Primary Progressive Form Research Articles

Positive correlation between functional disability, excessive daytime sleepiness, and fatigue in relapsing-remitting multiple sclerosis.

Retrospective review of medical records from patients with multiple sclerosis to collect data on severity of fatigue, disability, daytime sleepiness, and depression. From 912 medical records reviewed, 122 reported daytime sleepiness: 67% had relapsing remitting, 12% had primary progressive, and 21% had secondary progressive. In 95% of the patients with relapsing remitting who complained of daytime sleepiness and fatigue, association was found between these symptoms and neurological disability. Patients with relapsing remitting who complained of daytime sleepiness and fatigue also experienced depression (p = 0.001). No association between fatigue, excessive daytime sleepiness, depression, and disability was found in patients with progressive disease. In relapsing remitting, there is correlation between functional disability, excessive daytime sleepiness and fatigue, a finding not confirmed in primary progressive and secondary progressive form.

Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis.

Interleukin (IL)-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF) IL-33 concentrations in patients with multiple sclerosis (MS). Blood specimens were obtained from 140 patients with MS (46 males and 94 females) with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females), who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively). The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated) patients and patients treated with methylprednisolone or with interferon-β and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively). Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS), primary progressive (PPMS), and secondary progressive (SPMS) forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively). Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-β plus methylprednisolone has no influence on IL-33 concentrations.

P037. Headache in multiple sclerosis: prevalence and clinical features in a case control-study.

Methods One hundred and fifty adults (F/M = 98/52; mean age 40 years) with a diagnosis of MS and 150 sex and agematched controls (F/M = 101/49; mean age 40 years) from the general population were evaluated by means of an ad hoc semi-structured interview according to the International Classification Headache Disorders (ICHD-3-beta) criteria. All subjects filled out validated questionnaires about fatigue, Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). The c2 and Kruskal-Wallis tests were used when appropriate. Results The two groups differed significantly for education level and employment. Among the 150 patients with MS, 1 (0.7%) presented a radiologically isolated syndrome (RIS), 17 (11.3%) a clinically isolated syndrome (CIS), 20 (13.3%) a primary progressive form (PPMS), 96 (64%) a relapsing remitting form (RR), and 16 (10.7%) a secondary progressive form (SPMS). Headache was reported by 80 (53.3%) MS cases and 71 controls (47.3%), (p = 0.356); migraine was reported by 47 (31.33%) cases and 51 (34%) controls, tension-type headache was present in 21 (14%) MS affected vs 14 (9.33%) controls (p = 0.245). The simultaneous presence of migraine and tension-type headache was statistically higher (p = 0.002) in MS (28.8%) compared to controls (8.5%). Women with MS presented a low correlation between migraine and menstruation compared to controls while migraine normally improves during pregnancy as much as in controls (p = 0.65). The preliminary analysis of FSS and MFIS scores showed that fatigue resulted overall higher in MS patients with or without headache. Conclusions

Clinical and epidemiological analysis of multiple sclerosis in the Karaganda region

Results of an analysis of inpatients with multiple sclerosis in neurological units of Karaganda hospitals from 2006 to 2013 are presented. The following characteristics were identified: higher percentage of women of the age of 24-34, the prevalence of primary progressive and secondary progressive forms of multiple sclerosis that are most prognostically unfavorable, the level of disability of 52%. Attention is drawn to the fact that only 14% of the patients participate in therapeutic programs.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker.

ObjectivesConventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique).MethodsMulti-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale.ResultsBrain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04).InterpretationIn this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability.

MS in Maghrebian inhabitants and immigrants

Genetic predisposition, unknown environmental factors, or a combination of both may explain the variable prevalence of multiple sclerosis (MS) in the world. Few epidemiological data are available concerning MS patients in Maghreb. Studies of Maghrebian immigrants showed a more aggressive course of MS in Maghrebian population than in European patients. The prevalence of MS in the Maghreb was found to increase over the past few decades. Thus, Maghrebian population moved from a low prevalence area to a medium prevalence zone. An increase of female incidence of MS patients in the Maghreb was reported. MS in Maghrebian immigrants was well studied and results showed a more aggressive course in comparison to European population with mostly primary progressive forms and cerebellar symptoms. Despite an earlier onset in Maghrebian immigrants patients, the disease progresses more rapidly, with a higher proportion showing incomplete recovery from the first relapse, a shorter time between the first two relapses, a higher number of relapses in the first 5 years, and a shorter time to reach an EDSS of 4 and 6. Clinical course in Maghrebian population varies among recent studies. Some studies showed an aggressive course but not in others. However, in our experience through a multicentre Maghrebian study, MS patients have quite similar clinical feature and disability progression to European patients. Factors contributing to this variation include different methodology, short follow up period and lack of prospective studies. Prospective multicentre studies in Maghrebian population will better characterize the clinical course in the Maghreb.

