Faculty Bibliography

Failure to diagnose transient ischemic attack (TIA) or stroke in a timely fashion is associated with significant patient morbidity and mortality. In the outpatient or clinic setting, we suspect that patients with minor, transient, and atypical manifestations of cerebrovascular disease are most prone to missed or delayed diagnosis. We therefore detail common stroke chameleon symptoms as well as atypical stroke presentations, broadly review new developments in the study of diagnostic error in the outpatient setting, suggest practical clinical strategies for diagnostic error reduction, and emphasize the need for rapid consultation of stroke specialists when appropriate. We also address the role of psychiatric disease and vascular risk factors in the diagnostic evaluation and treatment of suspected stroke/TIA patients. We advocate incorporating diagnostic time-outs into clinical practice to assure that the diagnosis of TIA or stroke is considered in all relevant patient encounters after a detailed history and examination are conducted in the outpatient setting.

Background: Cognitive impairment is a common feature of multiple sclerosis (MS). A semi-structured interview, including informant input, can characterize the experience of individuals living with MS and cognitive involvement. Objective: We administered the Cognitive Assessment Interview (CAI), a patient- and informant-based semi-structured interview, to characterize the experience of cognitive impairments in those living with MS. Methods: Trained raters administered the CAI to a sample of MS participants and their informants enrolled for a trial of cognitive remediation. Cognitive impairments on the CAI were characterized and compared to those captured by neuropsychological and self-report measures. Results: A total of n = 109 MS participants (mean age = 50.3 ± 12.2) and their available informants (n = 71) were interviewed. Participants reported experiencing processing speed (90/106, 85%), working memory (87/109, 80%), and learning and memory (79/109, 72%) problems most commonly. CAI-based ratings were moderately correlated with a self-report measure (Multiple Sclerosis Neuropsychological Screening Questionnaire, r_s = 0.52, p < 0.001) and only mildly correlated with objective neuropsychological measures specific to executive functions (r

Background: To describe preliminary results of a multi-center, randomized, blinded, placebo-controlled, pilot trial of shunt surgery in INPH.
Method(s): Five sites randomized 18 patients scheduled for ventriculoperitoneal shunting based on CSF-drainage response. Patients were randomized to a Codman Certas Plus valve with SiphonGuard at either setting 4 (Active, N=9) or setting 8/virtual off (Placebo, N=9). Patients and assessors were blinded to the shunt setting. Outcomes included 10-meter gait velocity, cognitive function, and bladder activity scores. The prespecified primary analysis compared changes in 4-month gait velocity in the Active versus Placebo groups. After the 4 months follow up, all shunts were opened, i.e., adjusted to setting 4 whereafter patients underwent 8 and 12-month post-surgical assessment. At the 8-month follow-up, the Placebo group had had an open shunt for 4 months and the Active group for 8 months.
Result(s): At 4-months, gait velocity increased by 0.28+/-0.28m/s in the Active Group and 0.04+/-0.17m/s in the Placebo Group (p=0.071). Overactive Bladder (OAB-q) scores improved in the Active versus Placebo groups (p=0.007). At 8 months, Placebo gait velocity increased by 0.36+/-0.27m/s and was comparable to the Active Group (0.40+/-0.20m/s p=0.56).
Conclusion(s): This study shows a trend suggesting gait velocity improves more at an Active shunt setting than a Placebo shunt setting and demonstrates the feasibility of a placebo-controlled trial in iNPH

