Impact of smoking on outcomes following endovascular therapy for acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Smoking represents a leading risk factor for acute ischemic stroke (AIS). Previous literature has described a "smoking paradox", wherein smokers experience better outcomes following intravenous thrombolysis for AIS. It is unclear whether such a phenomenon exists in smokers undergoing endovascular therapy (EVT) for AIS. To assess outcomes in smokers following EVT for AIS, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase Web of Science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated mean difference (MD), pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Eight studies with 2633 patients comprised our analysis. On average, smokers were 10.14 years (MD = 10.14, [95% CI = -14.49 to -5.79], P-value < 0.001) younger than non-smokers. Smokers achieved mRS 0-2 (OR = 1.82, [95% CI, 1.34-2.48], P-value < 0.001) and TICI 2b-3 (OR = 1.61, [95% CI, 1.19-2.19], P-value = 0.002) at a higher rate than non-smokers. sICH rates were comparable between smokers and non-smokers (OR = 1.07, [95% CI, 0.62-1.85], P-value = 0.81). Smokers had a lower rate of 90-day mortality than non-smokers (OR = 0.54, [95% CI, 0.41-0.71], P-value < 0.001). CONCLUSIONS: In this meta-analysis of eight studies, we found that smokers with AIS undergoing EVT experienced better 90-day outcomes and higher rates of TICI 2b-3. This may be due to baseline differences between smokers and non-smokers, but future studies should explore alternative reasons that could explain this relationship between smoking and AIS treated with EVT.

Safety of peripheral 3% hypertonic saline bolus administration for neurologic emergency.

BACKGROUND/OBJECTIVE: Hypertonic sodium chloride (HTS) is used for emergent treatment of acute cerebral edema and other neurologic emergencies. Central access is not commonly available in emergent situations and 3% HTS is utilized peripherally. Many studies have shown the safety of its administration at rates up to 75 mL/h, but there is a lack of data to establish the safety of peripherally administered, rapid bolus dosing in emergent situations. The objective of this study is to describe the safety of rapid, peripherally administered (≥ 250 mL/h) 3% HTS for neurologic emergencies. METHODS: This is a retrospective, cohort study including adult patients receiving 3% HTS via a peripheral IV site for elevated intracranial pressure, cerebral edema, or other neurological emergencies at a rate of at least 250 m/h between May 5, 2018 - September 30, 2021. Patients were excluded if they simultaneously received another hypertonic saline fluid. Baseline characteristics collected included HTS dose, rate and site of administration, indication for use and patient demographics. The primary safety outcome was incidence of extravasation and phlebitis within one hour of HTS administration. RESULTS: There were 206 patients receiving 3% HTS who were screened, and 37 patients met inclusion criteria. The most common reason for exclusion was administration at a rate < 250 m/h. The median age was 60 (IQR 45, 72) with 51.4% being male. The most common indications for HTS were traumatic brain injury (45.9%) and intracranial hemorrhage (37.8%). The most common administration location was the emergency department (78.4%). The median IV-gauge (n = 29) was 18 (IQR 18, 20), with the most common placement site being antecubital (48.6%). The median dose of HTS was 250 mL (IQR 250, 350), with a median administration rate of 760 mL/h (IQR 500, 999). There were no episodes of extravasation or phlebitis noted. CONCLUSIONS: Rapid, peripheral administration of 3% HTS boluses is a safe alternative for treatment of neurologic emergencies. Administration at rates up to 999 mL/h did not result in extravasation or phlebitis.

Patient characteristics associated with delayed neurological improvement following acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Delayed neurological improvement (DNI) is a phenomenon that involves patient improvement in the absence of early neurological change following treatment for acute ischemic stroke. The patient characteristics associated with this condition are largely unexplored. METHODS: Following the PRISMA guidelines, a systematic review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. We calculated pooled odds ratios (ORs), mean differences (MDs), and their corresponding 95% confidence intervals (CIs) to test the association between patient characteristics and achievement of DNI. RESULTS: Seven studies, with 3266 patients, were included in our analysis. All studies reported a different definition of DNI, with five studies focusing on rates of good functional outcome at 90 days post-treatment in the absence of early neurological improvement. Use of intravenous thrombolytics was associated with increased rates of DNI (OR 1.96, 95% CI 1.28 to 3.00; p = 0.002). Atrial fibrillation was associated with decreased rates of DNI (OR 0.69, 95% CI 0.57 to 0.82; p < 0.001), as was hypertension (OR 0.66, 95% CI 0.53 to 0.83, p < 0.001), and diabetes mellitus (OR 0.71, 95% CI 0.56 to 0.90; p = 0.005). On average, patients who achieved DNI were 6.30 years younger than their non-DNI counterparts (MD -6.30, 95% CI -9.19 to -3.41; p < 0.001). There were modest associations between male sex and DNI (OR 1.36, 95% CI 1.01 to 1.74, p = 0.042), and smoking and DNI (OR 1.28, 95% CI 1.03 to 1.59, p = 0.027). CONCLUSIONS: DNI is a phenomenon that is not presently well understood. Lack of uniformity among definitions of DNI hinders efforts to explore DNI and the factors associated with its occurrence. Future studies should work to establish a consensus definition of DNI to determine its causes and significance more accurately.

