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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ 5 androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative autoimmune disease of the central nervous system (CNS) damaging myelin and axons. Diagnosis is based on the combination of clinical findings, magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid (CSF). Metabolomics is a systematic study that allows us to track amounts of different metabolites in a chosen medium. The aim of this study was to establish metabolomic differences between the cerebrospinal fluid of patients in the early stages of multiple sclerosis and healthy controls, which could potentially serve as markers for predicting disease activity. We collected CSF from 40 patients after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS, and the CSF of 33 controls. Analyses of CSF samples were performed by using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector. Significant changes in concentrations of arginine, histidine, spermidine, glutamate, choline, tyrosine, serine, oleic acid, stearic acid and linoleic acid were observed. More prominently, Expanded Disability Status Scale values significantly correlated with lower concentrations of histidine. We conclude that these metabolites could potentially play a role as a biomarker of disease activity and predict presumable inflammatory changes.

Background: Changes of white matter integrity in people with multiple sclerosis (MS) were documented following mainly motor/skill acquisitions physical therapy, while following neuroproprioceptive "facilitation, inhibition" (neurofacilitation) only by two pilot studies. Neurofacilitation has potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold. However stronger evidence is missing., Aim: This study investigates whether neurofacilitation (three physical therapy types) induce white matter changes and if they relate to clinical improvement., Design: The Three-Arm Parallel-group Exploratory Trial (NCT04355663)., Setting: Each group underwent different kinds of two months ambulatory therapy (Motor Program Activating Therapy, Vojta's reflex locomotion and Functional Electric Stimulation in Posturally Corrected Position)., Population: MS people with moderate disability., Methods: At baseline and after the program, participants underwent magnetic resonance diffusion tensor imaging (DTI) and clinical assessment. Fractional anisotropy maps obtained from DTI were further analyzed using tract-based spatial statistic exploring the mean values in the whole statistic skeleton. Moreover, additional exploratory analysis in 48 regions of white matter was done., Results: Ninety-two people were recruited. DTI data from 61 people were analyzed. The neurofacilitation (irrespective type of therapy) resulted in significant improvement on the Berg Balance Scale (P=0.0089), mainly driven by the Motor Program Activating Therapy. No statistically significant change in the whole statistic skeleton was observed (only a trend for decrement of fractional anisotropy after Vojta's reflex locomotion). Additional exploratory analysis confirmed significant decrement of fractional anisotropy in the right anterior corona radiata., Conclusions: Neurofacilitation improved balance without much evidence of white matter integrity changes in people with MS., Clinical Rehabilitation Impact: The study results point to the importance of neuroproprioceptive "facilitation and inhibition" physical therapy in the management of balance in people with multiple sclerosis; and the potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold.

Background: Guidelines and general recommendations are available for multiple sclerosis rehabilitation, but no specific guidance exists for physical therapists. Describing aspects of physical therapy content and delivery in multiple sclerosis and its determinants and analysing whether general recommendations connected with physical therapy are implemented in practice is important for interpreting clinical and research evidence. Methods: An online cross-sectional survey of physical therapists specialized in multiple sclerosis (212 specialists from 26 European countries) was used. Results : There was distinct diversity in service delivery and content across Europe. Perceived accessibility of physical therapy varied from most accessible in the Western region, and least in the Southern region. Sixty-four physical therapists adjusted their approach according to different disability levels, less so in the Eastern region. Duration, frequency and dose of sessions differed between regions, being highest in Southern and Western regions. "Hands on treatment" was the most commonly used therapeutic approach in all apart from the Northern regions, where "word instruction" (providing advice and information) prevailed. Conclusions: The content and delivery of physical therapy differs across Europe. Recommendations concerning access to treatment and adjustment according to disability do not appear to be widely implemented in clinical practice., Competing Interests: The Authors declares that there is no conflict of interest.

Major depression is the most common psychiatric disorder that occurs in a number of neurological diseases. Symptoms and signs of major depression are sometimes inherent to the neurological disease, sometimes depression appears fi rst, followed by a neurological disorder. The diagnosis and treatment of major depression has to be timely to prevent more severe and diffi cult to manage course of the neurological disease. Early recognition of depressive symptoms and its appropriate treatment signifi cantly improve patients' quality of life. Underlying mechanisms of major depression are still unknown. Interactions between many risk factors, such as biological, psychological, social and environmental are involved. The main clinical symptoms of major depression include persistent feeling of sadness, lack of interest in outside stimuli and slow psychomotor speed. Diff erential diagnostics have to exclude dementia and depressive syndrome induced by psychoactive substances and drugs. An acute depressive syndrome is known as a depressive phase and can be moderate or severe. Antidepressants and psychotherapy are the main treatment modalities for major depression. Therapeutic eff ect on the main symptoms of major depression is usually observed within 6-8 weeks after starting treatment. Major depression associated with stroke, multiple sclerosis, chronic pain, migraine, epilepsy and Parkinson's disease is discussed in detail, including currently recommended medical treatments. [ABSTRACT FROM AUTHOR]

Objective: Evoked potentials (EP) are functional neurophysiological methods that have been used in multiple sclerosis (MS) especially in its early diagnosis. Recently, multimodal EPs appears to be a prognostic factor for disease progression. Methods: The review is based on a literature search in PubMed and the author’s long experience of neurophysiological diagnostics. Results: Visual evoked potential (VEP) are preferentially used in early diagnosis of MS. They are highly sensitive to detect subclinical optic neuritis more than magnetic resonance. Somatosensory (SEP) and motor (MEP) evoked potentials can reveal subclinical lesions in the central nervous system and could be a supplementary diagnostic tests for sensory and motor system disturbances. MEP abnormalities correlate with the degree of motor impairment and disability assessed by EDSS. Abnormal multimodal EPs (”positive EP score”) at the first session are worse prognostic factor. Low and stable EP scores along with stable EDSS identify a ”benign” form of RS. The assessment of the disease progression and/or monitoring of the therapeutic effects have some limitations, e.g. abnormal response persists even in relative inactivity of the disease and it’s localization is non-specific. The sensitivity of EPs increases with the length of the tested neural pathways and with used EP modalities. Conclusion: Evoked potentials are highly sensitive in revealing ”silent lesions” especially at the beginning of MS and/or when no obvious neurological symptoms occur. Multimodal evoked potentials have indisputable benefit of prognostic value to determine non-responders, ”benign” course of the disease and patients with significant disease progression. Supported by Research Project of Charles University PRVOUK P34, Czech Republic. [ABSTRACT FROM AUTHOR]