Vitamin D levels in people with multiple sclerosis and community controls in Tasmania,Australia

Abstract Background Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. Objectives To examine the prevalence and determinants of vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. Methods We conducted a population based case-control study in Tasmania, Australia (latitude 41–43°S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. Results A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D ≤ 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). Conclusion The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case sample. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.     

Tumor necrosis factor beta (TNF-β) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1

This study evaluated the association of tumor necrosis factor beta (TNF-β) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-β genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting–relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p?=?0.0443). Brown patients presented higher disability (p?=?0.0234) and higher TNF-α levels (p?=?0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p?=?0.0354 and p?=?0.0309, respectively) than those with other geotypes. Association between TNF-β NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p?>?0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.     

Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial

Multiple sclerosis (MS) presents with optic neuritis (ON) in 20 % of cases and 50 % of ON patients develop MS within 15 years. In this study, we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS (primary outcome) and on the MRI lesions (secondary outcome) of ON patients with low serum 25 (OH) D levels. Thirty ON patients (15 in each of 2 groups, aged 20–40 years) with serum 25 (OH) D levels of less than 30 ng/ml were enrolled in a double blind, randomized, parallel-group trial. The treatment group (cases) received 50,000 IU of vitamin D3 weekly for 12 months and the control group (controls) received a placebo weekly for 12 months. Finally, the subsequent relapse rate and changes in MRI plaques were compared between the two groups. Risk reduction was 68.4 % for the primary outcome in the treatment group (relative risk = 0.316, p = 0.007). After 12 months, patients in the treatment group had a significantly lower incidence rate of cortical, juxtacortical, corpus callosal, new T2, new gadolinium-enhancing lesions and black holes. The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group (p = 0.092). Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 (OH) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS.     

Determinants of the severity of comorbid migraine in multiple sclerosis

A high co-morbidity between multiple sclerosis (MS) and migraine has been reported, especially in young female patients affected by a relapsing-remitting (RR) course of MS. In this study, we aimed to elucidate the determinants of the severity of comorbid migraine in MS. Demographic, clinical and psychometric variables were collected from a cohort of 205 RR-MS patients regularly attending to an Italian outpatient MS Centre. Of them, 102 (49.8?%) were diagnosed as affected by comorbid migraine. About one-third of MS patients with comorbid migraine have asked the attending neurologist a specific anti-migraine treatment. Despite this, only few MS patients (10.8?%) reported a prior use of prophylactic drugs, and even fewer (2.9?%) took triptans as pain killers; these proportions were significantly lower when compared with those of a control group of 63 migraineurs subjects without MS (p?<?0.0001 for both comparison). Factors associated with a moderate or severe disability (MIDAS grades III or IV) due to comorbid migraine in MS patients were the depressive state (OR?=?4.294; p?=?0.001), the anxiety trait (OR?=?5.786; p?=?0.004) and an ongoing IFNB treatment (OR?=?2.337; p?=?0.028). Likewise, depression (OR?=?3.453; p?=?0.048) and anxiety (OR?=?4.582; p?=?0.014) were both independent predictors for having a MIDAS grades of III or IV also in migraineurs subjects without MS. Investigating the determinants of migraine severity may allow a better management of MS patients with comorbid migraine. In these patients, a tailored therapeutic approach is warranted to improve their quality of life and reduce the burden of these two chronic and disabling conditions.     

Natalizumab reduces serum pro-angiogenic activity in MS patients

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0?±?3.9 and 22.5?±?2.6, p?<?0.0001) and higher osteopontin levels (65.7?±?24.3 ng/ml and 65.9?±?16.6 ng/ml, p?=?0.019 and p?=?0.029, respectively) than HCs (9.0?±?2.2; 48.5?±?7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs?=?0.373, p?=?0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9?±?2.1, p?<?0.005; 49.3?±?20.0 ng/ml, p?=?0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.     

