Faculty Bibliography

BACKGROUND:We aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without. METHODS:We performed a retrospective analysis using the Vizient Clinical Data Base and included hospital discharges from April 1 to July 31 2020 with ICD-10 codes for AIS and EVT. The primary outcome was in-hospital death and the secondary outcome was favorable discharge, defined as discharge home or to acute rehabilitation. We compared patients with laboratory-confirmed COVID-19 to those without. As a sensitivity analysis, we compared COVID-19 AIS patients who did not undergo EVT to those who did, to balance potential adverse events inherent to COVID-19 infection. RESULTS:We identified 3165 AIS patients who received EVT during April to July 2020, in which COVID-19 was confirmed in 104 (3.3%). Comorbid COVID-19 infection was associated with younger age, male sex, diabetes, black race, Hispanic ethnicity, intubation, acute coronary syndrome, acute renal failure, and longer hospital and intensive care unit length of stay. The rate of in-hospital death was 12.4% without COVID-19 vs 29.8% with COVID-19 (P<0.001). In mixed-effects logistic regression that accounted for patient clustering by hospital, comorbid COVID-19 increased the odds of in-hospital death over four-fold (OR 4.48, 95% CI 3.02 to 6.165). Comorbid COVID-19 was also associated with lower odds of a favorable discharge (OR 0.43, 95% CI 0.30 to 0.61). In the sensitivity analysis, comparing AIS patients with COVID-19 who did not undergo EVT (n=2139) to the AIS EVT patients with COVID-19, there was no difference in the rate of in-hospital death (30.6% vs 29.8%, P=0.868), and AIS EVT patients had a higher rate of favorable discharge (32.4% vs 47.1%, P=0.002). CONCLUSION/CONCLUSIONS:In AIS patients treated with EVT, comorbid COVID-19 infection was associated with in-hospital death and a lower odds of favorable discharge compared with patients without COVID-19, but not compared with AIS patients with COVID-19 who did not undergo EVT. AIS EVT patients with COVID-19 were younger, more likely to be male, have systemic complications, and almost twice as likely to be black and over three times as likely to be Hispanic.

BACKGROUND:It is well documented that ambulatory disability in MS worsens over time, but there is a dearth of information on symptom evolution in other domains commonly affected by MS. METHODS:SymptoMScreen (SyMS) is a validated tool for assessing symptom severity in 12 domains commonly affected by MS. Patients who attended two specialized MS centers filled out SyMS at each visit. We included in the study patients with neurologist-diagnosed MS who completed two SyMS questionnaires separated at least 12 months. We used the first and final assessment and adjusted for time on study, baseline SyMS score, age, sex, race, MS type, disability strata, and site. Changes over time were also examined using Markov chain estimates of moving from one level of botheration to another for each domain over 1-year periods. RESULTS:A total of 1,014 MS patients met the inclusion criteria. Mean composite SyMS score was 1.4 (±1.16) at baseline and increased by 0.084 (±0.73) points during 21.0 (±5.5) months of followup (p<0.0001). The initial mean composite SyMS score correlated strongly with the final mean composite SyMS score (r=0.81). Individual domain SyMS scores at baseline were highest for fatigue: 2.2 (±1.7), and lowest for vision: 1.1 (±1.3) and dexterity: 1.1 (±1.4). Small but significant increases during followup were seen in dexterity, bladder, vision, and pain domains, while significant decreases were seen in anxiety and sensory domains. We observed a high degree of inter-individual variability in symptom severity with the more extreme scores tending to resolve over time. CONCLUSIONS:Symptom botheration increases modestly year-to-year, as would be expected in a slowly progressive disease that evolves over decades. Initial symptom burden strongly correlated with final symptom burden, but there was a high degree of individual variability in symptom severity.