Is multiple sclerosis more disabling in North African patients?

Ethnic and environmental factors are major determinant of prevalence and severity of Multiple Sclerosis (MS). Data relating to the severity of MS in North-African are scarce and conflicting and concern mainly migrants to Europe. To Answer this question, the authors have conducted a multicenter study enrolling patients with MS (Revised Mc Donald Criteria 2005) seen between 1998 and 2010 in the university hospitals of Casablanca, Fes and Marrakesh. Severity of MS was evaluated by the Progression Index (PI), time to reach an EDSS of 6.0 and the Multiple Sclerosis Severity Score (MSSS). The study included 460 patients. The sex ratio was 2.1. The mean age of MS onset was 30.2 years, with a mean follow up of 88.8 months. The relapsing-remitting MS accounted for 82.1% and the primary progressive form represented 17.9%. The median MSSS was 6.39, fast progressor (MSSS>5) represented 62.6%.The mean PI was 0.97 with 20% of Malignant forms (PI>1.2). Time to reach an EDSS score of 6 was 18 years (16.5–19.5). Previous studies comparing the MS severity between Caucasian and NA migrants in Europe have concluded to more severe disease in NA population. Our study is the first conducted in the autochthone population (Morocco) founding a similar result with a rapidly disabling disease. Subsequent Multicenter study from Algeria corroborates these findings. The Authors review and discuss possible factors and bias that could explain these data.

N-acetylaspartate and neurofilaments as biomarkers of axonal damage in patients with progressive forms of multiple sclerosis.

Primary and secondary progressive forms of multiple sclerosis (PPMS and SPMS) have different pathological characteristics. However, it is unknown whether neurodegenerative mechanisms are shared. We measured cerebrospinal fluid (CSF) levels of neurofilament (Nf) light and heavy isoforms and N-acetylaspartic acid (NAA) in 21 PP, 10 SPMS patients and 15 non-inflammatory neurological disease controls (NINDC). Biomarkers were related to Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) over a long period of follow-up [median (interquartile range) 9 (5.5-12.5) years] in 19 PPMS and 4 SPMS patients, and to T2 lesion load, T1 lesion load, and brain parenchymal fraction at the time of lumbar puncture. Nf light was higher in PPMS (p < 0.005) and Nf heavy was increased in both SPMS and PPMS (p < 0.05 and p < 0.01) compared to NINDC, but were comparable between the two MS subtypes. Nf heavy was a predictor of the ongoing disability measured by MSSS (R(2) = 0.17, β = 0.413; p < 0.05). Conversely, Nf light was the only predictor of the EDSS annual increase (R(2) = 0.195, β = 0.441; p < 0.05). The frequency of abnormal biomarkers did not differ between the two MS progressive subtypes. Our data suggest that PP and SPMS likely share similar mechanisms of axonal damage. Moreover, Nf heavy can be a biomarker of ongoing axonal damage. Conversely, Nf light can be used as a prognostic marker for accumulating disability suggesting it as a good tool for possible treatment monitoring in the progressive MS forms.

Prevalence of multiple sclerosis in Csongrád County, Hungary

Recent epidemiological studies were mainly based on the Poser or other diagnostic criteria. There have been no previous data from Hungary, which were assessed with the more up-to-date McDonald criteria and which give comparable standardized data from the region. Data were collected from the MS Register of the Department of Neurology at the University of Szeged. All possible and definitive patients with MS living in the county on the prevalence day were included in the study. Direct standardization was based on the European standard population. On 1 January 2013, 379 registered patients with MS were alive in the county, that is, a crude MS prevalence of 89.8/100,000, 46.6/100,000 in males and 128.6/100,000 in females; standardized prevalence: 83.7/100,000 (42.3/100,000 for males, 122.6/100,000 for females). The distribution of the clinical forms: 11% clinically isolated syndrome, 69% relapsing-remitting form, 14% secondary progressive form, 6% primary progressive form. Patients with no or only mild symptoms comprised 91.9% of the relapsing-remitting population. This is the first standardized epidemiological study based on the McDonald criteria in Central Europe. Hungary is a medium-risk country as concerns the prevalence of MS. The crude prevalence appears to have increased relative to previous reports from the county.

