Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome.

Sequential Brain Perfusion Findings in a Case of Osmotic Demyelination Syndrome.

ABSTRACT: A 60-year-old man with chronic alcoholism for 30 years was admitted to the hospital for an acute alcoholic syndrome with global confusional state, cognitive disorders, and ataxia. MRI detected bilateral mamillary bodies T 2 hypersignal related to Wernicke encephalopathy. It was treated by oral thiamine supplementation with clinical improvement. Two months later, he was rehospitalized for rapidly progressive dementia symptoms. Brain perfusion scintigraphy revealed pontine hyperperfusion and right hippocampal hypoperfusion. One month after IV thiamine supplementation, brain perfusion scintigraphy showed normalization of perfusion abnormalities in the pons and right hippocampus, leading to the diagnosis of alcoholic-related osmotic demyelination syndrome.

Differential outcomes for frontal versus posterior demyelination in childhood cerebral adrenoleukodystrophy.

In the most common variant of childhood cerebral adrenoleukodystrophy (cALD), demyelinating brain lesions are distributed predominately in parieto-occipital white matter. Less frequently, lesions first develop in frontal white matter. This matched cohort study examined whether outcomes after standard treatment with hematopoietic cell transplantation (HCT) differ in patients with early stage frontal lesions as compared to parieto-occipital lesions. Retrospective chart review identified seven pediatric patients with frontal cALD lesions and MRI severity score < 10 who underwent a single HCT at our center between 1990 and 2019. Concurrent MRI, neurocognitive and psychiatric outcomes at last comprehensive follow-up (mean 1.2 years; range 0.5-2.1 years) were compared with a group of seven boys with the parieto-occipital variant matched on pre-HCT MRI severity score. Both groups showed similar rates of transplant complications and radiographic disease advancement. Neurocognitive outcomes were broadly similar, with more frequent working memory deficits among individuals with frontal lesions. Psychiatric problems (hyperactivity, aggression, and atypical behavior) were considerably more common and severe among patients with frontal lesions. Aligned with the critical role of the frontal lobes in emotional and behavioral regulation, functional disruption of self-regulation skills is widely observed among patients with frontal lesions. Comprehensive care for cALD should address needs for psychiatric care and management.

Brain stem and spinal cord demyelination due to acute carbon monoxide poisoning.

Demyelination throughout the brain stem and spinal cord caused by acute carbon monoxide (CO) poisoning has not been previously reported. Magnetic resonance imaging (MRI) has revealed that acute CO poisoning primarily affects the subcortical white matter of the bilateral cerebral hemispheres and basal ganglia. Here we report the case of a patient with delayed neuropsychological sequelae (DNS) due to acute CO poisoning. A 28-year-old man was admitted to our department following a suicide attempt by acute CO poisoning. After a six-month pseudo-recovery period, he was diagnosed with DNS, with MRI evidence of demyelinating change of the bilateral cerebral peduncles. Demyelination was identified throughout the brain stem, expanding from the bilateral cerebral peduncles to the medulla oblongata, occurring approximately six months after poisoning. One and a half years after acute CO poisoning, demyelination of the cervical and thoracic spine was observed, most notable in the lateral and posterior cords. It is evident that previously published research on this topic is extremely limited. Perhaps in severe cases of acute CO poisoning the fatality rate is higher, leading to fewer surviving cases for possible study. This may be because a more severe case of acute CO poisoning would result in the higher likelihood of secondary demyelination. This research indicates that clinicians should be aware of the risk of secondary demyelination and take increased precautions such as vitamin B supplementation and administration of low-dose corticosteroids for an extended period of time in order to reduce the extent and severity of demyelination.

Retinal thinning and brain atrophy in early MS and CIS.