Artificial intelligence-guided screening for atrial fibrillation using electrocardiogram during sinus rhythm: a prospective non-randomised interventional trial.

BACKGROUND: Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation. METHODS: For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971. FINDINGS: 1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11-11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3-5·4] with usual care vs 10·6% [8·3-13·2] with AI-guided screening, p<0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1-11·0). INTERPRETATION: An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening. FUNDING: Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.

Development and Results of the First Certification Examination in the American Board of Medical Specialties Neurocritical Care Subspecialty.

This article reviews the development of the American Board of Medical Specialties subspecialty in neurocritical care (NCC) and describes the requirements for certification and the results of the first certification examination administered in October 2021. The American Board of Psychiatry and Neurology (ABPN) is the administrative board, and the sponsoring boards are the American Board of Anesthesiology (ABA), American Board of Emergency Medicine (ABEM), American Board of Internal Medicine (ABIM), and American Board of Neurological Surgery. The American Board of Medical Specialties approved the subspecialty in 2018, and the Accreditation Council for Graduate Medical Education developed and approved the training requirements in 2021. The fellowship programs are either 12 or 24 months in length and may become available in Academic Year 2022-2023. The first NCC examination was developed by a multispecialty group of subject matter experts following established test development procedures and was successfully administered to 1,011 candidates in October 2021. There were 406 (40.2%) ABIM candidates, 356 (35.2%) ABPN candidates, 208 (20.6%) ABA candidates, and 41 (4.1%) ABEM candidates. The end-of-test survey indicated that most examinees were satisfied with their test taking experience, and the .92 reliability index indicated that the test scores were reliable. An established process was also followed to set the criterion-referenced passing standard, and the resulting pass rate of 72.7% was judged to be reasonable. In summary, the combined efforts of representatives from the ABPN, ABA, ABEM, ABIM, and American Board of Neurological Surgery yielded a quality assessment instrument to identify physicians who possess the expertise required to be certified in NCC. The test development committee will continue to expand and improve the pool of test questions for the next examination, which is scheduled for October 2022.

Association of plasma biomarkers of amyloid and neurodegeneration with cerebrovascular disease and Alzheimer's disease.

The objective of this study was to determine the differential mapping of plasma biomarkers to postmortem neuropathology measures. We identified 64 participants in a population-based study with antemortem plasma markers (amyloid-ß [Aß] x-42, Aßx-40, neurofilament light [NfL], and total tau [T-tau]) who also had neuropathologic assessments of Alzheimer's and cerebrovascular pathology. We conducted weighted linear-regression models to evaluate relationships between plasma measures and neuropathology. Higher plasma NfL and Aß42/40 ratio were associated with cerebrovascular neuropathologic scales (p < 0.05) but not with Braak stage, neuritic plaque score, or Thal phase. Plasma Aß42/40 and NfL explained up to 18% of the variability in cerebrovascular neuropathologic scales. In participants predominantly with modest levels of Alzheimer's pathologic change, biomarkers of amyloid and neurodegeneration were associated with cerebrovascular neuropathology. NfL is a non-specific marker of brain injury, therefore its association with cerebrovascular neuropathology was expected. The association between elevated Aß42/40 and cerebrovascular disease pathology needs further investigation but could be due to the use of less specific amyloid-ß assays (x-40, x-42).

Etiologies and Utility of Diagnostic Tests in Trigeminal Neuropathy.