Urinary dysfunction in women with multiple sclerosis: analysis of 61 patients from Rio de Janeiro, Brazil

The aim of the present study is to describe the type and frequency of bladder dysfunction in a series of female patients with multiple sclerosis (MS) from Rio de Janeiro, and analyze the role of the urologist in the multidisciplinary team. A team of urologists and a neurologist from the Hospital da Lagoa, Rio de Janeiro, Brazil, interviewed female patients with MS about illness onset, urologic follow-up since diagnosis, current stage of the disease and current urological symptoms. The interview was followed by an urodynamic testing, ultrasound of the urinary tract and urinalysis. Data resulting from the interviews and exam results were gathered and submitted to statistical evaluation. Sixty one patients were evaluated, with average age of 41.4 years. Urinary symptoms such as urinary incontinence, urinary hesitancy, urinary retention, urinary urgency and incomplete bladder emptying were reported in 44% of patients as initial signs of MS disease. Mean disease duration was 8 years and all patients (100%) with the primary progressive form of the disease and 63.5% with the relapsingremitting presentation had urological symptoms. Analysis of complementary exams showed that 37.7% of urinalysis, 8.2% of the urinary tract ultrasound exams and 66.7% of the urodynamic evaluations were abnormal and the most frequent abnormality were overactive neurogenic bladder. Only 4 patients (6.6%) had seen an urologist during the course of their disease and only 1.6% had performed an urodynamic evaluation. This study shows a high prevalence (68%) of urinary dysfunction in a female population with MS. Urologic care should be part of the multidisciplinary team since the beginning of the disease. An urodynamic evaluation and simple urinalysis should be included in the routine testing during disease follow-up due to the high incidence of neurogenic bladder and other urologic complications.

Is MS an inflammatory or primary degenerative disease?

Multiple sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Multiple molecular and cellular components mediate neuroinflammation in MS. They involve: adhesion molecules, chemokines, cytokines, matalloproteases and the following cells: CD4+ T cells, CD8+ T cells, B cells, microglia and macrophages. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of chemokines, expression of adhesion molecules and can be factors that cause damage to the myelin sheath and axons. Chemokines stimulate integrin activation, mediate leukocyte locomotion on endothelial cells and participate in transendothelial migration. CD8+ cells can directly damage axons. B cells are involved in the production of antibodies which can participate in demyelination. B cells can also function as antigen presenting cells and contribute to T cell activation. Neuroinflammation is not only present in relapsing–remitting MS, but also in the secondary and primary progressive forms of the disease. The association between inflammation consisting of T cells, B cells, plasma cells and macrophages and axonal injury exists in MS patients including the progressive forms of the disease. The above association does not exclude the possibility that neurodegeneration can exist independently from inflammation. Very little inflammation is seen in cortical MS plaques. Anti-inflammatory therapies with different mode of action change the course of MS. Anti-inflammatory and immunomodulatory treatments are beneficial in the early relapsing stage of MS, but these treatments are ineffective in secondary progressive and primary progressive MS. In the stage of progressive MS, inflammation becomes trapped behind a closed or repaired blood–brain barrier. In such a situation current immunomodulatory, immunosuppressive or anti-inflammatory treatments might not reach this inflammatory process to exert a beneficial effect.

Genetic burden in multiple sclerosis families

A previous study using cumulative genetic risk estimations in multiple sclerosis (MS) successfully tracked the aggregation of susceptibility variants in multi-case and single-case families. It used a limited description of susceptibility loci available at the time (17 loci). Even though the full roster of MS risk genes remains unavailable, we estimated the genetic burden in MS families and assess its disease predictive power using up to 64 single-nucleotide polymorphism (SNP) markers according to the most recent literature. A total of 708 controls, 3251 MS patients and their relatives, as well as 117 twin pairs were genotyped. We validated the increased aggregation of genetic burden in multi-case compared with single-case families (P=4.14e-03) and confirm that these data offer little opportunity to accurately predict MS, even within sibships (area under receiver operating characteristic (AUROC)=0.59 (0.55, 0.53)). Our results also suggest that the primary progressive and relapsing-type forms of MS share a common genetic architecture (P=0.368; difference being limited to that corresponding to ± 2 typical MS-associated SNPs). We have confirmed the properties of individual genetic risk score in MS. Comparing with previous reference point for MS genetics (17 SNPs), we underlined the corrective consequences of the integration of the new findings from GWAS and meta-analysis.

