Faculty Bibliography

We report 13 SUDEP cases in the North American SUDEP Registry with both psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) among a consecutive series of 231 cases (excluding epileptic encephalopathies). On average, cases of PNES + ES died at a younger age (23 ± 11 years) than the ES-only cohort (30 ± 14 years), and died an average of 3 years after PNES diagnosis. We found no statistically significant confounding cardiac, respiratory, or psychiatric comorbidities and equal rates of anti-seizure medication adherence, although there was a trend for higher rates of psychiatric disorders in the PNES group. Our findings confirm that patients with comorbid ES and PNES can die from SUDEP and that there may be a high-risk period after the diagnosis of PNES is made in patients with comorbid ES. Such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

Objective: The FOCUS study of fremanezumab, a fullyhumanised monoclonal antibody (IgG2DELTAa) that selectively targets calcitonin gene-related peptide (CGRP), was the first and largest study of a migraine preventive treatment in adults with both chronic and episodic migraine (CM and EM) and documented inadequate response to 2-4 classes of migraine preventive medications. Efficacy in a subgroup of patients with medication overuse (use of any acute medication on >=15 days/month or triptans/ergots/combination medications on >=10 days/month) at baseline (BL) was evaluated.
Method(s): Patients were randomised (1:1:1) to quarterly (qtly) fremanezumab (Month [Mo] 1: 675 mg; Mo 2 and 3: placebo), monthly (mthly) fremanezumab (Mo 1: CM, 675 mg; EM, 225 mg; Mo 2 and 3: 225 mg), or matched mthly placebo for 12 weeks. Changes from BL in mthly migraine days and headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were compared using a mixed-effect model for repeated measures.
Result(s): Of 838 randomised patients, 427 had medication overuse. Reductions from BL in mthly average migraine days and headache days of at least moderate severity at 4 weeks and during 12 weeks of treatment were significantly greater with both fremanezumab regimens vs placebo (all P<=0.0001; Table).
Conclusion(s): Qtly and mthly fremanezumab provided early and sustained reductions in migraine and headache days vs placebo in patients with medication overuse and documented inadequate response to 2-4 classes of migraine preventive medications. (Table Presented)

BACKGROUND:Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options. EVIDENCE ACQUISITION/METHODS:With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention. RESULTS:Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise. CONCLUSIONS:This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.

PURPOSE/OBJECTIVE:Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis affecting an estimated 40-60% of patients, and reducing their quality of life. We reviewed the epidemiology and pathophysiology of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis, summarize non-pharmacologic and pharmacological treatment strategies and discuss the impact of novel disease-modifying treatments such as transthyretin stabilizers (diflunisal, tafamidis) and RNA interference agents (patisiran, inotersen). METHODS:Literature review. RESULTS:Orthostatic hypotension in patients with hereditary transthyretin amyloidosis can be a consequence of heart failure due to amyloid cardiomyopathy or volume depletion due to diarrhea or drug effects. When none of these circumstances are apparent, orthostatic hypotension is usually neurogenic, i.e., caused by impaired norepinephrine release from sympathetic postganglionic neurons, because of neuronal amyloid fibril deposition. CONCLUSIONS:), a synthetic norepinephrine precursor, has shown efficacy in controlled trials of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis and is now approved in the US and Asia. Although they may be useful to ameliorate autonomic dysfunction in hereditary TTR amyloidosis, the impact of disease-modifying treatments on neurogenic orthostatic hypotension is still uninvestigated.

