Sample Of Multiple Sclerosis Patients Research Articles

Detection of JCPyV microRNA in blood and urine samples of multiple sclerosis patients under natalizumab therapy.

Polyomavirus JC (JCPyV) reactivation and development of progressive multifocal leukoencephalopathy is a health concern in multiple sclerosis patients under natalizumab therapy. Here, the JCPyV microRNA-J1-3p and microRNA-J1-5p expressions and genomic variability were investigated in blood and urine samples of multiple sclerosis patients before and under natalizumab therapy and in healthy controls. The two JCPyV microRNAs were detected in the JCPyV-DNA-positive peripheral blood mononuclear cell samples and in the exosomes derived from plasma and urine obtained from JCPyV-DNA-positive and JCPyV-DNA-negative patients. In particular, the increased JCPyV microRNA expression in samples of multiple sclerosis patients under natalizumab therapy was consistent with the high JCPyV-DNA positivity observed in these samples. Moreover, JCPyV microRNA genomic region showed few nucleotide differences in samples obtained from blood and urine of multiple sclerosis patients and healthy controls. Overall, these data suggest a potential role of the JCPyV microRNA expression in counteracting the viral reactivation to maintain JCPyV asymptomatic persistence in the host.

Psychometric properties of the Hamilton Depression Rating Scale in multiple sclerosis.

Multiple sclerosis (MS) is frequently associated with depressive symptoms and major depression. We assessed psychometric properties of the Hamilton Depression Rating Scale (HDRS, 17-item version) for assessing depressive symptomatology in a sample of MS patients. Seventy patients (aged 43.3 ± 10.3 years) completed the HDRS and a thorough clinical and neuropsychological assessment, including diagnosis of major depression according to the established clinical criteria. HDRS was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha = 0.8). The HDRS showed good convergent validity with respect to neuropsychiatric inventory (NPI) subdomain of depression (r rho = .85) and good divergent validity with respect to remaining NPI subdomains (r rho < .30). Moreover, HDRS's total score correlated moderately with functional disability and apathetic symptomatology, and poorly with general cognitive status. Receiver operating characteristics curve analysis demonstrated that a cutoff >14.5 can identify clinically relevant depressive symptoms with good sensitivity (93 %) and specificity (97 %) with respect to the diagnosis of major depression. Such a cutoff identified clinically relevant depressive symptoms in 42 % of our MS sample, whereas 44.2 % patients met established clinical criteria for major depression. The HDRS can be considered as an easy, reliable, and valid tool to assess depressive symptomatology for clinical and research purposes in non-demented MS patients.

Decreased Dicer expression is linked to increased expression of co-stimulatory molecule CD80 on B cells in multiple sclerosis

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system. B cells have been strongly implicated in disease pathogenesis based on clinical trials with B-cell ablation. There is a growing body of evidence linking microRNAs with regulation of the immune system. Dicer, a key enzyme involved in microRNA biogenesis, is necessary for normal B-cell function. Objective: We aimed to determine whether Dicer expression is impaired in B cells and is linked to increased expression co-stimulatory molecules in patients with MS. Methods: B cells were separated from blood samples of MS patients and healthy subjects. Expression of Dicer and co-stimulatory molecules CD80 and CD86 was tested. The effect of Dicer modulation on CD80 and CD86 expression in B cells was studied. Results: Dicer expression was decreased in B cells but not in monocytes of patients with MS compared with healthy subjects. CD80 and CD86 expression was increased on B cells of MS patients compared with healthy subjects. Inhibition of Dicer expression in B cells by small interfering RNA led to increased expression of CD80. Conclusion: Dicer expression is decreased and is mechanistically linked to increased expression of co-stimulatory molecule CD80 in B cells of patients with MS. This may contribute to activation of immune responses in MS.

Disruption of structural and functional networks in long-standing multiple sclerosis.

Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter morphology and functional coactivation. We investigated, how gray matter and functional networks were affected within the same MS sample and examined their interrelationship. Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102 MS patients and 42 healthy controls. Gray matter networks were computed at the group-level based on cortical thickness correlations between 78 regions across subjects. MEG functional networks were computed at the subject level based on the phase-lag index between time-series of regions in source-space. In MS patients, we found a more regular network organization for structural covariance networks and for functional networks in the theta band, whereas we found a more random network organization for functional networks in the alpha2 band. Correlation analysis revealed a positive association between covariation in thickness and functional connectivity in especially the theta band in MS patients, and these results could not be explained by simple regional gray matter thickness measurements. This study is a first multimodal graph analysis in a sample of MS patients, and our results suggest that a disruption of gray matter network topology is important to understand alterations in functional connectivity in MS as regional gray matter fails to take into account the inherent connectivity structure of the brain.

