Faculty Bibliography

BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

OBJECTIVE:We assessed the effect of visual learning and recall impairment on Victoria Symptom Validity Test (VSVT) accuracy and response latency for Easy, Difficult, and Total Items. METHOD/METHODS:A sample of 163 adult patients administered the VSVT and Brief Visuospatial Memory Test-Revised were classified as valid (114/163) or invalid (49/163) groups via independent criterion performance validity tests (PVTs). Classification accuracies for all VSVT indices were examined for the overall sample, and separately for subgroups based on visual memory functioning. RESULTS:In the overall sample, all indices produced acceptable classification accuracy (areas under the curve [AUCs] ≥ 0.79). When stratified by visual learning/recall impairment, accuracy indices yielded acceptable classification for both the unimpaired (AUCs ≥0.79) and impaired subsamples (AUCs ≥0.75). Latency indices had acceptable classification accuracy for the unimpaired subsample (AUCs ≥0.74), but accuracy and sensitivity dropped for the impaired sample (AUCs ≥0.67). CONCLUSIONS:VSVT accuracy and response latency yielded acceptable classification accuracies in the overall sample, and this effect was maintained in those with and without visual learning/recall impairment for the accuracy indices. Findings indicate that the VSVT is a psychometrically robust PVT with largely invariant cut-scores, even in the presence of bona fide visual learning/recall impairment.

The increased life expectancy of individuals with Down syndrome (DS) is associated with increased prevalence of trisomy 21-linked early-onset Alzheimer's disease (EOAD) and dementia. The aims of this study of 14 brain regions including the entorhinal cortex, hippocampus, basal ganglia, and cerebellum in 33 adults with DS 26-72 years of age were to identify the magnitude of brain region-specific developmental neuronal deficits contributing to intellectual deficits, to apply this baseline to identification of the topography and magnitude of neurodegeneration and neuronal and volume losses caused by EOAD, and to establish age-based staging of the pattern of genetically driven neuropathology in DS. Both DS subject age and stage of dementia, themselves very strongly correlated, were strong predictors of an AD-associated decrease of the number of neurons, considered a major contributor to dementia. The DS cohort was subclassified by age as pre-AD stage, with 26-41-year-old subjects with a full spectrum of developmental deficit but with very limited incipient AD pathology, and 43-49, 51-59, and 61-72-year-old groups with predominant prevalence of mild, moderately severe, and severe dementia respectively. This multiregional study revealed a 28.1% developmental neuronal deficit in DS subjects 26-41 years of age and 11.9% AD-associated neuronal loss in DS subjects 43-49 years of age; a 28.0% maximum neuronal loss at 51-59 years of age; and a 11.0% minimum neuronal loss at 61-72 years of age. A total developmental neuronal deficit of 40.8 million neurons and AD-associated neuronal loss of 41.6 million neurons reflect a comparable magnitude of developmental neuronal deficit contributing to intellectual deficits, and AD-associated neuronal loss contributing to dementia. This highly predictable pattern of pathology indicates that successful treatment of DS subjects in the fourth decade of life may prevent AD pathology and functional decline.

Background Vasospasm is a treatable cause of deterioration following aneurysmal subarachnoid hemorrhage. Cerebral computed tomography perfusion mean transit times have been proposed as a predictor of vasospasm but suffer from well-known technical limitations. We evaluated fully automated, thresholded time-to-maxima of the tissue residue function (T

BACKGROUND:Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. METHODS:Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. RESULTS:The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p<0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p<0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p<0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. CONCLUSIONS:The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics.

Objectives: While national medical guidelines recommend genetic testing for all individuals with non-syndromic autism spectrum disorder (ASD), there is underutilization of genetic testing. This study aims to define the perspectives and approaches to initial genetic testing of ASD diagnosticians in order to improve utilization. Methods: A prospective cross-sectional study was conducted using an anonymous online survey distributed to 59 staff neurologists, developmental-behavioral pediatricians, psychologists, post-graduate physician fellows, and nurse practitioners from a single academic medical center. Questions explored knowledge, attitudes, and practices of initial genetic testing for ASD among diagnosticians. Results: Among the 30 respondents (51% response rate), a lack of comprehensive pre-test genetic counseling was identified and forgetfulness was the most prevalent reason for not recommending genetic testing (n = 7/23, 30%). Insurance prior authorization (PA) for genetic testing was a major barrier for clinicians. More than half of respondents (n = 13/25, 52%) reported being uncomfortable with the PA process. Conclusions: Variability in knowledge and practices among ASD diagnosticians regarding genetic testing was identified. Therefore, potential interventions like clinician and administrative staff education, as well as genetic counselor integration into ASD clinics, may be useful to improve genetic testing utilization.

ABSTRACT:This article presents the telehealth version of the Buffalo Concussion Physical Examination (BCPE) (Tele-BCPE). It is a brief, focused telehealth PE for use in the outpatient setting by sports medicine physicians, pediatricians, neurologists, and primary care physicians. It is derived from the BCPE and includes general considerations for providers performing telehealth services and instructions for adapting traditional clinical tests for virtual use. The Tele-BCPE includes an orthostatic intolerance screen, examination of the cranial nerves, and tests of the oculomotor, vestibular, and cervical systems. It is meant to be used at initial and follow-up outpatient visits for patients acutely after concussion and in those with prolonged symptoms. This telehealth PE, when combined with other assessments, can help provide direct treatment to patients at any stage after concussion and reduce barriers to healthcare access posed by the COVID-19 pandemic and for patients living in rural or underserved areas.

Background: Remotely-supervised transcranial direct current stimulation (RS-tDCS) is a telerehabilitation protocol that provides access to tDCS treatment to participants with aphasia in their homes using real-time monitoring via videoconference and overcomes barriers associated with in-person tDCS treatment of neurological disease. Aims: Two feasibility studies for participants with aphasia are presented herein that investigate (1) RS-tDCS procedural implementation, acceptability, and demand, and (2) acceptability of ten repeated consecutive RS-tDCS sessions. Methods & Procedures: Thirteen participants with aphasia were enrolled in Study 1: (1) seven participants with stroke-induced latent aphasia, (2) four participants with stroke-induced clinically diagnosed aphasia, and (3) two participants with logopenic variant primary progressive aphasia (lvPPA). Four supervisors (1 certified speech-language pathologist [SLP], 3 graduate SLPs-in-training) were trained to supervise RS-tDCS and also provided survey responses. All participants participated in RS-tDCS training and a virtual simulation of home delivery. Two participants with stroke-induced aphasia (1 latent aphasia, 1 clinically diagnosed aphasia) were enrolled in 10 consecutive sessions of RS-tDCS alongside computerized treatment in their home for Study 2. Outcomes & Results: This work provides preliminary evidence for the feasibility of RS-tDCS for people with stable and progressive aphasia of varying severity and typology and includes both participant and clinician perspectives. Importantly, no major barriers to use of RS-tDCS were revealed for people with aphasia, though eHelpers were required for two participants. Conclusions: This work confirms that remotely supervised at-home tDCS studies can be used to enable much-needed efficacy trials, with sufficient sample size, power, and dosing considerations, that will determine the clinical efficacy of tDCS as a treatment adjuvant to aphasia treatment.