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Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. “The Neurotherapeutics Symposium 2019—Neurological Emergencies” conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30–40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for cardiorespiratory support in medically refractory cases. The high rate of neurologic complications, specifically cerebrovascular disorders such as acute ischemic stroke, in VA-ECMO patients frequently prompts the acquisition of neuroimaging studies such as computed tomography with angiography and perfusion imaging (CTA and CTP). Clinicians must be familiar with the ECMO-related artifacts when interpreting such studies. Here we describe a case of asymmetric contrast opacification in a VA-ECMO patient with axillary artery cannulation.

The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being “light cotton touch” (59.2%), followed by “cotton-tipped applicator with pressure” (23.9%), “saline or water squirt” (15.9%), and “puff of air” (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosis of brain death, and loss of public trust.

Supplemental Digital Content is available in the text., OBJECTIVES: To determine the performance of the Modified Early Warning Score and Modified Early Warning Score-Sepsis Recognition Score to predict sepsis, morbidity, and mortality in neurocritically ill patients. DESIGN: Retrospective cohort study. SETTING: Single tertiary-care academic medical center. PATIENTS: Consecutive adult patients admitted to the neuro-ICU from January 2013 to December 2016. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Baseline and clinical characteristics, infections/sepsis, neurologic worsening, and mortality were abstracted. Primary outcomes included new infection/sepsis, escalation of care, and mortality. Patients with Modified Early Warning Score-Sepsis Recognition Score/Modified Early Warning Score greater than or equal to 5 were compared with those with scores less than 5. 5. Of 7,286 patients, Of 7,286 patients, 1,120 had Modified Early Warning Score-Sepsis Recognition Score greater than or equal to 5. Of those, mean age was 58.9 years; 50.2% were male. Inhospitality mortality was 22.1% for patients (248/1,120) with Modified Early Warning Score-Sepsis Recognition Score greater than or equal to 5, compared with 6.1% (379/6,166) with Modified Early Warning Score-Sepsis Recognition Score less than 5. Sepsis was present in 5.6% (345/6,166) when Modified Early Warning Score-Sepsis Recognition Score less than 5 versus 14.3% (160/1,120) when greater than or equal to 5, and Modified Early Warning Score elevation led to a new sepsis diagnosis in 5.5% (62/1,120). Three-hundred forty-three patients (30.6%) had neurologic worsening at the time of Modified Early Warning Score-Sepsis Recognition Score elevation. Utilizing the original Modified Early Warning Score, results were similar, with less score thresholds met (836/7,286) and slightly weaker associations. CONCLUSIONS: In neurocritical ill patients, Modified Early Warning Score-Sepsis Recognition Score and Modified Early Warning Score are associated with higher inhospital mortality and are preferentially triggered in setting of neurologic worsening. They are less reliable in identifying new infection or sepsis in this patient population. Population-specific adjustment of early warning scores may be necessary for the neurocritically ill patient population.

A 45-year-old right-handed hypertensive man presented with a 6-month history of worsening neuropsychiatric symptoms, abnormal movements, and weight loss. He was hallucinating, apathetic, and having severe insomnia (total sleep duration of 1–2 hours/night). During sleep, his wife noted labored and sonorous breathing. Six months before admission, he led a healthy and active lifestyle.

