A low-fat diet improves fatigue in multiple sclerosis: Results from a randomized controlled trial.

Background: Fatigue can be a disabling multiple sclerosis (MS) symptom with no effective treatment options.

Objective: Determine whether a low-fat diet improves fatigue in people with MS (PwMS).

Methods: We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group.

Effect of Vascular Comorbidity on Visual and Disability Outcomes in a Secondary Progressive Multiple Sclerosis Clinical Trial Cohort.

Background: Vascular comorbidity (VC) is associated with multiple sclerosis (MS) disease progression and visual dysfunction. The longitudinal effect of VC in people with secondary progressive MS (SPMS) is unclear. This study explored the impact of VC on standard clinical, MRI, and visual outcomes in people with SPMS enrolled in a clinical trial.

A cross-sectional survey of cannabis use by people with MS in Oregon and Southwest Washington.

Background: Evidence supports that cannabinoids reduce self-reported spasticity and neuropathic pain in people with MS (PwMS), and legal access to cannabis for medical and recreational use continues to rise. However, there are limited data regarding patterns of cannabis use and perceived benefits of cannabis among PwMS in the US. This study describes the prevalence of cannabis use, routes of administration, perceived benefit of cannabis for MS, and characteristics associated with cannabis use and perception of benefit among a population of PwMS living in two states where cannabis is legal for both medical and recreational use.

ANA Webinars: implementation of a conference-based virtual networking event.

Objective: To describe the design and implementation of a virtual network event at the American Neurological Association (ANA) annual meeting led by the Junior and Early Career Member (JECM) Committee.

Methods: We designed a one-hour virtual networking session featuring three 15-minute small group meetings preceded and followed by general remarks. Each small group session consisted of one senior mentor, a junior/early career faculty moderator, and three to four junior/early career mentees.

Enlarged perivascular spaces are not associated with vascular co-morbidities, clinical outcomes, and brain volumes in people with secondary progressive multiple sclerosis.

In secondary progressive multiple sclerosis (SPMS) significance of enlarged perivascular spaces (ePVS) is unknown. Analysis of associations between vascular co-morbidities, clinical outcomes, and volumetrics with categorical ePVS scores in midbrain, basal ganglia (BG), and centrum semiovale (CSO) in SPMS(n-46). In BG, advancing age (Z = 2.

Spinal adhesive arachnoiditis mimicking sarcoid myelitis with nodular dural enhancement: A case report.

Spinal adhesive arachnoiditis (SAA) is a rare, but often devastating, cause of compressive myelopathy. We report a patient with SAA resulting in a longitudinally extensive T2-hyperintense spinal cord lesion with initial nodular pial and dural enhancement mimicking neurosarcoidosis. Neurologists should be aware of this entity, especially in patients who have pertinent risk factors, such as prior meningitis, spinal cord trauma, or surgery.

Cross-sectional survey of complementary and alternative medicine used in Oregon and Southwest Washington to treat multiple sclerosis: A 17-Year update.

Background: In 2001, we conducted a survey on use of complementary and alternative medicine (CAM) in people with multiple sclerosis (pwMS) in Oregon and Southwest Washington to treat their disease.

Objectives, Methods: In 2018, we administered a revised survey in the same region to describe updated patterns of CAM use in pwMS and to compare changes in use, perceived benefit, and patterns of communication between participants and providers regarding CAM over the past 17 years.

Results: 81% of respondents in 2018 (n = 1014) used a CAM supplement (vitamins, minerals, herbs), 39% used mind-body therapies (mindfulness, massage), 41% used specific diet, and 81% used exercise to treat their multiple sclerosis.

Approaches to Remyelination Therapies in Multiple Sclerosis.

Purpose Of Review: While there are a growing number of therapies targeting relapse prevention in multiple sclerosis (MS), there are no approved therapies promoting remyelination. Understanding endogenous myelin formation, remyelination strategies, pre-clinical models, and clinical outcomes is essential to the interpretation of current and future clinical trials of remyelinating agents.

Recent Findings: Several recent clinical trials of remyelination therapies, including opicinumab, clemastine, and GSK239512, showed negative or modest results.

Using the Anterior Visual System to Assess Neuroprotection and Remyelination in Multiple Sclerosis Trials.

Purpose Of Review: Clinical trials using agents directed at neuroprotection and remyelination in multiple sclerosis (MS) are needed. As optic neuritis (ON) is common in people with MS and the pathology of ON is similar to other MS lesions in the brain, measurements of the anterior visual system are frequently utilized in neuroprotection and remyelination trials. Understanding the strengths and weaknesses of the measurements is vital when interpreting the results of this research.

Potential Co-Factor Role of Tobacco Specific Nitrosamine Exposures in the Pathogenesis of Fetal Alcohol Spectrum Disorder.

