Anti-myelin Antibodies Research Articles

フィンゴリモド投与中に帯状疱疹を発症した多発性硬化症の検討

Fingolimod, a sphingosine-1-phosphate receptor modulator, inhibits the egress of CCR7-positive lymphocytes, including encephalitogenic lymphocytes, from lymph nodes and may sometimes cause lymphopenia. A recent study reported that varicella zoster virus reactivation occurred in the saliva of 20% of multiple sclerosis (MS) patients treated with fingolimod. I compared the risk of developing herpes zoster between 32 MS patients treated with fingolimod (FTY-MS) and 45 patients, including those with neuromyelitis optica spectrum disorder, horizontal hemianopsia without anti-aquaporin-4 antibodies, and myelitis with anti-myelin oligodendrocyte glycoprotein antibodies, treated with tacrolimus (TCR-NMO). The risk of developing herpes zoster in FTY-MS (40/1,000 patient-years) was significantly higher than that in TCR-NMO (6/1,000 patient-years) (P < 0.0001, odds ratio: 6.90). The incidence of herpes zoster of patients with rheumatoid arthritis treated with Tofacitinib in Asian countries has been shown to be higher than those of patients in the United States or European countries. It may be better to pay more attention to develop herpes zoster in Japanese MS patients treated with fingolimod.

Clinical Profile of Anti-Myelin Oligodendrocyte Glycoprotein Antibody Seropositive Cases of Optic Neuritis

We have studied the clinical picture of anti-aquaporin antibody (AQP4-Ab)– and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)–positive optic neuritis. However, optic neuritis associated with MOG-Abs has not been elucidated using new methods such as cell-based assay. Hence, we conducted a comprehensive investigation on its clinical profile. Serum samples from 70 patients (17 males and 53 females, mean age 43.1 years) with optic neuritis were tested for MOG-Abs by cell-based assay. In MOG-Ab seropositive patients, the disease type, recurrence status, and visual function outcome were analysed. Among 70 patients, 18 were MOG-Ab seropositive. The 18 patients comprised 2 with chronic relapsing inflammatory optic neuropathy, 2 with AQP4-Ab seropositive optic neuritis (neuromyelitis optica), 12 with idiopathic optic neuritis, and 2 with optic neuritis associated with multiple sclerosis. Excluding two cases that were also AQP4-Ab seropositive, MOG-Ab seropositive cases had relatively favourable visual acuity outcome (although not significantly different from seronegative cases) but had significant residual visual field deficit (p = 0.0015). Furthermore, the number of relapses of optic neuritis per year was significantly greater in MOG-Ab seropositive cases than in seronegative cases (0.82 vs. 0.40; p = 0.0005). MOG-Abs may contribute to the heterogeneous clinical picture of optic neuritis, and although visual acuity outcome is favourable, there is a tendency of residual visual field deficit and a possibility of repeated relapses.

Pediatric anti-myelin oligodendrocyte glycoprotein syndrome: case series of a newly recognized central nervous system inflammatory disease

Pediatric acquired demyelinating syndromes have overlapping clinical and imaging features, but management and prognosis vary. We describe four children between the ages of 3 and 10 presenting with inflammatory brain disease - one with polyfocal neurological symptoms, one with severe bilateral optic neuritis and two with transverse myelitis, all without encephalopathy. All brain MRIs had extensive involvement of both deep grey and subcortical white matter. Three patients had longitudinally extensive spinal cord lesions. Clinical and radiological findings did not meet criteria for multiple sclerosis, acute disseminated encephalomyelitis, or neuromyelitis optica (NMO). NMO IgG testing was negative. All patients had resolution of clinical and imaging findings after treatment with steroids and IVIg. We found, elevated levels of anti-myelin oligodendrocyte glycoprotein antibodies in all four patients. Three of the children receive monthly IVIg infusions. Two of the patients relapsed once within 18 months of their initial attack and have since remained relapse free for 32 months and 43 months, respectively. The third patient (transverse myelitis) has not had any relapses since her initial attack 15 months ago. It appears that children with this syndrome may have more favourable outcomes when compared to other CNS relapsing inflammatory conditions.