The evaluation of vitamin D levels in patients with carpal tunnel syndrome

The aim of this study was to evaluate the relationship between 25-hydroxyvitamin D (25(OH)D) levels and carpal tunnel syndrome (CTS). 25(OH)D levels were checked in 108 consecutive patients with CTS symptoms and 52 healthy controls. All patients underwent nerve conduction studies and completed Boston Carpal Tunnel Questionnaire (BQ) symptom severity and functional status scales to quantify symptom severity, pain status and functional status. There were 57 patients with electrophysiological confirmed CTS (EP+ group) and 51 electrophysiological negative symptomatic patients (EP? group). 25(OH) D deficiency (25(OH)D < 20 ng/ml) was found in 96.1 % of EP? group, in 94.7 % of EP+ group and in 73.8 % of control group. 25(0H) D level was found significantly lower both in EP+ and EP? groups compared to control group (p = 0.006, p < 0.001, respectively). Although mean vitamin D level in EP? group was lower than EP+ group, statistically difference was not significant between EP+ and EP? groups (p = 0.182). BQ symptom severity and functional status scores and BQ pain sum score were not significantly different between EP+ and EP? groups. We found no correlation with 25(OH) D level for BQ symptom severity, functional status and pain sum scores. 25(OH) D deficiency is a common problem in patients with CTS symptoms. As evidenced by the present study, assessment of serum 25(OH)D is recommended in CTS patients even with electrophysiological negative results.     

Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients

Multiple sclerosis (MS) is an auto-immune disease whose etiology remains controversial. Both genetic and environmental factors are thought to be involved in the risk of developing the disease. The purpose of our study was to assess the association of Vitamin D receptor (VDR) polymorphisms with MS and to investigate the interaction of these polymorphisms with vitamin D levels. A total of 179 Sicilian subjects, including 104 MS patients and 75 healthy controls, were studied. The most common VDR polymorphisms (Fok-I, Bsm-I, Taq-I and Apa-I) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analyses in both groups and serum 25-hydroxyvitamin D [25(OH)D] levels were determined in MS patients by high-performance liquid chromatography (HPLC). The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I. Moreover, MS patients with FF and Ff genotype had a significantly lower serum levels of 25(OH)D compared with ff carriers (P < 0.05 FF vs Ff and Ff vs ff). Our findings showed no association between VDR polymorphisms and risk of MS. Interestingly, F allele could confer a genetic predisposition to lower 25(OH)D levels.     

The association between serum vitamin B<Subscript>12</Subscript> deficiency and tension-type headache in Turkish children

This study aimed to determine the relationship between serum vitamin B₁₂ level and tension-type headache. The study groups consisted of 75 patients (40 females, 35 males) with headache and a control group of 49 healthy children (25 females, 24 males). Serum vitamin B₁₂ level <?200 pg/ml was defined as deficient, and <?160 pg/ml as severely deficient. The serum vitamin B₁₂ level was measured by the electrochemiluminescence (ECLIA) method. The serum vitamin B₁₂ levels in the headache and control groups were 273.01?±?76.77 and 316.22?±?74.53 pg/ml, with the difference determined as statistically significant (p?=?0.003). In the case group, 18/75 patients (24%) had a serum vitamin B12 level below the normal of 200 pg/ml, and in the control group 4/49 (8%) patients were also below the normal range (p?=?0.021). The serum vitamin B₁₂ level in the children with tension-type headache was significantly lower than that in the control group. From the results of the study, it was concluded that there may be an association between vitamin B₁₂ level and tension-type headache. However, further clinical studies are needed.     

Vitamin D status in multiple sclerosis: Are there any correlations with the health related quality of life

ObjectiveOne of the factors implicated in increased risk of developing MS is low serum levels of 25-hydroxyvitamin D (25(OH)D). MS, on the other hand, may affect the quality of life of the patients’ including physical and social functioning among others. The aim of this study was to investigate 25(OH)D levels and to assess health related quality of life of patients by giving emphasis to possible correlations between these variables.Material and methodsFifty MS patients and 30 controls were enrolled in the study. Gender and age of patients, duration of disease, MS subtypes, Expanded Disability Status Scale (EDSS) scores and duration of sunlight exposure were recorded, 25(OH)D levels and bone mineral density (BMD) measurements were all performed. All the subjects in both groups were administered Short Form-36 (SF-36) for the assessment of quality of life.Results25(OH)D levels were found to be significantly decreased in MS patients (p < 0.05). BMD values including L1–L4 t score, L1–L4 z score, femur neck t and z scores were significantly reduced in the patient group (p < 0.05). All SF-36 subscale scores were significantly (p < 0.05) lower in MS group and all SF-36 subscale scores except bodily pain were significantly correlated with the EDSS scores.Conclusion25(OH)D and BMD screening should be considered as a routine procedure in the assessment of MS patients. In the long term treatment and follow-up of patients with MS, functional outcomes and quality of life issues should be kept in mind by all the physicians engaged in MS.     

