First Episode Of Multiple Sclerosis Research Articles

CSF inflammatory profile in clinically isolated syndrome and definite multiple sclerosis patients

Clinically isolated syndrome (CIS) characterizes the first episode of multiple sclerosis (MS). IgG oligoclonal bands (OCBs) and high levels of inflammatory factors in CSF represent promising biochemical markers of CIS and MS. Here we evaluated the levels of a complex panel of CSF inflammatory mediators in CIS and relapsing-remitting MS (RRMS) patients at time of diagnosis, both with and without OCB, compared with a control group.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Mitoxantrone treatment in a patient with multiple sclerosis and pattern III lesions

AbstractBackgroundBrain biopsies of multiple sclerosis patients identified three intraindividually stable lesion patterns. Apart from beneficial effects of plasma exchange in patients with type II lesions, little is known about how multiple sclerosis lesion histology could guide therapeutic decisions.Case presentationHere, we report on a 53‐year‐old male patient with polysymptomatic cerebral syndrome as the first episode of multiple sclerosis. Brain biopsy showed an inflammatory demyelinating lesion with apoptotic oligodendrocytes and a loss of myelin‐associated glycoprotein, pathological features typical for pattern III lesions. High‐dose steroids and immunosuppressive treatment with mitoxantrone led to a substantial improvement of disability and long‐term clinical stability.ConclusionMitoxantrone therapy along with steroid pulses could potentially be considered as a therapeutic option for pattern III lesions.

Neurochemical and neuroendocrine correlates of overactive bladder at first demyelinating episode.

Bladder dysfunction is frequent during the course of multiple sclerosis (MS), observed in up to 75% of patients. Urinary symptomatology can be a feature of the first episode of MS in a minority of cases, and most often shows characteristics of an overactive bladder (OAB), with voiding symptoms seen less frequently, often in combination with OAB. The neural control of micturition is complex, involving systems located in the brain, spinal cord, and periphery, and implicating central noradrenergic, serotonergic, and dopaminergic activities. Urinary disorders are also linked to anxiety and depression, conditions connected to hypothalamus-pituitary-adrenal axis activity. In this study we aimed to investigate neurochemical and neuroendocrine correlates of bladder dysfunction in early MS. We included 101 patients at first demyelinating episode suggestive of MS that were drug-free at assessment. We evaluated the presence of urinary symptomatology and estimated CSF levels of the main metabolites of noradrenaline, serotonin, and dopamine, as well CSF-ACTH and serum cortisol. In total, 15 patients (15%) reported urinary dysfunction suggestive of OAB. Four of these had coexistent voiding symptomatology. The serotonin metabolite 5-HIAA was significantly reduced (P = 0.017) in patients with OAB syndrome, while there were no differences in the metabolites of noradrenaline (MHPG) and of dopamine (HVA). Additionally, significantly lower serum cortisol (P = 0.009) and borderline lower CSF-ACTH (P = 0.08) were found in patients with OAB. MS patients with OAB syndrome at the first demyelinating episode show reductions in central serotonergic activity and stress hormones. Whether the same changes persist at later disease stages remains to be investigated. Neurourol. Urodynam. 35:955-958, 2016. © 2015 Wiley Periodicals, Inc.

Pediatric Multiple sclerosis

Multiple sclerosis (MS) is considered as the major cause of acquired neurological insult in young adults and the most common demyelinating disease of the central nervous system (CNS). It is an inflammatory disease characterized by multiple areas of demyelination, rupture of the blood-brain barrier and diffused disorder of the white matter. MS is relatively rare in childhood. However, 3-10% of children develop the first episode of MS before the 16 th year of age. Diagnosis of MS in childhood requires clinical and laboratory data, that localize the demyelinating episodes of the CNS, helping to exclude other pathological conditions. The therapeutic options vary and mainly focus on the use of steroids and intravenous immunoglobulins, while recent data suggest the use of interferon. In this review, we present the latest bibliographic data concerning the epidemiological characteristics, the etiology, the clinical course, the available diagnostic methods and the main treatment options of MS.

Acute disseminated encephalomyelitis associated with hepatitis B virus reinfection – Consequence or coincidence?

Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis. ADEM typically occurs as a post-infectious phenomenon, and usually presents a monophasic episode, but also includes recurrent and multiphasic forms. We report a case of ADEM associated with hepatitis B virus (HBV) reinfection. After steroid and IV immunoglobulin treatment, neurologic symptoms were improved. We suppose that the HBV reinfection was the cause of ADEM, but possible pathogenetic mechanism is still obscure.

