020 and October 2020 (post-app group). Mann-Whitney U test and Kruskal-Wallis tests were used to examine variables that are not normally distributed. In a secondary analysis we analyzed interhospital time metrics between primary stroke centers and our comprehensive stroke center. RESULTS: Baseline demographic and vascular risk factors were similar in both groups. Use of Rapid Mobile App resulted in 33 min reduction in DGPT (P=0.02), 35 min reduction in door to first pass time (P=0.02), and 37 min reduction in door to recanalization time (P=0.02) in univariate analyses when compared with patients treated pre-app. In a multiple linear regression model, utilization of Rapid Mobile App significantly predicted shorter DGPT (P=0.002). In an adjusted model, National Institutes of Health Stroke Scale (NIHSS) 24 hours after procedure and at discharge were significantly lower in the post-app group (P=0.03). Time of transfer between primary and comprehensive stroke center was comparable in both groups (P=0.26). CONCLUSION: In patients with LVOs, the implementation of the RapidAI mobile application was independently associated with reductions in intrahospital treatment times.

Value of smartphone videos for diagnosis of seizures: Everyone owns half an epilepsy monitoring unit.

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.

The Yield of Ambulatory EEG-Video Monitoring.

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.

First Pass Effect in Patients Treated With the Trevo Stent-Retriever: A TRACK Registry Study Analysis.

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.

Large Vessel Occlusion in Acute Ischemic Stroke Patients: A Dual-Center Estimate Based on a Broad Definition of Occlusion Site.

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.

Stent-assisted coiling of cerebral aneurysms: multi-center analysis of radiographic and clinical outcomes in 659 patients.

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.

Indications and Safety of the Zygomatic Osteotomy in Middle Cranial Fossa Surgery: A Retrospective Cohort Review.

Background Zygomatic osteotomy, an adjunct to middle cranial fossa (MCF) surgical approaches, improves the superior-inferior angle of approach and minimizes temporal lobe retraction. However, a decision-making algorithm for selective use of the zygomatic osteotomy and the impact of the zygomatic osteotomy on surgical complications have not been well documented. Objective We described an algorithm for deciding whether to use a zygomatic osteotomy in MCF surgery and evaluated complications associated with a zygomatic osteotomy. Methods A retrospective review of MCF cases over 11 years at our academic tertiary referral center was conducted. Demographic variables, tumor characteristics, surgical details, and postoperative complications were extracted. Results Of the 87 patients included, 15 (17%) received a zygomatic osteotomy. Surgical trajectory oriented from anterior to posterior (A-P) was significantly correlated with the use of the zygomatic osteotomy. Among the cases approached from A-P, we found (receiver-operating characteristic curve) that the cut-off tumor size that predicted a zygomatic osteotomy was 30 mm. Of the 87 cases included, 15 patients had a complication. The multivariate logistic regression model failed to reveal any significant correlation between complications and zygomatic osteotomies. Conclusions We found that the most important factor determining the use of a zygomatic osteotomy was anticipated trajectory. A-P approaches were most highly correlated with zygomatic osteotomy. Within those cases, a lesion size cut-off of 30 mm was the secondary predicting factor of zygomatic osteotomy use. The odds of suffering a surgical complication were not significantly increased by use of zygomatic osteotomy.

Direct Aspiration versus Stent Retriever Thrombectomy for Acute Stroke: A Systematic Review and Meta-Analysis in 9127 Patients.

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.

Targeting Dopamine D2, Adenosine A2A, and Glutamate mGlu5 Receptors to Reduce Repetitive Behaviors in Deer Mice.

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 D2, adenosine A2A, and glutamate mGlu5 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 D3 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.

A2, M2, P2 aneurysms and beyond: results of treatment with pipeline embolization device in 65 patients.

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.

Treatment of blood blister aneurysms of the internal carotid artery with flow diversion.

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.

ASPECTS, Large Vessel Occlusion, and Time of Symptom Onset: Estimation of Eligibility for Endovascular Therapy.

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.

Neuroimaging of Cavernous Malformations.

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.

Hexokinases link DJ-1 to the PINK1/parkin pathway.

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.