Expression Analysis of Vitamin D Signaling Pathway Genes in Epileptic Patients

Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprotection, brain cell proliferation, and differentiation. Consequently, vitamin D supplementation has been suggested as an alternative treatment in epileptic patients. We aimed at assessment of vitamin D signaling pathway in epileptic patients. In the present study, we evaluated vitamin D serum concentration as well as expression of vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) in epileptic patients compared with healthy individuals. We found significant lower levels of vitamin D in epileptic patients compared with healthy subjects. Expression analyses showed significant downregulation of VDR expression in peripheral blood of epileptic patients compared with healthy subjects (relative expression (REx)?=?0.16, P?<?0.001). However, there was no significant difference in CYP24A1 expression between epileptic patients and normal subjects. CYP27B1 expression analysis showed significant upregulation in male patients aged between 30 and 40 (REx?=?5.43, P?=?0.013). After using two-way ANCOVA for adjusting the effects of sex and age, there was a statistically significant difference in the VDR expression values between patient and control groups (P?<?0.001). Spearman’s correlation analysis showed no significant correlation between genes expression levels and patients’ age or vitamin D serum concentrations. However, we found significant correlations between VDR expression levels and CYP24A1/ CYP27B1 expression levels in epileptic patients (r?=?0.435 and P?<?0.001; r?=?0.26 and P?=?0.02 respectively). There was also a significant correlation between the expression levels of CYP24A1 and CYP27B1 (r?=?0.349 and P?=?0.001). Our study shows a possible role for VDR in the pathogenesis of epilepsy.     

Eyes are mirror of the brain: comparison of multiple sclerosis patients and healthy controls using OCT

Abstract

Objective: To evaluate the thickness of choroid and retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis using enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods: In this cross-sectional study, both eyes of 52?MS patients [n?=?104 eyes; 62 eyes of MS patients without optic neuritis (MS-NON) and 42 eyes of MS patients with optic neuritis (MS-ON)] and only one eye of 36 healthy control subjects (n?=?36 eyes) were evaluated. Complete ophthalmologic examination and EDI-OCT scanning were completed for all participants. Choroidal thickness measurements were executed at three different points.

Results: Choroidal thickness measurements were similar between MS patients and healthy control subjects. However, the mean subfoveal choroidal thickness was increased significantly in MS-ON group (399.13?±?82.91?μm) compared to MS-NON group (342.71?±?82.46?μm; p?=?0.004). Mean RNFL thickness was significantly reduced in MS patients (90.42?±?13.31?μm) compared to healthy controls (101.18?±?10.75?μm; p?<?0.001). Moreover, temporal RNFL thickness was significantly thinner in MS-ON group (54?±?14.50?μm) than MS-NON group (62.15?±?15.88?μm; p?=?0.01). In MS patients, temporal RNFL thickness was correlated with both Expanded Disability Status Score (r?=?0.383; p?<?0.001) and longer disease duration (r=–0.202; p?=?0.04).

Conclusion: The results of the present study suggest that RNFL thickness can be used as an important parameter while following up with MS patients. However, more studies using EDI-OCT are required with larger MS patient groups and automated method.     