OBJECTIVES/OBJECTIVE:To analyze and compare differences between epidemiological and clinical aspects, as well as radiologic findings and treatment, in a series of adult patients with traumatic intracranial hypotension (TIH) and spontaneous intracranial hypotension (SIH) treated at our institution in order to identify predictors of recurrence. BACKGROUND:Cerebrospinal fluid hypotension headache (CSF-HH) is often caused by orthostasis and relieved by recumbency. Etiology can be either traumatic or spontaneous. Indirect signs of CSF hypotension are often observed on brain MRI. The most common therapeutic approach is conservative management and, when necessary, the use of an epidural blood patch. METHODS:Medical history and brain MRI of adult patients consulting our institution with a diagnosis of CSF-HH between January 2010 and March 2019, were retrospectively reviewed. Clinical criteria as per the International Classification of Headache Disorders, 3rd edition, were applied. Presence of typical MRI findings were assessed by two experienced neuroradiologists, previously informed of patients' clinical characteristics. Patients were divided into two different groups, namely: Group A: Spontaneous Intracranial Hypotension (SIH) and Group B: Traumatic Intracranial Hypotension (TIH). Recurrence was defined as return of symptoms after one month of remission. In order to find predictors of recurrent intracranial hypotension the patients were divided into three groups: Recurrent Orthostatic headache (ROH); (33 cases; 25%); Non-Recurrent Orthostatic headache (NROH) (84; 61%) and Patients missing follow-up (20; 15%). The latter were excluded from the regression analysis. RESULTS:137 patients with CSF-HH were identified: 80 traumatic (54 women, age 33.8 ± 10.4 years) and 57 spontaneous (31 women, age 43.9 ± 15.2 years). Median follow-up was 35 months (range: 8 months-9 years). Compared with TIH, patients with SIH showed lower frequency of orthostatic headache and higher frequency of aural fullness. Also, in patients with SIH, brain MRI showed a higher frequency of pachymeningeal enhancement, ventricular collapse, cisternal obliteration, posterior fossa crowding, brainstem distortion, and a more likely presence of subdural collections. Patients with SIH required an epidural blood patch treatment more often, showed higher recurrence rates, and were more prone to develop subdural hematomas. RECURRENCE/UNASSIGNED:As more days elapsed between headache onset and clinical consultation, the presence of spontaneous intracranial hypotension, tinnitus, and thoraco-lumbo-sacral pain were all more common in patients with recurrence. Findings on brain MRI suggesting higher recurrence rates in patients included: ventricular collapse, brainstem distortion, and posterior fossa crowding. Patients treated with invasive therapy (epidural blood patch) presented a higher recurrence rate. In the multivariate regression analysis, the only independent predictor of recurrence after adjusting for age, sex and traumatic vs spontaneous cause of IH, was brainstem distortion diagnosed on MRI (OR 5.13, 95% CI: 1.2-21.7; p = 0.026). CONCLUSIONS:SIH and TIH can no longer be likened, since there is considerable variability in clinical presentation, imaging findings, response to treatment and recurrence rates. Anatomical abnormalities underlying SIH leaks are often complex and not simply a disruption of normal structures as encountered in TIH, which could explain why treatment success is poor and recurrence rates remain high.

BACKGROUND:Some patients with chronic pain and implanted spinal cord stimulators (SCS) or intrathecal (IT) pumps fail to obtain significant pain relief. The use of dual-modality treatment with both therapies is understudied. This is the first study evaluating comprehensive outcomes in this patient population, and to report outcomes primarily using IT ziconotide. METHODS:We retrospectively analyzed 11 patients with chronic pain treated with both SCS and IT therapy. When a primary treatment failed to capture significant pain relief, a secondary device was trialed and implanted. Pain severity (measured by the numeric rating scale, NRS) was assessed by the change from baseline to after the first and second intervention. In a subset of patients (n=6), quality of life metrics were also assessed. Outcome measures were analyzed closest to the one-year follow-up date after implantation of the first modality, then at the most recent follow-up following implantation of the second modality. RESULTS:SCS leads were percutaneous (n=2) or paddle (n=9), and commonly covered T8-10. IT medication included ziconotide (n=8), baclofen (n=1), hydromorphone (n=1), or morphine-clonidine (n=1). There was a mean of 19.64±3.17 months between primary and secondary intervention. There was a significant improvement in pain severity from baseline to implantation of the second modality (p=0.032) at a mean follow-up of 50.18±11.83 months. CONCLUSIONS:We suggest dual-modality therapy is a potential treatment option in patients who have lost efficacy with a single neuromodulation modality. Further study is required to identify potential responders and non-responders.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.

BACKGROUND:Leucine-rich repeat kinase 2 kinase inhibitors are being vigorously pursued as potential therapeutic options; however, there is a critical need for sensitive and quantitative assays of leucine-rich repeat kinase 2 function and target engagement. OBJECTIVES/OBJECTIVE:Our objective was to compare collection and storage protocols for peripheral blood mononuclear cells, and to determine the optimal conditions for downstream analyses of leucine-rich repeat kinase 2 in PD cohorts. METHODS:Here, we describe enzyme-linked immunosorbent assay-based assays capable of detecting multiple aspects of leucine-rich repeat kinase 2 function at endogenous levels in human tissues. RESULTS:In peripheral blood mononuclear cells from both healthy and affected carriers of the G2019S mutation in leucine-rich repeat kinase 2, we report, for the first time, significantly elevated in vitro kinase activity, while detecting a significant increase in pS935/leucine-rich repeat kinase 2 in idiopathic PD patients. CONCLUSIONS:Quantitative assays such as these described here could potentially uncover specific markers of leucine-rich repeat kinase 2 function that are predictive of disease progression, aid in patient stratification, and be a critical component of upcoming clinical trials. © 2020 International Parkinson and Movement Disorder Society.