Predictors of Body Image Related Sexual Dysfunction in Men and Women with Multiple Sclerosis

Sexual dysfunction (SD) is a common symptom in multiple sclerosis (MS). As body image concerns may be related to SD, this study focused on predictors of body image related SD in a sample of MS patients. To evaluate correlates of body image related SD, including sociodemographics, mental health, and select illness variables including help-seeking behaviors for sexual problems, time since MS diagnosis, and self-reported disability status. This study utilized de-identified, archived data from a MS patient registry, the North American Research Committee on Multiple Sclerosis (NARCOMS). The sample consisted of 4,267 respondents to the NARCOMS questionnaire, which included a reliable and valid instrument for assessing SD. People who had higher scores on body image related SD were less educated, female, with longer disease duration and greater disability. They reported poorer mental health and seeking treatment for sexual problems less frequently. In the final regression model, age, employment status, and race were not significantly related to body image related SD in MS. The results of the study offer evidence that body image related SD in MS is a complex, multi-factorial phenomenon that is related to a variety of demographic, mental health, and disease related variables.

Prevalence of human Herpesviridae in cerebrospinal fluid of patients with multiple sclerosis and noninfectious neurological disease in the Netherlands

Prevalence of eight human herpesviruses (HHV1-8) was determined by real-time PCR in cell-rich cerebrospinal fluid (CSF) samples, obtained early after disease symptoms, of Dutch patients with multiple sclerosis (MS) and other noninfectious central nervous system diseases (NIND). Whereas HHV1-8 DNA was undetectable in CSF samples of MS patients, HHV6 DNA was detected in a plexus neuritis case and HHV7 DNA in an ependymoma and a Behçets' disease patient. However, intrathecal HHV infection was not detected. Data indicate that HHV1-8 are rarely detected in CSF of Dutch NIND patients and do not support the role of intrathecal HHV infection early after onset of disease symptoms in MS.

Domestic accidents and multiple sclerosis: an exploratory study of occurrence and possible causes

Purpose: Domestic accidents are widespread, but no data are available on their occurrence in pathological populations such as patients with multiple sclerosis (MS). Aim was to investigate domestic habits and occurrence of different types of domestic accidents and near falls in a sample of MS patients compared with healthy controls and to determine whether patients’ domestic accidents are linked to any disease characteristics. Method: Descriptive survey of 50 patients and 50 healthy controls. Participants were administered an ad-hoc questionnaire to collect data on domestic habits and accidents they had in the past 2 months. Their physical and neuropsychological functioning, mood and fatigue were also assessed. Results: Results showed that patients spend most of their time at home with caregivers. No differences emerged for total number of domestic accident types, but there were differences in bumps and near falls. The latter seem to be linked to patients’ walking ability and to bowel/bladder functioning and the former to reasoning ability and fatigue. Conclusions: This study provides the first data on the occurrence of domestic accidents and possible causes in MS patients. It encourages further studies on the topic, with the final goal of designing preventive and rehabilitation strategies.Implications of RehabilitationDomestic accidents can cause further suffering, disability and decreased productivity and increased economic burden to MS patients.Our study evidenced that, within DA, bumps occur more frequently in MS patients compared to healthy controls. A highly significant difference was also found between the two groups for number of near falls.These results should help clinicians addressing patients to preventive and rehabilitation programs in order to avoid the occurrence of DA.

Chronic pain in multiple sclerosis: Is there also fibromyalgia? An observational study

BackgroundChronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients’ health-related quality of life (HRQoL).Material/Methods133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales.ResultsChronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM−); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL.ConclusionsIn our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients’ QoL.

Longitudinal cortex reorganization and white matter tracts structural changes analysis in relapsing-remitting multiple sclerosis patients with hand palsy

Motor disorders are a frequent syndrome in multiple sclerosis (MS), leading to severe disability, possibly associated with inefficiency of adaptive mechanisms, probably because of widespread structural changes. Hand palsy with fine motor skills damage influences greatly on quality of life, because hand function plays an important role in everyday activities and working practices. Thus the aim of the study was to investigate functional and structural features of hand palsy in homogenous sample of MS patients during the relapse and in three months. Data were acquired from 25 relapsing-remitting MS patients during relapse also characterized by unilateral light hand palsy, and in three months. 12 age-matched healthy controls entered the control group. All patients underwent neurologica examination, including nine-hole peg test and dynamometry, and magnetic resonance imaging of cervical spine and brain, including functional MRI and diffusion tensor imaging (DTI) sequences. All patients had lesions in spinal cord on cervical spine MRI. fMRI data analysis during relapse showed differently directed activation changes and allowed to divide all patients in two subgroups. These subgroups differed from each other and control group by deep sensitivity and DTI values. In three months patients in the first subgroup had less complete fine motor skills recovery, which was accompanied also by preservation of activation changes and deep sensitivity asymmetry in comparison with the second subgroup. Received data allow us to assume that clinically similar palsy, caused by spinal cord lesion, could be characterized by greater or lesser sensation impairment contribution. In three months heterogeneous structural and functional changes were observed, depending, possibly, on initially different pathologic mechanisms. Revealed differences should be taken into consideration while rehabilitation planning.