Ultra-high resolution in-vivo 7.0 T structural imaging of the human hippocampus reveals the endfolial pathway

The hippocampus is a very important structure in memory formation and retrieval, as well as in various neurological disorders such as Alzheimer's disease, epilepsy and depression. It is composed of many intricate subregions making it difficult to study the anatomical changes that take place during disease. The hippocampal hilus may have a unique neuroanatomy in humans compared to that in monkeys and rodents, with field CA3h greatly enlarged in humans compared to that in rodents, and a white-matter pathway, called the endfolial pathway, possibly only present in humans. In this study we have used newly developed 7.0T whole brain imaging sequence, balanced steady-state free precession (bSSFP) that can achieve 0.4mm isotropic images to study, in vivo, the anatomy of the hippocampal hilus. A detailed hippocampal subregional segmentation was performed according to anatomic atlases segmenting the following regions: CA4, CA3, CA2, CA1, SRLM (stratum radiatum lacunosum moleculare), alveus, fornix, and subiculum along with its molecular layer. We also segmented a hypointense structure centrally within the hilus that resembled the endfolial pathway. To validate that this hypointense signal represented the endfolial pathway, we acquired 0.1mm isotropic 8-phase cycle bSSFP on an excised specimen, and then sectioned and stained the specimen for myelin using an anti-myelin basic protein antibody (SMI 94). A structure tensor analysis was calculated on the myelin-stained section to show directionality of the underlying fibers. The endfolial pathway was consistently visualized within the hippocampal body in vivo in all subjects. It is a central pathway in the hippocampus, with unknown relevance in neurodegenerative disorders, but now that it can be visualized noninvasively, we can study its function and alterations in neurodegeneration.

Anti-myelin antibody responses following induction of antigen-specific tolerance with antigen-coupled cells

Anti-myelin antibody responses following induction of antigen-specific tolerance with antigen-coupled cells

Epstein–Barr virus and Mycobacterium avium subsp. paratuberculosis peptides are cross recognized by anti-myelin basic protein antibodies in multiple sclerosis patients

Epstein–Barr virus and Mycobacterium avium subsp. paratuberculosis (MAP) have been associated to multiple sclerosis (MS). We searched for antibodies against the homologous peptides Epstein–Barr virus nuclear antigen 1 (EBNA1)400–413, MAP_0106c protein (MAP)121–132, and myelin basic protein (MBP)85–98 on a MS Sardinian cohort, showing that these antibodies are highly prevalent among MS patients compared to healthy controls. Competitive assay demonstrated that antibodies recognizing EBNA1400–413 and MAP121–132 cross-react with MBP85–98, possibly through a molecular mimicry mechanism. Indeed, the fact that peptides from different pathogens can be cross-recognized by antibodies targeting self-epitopes supports the hypothesis that EBV and MAP might trigger autoimmunity through a common target.

Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood-brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139-151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE.

Antimyelin antibodies as predictors of disability after clinically isolated syndrome

There is controversy whether determination of antibodies against myelin, myelin oligodendrocyte glycoprotein, and myelin basic protein in serum from patients with a first episode suggestive of multiple sclerosis is of prognostic value. We evaluated whether detection of antimyelin antibodies in serum indicates a worse course with earlier time to a second relapse and increased progression of disability. We conducted a prospective study at the Department of Neurology, Inselspital Bern, Switzerland from 2004 to 2008 in patients presenting with a clinically isolated syndrome (CIS) and a follow-up of at least 4 months. Antimyelin antibodies were assessed by Western blot. Results were correlated with clinical course and sex. Among 93 consecutive patients with a CIS, 74 (80%) were positive for either one or both antimyelin antibodies. A relapse occurred in 49 (53%) and the median EDSS was 2 (range 1–3.5) after a mean observation period of 20 months. Presence of antimyelin antibodies at CIS neither increased the risk for a second relapse nor for progression of disability. Stratification for gender did not reveal differences for any of the clinical surrogates. The sole determination of antimyelin antibodies in serum is of limited prognostic value for the identification of patients with different short-term course.

