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Journal of Clinical Apheresis 2001Plasma exchange has not been widely accepted as a treatment for multiple sclerosis. However, several uncontrolled studies have suggested that patients with severe... (Review)
Review
Plasma exchange has not been widely accepted as a treatment for multiple sclerosis. However, several uncontrolled studies have suggested that patients with severe attacks of MS and other inflammatory demyelinating disease may improve rapidly after plasma exchange treatment. We recently completed a randomized, sham-controlled, crossover clinical trial of plasma exchange in 22 patients with idiopathic inflammatory demyelinating diseases of the central nervous system. Twelve had MS and ten had other inflammatory demyelinating disease syndromes. Forty-two percent of patients experienced moderate or greater recovery over 2 weeks of active treatment administered every other day while only 6% of patients experienced similar improvement while receiving sham treatment. Three patients who failed the sham treatment subsequently improved rapidly after crossover to active treatment; no patient who failed active treatment improved after crossover to sham. This study illustrates the importance of designing randomized clinical trials based on the treatment regimen and patient population studied in the uncontrolled reports that suggested treatment efficacy. Plasma exchange should be considered for patients with idiopathic inflammatory demyelinating disease syndromes when they have failed corticosteroid therapy.
Topics: Demyelinating Autoimmune Diseases, CNS; Humans; Plasma Exchange; Randomized Controlled Trials as Topic
PubMed: 11309833
DOI: 10.1002/jca.1010 -
Neurotherapeutics : the Journal of the... Jan 2013Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin... (Review)
Review
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin and axons. All therapeutics used to treat MS have been developed to target an overactive immune response, with aims to reduce disease activity. Chronic demyelinated axons are further prone to irreversible damage and death, and it is imperative that new therapies address this critical issue. Remyelination, the generation of new myelin in the adult nervous system, is an endogenous repair mechanism that restores function of denuded axons and delays their deterioration. Although remyelination can be extensive in some patients, the majority of cases limit repair only to the acute phase of disease. A significant current drive in new MS therapeutics is to identify targets that can promote remyelination by boosting endogenous oligodendrocyte precursor cells to form new myelin. Also, a number of inhibitory pathways have been identified in chronic MS lesions that prevent oligodendrocyte precursor cells from being properly recruited to demyelinated lesions or interfere with their differentiation to myelin-forming oligodendrocytes. In this review, we introduce the phenomenon of remyelination from the view of experimental models and studies in MS patients, describe a potential role in remyelination for currently available MS mediations, and discuss many avenues that are being actively studied to promote remyelination. The next frontier in MS therapeutics will supplement immunomodulation with agents that directly foster myelin repair, with aims to delay disease progression and recover lost neurological functions.
Topics: Animals; Demyelinating Diseases; Humans; Immunologic Factors; Multiple Sclerosis; Myelin Sheath
PubMed: 23070731
DOI: 10.1007/s13311-012-0152-7 -
Pediatric Neurology Apr 2015Cerebrospinal fluid opening pressure is elevated with central nervous system infection and vasculitis, but has not been studied in inflammatory demyelinating disease....
BACKGROUND
Cerebrospinal fluid opening pressure is elevated with central nervous system infection and vasculitis, but has not been studied in inflammatory demyelinating disease. This retrospective study sought to determine whether children with demyelinating disease demonstrate elevated cerebrospinal fluid opening pressure, and to explore possible clinical and radiologic correlates.
METHODS
Pediatric patients with acute disseminated encephalomyelitis, multiple sclerosis, or a clinically isolated syndrome (including optic neuritis and transverse myelitis) who had a lumbar puncture within 1 month of presentation were eligible for inclusion, and were compared with a reference cohort of healthy children from the same institution. Regression analyses were used to determine the association of variables collected with opening pressure.
RESULTS
Opening pressure was elevated in 15 of 53 (28%) children, which was significantly higher than the reference cohort (P = 0.001). There was no relationship between elevated opening pressure and any of the clinical or radiologic variables collected.
CONCLUSION
Although almost one third of children with inflammatory demyelinating disease have an elevated cerebrospinal fluid opening pressure, the clinical and radiologic variables evaluated in this study did not explain this finding, and further understanding may require assessment of cerebrospinal fluid flow dynamics.
Topics: Cerebrospinal Fluid Pressure; Child; Demyelinating Diseases; Female; Humans; Male; Regression Analysis; Retrospective Studies; Spinal Puncture
PubMed: 25681000
DOI: 10.1016/j.pediatrneurol.2015.01.002 -
Progressive motor impairment from "critical" demyelinating lesions of the cervicomedullary junction.Multiple Sclerosis (Houndmills,... Jan 2023Progressive motor impairment anatomically associated with a "critical" lesion has been described in primary demyelinating disease. Most "critical" lesions occur within... (Observational Study)
Observational Study
BACKGROUND
Progressive motor impairment anatomically associated with a "critical" lesion has been described in primary demyelinating disease. Most "critical" lesions occur within the spinal cord.
