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Multiple Sclerosis (Houndmills,... Apr 2014Glioma-like inflammatory demyelinating lesions can be found in patients with pre-diagnosed multiple sclerosis, but they have also been described as an isolated disease...
Glioma-like inflammatory demyelinating lesions can be found in patients with pre-diagnosed multiple sclerosis, but they have also been described as an isolated disease entity. The initial diagnostic work-up usually includes a biopsy for histopathological analysis. However, even after unambiguous histopathologic classification, tumefactive lesions pose a therapeutic challenge. Until now, there have been no guidelines on how to treat patients with these rare and extreme lesion phenotypes. Here we report a patient with a relapsing unifocal tumefactive demyelinating lesion. The patient initially showed a good response to steroid treatment, with full clinical recovery. However, after relapse of the same lesion, recovery was incomplete. Although immunosuppression was initiated, the patient presented with subsequent further deterioration. Only maximal escalation of immunosuppression was able to stop the inflammatory activity. Due to the length of time of the step-wise escalation treatment however, the lengthy lesion activity led to irreversible tissue destruction and residual non-remitting disability. Early aggressive treatment with an induction therapy regimen might be more appropriate for these rare and often strongly disabling lesion subtypes.
Topics: Biopsy; Demyelinating Diseases; Drug Administration Schedule; Drug Substitution; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged; Recurrence; Steroids; Time Factors; Treatment Outcome
PubMed: 24347182
DOI: 10.1177/1352458513516891 -
Journal of Neural Transmission.... 1997Interferon beta 1b (Betaseron) was licensed by the U.S. Federal Food and Drug Administration in July 1993 as the first treatment to alter the natural history of multiple... (Review)
Review
Interferon beta 1b (Betaseron) was licensed by the U.S. Federal Food and Drug Administration in July 1993 as the first treatment to alter the natural history of multiple sclerosis (MS). The drug, injected subcutaneously every other day, reduced the frequency of relapses and the expansion of central white matter pathology as measured by MRI. Twelve previous interferon trials in MS, employing a variety of interferon preparations, doses and routes of administration, preceded this trial and provided the scientific foundation for its success. Beta interferon therapy probably inhibits gamma interferon to achieve its therapeutic effect. Future MS therapy may require combination treatment with multiple agents with complimentary immunologic effects.
Topics: Brain; Demyelinating Diseases; Humans; Interferon beta-1a; Interferon beta-1b; Interferon-beta; Interferon-gamma; Magnetic Resonance Imaging; Models, Immunological; Multiple Sclerosis; Recombinant Proteins; United States; United States Food and Drug Administration
PubMed: 9266420
DOI: 10.1007/978-3-7091-6844-8_12 -
Revue Neurologique Jun 2018The diagnosis of multiple sclerosis (MS) and other demyelinating diseases of the central nervous system is challenging, and although the currently available biological... (Review)
Review
The diagnosis of multiple sclerosis (MS) and other demyelinating diseases of the central nervous system is challenging, and although the currently available biological and imaging tools offer considerable support to physicians, these tools often fail to provide a simple and final answer at the time of a first event. Thus, sets of diagnostic criteria have been published and tested on patient cohorts, and are now used in clinical trials and in daily clinical practice. These criteria have evolved over time to take into account physicians' and patients' needs, along with emerging paraclinical tests. The different presentations of MS have given rise to the use of a common classification system to identify patient profiles and adapt care protocols accordingly. This article reviews the various classifications of the forms and diagnostic criteria of MS and related syndromes, including neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSDs), acute disseminated (demyelinating) encephalomyelitis (ADEM) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Also discussed is their validity in the light of the currently available literature.
Topics: Central Nervous System Diseases; Demyelinating Diseases; Encephalomyelitis, Acute Disseminated; Humans; Inflammation; Multiple Sclerosis; Neuromyelitis Optica; Syndrome
PubMed: 29673575
DOI: 10.1016/j.neurol.2018.01.368 -
Brain & Development Oct 2017The clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are...
