Primary Progressive Multiple Sclerosis-A Key to Understanding and Managing Disease Progression.

Primary progressive multiple sclerosis (PPMS), the least frequent type of multiple sclerosis (MS), is characterized by a specific course and clinical symptoms, and it is associated with a poor prognosis. It requires extensive differential diagnosis and often a long-term follow-up before its correct recognition. Despite recent progress in research into and treatment for progressive MS, the diagnosis and management of this type of disease still poses a challenge. Considering the modern concept of progression "smoldering" throughout all the stages of disease, a thorough exploration of PPMS may provide a better insight into mechanisms of progression in MS, with potential clinical implications. The goal of this study was to review the current evidence from investigations of PPMS, including its background, clinical characteristics, potential biomarkers and therapeutic opportunities. Processes underlying CNS damage in PPMS are discussed, including chronic immune-mediated inflammation, neurodegeneration, and remyelination failure. A review of potential clinical, biochemical and radiological biomarkers is presented, which is useful in monitoring and predicting the progression of PPMS. Therapeutic options for PPMS are summarized, with approved therapies, ongoing clinical trials and future directions of investigations. The clinical implications of findings from PPMS research would be associated with reliable assessments of disease outcomes, improvements in individualized therapeutic approaches and, hopefully, novel therapeutic targets, relevant for the management of progression.

Sphingolipid Players in Multiple Sclerosis: Their Influence on the Initiation and Course of the Disease.

Sphingolipids (SLs) play a significant role in the nervous system, as major components of the myelin sheath, contributors to lipid raft formation that organize intracellular processes, as well as active mediators of transport, signaling and the survival of neurons and glial cells. Alterations in SL metabolism and content are observed in the course of central nervous system diseases, including multiple sclerosis (MS). In this review, we summarize the current evidence from studies on SLs (particularly gangliosides), which may shed new light upon processes underlying the MS background. The relevant aspects of these studies include alterations of the SL profile in MS, the role of antibodies against SLs and complexes of SL-ligand-invariant NKT cells in the autoimmune response as the core pathomechanism in MS. The contribution of lipid-raft-associated SLs and SL-laden extracellular vesicles to the disease etiology is also discussed. These findings may have diagnostic implications, with SLs and anti-SL antibodies as potential markers of MS activity and progression. Intriguing prospects of novel therapeutic options in MS are associated with SL potential for myelin repair and neuroprotective effects, which have not been yet addressed by the available treatment strategies. Overall, all these concepts are promising and encourage the further development of SL-based studies in the field of MS.

Vocational activity for patients with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) usually occurs in young adults and, due to its long-lasting course and variety of symptoms, can affect their vocational activity. Our study aimed to evaluate employment status and working activity for persons with MS with regard to disease-related factors, quality of life, and depression. MATERIAL AND METHODS: 250 subjects with MS (62 men, 188 women, aged 19-71 years, mean 42.2) responded to a survey into various aspects of their employment. Relationships were sought between work-related issues and disease-related variables [MS type and duration, major symptoms, disability level on the Expanded Disability Status Scale (EDSS)], quality of life (WHOQOL- -BREF, World Health Organisation Quality of Life brief questionnaire) and depression (BDI, Beck Depression Inventory). Statistical analysis included Mann-Whitney U, Student's t, and Pearson's chi-squared tests. RESULTS: 71.2% of the patients were employed, and 49.1% perceived an impact of the disease upon their working activity (i.e. job loss, problems with finding a new one, and/or forced change of type and/or character of employment). Unemployed subjects had higher EDSS scores (4.05 vs. 2.34, p < 0.001) and longer disease durations (13.6 vs. 9.4, p < 0.001) than employed ones. They also scored higher on BDI (15.4 vs. 9.05, p < 0.001) and lower in all domains of WHOQOL-BREF (p < 0.001). CONCLUSIONS: The consequences of MS negatively influence many work-related factors. Unemployment is associated with a higher frequency of depression and a lower quality of life in MS patients.

What can we learn from the online learning experiences of medical students in Poland during the SARS-CoV-2 pandemic?