Association between a Genetic Variant of Type-1 Cannabinoid Receptor and Inflammatory Neurodegeneration in Multiple Sclerosis

Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS.

Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.

Background/AimsLarge-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years.Methods1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms.ResultsCognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p = 0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p = 0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p = 0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years.ConclusionsThe rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis

Background: Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS). Objective: To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS. Methods: A sample of MS patients, 60 relapsing–remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT). Results: The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. Conclusion: The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.

Elevated CSF histamine levels in multiple sclerosis patients

BackgroundHistamine is an ubiquitous inflammatory mediator of numerous physiological processes. Histamine and its receptors have been implicated in multiple sclerosis (MS) disease pathogenesis. We prospectively enrolled 36 MS patients and 19 age and gender-matched healthy volunteers for cerebrospinal fluid (CSF) histamine analysis.FindingsCSF histamine levels in MS patient samples were significantly higher (median: 35.6 pg/ml) than in controls (median: 5.5 pg/ml; Beta = 0.525, p < 0.001). In addition, histamine increased with age (Pearson’s correlation, p < 0.003).ConclusionsHistamine may be an important factor for both the initiation and maintenance of chronic inflammatory diseases of the central nervous system. Our observation encourages a deeper investigation of the role of histamine in MS.

How Patients With Multiple Sclerosis Perceive Cognitive Slowing

Slowed processing speed is the primary cognitive deficit in multiple sclerosis (MS). However, no studies have examined how patients perceive this deficit. The purpose of this paper is to examine perceived processing speed difficulties in clinical and community samples of MS patients. As expected, MS patients reported more processing speed difficulties than controls. Perceived processing speed difficulties were significantly associated with impulsivity, slowed motor speed, greater anxiety, and increased introversion. In contrast, perceived processing speed did not correlate well with objective measures of processing speed. Findings showed that MS patients perceive their thinking to be significantly slowed. Perceived cognitive slowing was most related to performance on motor tasks and elevated anxiety. Evaluation of anxiety and patient education about objective measures versus subjective perceptions of slowed processing speed may be helpful to MS patients who report significant cognitive slowing.

The frequency of slime, adhesin and methicillin resistance genes among staphylococci isolated from nasal samples of multiple sclerosis patients

It was aimed to determine the carriage rate of Staphylococcus aureus and the occurrence of methicillin resistance, slime and adhesin genes in staphylococcal strains isolated from the nasal cavities of multiple sclerosis (MS) patients. The presence of mecA and femA, and the genes implicated in adhesion were determined by multiplex PCR in all strains. The femA gene was detected in 46.6% of 105 MS patients. While 18.1% of isolates carried the mecA gene, 81.9% of isolates were negative for the mecA gene. The presence of icaA/icaD genes was determined in a total of 84.8% of all strains. While 85.7% of Staphylococcus epidermidis isolates were positive in terms of slime genes, this ratio was determined as 81.6% among the Staphylococcus aureus strains. The occurrence of clfA gene was determined in 29 of 49 (59.2%) S. aureus isolates. Also, 45 out of 49 (91.8%) S. aureus was found to carry the fnbA gene. The carriage rate of thecna gene was determined in 40 (81.6%) isolates among the 49 S. aureus strains. The rate of methicillin resistance gene, slime production and the frequency of adhesin genes in MS patients were also significantly higher than the healthy control population. Determination of the nasal S. aureus carriers and the virulence of these strains will be important for prediction of the MS prognosis in these patients. And treating these S.aureus carriers will be very useful in preventing MS relapses. Key words: Multiple sclerosis, Staphylococcus aureus, nasal carriage, methicillin resistance, adhesins, slime.

Ultra-trace Arsenic Determination in Urine and Whole Blood Samples by Flow Injection-Hydride Generation Atomic Absorption Spectrometry after Preconcentration and Speciation Based on Dispersive Liquid-Liquid Microextraction

A noble method for pre-concentration and speciation of ultra trace As (III) and As (V) in urine and whole blood samples based on dispersive liquid-liquid microextraction (DLLME) has been developed. In this method, As (III) was complexed with ammonium pyrrolidine dithiocarbamate at pH = 4 and Then, As (III) was extracted into the ionic liquid (IL). Finally, As (III) was back-extracted from the IL with hydrochloric acid (HCl) and its concentration was determined by flow injection coupled with hydride generation atomic absorption spectrometry (FI-HGAAS). Total amount of arsenic was determined by reducing As (V) to As (III) with potassium iodide (KI) and ascorbic acid in HCl solution and then, As (V) was calculated by the subtracting the total arsenic and As (III) content. Under the optimum conditions, for 5-15 mL of blood and urine samples, the detection limit (3σ) and linear range were achieved 5 ng L �1 and 0.02-10 μg L �1 , respectively. The method was applied successfully to the speciation and determination of As (III) and As (V) in biological samples of multiple sclerosis patients with suitable precision results (RSD < 5%). Validation of the methodology was performed by the standard reference material (CRM).

