Direct and Indirect Care of Patients With Multiple Sclerosis: Burden on Providers and Impact of Portal Messages.

BACKGROUND: Multiple sclerosis (MS) indirect patient-care time is often underreported and uncompensated. Data on time spent on indirect and direct care by MS providers is lacking. METHODS: A survey was designed to understand the practice patterns among MS providers in the United States, including time spent on direct and indirect patient care, as well as managing electronic medical record portal messages. The National MS Society and the American Academy of Neurology facilitated the distribution of the survey to MS providers. RESULTS: Most providers spent at least 1 hour on new and at least 30 minutes on follow-up direct patient care. For indirect patient care, 77% of providers spent more than 1 hour and 57% spent more than 2 hours per day. While some providers have support staff to help with portal messages, many do not have protected time or compensation for portal messages. CONCLUSIONS: Multiple sclerosis providers spent a higher-than-average time on direct and indirect patient care tasks, including portal messages, and most lack protected time or compensation for portal messages. These results highlight the potential impact of indirect patient care (notably portal messages) on provider workload and burnout. Better support, protected time and/or compensation for indirect patient care can help ease physician burden and decrease burnout.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

Susac syndrome with a unique involvement of the thoracic spinal cord.

A woman in her late 20s presented with headaches and subacute encephalopathy. MRIs showed multiple punctate subcortical and periventricular white matter hyperintensities with diffusion restriction, infratentorial lesions, leptomeningeal enhancement of the cervical spinal cord, brainstem and cerebellum and two areas of high-signal abnormality at T4 and T6 raising suspicion for multiple sclerosis or acute disseminated encephalomyelitis.Further studies and evolution of her symptoms during her hospital stay confirmed the clinical triad of encephalopathy, branch retinal artery occlusions and hearing loss pathognomonic for Susac's syndrome.While cervical spinal cord and cauda equina involvement have been reported in Susac's syndrome previously, no thoracic spinal cord involvement has been reported.We report the novel MRI finding of thoracic spinal cord involvement in Susac's syndrome. In order to avoid misdiagnosis, neurologists and neuroradiologists should be aware that any part of the spinal cord can be involved in Susac's syndrome.

Modifying Diet and Exercise in MS (MoDEMS): Study design and protocol for a telehealth weight loss intervention for adults with obesity & Multiple Sclerosis.

Weight loss improves overall health, and reduces inflammation, risk of stroke, heart attack, diabetes, certain cancers, and death among individuals with obesity. Weight loss also improves mobility, increases stamina, and elevates mood. Between 25 and 33% of people with Multiple Sclerosis (pwMS) have obesity. Multiple Sclerosis (MS) and obesity are independently associated with reduced mobility, increased fatigue, and depression. Most behavioral weight loss trials exclude individuals with neurologic disease. Consequently, few studies have examined the effects of weight loss on symptom presentation and health outcomes among pwMS and obesity. This is the first study examining the efficacy of a comprehensive behavioral weight loss intervention designed specifically for pwMS. The purpose of this study is to develop and assess the efficacy of a telehealth administered weight loss intervention tailored for pwMS. Additionally, we aim to determine if weight loss reduces physical and emotional symptoms in individuals with obesity and MS. We will enroll 70 pwMS in a wait-list crossover trial to examine the efficacy of our intervention. If successful, findings will help determine whether we can help participants lose clinically significant weight - and whether weight loss among pwMS and overweight/obesity reduces fatigue, and improves mobility, mood, and quality of life.

Alterations at Arg76 of human connexin 46, a residue associated with cataract formation, cause loss of gap junction formation but preserve hemichannel function.