BACKGROUND
The clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are unknown. We investigated the clinical characteristics and described detailed treatment of weekly intramuscular interferon β-1a (IFNβ-1a) in children aged <4years with ADS and the anti-MOG antibody.
METHODS
We conducted a retrospective chart review of patients with anti-MOG positivity who were diagnosed as having multiple sclerosis (MS) at <4years of age.
RESULTS
Subjects comprised 2 boys and 2 girls. Initial symptoms included ataxia, facial paresis, status epilepticus, and encephalopathy. Abnormal lesions on magnetic resonance imaging scans were often detected in the brainstem and cerebellum as well as the cerebrum. All patients started receiving IFNβ-1a at age 3.1-3.5years. The initial doses ranged from 3 to 6μg, which were 1/10-1/5 doses, respectively, for adults. During 0.6-4.3years of IFNβ-1a administration, all patients had flu-like symptoms, and 1 patient had an increased liver enzyme level. Although 1 patient discontinued IFNβ-1a therapy because of frequent relapses, no patient discontinued therapy due to severe adverse events.
CONCLUSIONS
This case series adds novel information regarding the clinical features of children <4years old with ADS and the anti-MOG antibody.
Topics: Adjuvants, Immunologic; Age of Onset; Autoantibodies; Child, Preschool; Demyelinating Diseases; Female; Humans; Injections, Intramuscular; Interferon beta-1a; Magnetic Resonance Imaging; Male; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies
PubMed: 28551039
DOI: 10.1016/j.braindev.2017.05.004 -
Current Opinion in Neurology Jun 2001The classical demyelinating diseases include the 'autoimmune' inflammatory demyelinating diseases, the inflammatory demyelinating diseases of infectious aetiology, and... (Review)
Review
The classical demyelinating diseases include the 'autoimmune' inflammatory demyelinating diseases, the inflammatory demyelinating diseases of infectious aetiology, and the demyelinating or dysmyelinating diseases of genetic/hereditary background. In addition, primary demyelination is present in other conditions, such as brain ischaemia and intoxication. Irrespective of the primary aetiology, selective demyelination can be mediated through various pathogenetic pathways: the immune-mediated inflammatory pathway; the metabolic pathway; and the ischaemic/excitotoxic pathway. These pathways are only partly segregated with distinct aetiologies of demyelinating diseases, but they also reflect the way in which the patient copes with the disease-inciting event in relation to their particular genetic background. For future therapeutic strategies it will be important to interfere with the specific pathogenetic pathways of demyelination, which may be common to various demyelinating diseases, but may differ in subgroups of patients who suffer from a particular clinical demyelinating disease entity.
Topics: Animals; Brain; Demyelinating Diseases; Diagnosis, Differential; Humans
PubMed: 11371746
DOI: 10.1097/00019052-200106000-00001 -
Current Medicinal Chemistry 2012Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting... (Review)
Review
Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current "immunomodulatory" treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.
Topics: Animals; Central Nervous System; Demyelinating Diseases; Glutamic Acid; Humans; Multiple Sclerosis; Oxidative Stress
PubMed: 22304707
DOI: 10.2174/092986712799462559 -
Nature Reviews. Neurology Nov 2009Incidentally identified anomalies within the CNS that are highly suggestive of demyelinating disease have been extensively described in neuropathological series, and are... (Review)
Review
Incidentally identified anomalies within the CNS that are highly suggestive of demyelinating disease have been extensively described in neuropathological series, and are increasingly being detected during premortem investigations. With the exception of studies that focused specifically on the prevalence of this entity, the observed anomalies are unanticipated and unrelated to the intended purpose of the examination. The discovery of MRI technology, and its subsequent widespread adoption in the clinic, has facilitated the identification of such cases. The natural course of individuals with incidentally identified demyelinating anomalies is unknown at present. This Review focuses on the history and nosology of unexpected demyelinating pathology, encompassing both autopsy data and MRI-based antemortem investigations of large cohorts, as well as family members at high risk of developing multiple sclerosis. Longitudinal clinical data acquired from prospectively followed cohorts will also be reviewed. In addition, I discuss the estimated prevalence of demyelinating pathology, the currently proposed criteria for its identification, implications for therapeutic intervention, and predictors of disease progression.