Objective: To systematically examine the electro-clinical characteristics of post anoxic myoclonus (PAM) and their prognostic implications in comatose cardiac arrest (CA) survivors. Methods: Fifty-nine CA survivors who developed myoclonus within 72 h of arrest and underwent continuous EEG monitoring were included in the study. Retrospective chart review was performed for all relevant clinical variables including time of PAM onset (“early onset” when within 24 h) and semiology (multi-focal, facial/ocular, whole body and limbs only). EEG findings including background, reactivity, epileptiform patterns and EEG correlate to myoclonus were reviewed at 6, 12, 24, 48 and 72 h after the return of spontaneous circulation (ROSC). Outcome was categorized as either with recovery of consciousness (Cerebral Performance Category (CPC) 1–3) or without recovery of consciousness (CPC 4–5) at the time of discharge. Results: Seven of the 59 patients (11.9%) regained consciousness, including 6/51 (11.8%) with early onset PAM. Patients with recovery of consciousness had shorter time to ROSC, and were more likely to have preserved brainstem reflexes and normal voltage background at all times. No patient with suppression burst or low voltage background (N = 52) at any point regained consciousness. In the subset where precise electro-clinical correlation was possible, all (5/5) those with recovery of consciousness had multi-focal myoclonus and most (4/5) had midline-maximal spikes over a continuous background. No patient with any other semiology (N = 21) regained consciousness. Conclusions: Early onset PAM is not always associated with lack of recovery of consciousness. EEG can help discriminate between patients who may or may not regain consciousness by the time of hospital discharge., SCOPUS: ar.j, info:eu-repo/semantics/published

A 36-year-old woman, G1P0, 22 weeks pregnant, presented to the emergency department for evaluation of acute onset facial droop. Her medical history included ulcerative colitis, primary sclerosing cholangitis, and heterozygosity for the prothrombin G20210A mutation. She was on 10,000 units of subcutaneous heparin twice daily for a previous deep vein thrombosis secondary to her prothrombin mutation; she was noncompliant with prescribed aspirin.

Introduction: Vascular dementia is a significant cause of cognitive decline, gait instability, and is associated with stroke risk factors, ischemic and hemorrhagic stroke. The incidence of ischemic stroke has been declining over the past several decades with improved secondary stroke prevention and care systems. Of several stroke risk factors, diabetes and atrial fibrillation have been identified as co-variates associated with rates of vascular dementia in hospitalized patients. We hypothesize that the frequency of secondary diagnosis for vascular dementia will decline over time between 2006 to 2014 and that the rates of vascular dementia diagnosis may vary by region (Northeast, Midwest, South, West). Methods: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample Database from 2006-2014 was used to query patients with vascular dementia using ICD-9 codes 290.40, 290.41, 290.43. Two-way ANOVA was used to assess for differences in vascular dementia diagnosis frequency over time. Multivariable logistic regression was performed to test the trend of vascular dementia diagnosis code usage in the database over study years and its interaction with region while, controlling for age, gender, race, and diagnosis of diabetes and atrial fibrillation. Results: On average, there were 31,123,558 ± 800,912 total admissions per year between 2006-2014. The mean age was 79, 55% female, 31% non-Caucasian. There were no significant differences in patient demographics between the regions. The mean frequency of vascular dementia diagnosis per year nationwide was 0.33% (SD, 0.03), ranging from 0.28% in 2006 to 0.34% in 2014. The frequency of vascular dementia diagnosis did not decrease during the study period. After controlling for race, age, gender, diagnosis of atrial fibrillation, and diabetes, there was no association between frequency of vascular dementia diagnoses and region. Conclusion: Despite advances in cardiovascular disease risk reduction, the frequency of hospitalizations associated with vascular dementia diagnoses in this database remained unchanged over a nine-year time span. This demonstrates that more research is needed to develop more effective preventative therapies to decrease vascular dementia.