Multiple sclerosis: new measures to monitor the disease

In 2012, substantial progress has been made in multiple sclerosis research. Simplified diagnostic criteria, which were published in 2011, encompass clinical and imaging features in both adults and children presenting with clinical symptoms suggestive of a first episode of multiple sclerosis.1 In 2012, application of these criteria in a large cohort of children with acute demyelination has shown that the criteria have a high sensitivity and specificity for children older than 11 years with non-acute disseminated encephalomyelitis,2 whereas caution is still needed in the application of these criteria in younger children and in the context of acute disseminated encephalomyelitis-like presentations.

Multiple sclerosis typical clinical and MRI findings in a patient with HIV infection

Multiple sclerosis (MS) is a demyelinating disease seldom included in the differential diagnosis of leukoencephalopathy in HIV-positive patients. We describe the clinical findings and laboratory results of a 43-year-old male with HIV infection and MS, and reviewed 11 more cases reported in the literature. The first episode of MS occurred either during or after the recognition of the HIV infection except in the few cases reported in 1989. There has been a very strong male predominance. Age at onset was between 30 and 40 years old. The most common clinical course was relapsing and remitting. Most of the cases had a normal CD4+ cell count, usually exceeding 500 cells/mm(3). Despite that CD4+ cell counts were invariable high, all the patients had multiple tests to rule out opportunistic infections and HIV-associated illness. The clinical suspicion of MS was only considered after ruling out other opportunistic infections and was supported with brain imaging showing multiple white matter evanescent lesions, the presence of black holes, and a high myelin basic protein titer in the CSF. MS is usually considered late in patients with HIV. A typical MS course with suggestive MRI lesions and absence of severe immune suppression should suggest the diagnosis. It is possible that as with other MS patients, earlier initiation of specific treatments for MS will prevent the high burden of the disease and disability in these patients, but stronger evidence for specific recommendations remains to be obtained.

Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in MS

Progressive multifocal leukoencephalopathy (PML) has developed in more than 40 patients with multiple sclerosis (MS) treated with natalizumab.1 Clifford et al.2 recently described the first 28 confirmed cases in which, in almost all, PML presented as an aggressive disease with a short interval between first symptoms and diagnosis. ### Case report. In September 2002, a 30-year-old previously healthy woman presented with walking difficulties. Neurologic examination showed a bi-pyramidal syndrome, ataxia, and sensory disturbance in all extremities. After MRI of the brain and cervical spinal cord, which showed multiple typical T2-weighted white matter lesions, diagnosis of a clinically isolated syndrome suggestive of a first episode of MS was established. In January 2003, the patient started interferon-β-1a, which she discontinued in October 2003 because of depressive symptoms. From March 2004 until December 2006, she used glatiramer acetate. Still, several clinical relapses occurred. In March 2007, the patient started natalizumab infusions. She had no clinical exacerbations since. Routine MRI of the brain 1 year later showed no active lesions. A second MRI in February 2009 was initially interpreted as showing no new lesions. In retrospect, subtle and diffuse abnormalities were visible in cortical and subcortical areas (figure). Since June 2009, she had mild progressive cognitive problems. For example, she made repetitive phone calls up to 6 times a day and was forgetting appointments. For that reason, in October 2009, a new MRI was performed, showing a new pontine lesion and progression of the diffuse abnormalities in both hemispheres (figure). Figure MRI (A) Evolution of MRI manifestations during treatment with natalizumab. Transverse T2-weighted MRI of the supratentorial and infratentorial brain. The MRI in January 2007 (A.a) was performed prior to the initiation of natalizumab therapy; …

Case 173: Acute Disseminated Encephalomyelitis Confined to the Brainstem

Three diagnostic considerations should be offered for the cause of an isolated ring-enhancing lesion of the brainstem: primary or secondary brainstem tumors, abscesses, or acute disseminated encephalomyelitis; a first episode of multiple sclerosis also might be considered.

