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.

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:Patients with Parkinson's disease (PD) are at higher risk of vaccine-preventable respiratory infections. However, advanced, homebound individuals may have less access to vaccinations. In light of COVID-19, understanding barriers to vaccination in PD may inform strategies to increase vaccine uptake. OBJECTIVE:To identify influenza and pneumococcal vaccination rates, including barriers and facilitators to vaccination, among homebound and ambulatory individuals with PD and related disorders. METHODS:Cross-sectional US-based study among individuals with PD, aged > 65 years, stratified as homebound or ambulatory. Participants completed semi-structured interviews on vaccination rates and barriers, and healthcare utilization. RESULTS:Among 143 participants, 9.8% had missed all influenza vaccinations in the past 5 years, and 32.2% lacked any pneumococcal vaccination, with no between-group differences. Homebound participants (n = 41) reported difficulty traveling to clinic (p < 0.01) as a vaccination barrier, and despite similar outpatient visit frequencies, had more frequent emergency department visits (31.7% vs. 9.8%, p < 0.01) and hospitalizations (14.6% vs. 2.9%, p = 0.03). Vaccine hesitancy was reported in 35% of participants, vaccine refusal in 19%, and 13.3% reported unvaccinated household members, with no between-group differences. Nearly 13% thought providers recommended against vaccines for PD patients, and 31.5% were unsure of vaccine recommendations in PD. CONCLUSION/CONCLUSIONS:Among a sample of homebound and ambulatory people with PD, many lack age-appropriate immunizations despite ample healthcare utilization. Many participants were unsure whether healthcare providers recommend vaccinations for people with PD. In light of COVID-19, neurologist reinforcement that vaccinations are indicated, safe, and recommended may be beneficial.

Introduction: Activities of daily living (ADLs) are performed through a sequence of fundamental units of motion, called primitives. We previously observed that during ADLs, one upper extremity (UE) may engage two objects simultaneously, such as turning on a faucet while holding a toothbrush. These dual-object primitives (DOPs) may demand increased neural resources, as they likely entail the simultaneous execution of two motor plans. Skilled movement by the nondominant healthy UE or the paretic UE has also been found to require increased neural activity. We posited that performance of DOPs would exceed the neural resources available to the nondominant or paretic side, reducing their performance on these sides. We also predicted that the frequency of DOP performance by the paretic UE would relate to its degree of motor impairment.
Method(s): We studied 19 right-hand dominant healthy subjects (10M:9F; 62.0 +/- 13.6 years) and 43 premorbidly right-hand dominant stroke subjects (23M:20F; 24L:19R paretic; 57.5 +/- 14.5 years; 5.7 +/- 6.5 years post stroke). We evaluated subjects on the UE Fugl-Meyer Assessment (FMA) and videotaped their performance of a feeding and toothbrushing task. We analyzed the videos to extract the incidence and count of DOP performance by each UE. To control for dominance and paresis, we normalized DOP counts to the total number of primitives performed by the UE. We used two-tailed Fisher's Exact tests to compare the incidence of DOPs performed by each UE, and Spearman's correlation to examine the relationship between FMA score and DOP frequency.
Result(s): In healthy subjects, the incidence of DOPs was lower on the nondominant than dominant side (12/19 vs. 19/19; p<0.01). In stroke subjects, the incidence of DOPs was lower on the paretic than nonparetic side (19/43 vs. 43/43; p<0.01). The laterality of paresis did not affect whether that UE would perform DOPs (11/19 dominant paretic vs. 8/24 nondominant paretic; p=0.132). In stroke subjects, lower FMA scores were related to a lower frequency of DOP performance on their paretic UE (rho=0.368, p=0.015).
Discussion(s): Our results suggest that UE laterality and impairment may impact DOP performance in healthy and stroke subjects, respectively. DOPs were less commonly performed by the nondominant UE and the paretic UE, and worse impairment was associated with lower DOP performance. We speculate that engaging two objects simultaneously requires additional neural resources that are unavailable to the nondominant or injured motor network. It is conceivable that the return of DOP performance by the paretic UE may track with the availability of a recovered neural substrate.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9-10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1-6, 7-12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1-6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.

Background: Hemodialysis (HD) can reduce amyloid-beta (Abeta) species in wholebody circulation by 30 to 50%. Due to the dynamic exchange of Abeta between the brain and the blood, we hypothesized that HD might lower Abeta levels in the cerebrospinal fluid (CSF).
Method(s): In a dialysis network with over 160,000 patients, we identified three maintenance HD patients (age 36+/-9 years) with ventriculo-peritoneal (VP) shunts who were subsequently recruited for this IRB-approved research study. Study subjects were dialyzed on Monday, Wednesday, and Friday. Plasma samples were collected at 6 timepoints during the 3 HD sessions. One subject was withdrawn over safety concern related to the VP shunt tap procedure. Two subjects further underwent VP shunt taps for CSF sample collection before and after the Wednesday and Friday HD sessions, and once on interdialytic days (Tuesday, Thursday). Abeta1-42 and Abeta1-40 were quantified by Neuro 3-Plex SIMOA assays (Quanterix, MA, USA).
Result(s): HD effectively reduced plasma Abeta1-40 by 41% and Abeta1-42 by 34% (Fig 1a and 1b, p < 0.01). In CSF, levels of Abeta increased after Wednesday HD sessions in subject 1 (Abeta1-40: 4.2-fold, Abeta1-42: 5.5-fold) and subject 2 (Abeta1-40 and Abeta1-42: 1.06-fold), while Abeta decreased after Friday HD sessions in both subject 1 (Abeta1-40: 0.1-fold, Abeta1-42: 0.1-fold) and 2 (Abeta1-40: 0.7-fold, Abeta1-42: 0.7-fold) shown in Figure 1c-f.
Conclusion(s): This is the first report of Abeta dynamics in the CSF and plasma of HD patients. While plasma levels were in similar ranges, we found high inter-individual variations of CSF levels. Different plasma-to-CSF ratios after HD may reflect individual brain Abeta pools that are accessed by HD. We corroborate previous reports demonstrating the removal of Abeta from the blood compartment by HD. (Figure Presented)