O27 – 2082 Anti-myelin oligodendrocyte glycoprotein antibody positivity in children with demyelinating episodes

O27 – 2082 Anti-myelin oligodendrocyte glycoprotein antibody positivity in children with demyelinating episodes

Role of inactivated influenza vaccine in regulation of autoimmune processes in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is characterized by appearance of anti-myelin autoantibodies in the blood and with the increased expression of MHC (major histocompatibility complex) class I and II antigens in the brain tissue. Although there is an evidence of possible linkage between influenza vaccination and development of autoimmune processes, the precise mechanisms of action of this vaccine on EAE-induction is still unclear. In this study, effects of influenza vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test and expression of MHC class I and II molecules immunohistochemistry were examined in the brain of C57BL mice with EAE. EAE was induced by MOG35–55 protein in 16 of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE mice and to eight previously nontreated mice. A significant increase of anti-influenza antibody was detected in vaccinated mice compared to nontreated mice. Also, significant increase of antimyelin antibodies was detected in mice with EAE compared to vaccinated group without EAE and control group, respectively. In EAE-influenza vaccinated mice, a mild but not significant increase of antimyelin antibodies was detected, compared to EAE mice. High expression of MHC-II and mild expression of MHC-I were detected in the brain of mice with EAE. No expressions were detected in vaccinated and normal intact brains. Similar staining was found between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes.

Autoantibodies against myelin antigens in patients with neuromyelitis optica

In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO); titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.

Anti-MOG antibody in different types of immune-mediated optic neuritis

To investigate the expression of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in different types of immune-mediated optic neuritis (IM-ON). Case-control and cross section study. The serum of 129 consecutive cases of immune-mediated optic neuritis (IM-ON group) seen in Neuro-ophthalmology clinic in Department of Neurology, Beijing Tongren Hospital during May 2010 and February 2011 were collected. All IM-ON cases were further classified into five different types as: 20 cases of multiple sclerosis related ON (MS-ON), 13 cases of neuromyelitis optical related ON (NMO-ON), 33 cases of autoimmune optic neuritis (AON), 43 cases of relapsing isolated optic neuritis (RION) and 20 cases of solitary isolated optic neuritis (SION). MOG-Ab was tested by ELISA. The positivity rate and titer of MOG-Ab among these groups were compared using chi-square test and ANOVA, t test by SPSS17.0 software. MOG-Ab was positive in 12 of all 129 tested IM-ON patients (9.3%), in which there were 5 of 20 MS-ON, none of 13 NMO-ON, 4 of 33 AON, 2 of 43 RION, and 1 of 20 SION patients. There were no statistical significant difference among five groups (Fisher's exact test, χ(2) = 7.051, P = 0.088), but MS-ON group showed statistically higher MOG-Ab positivity and titer than the "NMO spectrum optic neuritis" group which was merged from the other 4 IM-ON groups. MOG-Ab could be detected in different types of immune-mediated optic neuritis except NMO-ON and the expression of MOG-Ab was statistically higher in MS-ON group than the 'NMO spectrum optic neuritis' group.

Treatment with interferon-beta does not induce anti-nuclear and anti-neuronal serum autoantibodies in multiple sclerosis patients

Type I interferons (IFNs) are known to enhance humoral immunity. Here, we investigated the prevalence and titer of anti-nuclear and anti-neuronal IgG autoantibodies in 71 relapsing–remitting MS patients classified based on their clinical response to IFNβ in paired sera obtained at baseline and after 12months of treatment. All samples were negative for antibodies against cytoplasmic rods/rings, synaptic proteins and paraneoplastic antibodies. Regarding anti-nuclear, anti-filament and anti-myelin antibodies, pre- and post-treatment prevalence and titers did not differ significantly between IFNβ responders and non-responders. Thus, pattern of anti-nuclear and anti-neuronal autoantibodies does not predict the response to IFNβ in MS patients.