BACKGROUND: In March 2020, due to the SARS-CoV-2 pandemic, the Polish government ordered the closing of all medical faculties, with an obligatory shift to online learning. This lockdown continued, with a short period of blended learning, over the time of summer 2020. Distance learning had previously been rarely used within Polish medical schools, so such a sudden transfer was a major challenge. The aim of the study was to explore undergraduates' perception of online teaching provided at Polish medical faculties during the pandemic and to analyze how these experiences may inform future curriculum development. METHODS: The online survey was addressed to undergraduates at Polish medical faculties in November 2020. The questions captured demographics, epidemiological data and students' perception of various aspects of online teaching. Responses were subjected to thematic analysis and their distribution compared considering demographic parameters . RESULTS: Six hundred twenty students from thirteen medical faculties responded to the survey. Major benefits from online teaching perceived by respondents included increased convenience, enhanced quality, a sense of comfort and safety. Major complaints were associated with unsatisfactory content, technical issues, difficulties engaging, poor organization and lack of social life. Students claimed that online teaching required more self-directed learning and discipline and 57.9% considered this impact as negative. 44.5% of respondents took part in educational online activities beyond their scheduled classes. For 49.2% online examinations were reported as more stressful and for 24.8% - less stressful than traditional ones. Differences in the opinions on online teaching were found between men and women, students in early and senior years, Polish and non-Polish ones. CONCLUSIONS: The sudden move online inevitably was problematic for students. Their perspective afforded us the opportunity to consider shortcomings of pre-pandemic undergraduate curriculum. Online education requires a more self-directed learning, which was challenging for many students, so further enhancement of more autonomous study skills seems necessary. Distress expressed by students indicates the need for urgent support with mental health issues.

New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration.

Multiple sclerosis (MS) is a central nervous system disease with complex pathogenesis, including two main processes: immune-mediated inflammatory demyelination and progressive degeneration with axonal loss. Despite recent progress in our understanding and management of MS, availability of sensitive and specific biomarkers for these both processes, as well as neuroprotective therapeutic options targeted at progressive phase of disease, are still being sought. Given their abundance in the myelin sheath, lipids are believed to play a central role in underlying immunopathogenesis in MS and seem to be a promising subject of investigation in this field. On the basis of our previous research and a review of the literature, we discuss the current understanding of lipid-related mechanisms involved in active relapse, remission, and progression of MS. These insights highlight potential usefulness of lipid markers in prediction or monitoring the course of MS, particularly in its progressive stage, still insufficiently addressed. Furthermore, they raise hope for new, effective, and stage-specific treatment options, involving lipids as targets or carriers of therapeutic agents.

Neuromyelitis Optica Spectrum Disorder Treatment-Current and Future Prospects.

Neuromyelitis optica (NMO) is an immune-mediated demyelinative disorder of the central nervous system affecting mainly the optical nerves and the spinal cord. The recurrent course of the disease, with exacerbations and incomplete remissions, causes accumulating disability, which has a profound impact upon patients' quality of life. The discovery of antibodies against aquaporin 4 (AQP4) and their leading role in NMO etiology and the formulation of diagnostic criteria have improved appropriate recognition of the disease. In recent years, there has been rapid progress in understanding the background of NMO, leading to an increasing range of treatment options. On the basis of a review of the relevant literature, the authors present currently available therapeutic strategies for NMO as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of the disease.

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies - the Polish experience.

INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.

Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.

Attitudes towards neurology among medical undergraduates.

Diseases of the nervous system are an important contributor to clinical and social problems. Therefore there is a need to provide undergraduates and postgraduates of medical faculties with adequate training in neurology. However, many shortcomings have been observed in this field, often associated with students' negative perception of neurology. The aim of this study was to explore attitudes towards neurology amongst undergraduates of the medical faculty at Wroclaw Medical University, and the reasons for these attitudes. As a qualitative component of the study, a focus group discussion was conducted with six fifth year undergraduates. The findings of the focus group and a literature search informed the content of a questionnaire distributed among fifth year students of the medical faculty, including non-Poles attending English Division. The responses to the closed questions were analysed quantitatively and subjected to statistical analysis while the free text comments were analysed qualitatively. Triangulation of the findings from the focus group and the survey was performed. 134 Polish students and 75 English-speaking ones responded to the survey. The majority of participants perceived neurology to be interesting and important for medical education, and it was highly ranked as a potential future speciality. The majority of the survey respondents regarded neurology as difficult and mentioned specific drawbacks. In spite of similar general perceptions of neurology, Polish and English- -speaking students differed in their perceptions of particular aspects, conditioned by diversity in cultural backgrounds and earlier experiences associated with neurology. The course in neurology affected attitudes towards the subject more than preceding experiences, mostly in a positive manner. The fifth year medical undergraduates expressed mostly positive attitudes towards neurology. Cultural background and the course in neurology were the main factors contributing to attitudes in these students.

Quantitative magnetic resonance assessment of brain atrophy related to selected aspects of disability in patients with multiple sclerosis: preliminary results.