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 from different sources is inversely associated with Parkinson disease

An inverse association between Parkinson disease (PD) and total vitamin D levels has been reported, but whether vitamin D from different sources, that is, 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association is unknown. Plasma total 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were measured by liquid chromatography–tandem mass spectrometry in PD patients (n = 478) and controls (n = 431). Total 25(OH)D was categorized by clinical insufficiency or deficiency; 25(OH)D2 and 25(OH)D3 were analyzed in quartiles. Vitamin D deficiency (total 25[OH]D < 20 ng/mL) and vitamin D insufficiency (total 25[OH]D < 30 ng/mL) are associated with PD risk (odds ratio [OR] = 2.6 [deficiency] and 2.1 [insufficiency]; P < 0.0001), adjusting for age, sex, and sampling season. Both 25(OH)D2 and 25(OH)D3 levels are inversely associated with PD (P_trend < 0.0001). The association between 25(OH)D2 and PD risk is largely confined to individuals with low 25(OH)D3 levels (P_trend = 0.0008 and 0.12 in individuals with 25[OH]D3 < 20 ng/mL and 25[OH]D3 ≥ 20 ng/mL, respectively). Our data confirm the association between vitamin D deficiency and PD, and for the first time demonstrate an inverse association of 25(OH)D2 with PD. Given that 25(OH)D2 concentration is independent of sunlight exposure, this new finding suggests that the inverse association between vitamin D levels and PD is not simply attributable to lack of sunlight exposure in PD patients with impaired mobility. The current study, however, cannot exclude the possibility that gastrointestinal dysfunction, a non‐motor PD symptom, contributes to the lower vitamin D2 levels in PD patients. © 2014 International Parkinson and Movement Disorder Society     

What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year?

Vitamin D sufficiency has been associated with lower risk of multiple sclerosis and may also have a favorable effect on the course of the disease. The aim of this work was to identify predictors of serum 25-hydroxy vitamin D (25[OH]D) levels in persons with multiple sclerosis (MS) and to assess the effect of high-dose vitamin D₃ supplementation on vitamin D status. A 96-week randomized controlled trial was performed to assess the effect of supplementation with 20,000 IU of vitamin D₃ weekly on bone mineral density in 68 patients. We collected data on vitamin D intake and UV-exposure and repeatedly measured serum 25(OH)D levels. Half of the participants had sufficient winter vitamin D levels at baseline (≥50 nmol/l). Vitamin D status was predicted by sun exposure during the last 3 months and by ingested vitamin D from diet and supplements. In the placebo group, the proportion of the participants with sufficient levels increased from 55 % in winter to 92 % during the summer. In the intervention group, all participants had winter 25(OH)D levels above 50 nmol/l at the end of the study. MS patients who have no sun exposure and low dietary vitamin D intake during the winter months should be recommended to take vitamin D supplements to achieve serum 25(OH)D levels of at least 50 nmol/l.     

The association between 25-hydroxyvitamin D levels and children's sleep-wake patterns: a prospective cohort study

ObjectiveTo explore the association between vitamin D in cord blood or in venous blood and children's sleep-wake patterns at two years of age.MethodsData were from 209 children in a birth cohort, Shanghai Sleep Birth Cohort Study (SSBC). 25-Hydroxyvitamin D (25(OH)D) was assessed in cord blood and venous blood samples at two years of age by electrochemiluminescence immunoassay. Children's sleep-wake patterns were measured with the Brief Infant Sleep Questionnaire (BISQ) and Acti-Watch at two years of age.ResultsThe prevalence of vitamin D deficiency (defined as <50 nmol/L) was 50.4% in cord blood and 28% at two years of age. The cord blood 25(OH)D level was not significantly associated with children's sleep at two years of age. Children with 25(OH)D deficiency at two years old had shorter reported and actigraphic night sleep duration (NSD) and total sleep duration (TSD) than those with normal 25(OH)D concentration. 25(OH)D level at two years old was positively associated with night and total sleep duration (β_reported-NSD = 0.6, p = 0.011; β_reported-TSD = 0.6, p = 0.029; β_{actigraphic-NSD} = 0.82, p = 0.003; β_{actigraphic-TSD} = 0.78, p = 0.006), but was not associated with daytime sleep duration. There was no significant association between 25(OH)D level with night waking duration and midpoint of sleep either measured subjectively or objectively.ConclusionWe found that not cord blood 25(OH)D level but two-year-old 25(OH)D level was associated with children's sleep-wake patterns at two years of age. These findings suggest more attention should be paid to the assessment of 25(OH)D levels in children with short sleep duration.     

