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.

Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection.

BACKGROUND AND PURPOSE: Vitamin D status has been associated with inflammatory activity in multiple sclerosis (MS), but it is not known if it is associated with gray matter volume, the loss of which predicts long-term disability in MS. The association of vitamin D levels with brain volume measures and inflammatory activity in patients with clinically isolated syndrome (CIS) was investigated. METHODS: In the phase 2 CIS trial of atorvastatin, 25-hydroxyvitamin D levels were evaluated for their age-adjusted associations with normalized gray matter and brain parenchymal volumes on brain magnetic resonance imaging (MRI). The relationships between 25-hydroxyvitamin D levels and clinical and MRI measures of inflammatory activity were also assessed. RESULTS: In 65 patients in this substudy, each 25 nmol/l higher 25-hydroxyvitamin D level was associated with 7.8 ml higher gray matter volume (95% confidence interval 1.0, 14.6, P = 0.025). There was a tendency for an inverse association of average 25-hydroxyvitamin D levels and the composite end-point of ≥3 new brain T2 lesions or ≥1 relapse within a year (odds ratio per 25 nmol/l higher 25-hydroxyvitamin D level 0.66, 95% confidence interval 0.41, 1.08, P = 0.096). CONCLUSIONS: Vitamin D status may impact neurodegeneration after CIS, although these results should be replicated in a second study. If confirmed in clinical trials, vitamin D supplementation may reduce long-term disability.

The physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: the Ausimmune study.

INTRODUCTION: Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. METHODS: This was a multicentre incident case-control study. Cases (n = 282) were aged 18-59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls (n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. RESULTS: A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. CONCLUSIONS: Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted campaigns will be required.

Lipid profiles are associated with lesion formation over 24 months in interferon-ß treated patients following the first demyelinating event.

OBJECTIVES: To investigate the associations of serum lipid profile with disease progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were obtained in pretreatment serum from 135 high risk patients with CIS (≥ 2 brain MRI lesions and ≥ 2 oligoclonal bands) enrolled in the Observational Study of Early Interferon ß-1a Treatment in High Risk Subjects after CIS study (SET study), which prospectively evaluated the effect of intramuscular interferon ß-1a treatment following the first demyelinating event. Thyroid stimulating hormone, free thyroxine, 25-hydroxy vitamin D3, active smoking status and body mass index were also obtained. Clinical and MRI assessments were obtained within 4 months of the initial demyelinating event and at 6, 12 and 24 months. RESULTS: The time to first relapse and number of relapses were not associated with any of the lipid profile variables. Higher LDL-C (p=0.006) and TC (p=0.001) levels were associated with increased cumulative number of new T2 lesions over 2 years. Higher free thyroxine levels were associated with lower cumulative number of contrast-enhancing lesions (p=0.008). Higher TC was associated as a trend with lower baseline whole brain volume (p=0.020). Higher high density lipoprotein was associated with higher deseasonalised 1,25-dihydroxy vitamin D3 (p=0.003) levels and a trend was found for deseasonalised 25-hydroxy vitamin D3 (p=0.014). CONCLUSIONS: In early multiple sclerosis, lipid profile variables particularly LDL-C and TC levels are associated with inflammatory MRI activity measures.

Iron status in children with recurrent episodes of tumefactive cerebral demyelination.

Iron is a vital element in the multifactorial initiation of myelination. It is required for cholesterol and lipid biosynthesis, both key components of myelin. Iron also plays an important role in energy production by mitochondrial oxidative metabolism which occurs in myelin-producing oligodentrocytes at a higher rate than in any other cell. Iron deficiency can, therefore, result in decreased oligodendrocyte survival and defective myelination. This led us to investigate iron status in 2 consecutive children with multiple sclerosis who presented with recurrent episodes of tumefactive demyelination. Testing revealed nonanemic iron deficiency in both patients. Discontinuation of iron supplementation in both children resulted in recurrent decreased iron parameters which can indicate mutations in proteins responsible for regulation of iron uptake. Further studies are warranted to explore the association of low iron in children presenting with recurrent episodes of tumefactive demyelination.

Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis.