Topics: Autopsy; Central Nervous System; Cohort Studies; Demyelinating Diseases; Disease Progression; Humans; Incidence; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 19806149
DOI: 10.1038/nrneurol.2009.157 -
Journal of Neurology, Neurosurgery, and... Sep 2008Clinical and electromyographic findings of chronic inflammatory demyelinating polyradiculopathy (CIDP) are occasionally observed in patients with multiple sclerosis (MS).
BACKGROUND
Clinical and electromyographic findings of chronic inflammatory demyelinating polyradiculopathy (CIDP) are occasionally observed in patients with multiple sclerosis (MS).
OBJECTIVE
To define a new inflammatory demyelinating disease unlike MS or CIDP.
RESULTS
This study reports on five patients with a demyelinating disease affecting the central nervous system (CNS) and peripheral nervous system (PNS). Each case presented a relapsing-remitting course in which CNS involvement preceded PNS involvement. All patients fulfilled Barkhof's criteria on MRI and the McDonald criteria for MS. Two patients had grey matter lesions with typical white matter changes. No systemic inflammatory disease and no metabolic or inflammatory factor for peripheral neuropathy were found. In all cases electromyography showed a demyelinating peripheral neuropathy without conduction block. Four patients fulfilled the European Federation of Neurological Societies/PNS guideline for CIDP and Nicolas et al's criteria for CIDP, one of whom also fulfilled the Ad Hoc Subcommittee criteria for CIDP. Nerve biopsy, performed in two patients, showed histological evidence of CIDP. An improvement in clinical status and neurophysiological parameters was observed in three patients after treatment with either intravenous immunoglobulin (n = 1) or cyclophosphamide (n = 2).
CONCLUSION
The CNS and PNS demyelination, the absence of oligoclonal bands and the peripheral demyelination without conduction block indicate pathogenic mechanisms different from MS and CIDP. The chronology of events suggests an entity unlike that involved in acute demyelinating encephalomyelitis. Immunological reactivity against antigens common to peripheral and central myelin may explain why the demyelinating disease affected both the CNS and PNS.
Topics: Adult; Aged; Biopsy; Brain; Demyelinating Diseases; Electromyography; Evoked Potentials, Visual; Extremities; Female; Hemianopsia; Humans; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Relapsing-Remitting; Neural Conduction; Peripheral Nerves; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Reflex, Abnormal; Reflex, Stretch; Spinal Cord
PubMed: 18208860
DOI: 10.1136/jnnp.2006.108290 -
Archives of Ophthalmology (Chicago,... Apr 1981
Topics: Adult; Demyelinating Diseases; Female; Humans; Uveitis
PubMed: 7224943
DOI: 10.1001/archopht.1981.03930010697023 -
Trends in Neurosciences Jan 1999Adrenoleukodystrophy (ALD) is caused by mutations in an ATP-binding-cassette transporter located in the peroxisomal membrane, which result in a fatal demyelinating... (Review)
Review
Adrenoleukodystrophy (ALD) is caused by mutations in an ATP-binding-cassette transporter located in the peroxisomal membrane, which result in a fatal demyelinating disease in boys and a milder phenotype in men and some heterozygous women. There is no molecular signature to indicate a particular clinical course. The underlying molecular mechanisms of this disease have yet to be targeted clinically. Is the increase in very-long-chain fatty acids (VLCFA) the disease trigger? Why is there no phenotype in ALD null mice that show this increase? Do VLCFA destabilize human myelin, once formed, and lead to the inflammation seen in this genetic disease? Bone-marrow transplantation might save a child by providing normal brain macrophages and allowing myelin regeneration early in disease. The processes that underlie ALD challenge neuroscientists to elucidate peroxisomal transporter functions in the nervous system and to pursue the gene-transfer strategies leading to remyelination until a preventive therapy emerges.
Topics: Adrenoleukodystrophy; Demyelinating Diseases; Genetic Linkage; Humans; Neurobiology; Peroxisomal Disorders; X Chromosome
PubMed: 10088993
DOI: 10.1016/s0166-2236(98)01319-8