Małgorzata Zajda

Sex hormone patterns in women with multiple sclerosis as related to disease activity — a pilot study

BACKGROUND AND PURPOSE The influence of sex hormones on immune system activity in multiple sclerosis (MS) has been suggested by clinical evidence. The aim of the study was to ana-lyse the pattern of sex hormones in MS women and to correlate the hormone pattern abnormalities to the disease course as well as to the magnetic resonance imaging (MRI) results. MATERIAL AND METHODS We studied the serum level of the progesterone, β-oestradiol and prolactin in 46 women with clinical definite MS aged from 19 to 65; mean disease duration was 11.80 ± 9.86 years. The evaluation of the intensity of hormonal changes was done using a scoring system (0-3). On the brain MRI, the presence of brain atrophy, of hypothalamic demyelination as well as demyelination intensity (or degree) were analysed. The evaluation of the degree of demyelination and brain atrophy was done using a scoring system (0-4). RESULTS The main hormonal abnormalities consisted of decreased progesterone level, increased oestradiol level or both. The sex hormone pattern was abnormal in 56% of patients. Hypothalamic lesions were found on MRI in 53% of cases. The abnormal hormonal pattern correlated with intensity of MR changes (p < 0.05, Fishers exact test), but neither with presence of hypothalamic changes nor with disease parameters (Expanded Disability Status Scale, relapse rate, disease duration). CONCLUSIONS It is important to check the hormonal pattern in MS women because according to our results it may be related to the disease activity and probably affects the type of therapeutic intervention. This pilot study will be extended in a larger population.

Bone metabolism and vitamin D status in patients with multiple sclerosis.

BACKGROUND Vitamin D (VD), an important factor for bone health immobilization and immune regulation, has been shown to have low serum concentration in multiple sclerosis (MS) patients. Those patients have also multiple fracture risk factors, including progressive immobilization and long-term glucocorticoids treatment. The aim of the study was to analyze bone health (osteopenia or osteoporosis prevalence) and VD serum concentration in MS patients as well as the influence of disease activity and treatment on bone health. MATERIALS AND METHODS The study involved 72 MS patients: 52 women and 20 men. Mean age was 40.3±10.5 yrs, mean EDSS (Expanded Disability Status Scale) 3.3±1.9. Bone health was analyzed using standard densitometry in the lumbar spine and femoral neck. Serum levels of VD, calcium, phosphate and parathormone were assessed. We compared two groups of patients with multiple sclerosis: relapsing - remitting MS (RRMS) and progressive relapsing MS (PRMS). RESULTS Densitometry revealed osteopenia in twenty-six (36.1%) patients and osteoporosis in eleven (15.3%), no bone fractures were presented. Sixty-eight MS patients (94.4%) had lower VD serum level if compared to population referential values. Thirteen patients (18.1%) had severe VD deficiency. Densitometry parameter (T-score of the lumbar spine) worsened with EDSS increase (r=-0.43, P=0.001). There was a statistically significant negative correlation between VD concentration and EDSS score (r=-0.31; P=0.009). CONCLUSIONS Our study indicates that patients with MS have high incidence of osteopenia and osteoporosis and vitamin D deficiency. Bone health disturbances studied by densitometry are related to the disability caused by MS.

The neurosteroid dehydroepiandrosterone sulfate, but not androsterone, enhances the antidepressant effect of cocaine examined in the forced swim test--Possible role of serotonergic neurotransmission.

One of the mechanisms of cocaines actions in the central nervous system is its antidepressant action. This effect might be responsible for increased usage of the drug by individuals with mood disorders. Higher endogenous levels of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS) were reported to correlate with successful abstinence from cocaine use in addicts, but a clinical trial showed that supplementation with a high dose of DHEA increased cocaine usage instead. Such ambiguous effects of DHEA(S) could potentially be linked to its influence on the antidepressant effect of cocaine. In this study we tested DHEAS and its metabolite, androsterone, for interactions with cocaine in animal model of depression (forced swim test) and examined the effects of both steroids and cocaine on serotoninergic neurotransmission. All substances were also tested for influence on locomotor activity. A cocaine dose of 5mg/kg, which had no significant effect on locomotor activity, was chosen for the forced swim test. Neither DHEAS nor androsterone showed any antidepressant action in this test, while cocaine manifested a clear antidepressant effect. Androsterone slightly reduced the antidepressant influence of cocaine while DHEAS markedly, dose-dependently enhanced it. Such an effect might be caused by the influence of DHEAS on serotonin neurotransmission, as this steroid decreased serotonin concentration and turnover in the striatum. When DHEAS and cocaine were administered together, the levels of serotonin in the striatum and hippocampus remained unchanged. This phenomenon may explain the additive antidepressant action of DHEAS and cocaine and why co-administration of DHEAS and cocaine increases drug use.

Aquaporin-4: A novel diagnostic biomarker for seronegative neuromyelitis optica

Neuromyelitis optica (NMO) and its spectrum disorders (NMOSDs) are a heterogenous group of demyelinating diseases, distinguished from others by the presence of NMO-IgG (immunoglobulin G). The results of recent studies revealed however, that some NMO/NMOSD patients are seronegative and cannot be distinguished from multiple sclerosis (MS) by NMO-IgG assessment.1 This differentiation is essential, as inadequately treated NMO or NMOSD has a poor prognosis. Also immunomodulation, now commonly used in treatment of early stages of MS, has either no influence on the course of NMO or may even worsen it.2 Other immunosuppressive agents used in more severe cases of MS, such as natalizumab, might also worsen the course of NMO.3 These data suggest that there is an increasing need for other biomarkers that might help to distinguish NMO/NMOSD from other demyelinating disorders. The aim of our study was to compare aquaporin-4 (AQP4) concentrations in the serum of NMO/ NMOSD and MS patients, as well as in controls, in order to establish whether it can be used as diagnostic biomarker for NMO/NMOSD and MS.