Un cas d’ophtalmoplégie horizontale bilatérale : le syndrome 1+1

Oculomotor deficiencies in multiple sclerosis (MS) are frequently characterized by internuclear ophthalmpoplegia or isolated abduction or adduction palsies. Complete unilateral conjugate gaze paralysis and the "one and a half" syndrome are rare. Complete bilateral horizontal gaze paralysis has been exceptionally reported. Here, we describe an unusual oculomotor paralysis as a suspected first event of MS. A 24-year-old woman with an uneventful medical history presented for sudden onset of binocular diplopia. On examination, abduction and adduction saccades were impossible, whereas vertical eye saccades and convergence were normal. Oculocephalic reflex failed to improve horizontal eye movement. No nystagmus and no other sign of brainstem dysfunction were observed. Visual acuity was 4/10 in the right eye and 6/10 in the left eye. A sign of Marcus Gunn was noted in the right eye. Blood samples and cerebrospinal fluid were normal, no oligoclonal bands were detected. Visual evoked potentials were significantly impaired in both eyes and argued for bilateral optic neuritis. Brain MRI scans showed white matter T2-hypersignal abnormalities, which fulfill Barkhof criteria for MS. A small symmetric lesion was noted in the posterior part of the medial pontine tegmentum. As a first episode of MS was suspected, treatment with methylprednisolone 1000 mg/d for 3 days was started, and was followed by complete recovery of eye movements and visual acuity after 3 weeks. To our knowledge, only two cases of complete horizontal bilateral ophthalmoplegia have been reported in the literature. Both were associated with peripheral facial nerve palsy as a first event in MS. In our case report, we describe for the first time a complete bilateral horizontal ophthalmoplegia with no other brainstem dysfunction. By analogy with the "one and a half" syndrome, such complete horizontal gaze paralysis could be named a "one and one" syndrome and seems to be specifically related to a first event of MS.

Diagnostic imaging in acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis, so called clinically isolated syndrome. Currently, no diagnostic criteria exist that could reliably differentiate these two diseases. More importantly no single clinical, neuroimaging or cerebrospinal fluid feature defines a disorder with absolute certainty. This review will summarize clinical and paraclinical characteristics of acute disseminated encephalomyelitis in adults, with special emphasis on diagnostic imaging.

Sorting through the pediatric MS spectrum with brain MRI

Distinguishing between a first episode of multiple sclerosis and acute disseminated encephalomyelitis in children who present with an initial demyelinating event can be a clinical challenge. New brain MRI criteria that aim to differentiate these clinical presentations, and revised McDonald MRI criteria specific for the pediatric population, are both worthy of note.

CSF proteome analysis in clinically isolated syndrome (CIS): Candidate markers for conversion to definite multiple sclerosis

Cerebrospinal fluid (CSF) is a promising source of biomarkers in clinically isolated syndrome (CIS), which frequently presents as a first episode of multiple sclerosis (MS). Using the two-dimensional difference in gel electrophoresis (2-D DIGE), we compared CSF samples from patients with CIS that remained CIS (CIS-CIS, n=8) over a follow-up time of 2 years and from patients with CIS that developed definite MS of the relapsing-remitting subtype (CIS-RRMS, n=8) over the same period. Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots ELISA experiments were performed. We identified one protein that was upregulated in CIS-RRMS (serin peptidase inhibitor) and eight proteins (alpha-1-B-glycoprotein, Fetuin-A, apolipoprotein A4, haptoglobin, human Zinc-alpha-2-glycoprotein (ZAG), Retinol-binding protein, superoxid dismutase 1, transferrin) that were down-regulated in CIS-RRMS vs. CIS-CIS. For Fetuin-A, our findings could be confirmed by ELISA. The pathophysiological role as well as clinical relevance of these candidate proteins in CIS remains to be further clarified by future studies.

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is a demyelinating syndrome of the central nervous system. It is considered to be an autoimmune response to an antecedent antigenic stimulus, most frequently a prior infectious illness (postinfectious encephalitis) or immunization (postvaccination encephalitis) occurring in the days or weeks before neurologic illness. Clinically, ADEM is characterized by encephalopathy, or focal/multifocal neurologic signs; brain MRI is characterized by diffuse multifocal or patchy areas of demyelination. The differentiation between ADEM and a first episode of multiple sclerosis, a chronic central nervous system demyelinating disease, may be difficult but has important prognostic and treatment implications. Although no clinical trials have assessed the efficacy of treatment modalities in patients with ADEM, immunomodulators, including corticosteroids and intravenous immunoglobulin, are frequently used empirically. ADEM outcome is generally favorable, with resolution over weeks to months.