Background: Cerebellar developmental abnormalities in Fetal Alcohol Spectrum Disorder (FASD) are linked to impairments in insulin signaling. However, co-morbid alcohol and tobacco abuses during pregnancy are common. Since smoking leads to tobacco specific Nitrosamine (NNK) exposures which have been shown to cause brain insulin resistance, we hypothesized that neurodevelopmental abnormalities in FASD could be mediated by ethanol and/or NNK.

Differential Effects of 3rd Trimester-Equivalent Binge Ethanol and Tobacco-Specific Nitrosamine Ketone Exposures on Brain Insulin Signaling in Adolescence.

Background: Fetal alcohol spectrum disorder (FASD) is associated with impairments in insulin and insulin-like growth factor (IGF) signaling through Akt pathways and altered expression of neuro-glial proteins needed for structural and functional integrity of the brain. However, alcohol abuse correlates with smoking, and tobacco smoke contains 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which like other nitrosamines, impairs insulin and IGF signaling.

Hypothesis: NNK exposure can serve as a co-factor in mediating long-term neuro-developmental abnormalities associated with FASD.

Differential Contributions of Alcohol and Nicotine-Derived Nitrosamine Ketone (NNK) to White Matter Pathology in the Adolescent Rat Brain.

Aim: Epidemiologic studies have demonstrated high rates of smoking among alcoholics, and neuroimaging studies have detected white matter atrophy and degeneration in both smokers and individuals with alcohol-related brain disease (ARBD). These findings suggest that tobacco smoke exposure may be a co-factor in ARBD. The present study examines the differential and additive effects of tobacco-specific nitrosamine (NNK) and ethanol exposures on the structural and functional integrity of white matter in an experimental model.

Potential contributions of the tobacco nicotine-derived nitrosamine ketone (NNK) in the pathogenesis of steatohepatitis in a chronic plus binge rat model of alcoholic liver disease.

Aims: Alcoholic liver disease (ALD) is linked to binge drinking and cigarette smoking. Heavy chronic ± binge alcohol, or low-level exposures to dietary nitrosamines cause steatohepatitis with insulin resistance and oxidative stress in animal models. This study examines hepatotoxic effects of sub-mutagenic exposures to tobacco-specific nitrosamine (NNK) in relation to ALD.

Small-fiber degeneration in alcohol-related peripheral neuropathy.

Background: Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status.

Methods: Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration.

Impaired insulin/IGF signaling in experimental alcohol-related myopathy.

Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8) or 35.

Role of aspartyl-(asparaginyl)-β-hydroxylase mediated notch signaling in cerebellar development and function.

Background: Aspartyl-(Asparaginyl)-β-Hydroxylase (AAH) is a hydroxylating enzyme that promotes cell motility by enhancing Notch-Jagged-HES-1 signaling. Ethanol impaired cerebellar neuron migration during development is associated with reduced expression of AAH.

Methods: To further characterize the role of AAH in relation to cerebellar development, structure, and function, we utilized an in vivo model of early postnatal (P2) intracerebro-ventricular gene delivery to silence AAH with small interfering RNA (siAAH), or over-express it with recombinant plasmid DNA (pAAH).

Ethanol inhibition of aspartyl-asparaginyl-beta-hydroxylase in fetal alcohol spectrum disorder: potential link to the impairments in central nervous system neuronal migration.

Fetal alcohol spectrum disorder (FASD) is caused by prenatal exposure to alcohol and associated with hypoplasia and impaired neuronal migration in the cerebellum. Neuronal survival and motility are stimulated by insulin and insulin-like growth factor (IGF), whose signaling pathways are major targets of ethanol neurotoxicity. To better understand the mechanisms of ethanol-impaired neuronal migration during development, we examined the effects of chronic gestational exposure to ethanol on aspartyl (asparaginyl)-beta-hydroxylase (AAH) expression, because AAH is regulated by insulin/IGF and mediates neuronal motility.

Hepatic ceramide may mediate brain insulin resistance and neurodegeneration in type 2 diabetes and non-alcoholic steatohepatitis.

Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) can be complicated by cognitive impairment and neurodegeneration. Experimentally, high fat diet (HFD)-induced obesity with T2DM causes mild neurodegeneration with brain insulin resistance. Since ceramides are neurotoxic, cause insulin resistance, and are increased in T2DM, we investigated the potential role of ceramides as mediators of neurodegeneration in the HFD obesity/T2DM model.

Ethanol impaired neuronal migration is associated with reduced aspartyl-asparaginyl-beta-hydroxylase expression.

Cerebellar hypoplasia in fetal alcohol spectrum disorders (FASD) is associated with inhibition of insulin and insulin-like growth factor (IGF) signaling in the brain. Aspartyl (asparaginyl)-beta-hydroxylase (AAH) is a mediator of neuronal motility, and stimulated by insulin and IGF activation of PI3 kinase-Akt, or inhibition of GSK-3beta. Since ethanol inhibits PI3 Kinase-Akt and increases GSK-3beta activity in brain, we examined the effects of ethanol and GSK-3beta on AAH expression and directional motility in neuronal cells.