Faculty Bibliography

Sialidosis type 1 is a rare lysosomal storage disorder caused by mutations of the neuraminidase gene. Specific features suggesting this condition include myoclonus, ataxia and macular cherry-red spots. However, phenotypic variability exists. Here, we present detailed clinical and video description of three patients with this rare condition. We also provide an in-depth characterization of eye movement abnormalities, as an additional tool to investigate pathophysiological mechanisms and to facilitate diagnosis. In our patients, despite phenotypic differences, eye movement deficits largely localized to the cerebellum.

Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk. Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05. Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2-137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up. Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD) but can have an adverse effect on speech. In normal speakers and in those with spinocerebellar ataxia, an inverse relationship between regional cerebral blood flow (rCBF) in the left inferior frontal (IFG) region and the right caudate (CAU) is associated with speech rate. This pattern was examined to determine if it was present in PD, and if so, whether it was altered by STN-DBS. Methods: Positron Emission Tomography (PET) measured rCBF during speech in individuals with PD not treated with STN-DBS (n = 7), and those treated with bilateral STN-DBS (n = 7). Previously reported results from non-PD control subjects (n = 16) were reported for comparison. The possible relationships between speech rate during scanning and data from the left and right IFG and CAU head regions were investigated using a step-wise multiple linear regression to identify brain regions that interacted to predict speech rate. Results: The multiple linear regression analysis replicated previously reported predictive coefficients for speech rate involving the left IFG and right CAU regions. However, the relationships between these predictive coefficients and speech rates were abnormal in both PD groups. In PD who had not received STN-DBS, the right CAU coefficient decreased normally with increasing speech rate but the left IFG coefficient abnormally decreased. With STN-DBS, this pattern was partially normalized with the addition of a left IFG coefficient that increased with speech rate, as in normal controls, but the abnormal left IFG decreasing coefficient observed in PD remained. The magnitudes of both cortical predictive coefficients but not the CAU coefficient were exaggerated with STN-DBS. Conclusions: STN-DBS partially corrects the abnormal relationships between rCBF and speech rate found in PD by introducing a left IFG subregion that increases with speech rate, but the conflicting left IFG subregion response remained. Conflicting IFG responses may account for some of the speech problems observed after STN-DBS. Cortical and subcortical regions may be differentially affected by STN-DBS.

Background/Objectives/UNASSIGNED:Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. Methods/UNASSIGNED:We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. Results/UNASSIGNED:= 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. Conclusion/UNASSIGNED:Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

Undiagnosed concussions increase the risk of additional concussion and persistent symptoms from concussion. Because there are no reliable objective markers of concussion, self-reporting of subjective and non-visible symptoms are critical to ensuring proper concussion management. For this reason, educational interventions target concussion reporting, but the majority of studies have examined the efficacy of single educational interventions or compared interventions to one another. This randomized crossover study sought to identify whether there was benefit to administering multiple concussion education programs in tandem, back to back. The study randomized 313 male high school football players to first receive CrashCourse concussion education (CC) or Centers for Disease Control and Prevention video concussion education (CDC) followed by crossover with the other education. Athlete concussion-reporting intention, attitudes, subjective norms, perceived behavioral control, and enjoyment of education were assessed at baseline and after each intervention. There were statistically significant improvements across all measures, both after single intervention and crossover (all p < 0.001). Secondary analyses examining differences between education found that athletes reported higher enjoyment of concussion education immediately after participating in CC, as compared to CDC (p < 0.001). These findings demonstrate an additive benefit to implementing CC and CDC education in tandem, without decrement in enjoyment of concussion education after experiencing dual educations; in fact, enjoyment of concussion education improved after receiving education programs back to back. These educational programs appear to complement one another, and the results support the use of multi-modal concussion education to differentially target and maximize concussion reporting.

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

Seizure clusters, an intermediate between single seizure and status epilepticus, are associated with morbidity, impaired quality of life, and premature mortality. The relationship between seizure clusters and sudden unexplained death in epilepsy (SUDEP) is poorly understood. Here, we define seizure clusters; review comorbid psychiatric disorders and memory deficits associated with seizure clusters; and review cases of witnessed SUDEP for which seizure frequency prior to death is available. Patients with a history of seizure clusters have a 2.5 fold increased risk for SUDEP, and one third of patients with monitored in hospital SUDEP experienced a cluster of generalized tonic clonic seizures prior to death. Understanding the effects of seizure frequency and duration on SUDEP risk could yield new insights in SUDEP pathophysiology and new targets for intervention.