BACKGROUND: Optical coherence tomography (OCT) could be complementary to magnetic resonance imaging (MRI) of the brain in monitoring course of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Thinning of neurons in ganglion cell-inner plexiform layer (GCIPL) measured by OCT is assumed to be associated with brain atrophy. OBJECTIVES: To evaluate association of GCIPL with brain parameters detected by quantitative MRI (qMRI) and MR-spectroscopy (MRS) in early MS and CIS. METHODS: Seventeen newly diagnosed MS and 18 CIS patients were prospectively included. The patients were assessed at baseline as well as at 1 year follow-up by OCT, qMRI and MRS. Brain parenchymal and myelin volumes (BPV, MYV respectively) and the corresponding fractions (BPF, MYF) were measured with qMRI. Metabolites including myo-inositol (myo-Ins) were measured in the normal-appearing white matter (NAWM) using MRS. T-tests and ANOVA were used to analyze group differences, and linear regression models to evaluate association of GCIPL with BPV, MYV and myo-Ins after correlation analysis. RESULTS: Disease activity reflected by lesions on MRI and presence of CSF oligoclonal IgG bands were more prominent in MS compared to CIS. GCIPL, BPV, MYV, BPF and MYF were reduced, while concentration of myo-Ins was increased in MS compared to CIS. Follow-up showed consistency of thinner GCIPL in MS compared to CIS. GCIPL thinning correlated with reduced BPV and MYV (P < .05 for both), but with increased myo-Ins (P < .01). CONCLUSIONS: Significant GCIPL thinning occurs in early MS and is associated with enhanced brain inflammation and atrophy.

Clinically Isolated Syndrome and Early Relapsing Multiple Sclerosis.

PURPOSE OF REVIEW: This article reviews management of clinically isolated syndrome and early relapsing-remitting multiple sclerosis (MS). It provides a general approach to patient management and determination of prognosis, reviews first-line disease-modifying therapies, and provides an approach to treatment selection. RECENT FINDINGS: Revision of the MS diagnostic criteria allows an earlier MS diagnosis, which reduces diagnostic uncertainty and often allows additional treatment options. Identification of factors that influence disease activity and progression highlights the importance of counseling patients about behavior modifications that, along with disease-modifying therapy, may improve long-term outcomes. Recommended lifestyle modifications include smoking cessation, vitamin D supplementation, a healthy diet, maintaining a healthy weight, remaining active, and management of cardiovascular risk factors. Identifying individuals at high risk for future disability allows them to make informed decisions about the use of highly effective, higher-risk disease-modifying therapies. SUMMARY: Patients with clinically isolated syndrome, even those with only dissemination in space but not dissemination in time, and patients with relapsing-remitting MS and disease activity within the prior 2 years, are at high risk of disease activity within the next 2 years. Lifestyle modification suggestions and disease-modifying therapy should be considered. Treatment decisions should be made in collaboration with patients using the shared decision-making approach.

Hypothalamic demyelination causing panhypopituitarism.

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed.

Does vitamin D deficiency predict early conversion of clinically isolated syndrome? A preliminary Egyptian study.

BACKGROUND: It has been suggested that vitamin D influences the immunoregulation and subsequently affects the risk for conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS). There is little information regarding the relationship between levels of vitamin D and CIS conversion to MS in Egyptian patients. OBJECTIVE: It is to study contribution of vitamin D deficiency to conversion of CIS to clinically definite multiple sclerosis (CDMS) and correlation of vitamin D level to cognitive and magnetic resonance imaging (MRI) results. PATIENTS AND METHODS: A longitudinal prospective case control study was conducted on 43 Egyptian patients diagnosed as CIS according to McDonald criteria (2010). Clinical presentation, brain MRI and 25-hydroxyvitamin D levels were evaluated at baseline and after one-year follow-up. RESULTS: The CIS patients that converted to MS showed significant lower vitamin D level (p < 0.001) than the non-convertors. Multivariate logistic regression analysis revealed that the CIS patients with lower 25-hydroxyvitamin D level (p < 0.001) are at higher risk for early conversion to MS. There was a significant positive correlation between the vitamin D level and PASAT (r = 0.36, p = 0.02). It was found that there was a significant negative correlation between vitamin D level and MRI T2 load (r = -0.38, p = 0.01). CONCLUSION: The low level of 25-hydroxyvitamin D may predict early conversion to clinically definite MS. Early vitamin D supplementation is recommended in patients with CIS.

Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: A proposed mechanistic relationship between inflammation and oligodendrocyte vitality.

Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). Thalamic pathology is one of the earliest hallmarks of MS and has been shown to correlate with cognitive dysfunction and fatigue, but the mechanisms underlying the thalamic pathology are poorly understood. We enrolled a total of 120 patients, 40 with CIS, 40 with Relapsing Remitting MS (RRMS), and 40 with Secondary Progressive MS (SPMS). For each of the three patient groups, we recruited 40 controls, group matched for age- and sex (120 total). We acquired quantitative susceptibility maps using a single-echo gradient echo MRI pulse sequence at 3 T. Group differences were studied by voxel-based analysis as well as with a custom thalamus atlas. We used threshold-free cluster enhancement (TFCE) and multiple regression analyses, respectively. We found significantly reduced magnetic susceptibility compared to controls in focal thalamic subregions of patients with RRMS (whole thalamus excluding the pulvinar nucleus) and SPMS (primarily pulvinar nucleus), but not in patients with CIS. Susceptibility reduction was significantly associated with disease duration in the pulvinar, the left lateral nuclear region, and the global thalamus. Susceptibility reduction indicates a decrease in tissue iron concentration suggesting an involvement of chronic microglia activation in the depletion of iron from oligodendrocytes in this central and integrative brain region. Not necessarily specific to MS, inflammation-mediated iron release may lead to a vicious circle that reduces the protection of axons and neuronal repair.

Magnetization transfer SWIFT MRI consistently detects histologically verified myelin loss in the thalamocortical pathway after a traumatic brain injury in rat.

Traumatic brain injury (TBI) is associated with various neurocognitive deficits, and rapid assessment of the damage is potentially important for the prevention and treatment of these deficits. Imaging assessment of mild or moderate damage outside the primary lesion area after TBI, however, remains challenging. Magnetization transfer (MT) has clearly been underutilized in imaging the damage caused by TBI. Here, we applied the MT ratio (MTR) using sweep imaging with Fourier transformation (SWIFT) to study microstructural tissue damage in the thalamocortical pathway outside the primary lesion in a lateral fluid percussion injury rat model of TBI, 5 months after injury. MTR was decreased in layers VIb-IV of the barrel cortex and related subcortical areas, mainly indicating demyelination, which was verified by histology. The largest MTR change in the cortex was in layer VIb (-8.2%, pFDR  = 0.01), and the largest MTR change in the subcortical areas was in the caudal-most portion of the internal capsule (-11.0%, pFDR  < 0.005). These areas exhibited the greatest demyelination and substantial cellularity attributed to gliosis. Correlation analysis of group-averaged results from the subcortical areas revealed an excellent correlation of MTR with myelin (r2  = 0.94, p < 0.001), but no correlation with increased cellularity as detected by Nissl staining. Thus, MTR using SWIFT can be a valuable tool for the assessment of subtle changes after TBI in both cortical and subcortical areas.

Sacroiliitis and polyneuropathy during isotretinoin treatment.

Isotretinoin, a medication for acne, has been reported to cause a variety of side effects on the musculoskeletal system. We present a case of sacroiliitis (a relatively uncommon feature) and sensorimotor demyelinating polyneuropathy, which has been reported previously in only a few cases during isotretinoin therapy. Clinical symptoms were improved after the withdrawal of isotretinoin and the follow-up electrophysiological study performed 2 years after the initial diagnosis of polyneuropathy showed mild improvement. Dermatologists are advised to be alert to symptoms of polyneuropathy and sacroiliitis during treatment with isotretinoin.

[MR tomography and computer tomography of alcohol-induced brain tissue changes]. / MR-Tomographie und Computertomographie von alkoholtoxischen Hirngewebsveränderungen.

Results of MRI in five alcoholics suffering from acute neurologic disorders such as ataxia, ophthalmoplegia and confusion are presented. The detection of focal cerebral lesions of high signal intensity in T2-weighted Spin-Echo- and Gradient-Echo-images in periventricular white matter, thalamus and pons combined with patients history and clinical presentation led to the diagnosis of Wernicke-Encephalopathia and Pontine Myelinolysis. MRI was far more sensitive compared with CT.

Computerized tomography in the diagnosis of central and extrapontine myelinolysis.

In two patients the diagnosis of central pontine myelinolysis (CPM), suspected on clinical grounds, was supported by computerized tomographic (CT) sections made perpendicular to the pons, and confirmed on postmortem examination. Extrapontine myelinolysis was suggested on CT scans in both cases, and confirmed in one. Computerized tomography may prove to be a sensitive and accurate diagnostic test for CPM, and may aid in the detection of associated extrapontine lesions.