25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis

Past sun exposure and vitamin D supplementation have been associated with a reduction in the risk of MS. We measured the serum concentration of 25-hydroxyvitamin D (25[OH]D) at the time of MS diagnosis in 40 MS patients and 40 controls. We found no difference in the serum levels of 25(OH)D between MS patients and controls when all samples or samples obtained during winter months were compared, but MS patients had significantly lower serum 25(OH)D concentrations in June to September than the controls. The vitamin D stores were adequate for bone metabolism (> 37 nmol/L) in 70% of MS patients throughout the year and within the hypovitaminosis level (< 37 nmol/L) in 30% of MS patients at some time of the year. During MS-relapses, 25(OH)D levels were lower than in remission, but mostly within the reference range observed in relation with normal bone metabolism. We conclude that the vitamin D stores in most MS patients are adequate for their normal bone metabolism. However, lower vitamin D levels during MS relapses than in remission suggest that vitamin D could be involved in the regulation of the clinical disease activity of MS. The optimal serum levels of vitamin D for the regulation of immune responses remain to be determined.     

Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration

To assess the presence and persistence of muscular edema and increased myoplasmic sodium (Na⁺) concentration in Duchenne muscular dystrophy (DMD). We examined eight DMD patients (mean age 9.5?±?5.4?years) and eight volunteers (mean age 9.5?±?3.2?years) with 3-tesla proton (¹H) and ²³Na density-adapted 3D-radial MR sequences. Seven DMD patients were re-examined about 7?months later without change of therapy. The eighth DMD patient was re-examined after 5 and 11?months under medication with eplerenone. We quantified muscle edema on STIR images with background noise as reference and fatty degeneration on T1-weighted images using subcutaneous fat as reference. Na⁺ was quantified by a muscular tissue Na⁺ concentration (TSC) sequence employing a reference containing 51.3?mM Na⁺ with 5?% agarose. With an inversion-recovery (IR) sequence, we determined mainly the myoplasmic Na⁺. The normalized muscular ²³Na IR signal intensity was higher in DMD than in volunteers (n?=?8, 0.75?±?0.07 vs. 0.50?±?0.05, p?<?0.001) and persisted at second measurement (n?=?7, 1st 0.75?±?0.07, 2nd 0.73?±?0.06, p?=?0.50). When compared to volunteers (25.6?±?2.0?mmol/l), TSC was markedly increased in DMD (38.0?±?5.9?mmol/l, p?<?0.001) and remained constant (n?=?7, 1st 37.9?±?6.4?mmol/l, 2nd 37.0?±?4.0?mmol/l, p?=?0.49). Muscular edema (15.6?±?3.5 vs. 6.9?±?0.7, p?<?0.001) and fat content (0.48?±?0.08 vs. 0.38?±?0.01, p?=?0.003) were elevated in DMD when compared to volunteers. This could also be confirmed during follow-up (n?=?7, p?=?0.91, p?=?0.12). Eplerenone slightly improved muscle strength and reduced muscular sodium and edema. The permanent muscular Na⁺ overload in all DMD patients is likely osmotically relevant and responsible for the persisting, mainly intracellular muscle edema that may contribute to the progressive muscle degeneration.     

Primary lateral sclerosis and the amyotrophic lateral sclerosis–frontotemporal dementia spectrum

Aim

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum of diseases.

Methods

Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n?=?27) and ALS–FTD (n?=?12). Clinical features, Addenbrooke’s Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS).

Results

Global cognition was impaired in PLS (mean total ACE score 82.5?±?13.6), similar to ALS–FTD (mean total ACE score 76.3?±?7.7, p?>?0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5?±?6.2) compared ALS–FTD (50.1?±?7.2, p?<?0.001) and ALS (62.3?±?12.6, p?=?0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4?±?22.4 months) and shortest in ALS–FTD (38.5?±?4.5 months, p?=?0.002). Bulbar onset disease (β?=???0.45, p?=?0.007) and RMT (β?=?0.54, p?=?0.001) were independent predictors of global cognition while motor scores (β?=?0.47, p?=?0.036) and SICI (β?=?0.58, p?=?0.006) were significantly associated with ALSFRS.

