Effect of Obesity on Retinal Integrity in African Americans and Caucasian Americans With Relapsing Multiple Sclerosis.

Objective: To study the effect of obesity on retinal structures in African Americans (AAs) and Caucasian Americans (CAs) with relapsing-remitting multiple sclerosis (RRMS). Methodology: About 136 patients with RRMS without history of optic neuritis were divided into two groups, based on body mass index (BMI): 67 obese (40 AA, 27 CA, mean BMI ± SD: 36.7 ± 5.8), and 69 non-obese (23 AA, 46 CA, mean BMI ± SD: 24.0 ± 3.1). The peripapillary retinal nerve fiber layer (pRNFL) thickness was quantified by optical coherence tomography (OCT) and was segmented into quadrant thickness: superior (S), inferior (I), temporal (T), and nasal (N). Papillomacular bundle (PMB) thickness, retinal nerve fiber layer (RNFL), ganglion cell + inner plexiform layer (GCIPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and total macular (TMV) volumes were obtained. Results: Obesity was associated with lower T thickness (58.54 ± 15.2 vs. 61.9 12.4, p = 0.044), higher INL (0.98 ± 0.07 vs. 0.96 ± 0.06, p = 0.034), and lower RNFL (0.77 ± 0.14 vs. 0.82 ± 0.12, p = 0.009) volumes. Obese AA had significantly thinner T (58.54 ± 15.19 vs. 61.91 ± 12.39, p = 0.033), N (68.94 ± 2.7 vs. 77.94 ± 3.3, p = 0.044), and TMV (8.15 ± 0.07 vs. 8.52 ± 0.09, p = 0.003), RNFL (0.74 ± 0.02 vs. 0.82 ± 0.02, p = 0.013), OPL (0.76 ± 0.01 vs. 0.79 ± 0.1, p = 0.050), ONL (1.68 ± 0.031 vs. 1.79 ± 0.038, p = 0.026), and GCIPL (1.78 ± 0.04 vs. 1.9 ± 0.05, p = 0.038) compared to obese CA. Among patients with non-obesity, the ONL was significantly lower in AA (1.78 ± 0.04 vs. 1.9 ± 0.05, p < 0.001). Conclusions: Obesity is associated with retinal structure abnormalities in patients with RRMS. Its impact might be more prominent in AA than CA. Large longitudinal studies are needed to validate our findings.

Cortical surface thickness, subcortical volumes and disability between races in relapsing-remitting multiple sclerosis.

BACKGROUND: The interplay between cortical surface thickness (CTh), subcortical volumes (SCV) and disability in patients with relapsing remitting multiple sclerosis (RRMS) is still not clear. OBJECTIVE: To examine the relationship between CTh, SCV, and disability and investigate differences in CTh, SCV and disability between African Americans (AA) and Caucasian Americans (CA). METHODS: Sixty-five RRMS (33AA, 32 CA) participants underwent Expanded Disability Status Scale and Multiple Sclerosis Functional Composite (MSFC) assessments, including timed 25-foot walk (T25FW), nine-hole peg test (9HPT) on dominant (D) and non-dominant hand (ND) and paced auditory serial addition test (PASAT-3). Symbol digit modalities test (SDMT) was also administered. All participants underwent 3T brain MRI. CTh was measured in the Frontal (FA), Parietal (PA), Temporal (TA), Occipital (OA), Cingulate (CA), and Global (GA) cortical surface areas (CSA). SCV measurements included Thalamus (TV), Caudate (CV), Putamen (PV), Pallidum (PaV), Hippocampus (HV), Amygdala (AV), Accumbens (AcV), Brain Stem (BSV), and Deep Gray Matter Total Volume (DGMTV). A general linear model with multivariate analysis (MANOVA) was used to determine the differences between the two cohorts (SPSS vs 25). Spearman rank correlation analysis was performed to investigate the relationship between CTh and MSFC. RESULTS: AA have significantly decreased FA, PA, TA, GA CTh compared to CA (p = 0.004, p = 0.018, p = 0.013, p = 0.015, respectively). SCV measurements were not significantly different. Only in CA, the MSFC measures correlate significantly with regional CSA CTh. In both races and in the entire group, T25FW correlates with TV, PV, AV, AcV and DGMTV (p < 0.05). Only in AA and the entire cohort, PASAT-3 correlates with TV and AcV(p = 0.041, p = 0.006, p = 0.006, p = 0.000 respectively). CONCLUSIONS: Differences in CSA CTh reinforce the different disease pathobiology between AA and CA. Regional CTh may represent a useful biomarker related to multi-domain disability only in CA, while in AA DGM injury might be a more important contributor to disability. Longitudinal, large-scale studies are warranted to confirm our findings.