Background: Central retinal artery occlusion (CRAO) results in sudden, painless loss of vision in the affected eye which is usually permanent. Despite 150 years of research, there is no treatment which has been proven to be effective to salvage visual acuity. Acute CRAO may also be amenable to treatment with intravenous tissue plasminogen activator (tPA). In the current work, we evaluated the efficacy of intravenous tPA in an ongoing prospective cohort study. Methods: We enrolled 107 patients with acute CRAO within 48 hours of symptoms onset and with a visual acuity of less than 20/200 from January 2009 until now. Those within 6 hours of onset were offered treatment with tPA; this interval was narrowed to 4.5 hours in July 2015 in response to new data. The primary outcomes were safety and functional visual acuity recovery defined as a final visual acuity of 20/100 or better. Results: Twenty-two patients (20.5% of the cohort) were treated with tPA. One patient had an asymptomatic intracerebral hemorrhage after tPA treatment and there were no other adverse events. Thirty-six percent of tPA-treated patients had recovery of visual acuity when treated within 4.5 hours while only 12.5% of patients who were not treated with tPA had recovery of visual acuity (p=0.009). None of the patients treated with tPA between 4.5 and 6 hours after onset (0/8) recovered. The median time to arrival in the ER after onset of symptoms for all patients with acute CRAO was 8.0 hrs (IQR 5.5 to 23), but the median time to initial contact with any provider was 3.9 hrs after onset (IQR 2.0 to 12) meaning a significant fraction of patients with acute CRAO may be candidates for fibrinolysis if they are efficiently routed to emergency departments. Finally we incorporated our results and those of several other recent cohort studies into an updated subject-level meta-analysis to estimate the effect-size of tPA treatment on visual acuity across a broader population and demonstrate the reproducibility of our findings. Conclusions: This study showed that visual outcomes for acute CRAO are greatly improved with tPA treatment and this treatment can be feasibly applied to a high percentage of affected patients. The results of our study strongly support proceeding to a clinical trial.

Background: Stroke survivors need therapy services to recover; however, coordination of therapy may not occur over time. An interdisciplinary stroke clinic (ISC) can improve communication and identify patients who have not reached their full recovery potential. We instituted an ISC with physical therapy (PT) to evaluate post-stroke or TIA survivors on the same day of the stroke clinic visit to determine if patients needed additional therapy. Methods: Patients with diagnosis of stroke or TIA seen in the ISC from 05/17 - 05/18 were included. Based on recommendations from the American Physical Therapy Association and AHA/ASA, the PT evaluation included the Berg Balance Scale (BBS), Ten Meter Walk Test (10MWT), Six Minute Walk Test (6MWT), Short Form Stroke Impact Scale (SF-SIS) and assessment of the patient’s knowledge of stroke risk factors and prevention. The physical therapist determined if the patient met criteria for additional therapy. Results: Among 161 patients in the study, 84% were ischemic stroke, 12% hemorrhagic stroke, and 4% TIA. The mean age was 63±14 years and there were 56% women and 75% Whites. At the time of therapy evaluation, 38% of patients were in the acute phase of recovery (0-6 months) and 62% in chronic phase (>6 months) of recovery from stroke or TIA. BBS was performed in 86%, median score 50 (41-54); 6MWT in 81%, median percent impaired 27(11-46), comfortable 10MWT in 86%, median 0.93 (0.72-1.11)m/s; fast 10MWT in 83%, median 1.31 (0.96-1.60)m/s; SF-SIS in 86%, median 33 (28-38), and SF-SIS stroke recovery rating in 81%, median 80% (50-90). Follow-up services were recommended for 62% of patients - PT (53%), occupational therapy (20%), and speech therapy (9%). Follow-up therapy recommendations were not associated with type of stroke (p=0.80, 68% hemorrhagic stroke, 61% ischemic stroke, and 67% TIA) or when stroke/TIA occurred in the past [p=0.24, 68% among patients in acute phase and 59% among patients in chronic phase of recovery]. Conclusion: In our pilot study, there was a need for follow-up services in 62% of patients due to functional limitations as determined by PT evaluation. It included patients in acute and chronic phase of recovery. Frequent therapy assessments may be needed for stroke survivors to help reach their best recovery potential.