OBJECTIVE: To evaluate the utility of diagnostic studies in identifying treatable etiologies of trigeminal neuropathy (TNP). PATIENTS AND METHODS: We performed a review of consecutive patients with nontraumatic, noniatrogenic TNP seen at Mayo Clinic between January 1, 2000, and August 31, 2019. Patients were excluded if they had trigeminal neuralgia without neuropathy or if their diagnostic work-up had been completed elsewhere. Data were analyzed to determine which diagnostic studies were most useful in identifying treatable etiologies. RESULTS: In total, 439 patients were included. The mean ± SD age was 56.3±13.6 years and 285 (64.9%) were female. Among the 180 cases in which an etiology was identified (41.0%), neoplasms were causative in 76 (42.2%), while specific connective tissue diseases were implicated in 71 (39.4%). Bilateral TNP (n=83) was associated with the presence of underlying connective tissue disease (P<.01). Identification of etiology was made by magnetic resonance imaging in 88 cases (48.8%), by abnormal connective tissue disease cascades combined with rheumatology consultation in 42 (23.3%), by a previously known connective tissue disorder in 30 (16.7%), and by abnormal connective tissue disease cascades alone in 8 (4.4%). Among the 439 study patients, electromyography was performed in 211 (48.1%) and lumbar puncture in 139 (31.7%), but their diagnostic utility was low. CONCLUSION: Underlying causes of nontraumatic, noniatrogenic TNP can be identified in approximately 40% of cases. Bilateral TNP is strongly associated with underlying connective tissue disease. Careful history taking, dedicated magnetic resonance imaging, and connective tissue panels have the greatest diagnostic utility. Electromyography and cerebrospinal fluid analysis are unlikely to elucidate treatable etiologies of TNP.

Association Between Plasma Biomarkers of Amyloid, Tau, and Neurodegeneration with Cerebral Microbleeds.

BACKGROUND: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. OBJECTIVE: To determine the association between plasma biomarkers (Aß40, Aß42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aß-PET imaging in patients with multiple CMBs. METHODS: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aß40, Aß42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aß-PET were evaluated using hurdle models and multivariable regression models. RESULTS: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aß42/Aß40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8-116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aß-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC -53.0). CONCLUSION: Lower plasma Aß42/Aß40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aß42/Aß40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Trends in Admissions and Outcomes for Treatment of Aneurysmal Subarachnoid Hemorrhage in the United States.

BACKGROUND: Lifestyle modifications and advances in surgical and endovascular techniques for treating unruptured intracranial aneurysm (UIA) have vastly evolved over the last few decades and may have reduced the incidence of aneurysmal subarachnoid hemorrhage (aSAH). However, the actual impact of these changes on the rates and outcomes of aSAH remain unexplored. Thus, we studied national aSAH admissions and outcome trends and changes of major risk factors over time. METHODS: We queried the National Inpatient Sample between 2006 and 2018 to identify adult patients admitted and treated for UIA or ruptured aneurysm with aSAH. The Cochran-Armitage test was conducted to assess the linear trend of proportion of prevalence, inpatient mortality, hypertension, and current smoking status among aSAH admissions. Multivariable logistic regression was conducted to assess the odds of presenting with aSAH versus UIA, in addition to the odds of inpatient mortality among patients with aSAH. RESULTS: A total of 159,913 patients presented with UIA and 133,567 presented with aSAH. Admissions for aSAH decreased by 0.97% (p < 0.001) per year. Current smoking and hypertension were associated with higher odds of being admitted for aSAH compared with the treatment for UIA (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.29-1.48; OR 1.15, 95% CI 1.08-1.22, respectively). Compared with White patients, Black patients (OR 1.32, 95% CI 1.21-1.43), Hispanic patients (OR 1.38, 95% CI 1.25-1.52), and patients of other races and/or ethnicities (OR 1.73, 95% CI 1.54-1.95) had a higher chance of presenting with aSAH. Rates of inpatient mortality among aSAH admissions showed no change over time (p = 0.21). Among patients admitted with aSAH, current smoking and hypertension showed an upward trend of 0.58% (p < 0.001) and 1.60% (p < 0.001) per year, respectively. CONCLUSIONS: Despite a downward trend in the annual frequency of hospitalizations for aSAH, inpatient mortality rates for patients undergoing treatment of the ruptured aneurysm have remained unchanged in the United States. Smoking and hypertension are increasingly prevalent among patients with aSAH. Thus, efforts to control these modifiable risk factors must be further strengthened.

Acute Intracranial Hypertension During Pregnancy: Special Considerations and Management Adjustments.

Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.

Repeat Catheter Angiography in Patients with Aneurysmal-Pattern Angiographically Negative Subarachnoid Hemorrhage.