Mesenchymal Stem Cells Expressing Vasoactive Intestinal Peptide Ameliorate Symptoms in a Model of Chronic Multiple Sclerosis

Multiple sclerosis (MS) is a severe debilitating disorder characterized by progressive demyelination and axonal damage of the central nervous system (CNS). Current therapies for MS inhibit the immune response and demonstrate reasonable benefits if applied during the early phase of relapsing–remitting MS (RRMS) while there are no treatments for patients that progress neither to the chronic phase nor for the primary progressive form of the disease. In this manuscript, we have studied the therapeutic efficacy of a cell and gene therapy strategy for the treatment of a mouse model of chronic MS [myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE)]. We used allogenic mesenchymal stem cells (MSCs) asa therapeutic tool and also as vehicle to deliver fully processed 3.3-kDa vasoactive intestinal peptide (VIP) to the peripheral immune organs and to the inflamed CNS. Intraperitoneal administrations of MSCs expressing VIP stopped progression and reduced symptoms when administered at peak of disease. The improvement in clinical score correlated with diminished peripheral T-cell responses against MOG as well as lower inflammation,lower demyelination, and higher neuronal integrity in the CNS. Interestingly, neither lentiviral vectors expressing VIP nor unmodified MSCs were therapeutic when administer at the peak of disease. The increased therapeutic effect of MSCs expressing VIP over unmodified MSCs requires the immunoregulatory and neuroprotective roles of both VIP and MSCs and the ability of the MSCs to migrate to peripheral lymph organs and the inflamed CNS.

Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis

The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple sclerosis. Inflammation in the leptomeninges has been identified as a key feature of secondary progressive multiple sclerosis and may contribute to the extensive cortical pathology that accompanies progressive disease. Our aim was to investigate the extent of perivascular and meningeal inflammation in primary progressive multiple sclerosis in order to understand their contribution to the pathogenetic mechanisms associated with cortical pathology. A comprehensive immunohistochemical analysis was performed on post-mortem brain tissue from 26 cases with primary progressive multiple sclerosis. A variable extent of meningeal immune cell infiltration was detected and more extensive demyelination and neurite loss in the cortical grey matter was found in cases exhibiting an increased level of meningeal inflammation. However, no tertiary lymphoid-like structures were found. Profound microglial activation and reduction in neuronal density was observed in both the lesions and normal appearing grey matter compared with control cortex. Furthermore, cases with primary progressive multiple sclerosis with extensive meningeal immune cell infiltration exhibited a more severe clinical course, including a shorter disease duration and younger age at death. Our data suggest that generalized diffuse meningeal inflammation and the associated inflammatory milieu in the subarachnoid compartment plays a role in the pathogenesis of cortical grey matter lesions and an increased rate of clinical progression in primary progressive multiple sclerosis.

Multiple sclerosis and CCSVI: a population-based case control study.

BackgroundChronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS).ObjectiveTo evaluate the possible association between CCSVI and MS, using a population-based control design.MethodsA random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled.ResultsCCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4).ConclusionsA higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Multigate Quality Doppler Profiles and Morphological/Hemodynamic Alterations in Multiple Sclerosis Patients

Venous echo-color-Doppler (ECD) showed that chronic cerebrospinal venous insufficiency (CCSVI) syndrome is related to multiple sclerosis (MS). Study aims were to assess interobserver variability in ultrasound evaluation of MS patients and to relate echo-markers to MS clinical symptoms and the disability degree. 277 MS patients (117 men, mean age 43.05+10.04 years) admitted to the Neurology Department of Bari University General Hospital, underwent clinical, Expanded Disability Status Scale (EDSS) evaluation, and a cerebro-venous system ECD evaluation. Two operators reevaluated 32 patients to calculate interobserver variability. McNemar test confirmed the procedure reproducibility between two operators (p=ns). Septa/membranes correlated with deep cerebral veins reflux [right: 16% absence vs. 58% presence, p < 0.0001; left: 26% vs. 50%, p < 0.0001]; their absence in Primary Progressive (PP) MS form [right: 11% vs. 2%, p < 0.001; left: 12% vs. 2%, p < 0.001]. Internal jugular veins (IJVs) reflux absence was in Relapsing-remitting (RR) form [right: 60% vs. 74%, p=0.036; left: 56% vs. 85%, p < 0.0001] like hemodynamically significant stenosis [right: 57% vs. 69%, p=0.033; left: 49% vs. 73%, p < 0.001] not present in PP [right: 11% vs. 2%, p < 0.001; left: 10% vs. 3%, p=0.009]. A supine IJVs blocked flow was related to the EDSS class [right: 4.8±1.5 vs. 5.4±1.4, p=0.006; left: 4.7±1.6 vs. 5.5±1.2, p < 0.0001]; its absence was linked to RR [right: 60% vs. 76%, p=0.016; left: 58% vs. 79%, p < 0.001]. ECD has an important value in MS patients with IJV anomalies detection and a good interobserver procedure reproducibility. MS is associated with CCSVI, although further studies are needed.