Introduction: The prevalence of stroke in young adults have increased with the prevalence of cerebrovascular risk factors in this population. The objective of this study was to compare stroke prevalence in age groups 18-45 years versus more than 45 years by demographics, risk factors, and outcome. Methods: We analyzed the National Inpatient Sample Database from the Healthcare Cost and Utilization Project for the years 2008-14. Patients with stroke were identified based on discharge DRG codes 61-66 for acute ischemic stroke with use of thrombolytic therapy, intracranial hemorrhage or cerebral infarction. Demographics, risk factors from comorbid condition codes, and outcomes were analyzed. Results: Out of a total of 3,624,243 adult patients with stroke hospitalized during the years 2008-14, 189103 (5.21%) hospitalizations were of patients aged 18-45 years. The ratio of stroke hospitalizations to overall hospitalizations increased from 154 to 185 per 10,000 hospitalizations from the year 2008 to 2014 with increase in stroke hospitalizations in both age groups. Stroke in young adults aged 18-45 years was more common in men, Blacks and Hispanics compared to those older than 45 years. Cerebrovascular risk factors were common in young adults with stroke and the prevalence of obesity, arterial malformation, tobacco use or alcohol abuse was higher in stroke patients aged 18-45 years compared to those older than 45 years (Table 1). There was up to 6% increase in the prevalence of cerebrovascular risk factors from 2008 to 2014. Young adults with stroke aged 18-45 years were more likely to be discharged home while older adults were more likely to be discharged to skilled nursing facility. Conclusions: There are gender and racial differences in stroke among adults aged 18-45 years compared to those older than 45 years age. Modifiable cerebrovascular risk factors are common in young adults with stroke. Most notably, both obesity and smoking were particularly higher in younger patients.

Background: Bystander cardiopulmonary resuscitation (CPR) after out-of-hospital cardiac arrest (OHCA) improves survival and neurological outcomes. Unfortunately many OHCA victims do not receive bystander CPR during a witnessed arrest. It is known that gender disparities play a role with lower rates of bystander CPR in women suffering OHCA in public places. Our aim was to identify potential factors influencing the decision to perform bystander CPR. Methods: Participants at CPR training events were surveyed prior to training. Using different scenarios, subjects were asked about their comfort level performing CPR on female, geriatric, and pediatric victims. Anonymous responses were collected and transformed into categorical variables by a psychometrist. Results: Of the 677 participants, 585 (86.4%) responded the survey, with 87.5% between 18-29 years of age, 58.8% without prior CPR training and 93.3% without prior CPR experience. Reasons to hesitate starting bystander CPR in women included concern about exposing the victim (12.9%), being accused of sexual assault (6.1%), and possible pregnancy (6.5%). In participants with prior CPR training, 61.1% reported concerns about performing CPR on women, with 18.9% having concerns about performing chest compressions in relation to breast location. In participants without prior CPR training, 73.2% reported having concerns about performing CPR on women. Causing injury and exposing the patient were top concerns to perform CPR in women amongst participants who were uncomfortable (30.5% and 17.5% respectively) and comfortable (14.5% and 9.8% respectively) performing CPR in public. Causing injury was the top concern in performing CPR on geriatric (45.4%) and pediatric patients (41.7%), followed by fragility (18.1% and 10.2% respectively). Lack of skills to perform CPR on children was reported in 22% of CPR-trained participants. Conclusion: Public perception of OHCA victims influences willingness to perform bystander CPR. Factors such as age, gender, fear of injury, pregnancy status and sexual assault concerns can negatively impact this life saving intervention. Awareness of the importance of bystander CPR on any cardiac arrest victim must be improved.

Cerebral microhemorrhages (CMHs) are detected on susceptibility weighted (SWI) and gradient recalled echo T2* (GRE-T2*) magnetic resonance imaging (MRI) and are useful biomarkers of microvascular diseases of the brain. Here we describe the characteristics and distribution of cerebral microhemorrhages in a series of subjects with aortic dissection, compared with an age- and sex-matched series of patient with severe, chronic hypertension. CMHs were discovered in 75% of subjects with aortic dissection with a median of 8 per subject and an average diameter of 2.6 mm. CMHs were primarily located within the frontal lobes, parietal lobes and deep white matter tracts in a pattern suggestive of a watershed distribution. The pattern of CMHs after aortic dissection was different from that related to severe hypertension, which may suggest a different mechanism. We propose that injury to distal arterioles from cholesterol microemboli may account for the pattern of CMH observed after aortic dissection. Aortic dissection is an important mimicker of the neuroimaging findings of cerebral amyloid angiopathy and severe hypertension.