BACKGROUND: A significant proportion of patients with subarachnoid hemorrhage have a normal cerebral angiogram. Patients with angiographically negative subarachnoid hemorrhage (anSAH) with either perimesencephalic- (panSAH) or aneurysmal-pattern hemorrhage (aanSAH, also known as diffuse anSAH) have an excellent prognosis, but only if underlying vascular abnormalities are completely excluded. The rate of occult aneurysms in patients with aanSAH varies widely across studies. The purpose of this study was to quantify the value of repeat DSA in these patients. METHODS: We reviewed the records of all patients initially diagnosed with aanSAH after a screening DSA at a single tertiary neurovascular referral center from January 2006-April 2018. Patients with panSAH and traumatic SAH were excluded. We also performed a systematic review and meta-analysis of positive second DSAs in previously published case series of patients with aanSAH who underwent two serial DSAs. For meta-analysis, PubMed Central, MEDLINE and Cochrane Library databases were searched for pertinent studies up to November 2019. The rate of aneurysm detection on repeat angiography was extracted from each study. Pooled rates for positive second angiogram were calculated as untransformed proportions in a binary random-effects model meta-analysis. Inter-study heterogeneity was calculated using an I2 statistic. RESULTS: Three of 27 patients (11.1%) with aanSAH and at least two DSAs were subsequently found to have a cerebral aneurysm in our institutional dataset. Twenty-six studies in our systematic review met inclusion criteria, and the pooled rate of positive second angiogram was 10.4% (95% CI 7.3%-13.5%, P < 0.001). Substantial inter-study heterogeneity was observed in the meta-analysis (I2 = 61.7%, P < 0.001). CONCLUSIONS: One in 10 patients with aanSAH has an occult ruptured aneurysm. A second-look DSA should be strongly considered in these cases.

Antiseizure Medication use in Gastric Bypass Patients and Other Post-Surgical Malabsorptive States.

Healthcare professionals are encountering an increasing number of patients who have undergone bariatric surgeries. Antiseizure medications (ASM) have a narrow therapeutic window, and patients with malabsorptive states receiving ASM present a complex situation as the pharmacokinetics of these drugs have only been studied in patients with a normal functioning gastrointestinal tract. Patients with malabsorptive states may have altered pharmacokinetics, and there is limited literature to guide drug selection and dosage adjustment in patients with malabsorptive states. This review highlights pharmacokinetic parameters of common ASM, and considerations when managing patients on them. The effect of pH, lipophilicity, absorption, and metabolism should be taken into account when selecting and managing ASMs in this patient population. Based on these parameters, levetiracetam, and topiramate have fewer issues referable to absorption related to bariatric surgery while oral formulations of phenytoin, carbamazepine, oxcarbamazepine and valproic acid have reduced absorption due to effects of bariatric surgery based on the pharmacokinetic properties of these medications. Extended formulations should be avoided and ASM serum concentrations should be checked before and after surgery. The care of patients with epilepsy who are scheduled to undergo bariatric surgery should be guided by a multidisciplinary team including a pharmacist and a neurologist who should be involved in the adjustment of the ASMs throughout the pre-surgical and post-surgical periods.

Neurological Complications in Patients with Heart Transplantation.

Neurological complications after heart transplantation are common and include cerebrovascular events (ischemic strokes, hemorrhagic strokes, and transient ischemic attacks), seizures, encephalopathy, central nervous system (CNS) infections, malignancies, and peripheral nervous system complications. Although most neurological complications are transient, strokes and CNS infections can result in high mortality and morbidity. Early recognition and timely management of these serious complications are crucial to improve survival and recovery. Diagnosing CNS infections can be challenging because their clinical presentation can be subtle in the setting of immunosuppression. Immunosuppressive medications themselves can cause a broad spectrum of neurological complications including seizures and posterior reversible encephalopathy syndrome. This article provides a review of the diagnosis and management of neurological complications after cardiac transplantation.

Use of Remdesivir in Myasthenia gravis and COVID-19.

Myasthenia gravis and the associated pharmacologic management options could place patients at higher risk of contracting severe acute respiratory syndrome coronavirus 2 and exhibiting more severe manifestations of the novel coronavirus disease 2019 (COVID-19). Multiple agents have been studied for the management of the COVID-19, including remdesivir. To date, no published reports have evaluated the utilization of the antiviral remdesivir in patients with myasthenia gravis. We describe the first reported clinical course of three patients with myasthenia gravis who safely received remdesivir in combination with dexamethasone for the management of COVID-19.

Neurologic complications of infective endocarditis.