Background and Aims: Knowledge about assumed causes and subsequent treatment in patients with atrial fibrillation (AF) and ischemic stroke despite anticoagulant therapy is limited.
Method(s): Retrospective analysis of patients with known AF and acute ischemic stroke despite therapy with vitamin-K-antagonists (VKA) or direct oral anticoagulants (DOAC). We determined probable stroke cause (s) as either (a)competing etiology other than AF (e.g. large artery atherosclerosis), (b)medication error (subtherapeutic DOAClevel or off-label DOAC-dosing/INR<2.0 or reported non-adherence) or (c)cardoembolic stroke despite anticoagulation (absence of medication error and competing etiology) and subsequent prevention therapies. The composite of recurrent ischemic stroke, intracranial hemorrhage, or allcause death was assessed at 3 months.
Result(s): We analyzed 2, 949 patients from 11 centers (age 81years, IQR [76-86], 48%Female, NIHSS 6, IQR[2-14], 57% DOAC, 913 with DOAClevels, median CHA2DS2-VASc score 4, IQR[4, 6]). Of those, 24% had competing etiology (DOAC vs VKA: 28% vs 20%, aOR1.3, 95%CI 0.96-1.7), 32% medication error (23% vs 43%, aOR0.5, 95%CI 0.4-0.6) and 44% cardoembolic stroke despite anticoagulation (49% vs 37%, aOR1.6, 95%CI 1.2-2.1). After index stroke, anticoagulant drug was changed in 45.8% of patients (1317/2877), antiplatelets were added in 7.1% (203/ 2873), 3.4% (94/2776) received carotid revascularization therapies and 1%(17/1764) underwent left atrial appendage occlusion. Eight centers collected 3-month outcome data (2, 084 patients). In those, stroke recurred in 4.6% (84/1844; completeness 88.5%). The composite outcome occurred in 27% (516/1908, completeness 91.6%), and no specific prevention strategy reduced its odds.
Conclusion(s): Stroke despite anticoagulation comprises heterogeneous causes with 1/3 of strokes potentially preventable and 1/4 attributable to competing etiologies. Recurrence rate is high and the optimal secondary prevention strategy needs to be determined. (Table Presented)

The management of women with epilepsy (WWE) presents many challenges for physicians. The primary goal during pregnancy is to achieve the best possible control of seizures with the least adverse effects associated with exposure to antiseizure medications (ASMs). Even though the guidelines for managing pregnant WWE are expanding, no definitive guidelines exist for the treatment of status epilepticus (SE). Additionally, much of our data comes from the effect of generalized tonic clonic seizures on the fetus. There is very little data on the effect of focal seizures and even less on focal SE. Here we present two cases of pregnant WWE who presented in focal SE, who underwent simultaneous video-EEG monitoring and fetal heart tracing (FHT). During each focal seizure the FHT demonstrated a normal baseline heart rate with moderate variability. In the second case due to continuous seizures more aggressive treatment had to be started. This led to maternal relative autonomic instability as well as absent variability on FHT. These findings raise many questions on the management of focal SE during pregnancy including if the effect of treatment is worse than the seizures, and how do we balance our goals for both mother and fetus?

Recent findings challenge the prior notion that the cerebellum remains unaffected by Alzheimer's disease (AD). Yet, it is unclear whether AD exacerbates age-related cerebellar grey matter decline or engages distinct structural and functional territories. We performed a meta-analysis of cerebellar grey matter loss in normal ageing and AD. We mapped voxels with structural decline onto established brain networks, functional parcellations, and along gradients that govern the functional organisation of the cerebellum. Importantly, these gradients track continuous changes in cerebellar specialisation providing a more nuanced measure of the functional profile of regions vulnerable to ageing and AD. Gradient 1 progresses from motor to cognitive territories; Gradient 2 isolates attentional processing; Gradient 3 captures lateralisation differences in cognitive functions. We identified bilateral and right-lateralised posterior cerebellar atrophy in ageing and AD, respectively. Age- and AD-related structural decline only showed partial spatial overlap in right lobule VI/Crus I. Despite the seemingly distinct patterns of AD- and age-related atrophy, the functional profiles of these regions were similar. Both participate in the same macroscale networks (default mode, frontoparietal, attention), support executive functions and language processing, and did not exhibit a difference in relative positions along Gradients 1 or 2. However, Gradient 3 values were significantly different in ageing vs. AD, suggesting that the roles of left and right atrophied cerebellar regions exhibit subtle functional differences despite their membership in similar macroscale networks. These findings provide an unprecedented characterisation of structural and functional differences and similarities in cerebellar grey matter loss between normal ageing and AD.