BACKGROUND: Vitamin D is important for bone health and immune regulation, and has been shown to be low in multiple sclerosis (MS). We sought to determine the effect of over the counter low dose cholecalciferol (LDC) and high dose ergocalciferol (HDE) on the vitamin D levels in MS patients. METHODS: We retrospectively evaluated serum 25-hydroxy-vitamin D [25(OH)D] levels of 199 patients (CIS, n = 32; RRMS, n = 115; PPMS, n = 10; SPMS, n = 16; Transverse Myelitis (TM), n = 9; other neurological diseases, n = 16) attending our clinic between 2004 and 2008. We examined the change in 25(OH)D levels in 40 MS patients who took either LDC (< or =800 IU/day) or HDE (50,000 IU/day for 7-10 days, followed by 50,000 IU weekly or biweekly). RESULTS: The average 25(OH)D level was 71 +/- 39 nmol/L (Mean +/- SD), and 167(84%) patients had insufficient levels (< or =100 nmol/L) of 25(OH)D. The patients supplemented with LDC did not have a significant increase in their 25(OH)D levels. However, 25(OH)D levels increased by 42 nmol/L (P = 0.01) in the patients originally taking LDC and then prescribed HDE. Optimal levels (> or =100 nmol/L) were only achieved in less than 40% of patients. CONCLUSIONS: We conclude that large numbers of patients with MS and TM in our cohort are deficient in vitamin D. HDE significantly elevated 25(OH)D levels in MS patients and was more effective at increasing 25(OH)D levels than LDC. Prospective studies are required to determine appropriate dosing regimen to achieve optimal levels in the majority of MS patients and to ascertain the safety, immunological response, and ultimately the clinical efficacy of vitamin D replacement therapy.

CNS demyelination associated with copper deficiency and hyperzincemia.

CNS demyelination is not a previously reported feature of acquired copper deficiency. The authors report two patients with idiopathic hypocupremia and hyperzincemia, hematologic changes of copper deficiency, and extensive CNS demyelination. Hematologic recovery followed copper supplementation, both initially and after relapse off copper therapy, while serum zinc levels remained high and the neurologic abnormalities only stabilized.

Root stimulation improves the detection of acquired demyelinating polyneuropathies.

Thirty-one patients with a presentation compatible with an acquired demyelinating polyradiculoneuropathy were prospectively evaluated for proximal conduction block using root stimulation (RS) of cervical and/or lumbar roots. These same techniques were applied to 78 controls (40 pathological). Proximal conduction block was noted in 20/31 cases and none of the controls. Only 7 of 31 cases met published demyelinating criteria. Intravenous immune globulin therapy was completed by 21/31 patients and 20/21 responded. RS is superior to published electrophysiologic criteria for identifying demyelinating polyneuropathies and predicting who will respond to treatment. RS should be performed in all patients suspected of having an acquired demyelinating polyneuropathy when traditional nerve conduction studies criteria are nondiagnostic. RS reliably predicts those likely to respond to immunosuppressive therapy.

Serially determined plasma alpha-tocopherol concentrations and results of the oral vitamin E absorption test in clinically normal horses and in horses with degenerative myeloencephalopathy.

Plasma alpha-tocopherol (vitamin E) values were monitored serially in 9 foals sired by a stallion with equine degenerative myeloencephalopathy (EDM) and in 5 age-matched control foals (sired by a clinically normal stallion) raised in the same environment for the first year of life. Clinical evaluation determined that 8 of the 9 foals sired by the stallion with EDM had neurologic deficits consistent with the disease on one or more occasions during the study period, whereas control foals had normal gait. From 6 weeks to 10 months of age, plasma alpha-tocopherol values in foals with signs of EDM were significantly (P less than 0.001) lower than those in control foals. An oral vitamin E absorption test was performed, and results for 8 of the affected horses and the affected stallion were compared with results for 4 of the monitored control horses and 4 additional control horses. Significant differences were not evident in any of the absorption indices. On the basis of data from this study and supported by reported prophylactic and therapeutic benefits of supplemented vitamin E, low plasma concentration of vitamin E is concluded to be a factor in the development of EDM in the first year of life of hereditarily predisposed foals. It was also concluded that the significantly lower alpha-tocopherol values seen in the foals in this study did not reflect a primary gastrointestinal tract absorption problem.