Cerebrospinal fluid anti-whole myelin antibodies are not correlated to magnetic resonance imaging activity in multiple sclerosis

BackgroundThe role of antimyelin antibodies as biomarker in multiple sclerosis is subject of debate. Here antimyelin antibody reactivity against native myelin is studied in CSF and serum. ObjectiveTo compare antimyelin antibody reactivity between patients with multiple sclerosis (MS) and patients with other neurological diseases in CSF and serum. In addition, MRI measures were studied in relation to antimyelin antibody reactivity. Methods77 MS patients (13 primary progressive, 27 secondary progressive and 37 relapsing remitting), 26 patients with other non-inflammatory neurological diseases and 9 patients with inflammatory neurological diseases other than MS were included. A myelin flow cytometry assay was used to detect anti-myelin antibody levels which were expressed as mean fluorescence intensity (myelin-MFI). MRI outcome measures were new or persistent T2 lesions, gadolinium enhancing T1 lesions and brain atrophy which were assessed by normalized brain volumes. ResultsThere was no significant difference between myelin-MFI values in serum and CSF between MS patients and controls (Mann–Whitney test p=0.19 and p=0.51). Myelin-MFI values in CSF were not correlated with number of T2 lesions (Spearman r=−0.023, p=0.85), number of gadolinium enhancing T1 lesions (Spearman r=−0.066, p=0.588) or normalized brain volume (Spearman r=−0.065, p=0.594). ConclusionsThese results do not confirm an association between anti-myelin antibody reactivity and the presence of MS or MRI measures of disease activity.

Immunopathological patterns from EAE and Theiler's virus infection: Is multiple sclerosis a homogenous 1-stage or heterogenous 2-stage disease?

Multiple sclerosis (MS) is a disease which can presents in different clinical courses. The most common form of MS is the relapsing-remitting (RR) course, which in many cases evolves into secondary progressive (SP) disease. Autoimmune models such as experimental autoimmune encephalomyelitis (EAE) have been developed to represent the various clinical forms of MS. These models along with clinico-pathological evidence obtained from MS patients have allowed us to propose ‘1-stage’ and ‘2-stage’ disease theories to explain the transition in the clinical course of MS from RR to SP. Relapses in MS are associated with pro-inflammatory T helper (Th) 1/Th17 immune responses, while remissions are associated with anti-inflammatory Th2/regulatory T (Treg) immune responses. Based on the ‘1-stage disease’ theory, the transition from RR to SP disease occurs when the inflammatory immune response overwhelms the anti-inflammatory immune response. The ‘2-stage disease’ theory proposes that the transition from RR to SP-MS occurs when the Th2 response or some other responses overwhelm the inflammatory response resulting in the sustained production of anti-myelin antibodies, which cause continuing demyelination, neurodegeneration, and axonal loss. The Theiler's virus model is also a 2-stage disease, where axonal degeneration precedes demyelination during the first stage, followed by inflammatory demyelination during the second stage.

Clinical and Neurophysiological Evaluation of Peripheral Nervous System Abnormalities in Patients with Lymphoproliferative Disorders (P06.018)