Fatigue in patients with hereditary neuropathy with liability to pressure palsies.

OBJECTIVE: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) is caused by a heterozygous deletion of peripheral myelin protein-22 (PMP22) gene resulting in focal sensorimotor deficits. Our lab has identified a disruption of myelin junctions in excessively permeable myelin that impairs action potential propagation. This mechanism is expected to cause fatigue in patients with HNPP. Therefore, the objective was to characterize fatigue in patients with HNPP and determine the relationship of fatigue to nerve pathology, disability, and quality of life. METHODS: Nine females with HNPP participated in a single visit that included genotyping, nerve conduction studies, neurological exam, quantitative magnetic resonance imaging, and a physical therapy exam incorporating upper and lower extremity function and survey measures of fatigue. This visit was followed by 2 weeks of ecological momentary assessment (wrist-worn device) that captured fatigue ratings five times per day. RESULTS: Participants demonstrated mild neurological impairment (CMTNS: 5.7 ± 2.8), yet reported high fatigue levels (average fatigue intensity over 2 weeks: 5.9 out of 10). Higher fatigue levels were associated with poorer quality of life and more pain. Higher fatigue was associated with significantly greater distal nerve proton density changes on peripheral nerve MRI, which is in line with hyper-permeable myelin in HNPP. INTERPRETATION: Fatigue is common and severe among patients with HNPP whose disabilities are minimal by conventional outcome measures. Therapeutic interventions targeting fatigue have the potential to improve quality of life and may serve as a robust outcome measure to show longitudinal changes for patients with HNPP.

Demyelination in hereditary sensory neuropathy type-1C.

OBJECTIVE: Sphingolipids are enriched in the nerves. Serine-palmitoyltransferase (SPT) catalyzes the key step of sphingolipids biosynthesis. Mutations in SPT subunits (SPTLC) lead to the excessive production of neurotoxic deoxysphingolipids (DoxSLs) in patients with Hereditary Sensory Neuropathy Type-1C (HSN1C). HSN1C is an autosomal dominant peripheral neuropathy characterized by sensory loss and distal muscle weakness. In this study, by leveraging a HSN1C family with a previously reported N177D mutation in SPTLC2, we aim to further define the spectrum of DoxSL species and the peripheral neve pathology of the disease. METHODS: Next-generation sequencing along with Sanger confirmation was performed for family members and healthy controls. LC-MS was used for lipidomic analysis in participants' plasma. Quantitative magnetic resonance imaging (qMRI) was performed to study sciatic nerve pathologies. RESULTS: A heterozygous N177D mutation in SPTLC2 was co-segregated in individuals with sensory-motor deficits in the limbs. Nerve conduction studies (NCS) revealed nonuniform slowing of conduction velocities. In line with the NCS, qMRI detected a pattern of nerve changes similar to those in acquired demyelinating polyneuropathies. Additionally, we detected a significant increase in multiple species of deoxysphingoid bases and deoxyceramides in patients' plasma. INTERPRETATION: Mutations in the SPTLC2 cause a demyelinating phenotype resembling those in acquired demyelinating polyneuropathy. The species of increased DoxSLs in HSN1C may be more diverse than originally thought.

Approved and Emerging Disease Modifying Therapies on Neurodegeneration in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune, chronic, progressive disease leading to a combination of inflammation, demyelination, and neurodegeneration throughout the central nervous system (CNS). The outcome of these processes can be visualized in magnetic resonance imaging (MRI) scans as brain atrophy, or brain volume loss (BVL), as well as lesions, "black holes" and spinal cord atrophy. MRI outcomes such as BVL have been used as biomarkers of neurodegeneration and other measures of MS disease progression in clinical research settings. Several FDA-approved medications seek to alleviate disease progression by reducing the impact of such factors as demyelination and neurodegeneration, but there are still many shortcomings that current clinical research aims to mitigate. This review attempts to provide an overview of the FDA-approved medications available for treating multiple sclerosis and their effect on neurodegeneration, measured by BVL.