The connexins are members of a family of integral membrane proteins that form gap junction channels between apposed cells and/or hemichannels across the plasma membranes. The importance of the arginine at position 76 (Arg76) in the structure and/or function of connexin 46 (Cx46) is highlighted by its conservation across the entire connexin family and the occurrence of pathogenic mutations at this (or the corresponding homologous) residue in a number of human diseases. Two mutations at Arg76 in Cx46 are associated with cataracts in humans, highlighting the importance of this residue. We examined the expression levels and macroscopic and single-channel properties of human Cx46 and compared them with those for two pathogenic mutants, namely R76H and R76G. To gain further insight into the role of charge at this position, we generated two additional nonnaturally occurring mutants, R76K (charge conserving) and R76E (charge inverting). We found that, when expressed exogenously in Neuro2a cells, all four mutants formed membrane hemichannels, inducing membrane permeability at levels comparable to those recorded in cells expressing the wild-type Cx46. In contrast, the number of gap-junction plaques and the magnitude of junctional coupling were reduced by all four mutations. To gain further insight into the role of Arg76 in the function of Cx46, we performed homology modeling of Cx46 and in silico mutagenesis of Arg76 to Gly, His, or Glu. Our studies suggest that the loss of interprotomeric interactions has a significant effect on the extracellular domain conformation and dynamics, thus affecting the hemichannel docking required for formation of cell-cell channels.

Acute demyelinating neuropathy in a patient with neurolymphomatosis.

Peripheral neurological complications of lymphomas are rare and much less frequent than central complications. Nonetheless, on occasion, systemic non-Hodgkin's lymphoma may directly infiltrate the peripheral nervous system at various levels. This report describes a man with non-Hodgkin's lymphoma and leptomeningeal disease who developed progressive areflexic quadraparesis. Initial electromyography (EMG) was consistent with a polyradiculopathy and a repeat EMG performed 1 month later for worsening symptoms showed evidence of demyelination. The patient expired due to systemic complications of his illness. Autopsy of the sural nerve showed moderately severe distal sensory axonal loss, direct infiltration of the brachial plexus by malignant lymphocytes and demyelination in brachial and lumbar plexus, most prominent in areas of neoplastic infiltration. Based on this patient's course and pathology, we suggest that widespread demyelination may accompany neurolymphomatosis and the clinical presentation may be indistinguishable from an acute demyelinating neuropathy.

A new fungal endophyte, Scolecobasidium humicola, promotes tomato growth under organic nitrogen conditions.

A new fungal endophyte, Scolecobasidium humicola, was identified as a common dark septate endophytic fungal (DSE) species under both natural and agricultural conditions. This fungus was found to grow endophylically in the roots of tomato seedlings. Light microscopy of cross-sections of colonized tomato roots showed that the intercellular, pigmented hyphae of the fungus were mostly limited to the epidermal layer and formed outer mantle-like structures. Two isolates of S. humicola, H2-2 and F1-3, have shown the ability to increase plant biomass with an organic nitrogen source. This finding is the first report of S. humicola as an endophyte and could help to improve plant growth with organic nitrogen sources.

Functional requirement for a highly conserved charged residue at position 75 in the gap junction protein connexin 32.

Charcot Marie Tooth disease (CMT) is a group of inherited disorders characterized clinically by exclusively or predominantly peripheral nerve dysfunction. CMT1X, the most common form of X-linked CMT is caused by mutations in connexin 32 (Cx32). In this work, we used dual whole cell patch clamp recording to examine the functional effects of mutations at the Arg(75) position. This residue is highly conserved among members of the connexin family, and disease-causing mutations have been identified at this (or the corresponding) position in Cx26, Cx43, and Cx46. Thus, a better understanding of the effects of mutations of this position in Cx32 may have relevance to pathogenesis of a number of different human diseases. All three mutants associated with CMT1X (R75P, R75Q, and R75W) showed very low levels of coupling similar to those of the cells transfected with vector alone. Heterotypic pairing with Cx32 WT showed that the absence of coupling for these mutants in the homotypic configuration could be explained by shifts in their hemichannel G(j)-V(j) relations. Examination of the expression levels and gating characteristics of seven additional mutants (R75A, R75D, R75E, R75H, R75K, R75L, and R75V) at this position suggest that the positive charge at position 75 in Cx32 is required for normal channel function but not for gap junction assembly. Our studies also suggest that disease treatment strategies for CMT1X, which correct trafficking abnormalities in Cx32, may be ineffective for the group of mutations also conferring changes in gating properties of Cx32 channels.