Objective: To evaluate clinical and neurophysiological manifestation in association with onconeural antibodies among patients with lymphoproliferative disorders. Background Lymphoproliferative disorders are recognized among important causes of paraneoplastic neurological syndromes (PNS). Subacute sensory neuropathy is the most frequents typical PNS, however other types of neuropathy are also observed. Systemic studies in homogenous group of patients with malignancies have not been conducted. Design/Methods: The study included in 25 patients with lymphoproliferative disorders: 8 lymphoma cases (32%), 13 myeloma (52%) and 4 leukemia ones 16%). According to the examination protocol, routine electromyographic examinations were carried out, and onconeuronal antibodies were evaluated by means of indirect immunofluorescence as a screening test and Western blotting for confirmation. Results: Symptoms of sensory-motor polyneuropathy were found in 36%, sensory polyneuropathy in 28%, and mononeuropathy in 8% of patients. Autoimmune reaction limited to anti-Myelin Associated Glycoprotein antibodies were detected in 16% of cases. In patients with abnormalities in neurological examination following neurophysiological findings were observed: reduction of amplitude of responses from motor fibres in the ulnar nerve (P=0.005), increased polyphasy in the right interossalis muscle (P=0.023) and right dorsiflexor (P=0.022) in comparison with subjects without clinical deficit. In lymphoma patients nerve conduction was decreased (P=0.041) when compared with myeloma patients, and the Motor Unit Action Potential (MUAP) in right tibial anterior was prolonged in myeloma cases (P = 0.029). Moreover, a proportion of MUAP polyphasy (r=-0.4624; P=0.0200) and amplitude of response from sensory fibers of median (r=-0.4149; P=0.0490) and ulnar nerve (r=- 0.5403; P=0.0139) correlated with the duration of chemotherapy. Conclusions: Sensory disorders are dominant among patients with lymphoproliferative disorders, clinically manifest as sensory or sensory-motor polyneuropathy, and neurophysiological examination reveals axonal changes. In subjects with lymphoma the neurophysiological disorders in peripheral nerves of lower limbs are significantly more advanced than in myeloma cases. Disclosure: Dr. Rogoziewicz has nothing to disclose. Dr. Wiszniewska has nothing to disclose. Dr. Wiszniewski has nothing to disclose. Dr. Michalak has nothing to disclose. Dr. Kozubski has nothing to disclose.

The Anti-Neuronal Autoantibodies in Patients with Endometrial and Breast Cancer (P06.007)

Objective: To evaluate the spectrum of neurological deficits and onconeural antibodies in patients with endometrial cancer and breast cancer. Background The detection of onconeural antibodies is crucial in definite diagnosis of neurological paraneoplastic syndromes (NPS). However, cancer-associated autoimmunity can be directed against other antigens expressed in nervous system. The aim of this study was to analyze the spectrum of onconeural and other neural antibodies in women with endometrial cancer (EC) and breast cancer (BC). Design/Methods: The study included 42 patients with EC hospitalized in Department of Gynecological Surgery Poznan University of Medical Sciences in Poznan and 15 patients with BC identified among 1552 subjects with suspicion of NPS and admitted to Department of Neurology at Poznan University of Medical Sciences. Indirect fluorescence was performed as a screening test and Western blotting (EUROIMMUN) as a confirmation test for the presence of onconeural antibodies in patients9 sera. Well-defined onconeural antibodies tested were : anti-Hu, anti-Yo, anti-Ri, anti-amphiphysin, anti-Ma/Ta, anti-CV2. The spectrum of evaluated anti-neural antigens included: anti-MAG (Myelin-Associated Glycoprotein), anti-GAD (Glutamic Acid Decarboxylase), anti-myelin, anti-neuroendothelium, and anti-GFAP (Glial Fibrillary Acidic Protein) antibodies. Results: EC patients frequently manifested neuropathy (21.4%), upper motor neuron syndrome (UMNS) (4.8%), bulbar palsy (2.4%), coexisting neuropathy with paraneoplastic cerebellar degeneration (PCD) (2.4%). In BC subjects PCD was the most frequent syndrome (33.3%), followed by neuropathy (13.3%), coexisting PCD with UMNS (6.7%) and plexopathy (6.6%). Anti-neural antibodies were the most frequent among EC patients (anti-myelin-9.5%, anti-MAG-7.1%) and onconeural antibodies were detected in 7.1% of patients (anti-Tr and coexisting anti-Ma/Ta with anti-CV2). In BC subjects anti-Ri were identified (26.6%), coexisting anti-Ri with anti-Yo (6.7%) as onconeural antibodies, and in 20% - anti-neural antibodies. Conclusions: Anti-neural autoimmunity is predominant in EC, while BC is associated with well defined onconeural antibodies. The dominating NPS manifestation in the course EC is neuropathy, but PCD in BC. Disclosure: Dr. Michalak has nothing to disclose. Dr. Poplawska has nothing to disclose. Dr. Szpurek has nothing to disclose. Dr. Michalak has nothing to disclose. Dr. Englert-Golon has nothing to disclose. Dr. Sajdak has nothing to disclose. Dr. Kozubski has nothing to disclose.