Conclusion

The cognitive profile in PLS resembles ALS–FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS–FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS–FTD. Overall, while these findings support the notion that PLS lies on the ALS–FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

     

Vitamin D and disability in relapsing–remitting multiple sclerosis in patients with a Mexican background

Previous studies of multiple sclerosis (MS) patients have reported an inverse correlation between disability, the number of relapses and vitamin D levels in mostly white patients. It is unclear if this relationship has the same behavior in individuals with Hispanic backgrounds. To determine the relationship between vitamin D serum levels and disability in a sample of Hispanics of a Mexican background with relapsing–remitting multiple sclerosis (RRMS). A cross-sectional study was conducted on 50 RRMS individuals of Mexican background. The Expanded Disability Status Scale (EDSS) score, progression index (PI) and annual relapse rate (ARR) were recorded for each patient. Vitamin D levels were assessed during the summer. Pearson’s test was used to evaluate the relationship between vitamin D and EDSS, PI, ARR, and duration of disease evolution. Most patients were females (n = 29, 58%). The mean vitamin D level was 22.3 (± 6.4) ng/ml; the mean EDSS score was 2.2 (± 0.7), ARR 1.3 (± 0.5) and PI1.08 (± 0.6). No correlation was found between vitamin D levels and EDSS scores, ARR, PI or duration of disease. Moderate negative association between vitamin D levels and EDSS was found just in females (<0.0001). No correlation between vitamin D levels and disability was found in this sample of RRMS Mexicans. Longitudinal studies are needed to better understand the impact of Vitamin D in disability and multiple time points.     

MSNA during prolonged post-faint hypotension

Background

Following tilt-induced syncope, blood pressure usually recovers rapidly after tilt back to the horizontal position. However, in some patients, hemodynamic recovery is delayed, a condition recently termed “prolonged post-faint hypotension” (PPFH). The mechanism is thought to be mediated by increased vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have been reported in this condition, so we aimed to confirm that neither vasodilatation nor MSNA withdrawal was responsible.

Objectives

To retrospectively select patients with satisfactory recordings of continuous BP and MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in patients with PPFH to patients with normal recovery (NR) after tilt-back.

Methods

All patients were studied in Christchurch, New Zealand, between 1998 and 2008 using continuous arterial BP monitoring, and microneurographic recordings of MSNA from the right leg. Only patients with satisfactory BP and MSNA data throughout baseline, head-up tilt and presyncope were selected. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived using Modelflow. After baseline measurements, patients were tilted to the head-up 60° position and given GTN spray if asymptomatic after 20?min. Following the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH was defined as systolic BP <85?mmHg for at least 2?min after tilt-back. Measurements were averaged at baseline, early tilt, presyncope, early and late recovery. Within-group comparisons were made between baseline and all other time points. Between-group comparisons were made over all time points.

Results

Patients with PPFH (7 males, age 46?±?5?years, n?=?8) and with NR (8 males, age 47?±?6 years, n?=?8) were selected. Presyncope was provoked by GTN in 4/8 patients in each group. In both groups, MAP remained below baseline during early and late recovery: PPFH 84?±?5 versus 51?±?5 and 64?±?5?mmHg (p?=?0.001, p?=?0.001); NR 104?±?5 versus 83?±?5 and 93?±?5?mmHg (p?=?0.001, p?=?0.03). However, MAP and HR were lower in the PPFH group (p?=?0.004, p?=?0.023). During early recovery, CO remained below baseline only in the PPFH group (p?=?0.001), whereas TPR remained constant in both groups. In both groups, all MSNA indices tended to remain above baseline levels during early and late recovery. PPFH 25?±?2 increased to 31?±?6 and 29?±?4 bursts/min (p?=?0.09, 0.02); NR 23?±?3 increased to 33?±?3 and 34?±?3 bursts/min (p?=?0.06, 0.01).

Conclusions

PPFH does not appear to be mediated by exaggerated vasodilatation or sympathetic withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a more likely mechanism.