Hepatitis B Vaccination and the Risk of Childhood-Onset Multiple Sclerosis

To investigate whether vaccination against hepatitis B (HB) increases the risk of incident multiple sclerosis (MS) in childhood in the short and long terms. Case-control study. Population-based study conducted in France from January 1, 1994, to December 31, 2003. The case patients had incident MS with onset before age 16 years. Each case was individually matched for age, sex, and geographic location (current place of residence) to 12 control participants randomly selected from the general population of France. Hepatitis B vaccine. The risk of MS associated with HB vaccine exposure. One hundred forty-three case patients with MS were matched to 1122 control participants. The rate of HB vaccination in the 3 years before the index date was approximately 32% for both cases and controls. Vaccination against HB within the 3-year study period was not associated with an increased rate of a first episode of MS (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.69). The rate was also not increased for HB vaccination within 6 months of the index date or at any time since birth or as a function of the number of injections or the brand of HB vaccine. Vaccination against HB does not seem to increase the risk of a first episode of MS in childhood.

Passive smoking increases the risk of multiple sclerosis in children

Smoking is associated with the risk of developing multiple sclerosis (MS) in adults, but the effects of passive smoking in children are unclear. To address this issue, Mikaeloff et al. studied children with MS and matched controls to investigate whether exposure to parental smoking in the home increased the risk of a first episode of MS before 16 years of age.

Parental smoking at home and the risk of childhood-onset multiple sclerosis in children

The possibility of a link between active smoking and incident multiple sclerosis (MS) has been raised. However, possible links between incidence of MS and passive smoking, particularly in children, have not been analysed. We conducted a population-based, case-control study. The cases were patients with incident MS occurring between 1994 and 2003, before the age of 16 years, in France. Each case was matched for age, sex and geographic origin with 12 controls, randomly selected from the French general population. Information about the smoking history of the parents of the cases and controls was collected with a standardized questionnaire. Conditional logistic regression was used to estimate the rate ratio (RR) of MS associated with parental smoking at home. The 129 cases of MS were matched with 1038 controls. Information about parental smoking was obtained for all these cases and controls. Exposure to parental smoking was noted in 62.0% of cases and 45.1% of controls. The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 (95% confidence interval: 1.43-3.15). Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases (over 10 years of age at the time of the index episode)-RR 2.49 (1.53-4.08)-than in younger cases. Children exposed to parent smoking have a higher MS risk. The duration of exposure also affects the level of risk.

Idiopathic acute transverse myelitis: a clinical study and prognostic markers in 45 cases

Objective The Transverse Myelitis Consortium Working Group has proposed new diagnostic criteria for idiopathic acute transverse myelitis (ATM). We reviewed patients admitted to our center diagnosed with myelitis with two objectives: (i) to evaluate the usefulness of these criteria in distinguishing between myelitis as the first episode of multiple sclerosis (MS) and idiopathic ATM; and (ii) to analyse the clinical and laboratory variables that may be used as functional prognostic markers. Methods We selected patients who met the criteria. We recorded clinical epidemiological data, patients treated with methylprednisolone, maximal disability reached and disability at final follow-up. We also recorded cerebrospinal fluid (CSF) data and the number of levels affected in the spinal magnetic resonance imaging (MRI). Results Twenty-four patients fulfilled the criteria for definite ATM and 21 for possible ATM. Five patients converted to MS. Mean follow-up time was 3.5 years. There was an association between younger patients and female patients with conversion to MS. The highest Rankin score reached and increased CSF glucose levels were associated with a poor outcome. In multivariate analysis, only the admission Rankin score was associated with outcome. Conclusions (i) About 10% of patients who met the criteria may convert to MS; and (ii) admission Rankin score was the only independent prognostic factor found.

Conversión a esclerosis múltiple clínicamente definida tras un síndrome medular aislado: valor de la resonancia magnética craneal y medular

Isolated spinal cord syndrome might be due to a first episode of multiple sclerosis. The aim of the study was to determine the clinical usefulness and paraclinical characteristics and of spinal and brain MR imaging predicting conversion to clinically definite multiple sclerosis (CDMS) in patients with an isolated spinal cord syndrome. We have evaluate thirty-eight patients with isolated spinal cord syndrome. A clinical protocol, lumbar puncture, evoked potential and brain-spinal cord MRI were performed. Twenty two percent of the patients fulfilling brain MRI Paty criteria (p < 0.01), 54.5% Fazekas (p = 0.007) and 80% of patients fulfilling Barkhof criteria (p = 0.009) presented CDMS. The spinal MR imaging from CDMS patients was always abnormal, showing cervical and marginal location with a diameter < 2 cm. Brain MRI is strongly predictive of the risk of developing CDMS and spinal cord MRI may increase the sensitivity to detect conversion to CDMS.