Infective endocarditis (IE) is an infection primarily affecting the endocardium of heart valves that can embolize systemically and to the brain. Neurologic manifestations include strokes, intracerebral hemorrhages, mycotic aneurysms, meningitis, cerebral abscesses, and infections of the spine. Neurologic involvement is associated with worse mortality, though it does not always portend a poor functional prognosis. Neuroimaging is indicated in patients who have neurologic symptoms, including cerebral vessel imaging in patients who have subarachnoid hemorrhage. In the case of acute ischemic stroke (IS), IV thrombolysis is contraindicated but endovascular thrombectomy may be a consideration. Neurologic findings understandably raise concern about valve surgery when indicated due to the risk of hemorrhage with perioperative anticoagulation. However, most neurologic complications do not preclude valve surgery and valve surgery may in fact be indispensable in some cases to prevent further neurologic problems. Management decisions in patients with IE and neurologic complications should therefore be multidisciplinary with a major contribution from the neurologist.

Serum Neurofilament to Magnetic Resonance Imaging Lesion Area Ratio Differentiates Spinal Cord Infarction From Acute Myelitis.

BACKGROUND AND PURPOSE: The diagnosis of spontaneous spinal cord infarction (SCI) is limited by the lack of diagnostic biomarkers and MRI features that often overlap with those of other myelopathies, especially acute myelitis. We investigated whether the ratio between serum neurofilament light chain levels and MRI T2-lesion area (neurofilament light chain/area ratio-NAR) differentiates SCI from acute myelitis of similar severity. METHODS: We retrospectively identified Mayo Clinic patients (January 1, 2000-December 31, 2019) with (1) SCI, (2) AQP4 (aquaporin 4)-IgG or MOG (myelin oligodendrocyte glycoprotein)-IgG-associated myelitis at disease clinical presentation, or (3) idiopathic transverse myelitis from a previously identified population-based cohort of patients seronegative for AQP4-IgG and MOG-IgG. Serum neurofilament light chain levels (pg/mL) were assessed at the Verona University (SIMOA, Quanterix) in a blinded fashion on available stored samples obtained ≤3 months from myelopathy presentation. For each patient, the largest spinal cord lesion area (mm2) was manually outlined by 2 independent raters on sagittal T2-weighted MRI images, and the mean value was used to determine NAR (pg/[mL·mm2]). RESULTS: Forty-eight patients were included SCI, 20 (definite, 11; probable, 6; possible, 3); acute myelitis, 28 (AQP4-IgG-associated, 17; MOG-IgG-associated, 5; idiopathic transverse myelitis, 6). The median expanded disability status scale score (range) at myelopathy nadir were 7.75 (2-8.5) and 5.5 (2-8), respectively. Serum neurofilament light chain levels (median [range] pg/mL) in patients with SCI (188 [14.3-2793.4]) were significantly higher compared with patients with AQP4-IgG-associated myelitis (37 [0.8-6942.9]), MOG-IgG-associated myelitis (45.8 [4-283.8]), and idiopathic transverse myelitis (15.6 [0.9-217.8]); P=0.01. NAR showed the highest accuracy for identification of SCI versus acute myelitis with values ≥0.35 pg/(mL·mm2) yielding 86% specificity and 95% sensitivity (area under the curve=0.93). The positive and negative likelihood ratios were 6.67 and 0.06, respectively. NAR remained independently associated with SCI after adjusting for age, gender, immunotherapy before sampling, and days from myelopathy symptoms onset to sampling (P=0.0007). CONCLUSIONS: NAR is a novel and promising clinical biomarker for differentiation of SCI from acute myelitis.

Leukoaraiosis and acute ischemic stroke: 90-day clinical outcome following endovascular recanalization, with proposed "L-ASPECTS".

BACKGROUND: To assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score. METHODS: A retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS ("L-ASPECTS") was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients. RESULTS: 174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (P<0.0001 and AUC=0.7 for L-ASPECTS; P=0.04 and AUC=0.59 for ASPECTS). In the validation cohort, the AUC for L-ASPECTS was 0.79 while the AUC for ASPECTS was 0.70. Of patients that had successful reperfusion (mTICI 2b/3), the AUC for traditional ASPECTS in predicting good functional outcome was 0.80: AUC for L-ASPECTS was 0.89. CONCLUSIONS: Leukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.

SMART syndrome: retrospective review of a rare delayed complication of radiation.

BACKGROUND: SMART (stroke-like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients. METHODS: We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. RESULTS: We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43-55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4-28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow-up of the patients in our cohort was 10 (IQR 6-32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1-52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1-45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age (p = 0.049), temporal lobe involvement (p < 0.001), and diffusion restriction (p = 0.043). CONCLUSIONS: SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one-third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.