Introduction: Although often characterized as a disease of white matter, gray matter (GM) pathology has been shown to play an important role in multiple sclerosis (MS).
Objective(s): We used diffusion kurtosis imaging (DKI), a clinically feasible extension of diffusion tensor imaging (DTI) to characterize pathology in cortical and subcortical GM regions in MS patients compared to controls and study how selected DKI parameters correlate with disease severity in comparison to traditional volumetric approaches.
Method(s): 36 MS patients and 24 age and gender matched controls were enrolled in the study. MS patients completed a Patient Determined Disease Steps Score (PDDS). All patients received MRI on a 3T MR Scanner (Siemens, Skyra, or Prisma), which included whole brain 3D magnetization-prepared rapid gradientecho (MPRAGE) (1 mm³ isotropic resolution) for extracting volumetrics and monopolar diffusion-weighted echo-planar imaging (EPI) (voxel size = 1.7 x 1.7 x 3 mm³, b=0, 250, 1000, and 2000 s/m² along 84 directions, TE/TR = 100/3500 ms, GRAPPA with acceleration 2, and multiband 2) for deriving diffusion metrics. Volume metrics from automatic segmentation from MPRAGE and diffusion metrics which included mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA) were derived for 7 subcortical and 5 cortical GM regions. We determined the partial correlations between PDDS and either GM volume or diffusion parameters covarying for gender and age. We also determined the differences in volume and diffusion metrics between MS patients and controls using ANCOVA with age as the covariate.
Result(s): We observed statistically significant differences in volumes between MS patients and controls for the amygdala, caudate, putamen, nucleus accumbens, cingulate lobe, and subcortical gray volumes with p-values ranging from 0.001 to 0.044. Statistically significant group differences were observed in a majority of the ROI for FA, MD, and MK. Overall, FA was increased, MD was increased, and MK was decreased for most ROI in MS patients compared to controls. There was an increased number of significant partial correlations between PDDS and diffusion metrics compared to PDDS and volume metrics, specifically positive correlations for occipital lobe MD and FA and negative correlations for hippocampal FA.
Conclusion(s): Our results suggest that DKI metrics are sensitive to changes in GM and complimentary to GM volumetrics as an index of GM pathology

The published version of this article unfortunately contained a mistake in Table 2. CGI-S and CGI-I values has been interchanged. The Table is corrected here.

Cognitive science research on learning and instruction is often not directly connected to discipline-based research. In an effort to narrow this gap, this essay integrates research from both fields on five learning and instruction strategies: active retrieval, distributed (spaced) learning, dual coding, concrete examples, and feedback and assessment. These strategies can significantly enhance the effectiveness of science instruction, but they typically do not find their way into the undergraduate classroom. The implementation of these strategies is illustrated through an undergraduate science course for nonmajors called Science in Our Lives. This course provides students with opportunities to use scientific information to solve real-world problems and view science as part of everyday life.

Introduction: Travel to clinic can be difficult due to barriers of time and cost and becomes even more burdensome for MS patients living with disabilities. Telemedicine platforms present a solution by providing supervised treatment and rehabilitation at home. Without barriers to access, patients may be more compliant and adherent to daily rehabilitation exercises. We have a large telerehabilitation research program in MS that pairs rehabilitation with transcranial direct current stimulation (tDCS), an emerging non-invasive brain stimulation technique used to improve outcomes. We provide real-time treatment administration and supervision via HIPAA compliant videoconference, termed remotely supervised tDCS or RS-tDCS.
Objective(s): To characterize the advantages of telemedicine for patients with MS in an urban setting.
Aim(s): To measure barriers to access for participants in our RS-tDCS telerehabilitation program, as well as compliance and adherence to a remotely supervised intervention.
Method(s): Participants with MS were recruited to complete a trial of cognitive remediation paired with RS-tDCS at-home. Participants were surveyed following completion of the intervention and asked to rate their difficulty in attending the clinic (on a 1-5 ordinal scale, 1 = no difficulty and 5 = nearly impossible difficulty) as well as the typical cost of attending clinic. Descriptive statistics and ordinal logistic regression models were used to evaluate the factors driving difficulty of travel.
Result(s): Participants (n=44) reported that round trip travel to the clinic requires an average of 2.3+/-2.3 hours of time and $27.04+/-38.13. Participants rated the difficulty associated with attending clinic as being moderate to significant (2.5+/-1.3). Regression analyses that included disease features produced better models and accounted for greater variance in difficulty attending the clinic, (p< 0.001, McFadden pseudo R2 = .515), as compared with socioeconomic variables alone (p< 0.001, McFadden pseudo R2 = .140). The RS-tDCS protocol was successful in providing treatment (95% compliance to treatment) and 93% of participants reported satisfaction with the treatment and remote protocols.
Conclusion(s): Participants with MS face considerable difficulty reaching the clinic, largely due to increasing neurologic disability. Telemedicine techniques such as RS-tDCS can increase treatment access, reduce physical and financial burden of travel and maintain high rates of treatment adherence