Pathogenic and regulatory roles for B cells in experimental autoimmune encephalomyelitis

A dual role of B cells in experimental autoimmune encephalomyelitis (EAE), the animal model of the human autoimmune disease multiple sclerosis (MS), has been established. In the first role, B cells contribute to the pathogenesis of EAE through the production of anti-myelin antibodies that contribute to demyelination. On the contrary, B cells have also been shown to have protective functions in that they play an essential role in the spontaneous recovery from EAE. In this review, we summarize studies conducted in a number of species demonstrating the conditions under which B cells are pathogenic in EAE. We also discuss the phenotype and anti-inflammatory mechanisms of regulatory B cells.

Improvement in Central Pontine Myelinosis with IV immunoglobulin

Improvement in Central Pontine Myelinosis with IV immunoglobulin Vesper Fe Marie Llaneza Ramos,1 J Americo Fernandes Filho,1 Arun Raj Antony,1 Jason T. Helvey,2 John Bertoni1 1Department of Neurological Sciences, University of Nebraska Medical Center; 2Department of Radiology, University of Nebraska Medical Center Introduction: Central pontine myelinolysis (CPM) is a rare, serious demyelinating disease, associated with rapid correction of chronic hyponatremia, usually in the setting of alcoholism and electrolyte disturbance.1 2 Magnetic resonance imaging (MRI) is a decisive diagnostic tool for CPM.3 The pathogenesis is unknown and there is no established treatment. There have been case reports on the efficacy of intravenous immunoglobulin (IVIG).4 5 Postulated mech-anisms include reduction of myelinotoxic agents, development of antimyelin antibodies, and promotion of remyelination.4 We report a case of CPM associated with chronic alcoholism and hyponatremia, with significant clinical improvement and resolution of MRI changes after treatment with IVIG.

Treatment of Exacerbations of Multiple Sclerosis without the Use of Corticosteroids: The Role of Metabolic and Antioxidant Therapy

A multicenter randomized post-registration case-control study was performed with 94 patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) in exacerbation. The patients were divided into two groups: group 1 (n = 53) received Cytoflavin and basal therapy (Trental and group B vitamins), while group 2 (n = 41) received only basal therapy. After five days, treatment results were used to further divide each group into two subgroups: patients of subgroup 1A (n = 22), with clear positive treatment effects, continued to receive Cytoflavin and basal therapy; group 1B (n = 31) additionally received corticosteroid (methipred) pulse therapy; subgroup 2A (n = 14), with significant positive effects, continued to receive basal therapy; group 2B (n = 27) additionally received corticosteroid pulse therapy. The complex treatment, with Cytoflavin, Trental, group B vitamins, and corticosteroids, was found to be safe and well tolerated. The positive effects of including Cytoflavin in complex treatment consisted of a reduction in the need for corticosteroids: 41.5% of patients receiving Cytoflavin no longer needed them, compared with 34% of patients receiving only basal therapy. Patients given Cytoflavin showed more significant regression of neurological symptomatology on the EDSS than the group not given Cytoflavin; there were no patients with no treatment response; lipid peroxidation and anti-myelin basic protein antibody levels decreased; cognitive functions improved.