The C609T inborn polymorphism in NAD(P)H:quinone oxidoreductase 1 is associated with susceptibility to multiple sclerosis and affects the risk of development of the primary progressive form of the disease

Oxidative stress plays a pivotal role in the pathogenesis of multiple sclerosis (MS). Inactivating polymorphisms of genes encoding detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), could influence susceptibility to MS. To test this hypothesis we performed a case–control study in which we compared the distribution of NQO1 genotypes between 231 MS patients and 380 controls, using both PCR–RFLP and real-time PCR assays. Correlations with MS clinical subtype classification and gender were also evaluated. A significantly higher frequency of the homozygous (T/T) and heterozygous (C/T) NQO1 C609T variant genotypes was observed among MS patients compared to controls (P=0.01), with MS patients showing a 1.5-fold increased risk of carrying at least one variant T allele (P=0.009). Interestingly, patients belonging to the primary progressive subgroup exhibited a significantly higher incidence of the heterozygous C/T variant genotype, compared to the other forms of MS (P=0.019). There was no correlation of the NQO1 polymorphism with gender. These results provide the first evidence for a pathogenetic role for the NQO1 C609T polymorphism in MS susceptibility and suggest a possible role for the NQO1 genetic background in the development of primary progressive MS.

Progressive primary form of multiple sclerosis: clinical and radiological improvement with methylprednisolone in continuous pulsetherapy in one case for 16 years

Multiple sclerosis (MS) might be considered as a disease with different clinical phenotypes. Approximately 10-15% of the patients have the primary progressive form (PPMS). Confavreux and Vukusic considered PPMS as a multiple sclerosis ‘amputated’ from the usual preceding relapsing-remitting phase, saying it as one disease with different clinical phenotypes rather than an entity encompassing several distinct diseases1. The treatment of MS is directly based in animals’ models […] Progressive primary form of multiple sclerosis: clinical and radiological improvement with methylprednisolone [...]

Mutations in the lamin B1 gene are not present in multiple sclerosis

Whole gene duplication of the lamin B1 gene (LMNB1), encoding for a protein of the nuclear lamina, causes an adult-onset autosomal dominant leukodystrophy (ADLD). Clinical features of ADLD (onset in adult life, dysautonomic symptoms, followed by pyramidal and cerebellar dysfunctions) partially resemble those of multiple sclerosis (MS), particularly the primary-progressive form. Our aim was to test whether LMNB1 gene mutations were present amongst patients with a diagnosis of MS. One hundred eighty-two MS patients were screened for copy number variations of the LMNB1 gene using a qPCR assay. Point mutations in the LMNB1 gene were searched by denaturing high-performance liquid chromatography and direct sequencing in a subgroup of 16 patients with familial MS. No duplication/deletion of the lamin B1 gene was found amongst MS patients, and no point mutation was identified in the familial cases. Our work indicates that lamin B1 defects are probably not responsible for signs and symptoms resembling multiple sclerosis.

Neuropsicología de la esclerosis múltiple primaria progresiva

Cognitive impairment is a symptom of multiple sclerosis (MS); however, in the primary progressive form of the disease (PPMS), data on the prevalence and type of cognitive impairment are controversial. To evaluate the frequency of cognitive impairment, according to the diagnostic criteria defined by Thompson, in Brazilian patients with PPMS attending a referral center for the treatment of MS in Rio de Janeiro, Brazil. A battery of neuropsychological tests was used to evaluate the following cognitive functions: screening for dementia, attention/concentration, speed of information processing, verbal fluency, memory and abstract/conceptual thought. The Beck scale was used to evaluate mood disorders. Twenty-six patients with PPMS and 26 controls paired for gender, age and education level were evaluated. Statistical analysis was based on the study performed by Rao. The frequency of cognitive impairment in the PPMS patients in the present study was 50%. The cognitive functions most affected were: recent memory (60%), verbal fluency (40%) and speed of information processing (40%). Depression was more common in the PPMS patients compared to the control group; however, no association was found between cognitive impairment and depression. These results confirm the presence of cognitive impairment in PPMS and emphasize the need for further studies with larger sample sizes.