We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders in order to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model, where the central nervous system shapes intrathecal immune responses to provide effective protection against persistent, especially by memory T cells, plasmacytoid dendritic cells and CD56bright NK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease and Aicardi-Goutieres syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared to patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment.

Background and Purpose— We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0–1) and moderate (mRS score, 2–3) prestroke disability treated with mechanical thrombectomy. Methods— Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ 2 , logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results— Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45–0.88], P =0.008; adjusted odds ratio, 0.90 [0.60–1.35], P =0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P =0.65), successful recanalization (86.7% versus 83.8%, P =0.33), and median length of hospital stay (5 versus 5 days, P =0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82–5.86], P <0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P <0.001). Conclusions— One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

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Background: The current AHA/ASA guidelines recommend only offering mechanical thrombectomy (MT) to patients without pre-stroke disability. We aimed to compare outcomes of acute ischemic stroke patients with none-to-minimal (modified Rankin score, mRS, 0-1) and moderate (mRS 2-3) pre-stroke disability treated with MT. Methods: Consecutive adult patients undergoing MT for an anterior circulation stroke were prospectively identified at two comprehensive stroke centers from 2012-2018. Procedural and 90-day functional outcomes were compared among patients with pre-stroke mRS 0-1 and 2-3 using Chi-squared, logistic, and linear regression tests and were adjusted for prespecified covariates. Results: A total of 881 patients were included (mean age 70±16 years; 45% female) and 259 (29.4%) had moderate pre-stroke disability. Primary outcome of no accumulation of additional disability at 90 days was observed in 22.4% and 26.7% of patients with no-to-minimal and moderate pre-stroke disability, respectively (OR 1.27[0.88-1.81], p=0.2; adjusted OR 1.90[1.24, 2.94], p=0.004, Figure). Rate of symptomatic intracerebral hemorrhage (7.3% vs 6.2%, p=0.65), successful recanalization (86.7% vs 83.8%, p=0.33), and median length of hospital stay (5 vs 5 days, p=0.06) were not significantly different. Mean change in utility weighted mRS from baseline to 90 days was 0.35±0.35 in pre-stroke mRS 0-1 vs -0.38 ±0.32 in pre-stroke mRS 2-3, p=0.17. Death by 90-days was higher in patients with moderate pre-stroke disability (14.3% vs 40.3%, OR 4.06[2.82-5.86], p<0.001; adjusted OR 2.83[1.84, 4.37], p<0.001). Interpretation: One-third of patients undergoing MT had a moderate pre-stroke disability. The odds of maintaining pre-stroke functional status at 90-days and procedural success rates were not different between patients with no-to-minimal and moderate pre-stroke disability. However, patients with pre-stroke disability were more likely to die by 90 days.

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