Cerebral microhemorrhages (CMHs) are detected on susceptibility weighted (SWI) and gradient recalled echo T2* (GRE-T2*) magnetic resonance imaging (MRI) and are useful biomarkers of microvascular diseases of the brain. Here we describe the characteristics and distribution of cerebral microhemorrhages in a series of subjects with aortic dissection, compared with an age- and sex-matched series of patient with severe, chronic hypertension. CMHs were discovered in 75% of subjects with aortic dissection with a median of 8 per subject and an average diameter of 2.6 mm. CMHs were primarily located within the frontal lobes, parietal lobes and deep white matter tracts in a pattern suggestive of a watershed distribution. The pattern of CMHs after aortic dissection was different from that related to severe hypertension, which may suggest a different mechanism. We propose that injury to distal arterioles from cholesterol micro emboli may account for the pattern of CMH observed after aortic dissection. Aortic dissection is an important mimicker of the neuroimaging findings of cerebral amyloid angiopathy and severe hypertension.

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that can result in blindness. At present, no proven therapy for CRAO exists. Treatment with fibrinolytic agents has shown promise but remains of unproven benefit.To assess the efficacy of systemic fibrinolytic therapy for patients with CRAO and to define a time window of efficacy.We systematically queried PubMed, Web of Science, and Scopus using the following index terms: "retinal artery occlusion" OR "retinal ischemia" AND "thrombolysis" OR "fibrinolysis" OR "tissue plasminogen activator" OR "streptokinase" OR "urokinase." Search was not limited by year of publication or language and was conducted in August 2014. In addition, we evaluated the references from relevant review articles.We assembled observational studies reporting on visual acuity outcomes after CRAO. Inclusion criteria were complete reporting of visual outcomes after CRAO (with or without fibrinolytic therapy) and a series of more than 5 patients for fibrinolysis treatment or more than 20 cases when untreated or treated with conservative modalities.Patient-level data were sought for studies reporting outcomes of treatment with fibrinolysis. Summary statistics were obtained for conservative treatment and natural history studies. The studies were weighted by the inverse of variance and merged in a random-effects model.Rate of visual recovery (defined as improvement of visual acuity from 20/200 or worse at presentation to 20/100 or better) was calculated for patients treated with fibrinolytic and conservative therapies and those who received no treatment.We obtained summary statistics from 7 studies that included 396 patients who received no treatment after CRAO and from 8 studies that included 419 patients treated with ocular massage, anterior chamber paracentesis, and/or hemodilution (conservative treatment). Patient-level data were obtained for 147 patients treated with systemic fibrinolysis. We found that fibrinolysis was beneficial at 4.5 hours or earlier after symptom onset compared with the natural history group (17 of 34 [50.0%] vs 70 of 396 [17.7%]; odds ratio, 4.7 [95% CI, 2.3-9.6]; P .001). Absolute risk reduction was 32.3%, with a number needed to treat of 4.0 (95% CI, 2.6-6.6). We also found that conservative treatment significantly worsened visual acuity outcomes and recovery rates after CRAO compared with the natural history group (31 of 419 [7.4%; 95% CI, 3.7%-11.1%] vs 70 of 396 [17.7%; 95% CI, 13.9%-21.4%]; P .001; number needed to harm, 10.0 [95% CI, 6.8-17.4]).Our analysis suggests that a clinical trial of early systemic fibrinolytic therapy for CRAO is warranted and that conservative treatments are futile and may be harmful.

The purpose of this project is to apply a modified fractal analysis technique to high-resolution T1 weighted magnetic resonance images in order to quantify the alterations in the shape of the cerebral cortex that occur in patients with Alzheimer’s disease. Images were selected from the Alzheimer’s Disease Neuroimaging Initiative database (Control N = 15, Mild-Moderate AD N = 15). The images were segmented using a semi-automated analysis program. Four coronal and three axial profiles of the cerebral cortical ribbon were created. The fractal dimensions (D f) of the cortical ribbons were then computed using a box-counting algorithm. The mean D f of the cortical ribbons from AD patients were lower than age-matched controls on six of seven profiles. The fractal measure has regional variability which reflects local differences in brain structure. Fractal dimension is complementary to volumetric measures and may assist in identifying disease state or disease progression.