PURPOSE: The aim of this volumetric study was to evaluate the relationship between brain atrophy quantification in multiple sclerosis (MS) patients and the progression of disability measured by neurological standardised tests. MATERIAL AND METHODS: Seventeen patients (mean age 40.89 years) with clinically definite MS and 24 control subjects (mean age 38.45 years) were enrolled in the study. Brain examinations were performed on a 1.5T MR scanner. Automatic brain segmentation was done using FreeSurfer. Neurological disability was assessed in all patients in baseline and after a median follow-up of two years, using EDSS score evaluation. RESULTS: In MS patients we found significantly (p < 0.05) higher atrophy rates in many brain areas compared with the control group. The white matter did not show any significant rate of volume loss in MS patients compared to healthy controls. Significant changes were found only in grey matter volume in MS subjects. At the follow-up evaluation after two years MS patients with deterioration in disability revealed significantly decreased cerebral volume in 14 grey matter areas at baseline magnetic resonance imaging (MRI) compared to MS subjects without disability progression. CONCLUSIONS: Grey matter atrophy is associated with the degree of disability in MS patients. Our results suggest that morphometric measurements of brain volume could be a promising non-invasive biomarker in assessing the volumetric changes in MS patients as related to disability progression in the course of the disease.

Event-related potentials and cognitive performance in multiple sclerosis patients with fatigue.

The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue.

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I-V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.

Effects of noise and mental task performance upon changes in cerebral blood flow parameters.

The objectives of this paper were to determine whether traffic noise influences the parameters of cerebral blood flow (CBF) measured by functional transcranial Doppler sonography (fTCD) during the performance of mental tasks, and to see whether impact of noise on CBF changes with age. The study comprised 36 healthy volunteers, 22 women and 14 men, aged 25-49 years. The fTCD was performed using a fixed 2-MHz probe, aiming for an evaluation of mean velocity (MFV) and the pulsatility index (PI) in the middle cerebral artery (MCA) on both sides. Subsequently, fTCD was monitored: At rest; during performance of the Paced Auditory Serial Addition Test (PASAT); during exposure to traffic noise; and during concomitant exposure to noise and PASAT performance. MFV and PI were compared for particular conditions and correlated with age. During exposure to noise, flow parameters did not change significantly. PASAT performance in silence increased MFV and decreased PI in MCA on both sides. During PASAT performance, on exposure to noise, MCV and PI changed significantly only in the left MCA. However, values of MFV were significantly lower during noise than in silence. Correlations with age were noted for velocities in the right MCA during PASAT performance in silence and for PI on both sides during PASAT performed in noise conditions. Noise impairs the CBF during mental tasks. A comparison of changes in CBF parameters correlated with age suggests that the involvement of the nondominant hemisphere in managing with noise effects increases with age.

Evaluation of the Degradation of the Selected Projectile, Commissural and Association White Matter Tracts Within Normal Appearing White Matter in Patients with Multiple Sclerosis Using Diffusion Tensor MR Imaging - a Preliminary Study.

BACKROUND: The aim of the study was to assess the impairment of the selected white matter tracts within normal appearing white matter (NAWM) in multiple sclerosis (MS) patients using diffusion tensor imaging (DTI). MATERIAL/METHODS: Thirty-six patients (mean age 33.4 yrs) with clinically definite, relapsing-remitting MS and mild disability (EDSS - Expanded Disability Status Scale 1-3.5) and 16 control subjects (mean age 34.4 yrs) were enrolled in the study. DTI examinations were performed on a 1.5T MR scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained with a small ROI method in several white matter tracts within NAWM including: the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFOF), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of the internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). There were no demyelinative lesions within the ROIs in any of the patients. RESULTS: A significant decrease in FA was found in MS patients in both the ILFs and IFOFs (p<0.001) and in the left MCP and right SLF (p<0.05), compared to the normal subjects. There were no significant differences in FA values in the remaining evaluated ROIs, between MS patients and the control group. A significant increase in ADC (p<0.05) was found only in the right PLIC and the right SLF in MS subjects, compared to the control group. CONCLUSIONS: The FA values could be a noninvasive neuroimaging biomarker for assessing the microstructural changes within NAWM tracts in MS patients.

The Impact of Comorbidities and Motor Impairment on the Quality of Life of Patients with Spinal Muscular Atrophy: A Case-Control Study.