Screening for Well-Characterized Paraneoplastic Antineuronal Antibodies in Multiple Sclerosis

ABSTRACTSome epidemiological surveys have shown an increased incidence of malignancies in patients with multiple Sclerosis (MS). Furthermore, in rare cases central demyelinating disorders like optic neuritis, encephalomyelitis, and myelitis could be of paraneoplastic origin. Antineuronal antibodies are frequently associated with paraneoplastic neurological syndromes (PNS) but are also described in cancer patients without neurological symptoms. In this study, we retrospectively analyzed sera from 247 patients with MS and clinically isolated syndrome (CIS) for the presence of anti-HuD, Yo, Ri, CV2/CRMP5, Ma2, and amphiphysin antibodies using ELISA employing recombinant onconeural antigens. None of the sera revealed high titers of antineuronal antibodies and only two sera from MS patients show weak reactivity, representing in all probability background activity. Furthermore, cancer incidence in our study is low (0.8%). Our analysis does not support an association between MS and well-characterized paraneoplastic antineuronal antibodies, suggestive of a secondary humoral autoimmune response, underlying latent malignancy, or paraneoplastic origin in our cohort. In reverse, negative screening results in samples of MS patients confirm the high specificity of these antibodies for PNS.

Increased expression of cystine/glutamate antiporter in multiple sclerosis

BackgroundGlutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter xc-, an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system xc- in glutamate homeostasis alterations in MS pathology.MethodsPrimary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and in samples of MS patients.Results and discussionWe show here that human activated monocytes release glutamate through cystine/glutamate antiporter xc- and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS) and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes.ConclusionsTogether, these results reveal that increased expression of the cystine/glutamate antiporter system xc- in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.

Depression, disability and cognitive impairment in multiple sclerosis: a cross sectional Italian study

The disability, cognitive impairment, fatigue and depression are interacting features in multiple sclerosis (MS), whose relation is still unclear. The objective of this study was to evaluate in a sample of MS patients, the frequency of depressive symptoms, its predicting factors and relation with cognitive impairment, fatigue and disability. 255 consecutive MS patients and 166 healthy subjects were assessed for the presence of depressive symptoms with the Beck Depression Inventory-Fast Screen (BDI-FS). Patients with BDI-FS ≥ 4 were further investigated for the presence of neuropsychological impairment. Depressive symptoms were significantly more frequent and severe in patients than in controls. EDSS score was the only predicting factor of depression (3.5 = threshold EDSS score for depressive symptoms) in patients, whereas neuropsychological impairment was not correlated with BDI-FS and fatigue was found to be significantly correlated with attention, executive function and memory test scores, as well as with BDI-FS score in patients.

Changed Histone Acetylation Patterns in Normal-Appearing White Matter and Early Multiple Sclerosis Lesions

The epigenetic identity of oligodendrocytes is modulated by posttranslational modifications of histones. Acetylation of histone H3 results from the balance between the activity of histone acetyltransferases (HATs) and histone deacetylases and modulates transcriptional activation. We have previously shown that, in rodents, histone deacetylation favors oligodendrocyte differentiation, whereas acetylation is associated with increased levels of transcriptional inhibitors of oligodendrocyte differentiation. Here, we report, in humans brains, a shift toward histone acetylation in the white matter of the frontal lobes of aged subjects and in patients with chronic multiple sclerosis (MS). Increased immunoreactivity for acetylated histone H3 was observed in the nuclei of NogoA+ oligodendrocytes in a subset of MS samples. These changes were associated with high levels of transcriptional inhibitors of oligodendrocyte differentiation (i.e., TCF7L2, ID2, and SOX2) and higher HAT transcript levels (i.e., CBP, P300) in female MS patients compared with non-neurological controls and correlated with disease duration. Chromatin immunoprecipitation from samples of MS patients revealed enrichment of acetyl-histone H3 at the promoter of the increased target genes (i.e., TCF7L2). The data in chronic lesions contrasted with findings in early MS lesions, where a marked oligodendroglial histone deacetylation was observed. Together, these data suggest that histone deacetylation is a process that occurs at the early stages of the disease and whose efficiency decreases with disease duration.