Introduction: Spinal muscular atrophy (SMA) is a genetically determined disease primarily leading to muscle weakness, but now, it is considered a systemic disease with changes in various tissues and organs. In our study, we aimed to compare quality of life (QoL) outcomes in patients with SMA in relation to the degree of motor limitation and comorbidities, mainly internal medicine diseases. Methods: We included 35 adult patients with SMA and 36 healthy volunteers. Thorough medical histories were taken focusing on comorbidities, and neurological examinations incorporating assessments using functional motor scales were performed. QoL was assessed based on the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire. Results: SMA patients and controls were comparable in terms of scores in the questionnaire's main domains. SMA patients presented significantly higher levels of satisfaction with their medical care than controls. Patients with more advanced SMA had significantly better scores on certain questions, e.g., those related to health satisfaction or leisure activities. A total of 71.4% of SMA patients had comorbidities, ranging from one to three in individual patients. SMA patients with comorbidities did not show worse QoL. Negative correlations were found between the number of comorbidities in SMA patients and individual questions on the WHOQOL-BREF questionnaire. Conclusions: Patients with SMA were satisfied with their medical care. Better scores on some questions in more advanced SMA may have been due to better adaptation to disease-related limitations. The presence of single comorbidities did not affect QoL, but a higher number of comorbidities negatively correlated with QoL.

Are Sirtuins 1 and 2 Relevant Players in Relapsing-Remitting Multiple Sclerosis?

SIRTs were demonstrated to play an important role in inflammatory, degenerative, and metabolic alterations, constituting the background of the central nervous system. Thus, they seem to be an appropriate object of investigation (as potential biomarkers of disease activity and/or novel therapeutic targets) in multiple sclerosis (MS), which has a complex etiology that comprises a cross-talk between all these processes. The aim of this study was to evaluate the levels of SIRT1 and SIRT2 in the serum of patients with the relapsing-remitting type of MS (RRMS), as well as their relationships with various aspects of MS-related disability. METHODS: A total of 115 patients with RRMS (78 women, 37 men, mean age 43 ± 9.9) and 39 healthy controls were included in the study. SIRT1 and SIRT2 were detected in the serum using the enzyme-linked immunoassay (ELISA) method. In the RRMS group, relationships were investigated between the SIRT 1 and 2 levels and the demographic data, MS-related clinical variables, and the results of tests evaluating fatigue, sleep problems, cognitive performance, autonomic dysfunction, and depression. RESULTS: The levels of SIRT1 and SIRT2 in RRMS patients were significantly lower than in the controls (11.14 vs. 14. 23, p = 0.04; 8.62 vs. 14.2, p < 0.01). In the RRMS group, the level of both SIRTs was higher in men than in women (15.7 vs. 9.0; 11.3 vs. 7.3, p = 0.002) and showed a significant correlation with the degree of disability (R = -0.25, p = 0.018). No other relationships were found between SIRT levels and the analyzed data. CONCLUSIONS: The serum levels of SIRT1 and 2 were decreased in the RRMS patients (especially in the female ones) and correlated with the degree of neurological deficit. The role of SIRTs as biomarkers of disease activity or mediators relevant for "invisible disability" in MS warrants further investigation.

Sleep disturbances in patients with multiple sclerosis.

Sleep disturbances constitute one of the important yet underestimated aspects of functioning of patients with multiple sclerosis (MS). The objective of this study was to evaluate sleep disturbances in patients with MS, with regard to demographic factors, disease-related variables, co-existing conditions and fatigue. In 100 MS patients, Epworth Sleepiness Scale (ESS) and a questionnaire about sleep disturbances (SlD) were implemented. ESS and SlD results were analyzed with regard to age, gender, duration of MS, type of its course, degree of disability in Expanded Disability Status Scale (EDSS), MS therapies, coexisting diseases, results of Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). ESS score indicated increased daytime sleepiness in 19 patients. In SlD, 49 subjects reported sleep disturbances and 35 more than one of their kind (most commonly terminal and middle insomnia). No relationships were found between ESS and SlD scores and age, gender, MS duration, type of its course, EDSS or coexisting diseases. In 36 patients, somatic complaints interfered with sleep. The patients with depression had significantly lower ESS result and those currently treated with immunomodulation had significantly lower SlD score. SlD score correlated positively with FSS and MFIS. Sleep disturbances in MS patients may occur independently from demographic and disease-related variables, but they are often influenced by the symptoms of MS and therapies used. Sleep disturbances may contribute to fatigue in the course of MS.

Bortezomib-induced painful neuropathy in patients with multiple myeloma.

Neurotoxicity towards the peripheral nervous system which appears clinically in the form of painful neuropathy is an essential dose-limiting factor during the treatment of multiple myeloma. In this review article different forms of this painful neuropathy are presented together with currently available diagnostic tools which are usually applied to confirm the diagnosis. Also, the most often used neurological scales estimating neurological deficit are presented. Special attention is paid to the management of the reversibility of bortezomib-induced neuropathic pain.

Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis.

Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.