OBJECTIVE
To describe the clinical and radiological features of "critical" lesions of the cervicomedullary junction (CMJ).
METHODS
Observational study on people presenting with a CMJ lesion associated with primary demyelinating disease-related progressive motor impairment. Clinical data were extracted by chart review. Brain and spinal cord magnetic resonance images were reviewed to characterize the CMJ lesion and determine additional demyelination burden.
RESULTS
Forty-one people were included: 29 (71%) had progression from onset and 12 (29%) had a relapse onset (secondary progressive) course. Most had progressive hemiparesis (21 (51%)) or progressive quadriparesis (15 (37%)) with a median Expanded Disability Status Scale (EDSS) of 5.5 (2.0-8.5) at last follow-up. No "critical" CMJ lesion enhanced; most were bilateral (25 (61%)). Brain magnetic resonance images were otherwise normal in 16 (39%) or with a restricted demyelination burden in 15 (37%). Cervical and thoracic cord MRIs were without additional lesions in 25 (61%) and 22/37 (59%), respectively.
CONCLUSION
CMJ "critical" lesions can correlate with progressive motor impairment even with few or no additional magnetic resonance imaging (MRI) lesions. Lesion location is an important determinant of progressive motor impairment in demyelinating disease.
Topics: Humans; Motor Disorders; Disease Progression; Disability Evaluation; Neoplasm Recurrence, Local; Spinal Cord; Brain; Magnetic Resonance Imaging; Demyelinating Diseases; Multiple Sclerosis
PubMed: 36000479
DOI: 10.1177/13524585221114438 -
Journal of the Neurological Sciences Sep 2021Baló's concentric sclerosis (BCS) is a rare, inflammatory demyelinating disease of the central nervous system (CNS). Historically, BCS was thought to be uniformly fatal... (Review)
Review
Baló's concentric sclerosis (BCS) is a rare, inflammatory demyelinating disease of the central nervous system (CNS). Historically, BCS was thought to be uniformly fatal and diagnosis was based on postmortem findings. With advances in modern neuroimaging, BCS is currently defined by the presence of concentric layered patterns composed of alternating rings of varying intensity. They are best appreciated on gadolinium-enhanced T1-weighted sequences and predominantly occur in the supratentorial cerebral white matter with sparing of cortical U-fibers. The lamellar pattern of the lesions likely reflects bands of demyelination and relative myelin preservation with minimal axonal loss. While BCS falls within the spectrum of atypical demyelinating diseases, there is ongoing debate over whether BCS is a phenotypical variant of multiple sclerosis (MS) or a separate entity. Corticosteroids comprise first-line therapy but there is ongoing controversy regarding appropriate maintenance therapy. First-line MS disease-modifying therapies such as interferon beta-1a are appropriate for patients who fulfill diagnostic criteria for relapsing-remitting MS. Fingolimod should likely be avoided as Baló-like lesions have been reported during its administration or after withdrawal. Monoclonal antibodies such as natalizumab and rituximab are potentially effective at reducing BCS relapses, but alemtuzumab may be relatively ineffective because humoral immunity does not play a central role in BCS pathogenesis.
Topics: Diffuse Cerebral Sclerosis of Schilder; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Myelin Sheath
PubMed: 34261000
DOI: 10.1016/j.jns.2021.117570 -
Archives of Neurology Jan 1984
Topics: Antigens, Viral; Demyelinating Diseases; Herpesvirus 4, Human; Humans; Multiple Sclerosis
PubMed: 6316879
DOI: 10.1001/archneur.1984.04050130016007 -
Multiple Sclerosis (Houndmills,... Nov 2015Whether or not recurrent tumefactive demyelinating lesions are a unique form of CNS demyelinating disease or part of the continuum of multiple sclerosis is a question...
Whether or not recurrent tumefactive demyelinating lesions are a unique form of CNS demyelinating disease or part of the continuum of multiple sclerosis is a question raised by the case report on which this commentary is based. Detailed review and immunopathologic study of biopsy material may not only confirm or refute a diagnosis of demyelinating disease, but potentially uncover unique features that may assist in understanding pathophysiology and nosology of rare cases with recurrent tumefactive demyelination.
Topics: Brain; Brain Neoplasms; Demyelinating Diseases; Encephalitis; Female; Hemianopsia; Humans
PubMed: 26362899
DOI: 10.1177/1352458515603801 -
Pediatric Neurosurgery 2016Cases of intracranial germinoma with granulomatous reaction are rare, so a pathological diagnosis of this disease is difficult. In this report, we describe the case of a...
Cases of intracranial germinoma with granulomatous reaction are rare, so a pathological diagnosis of this disease is difficult. In this report, we describe the case of a 13-year-old boy with a bilateral thalamic germinoma which initially mimicked tumefactive demyelinating disease with inflammation, based on the clinical symptoms, imaging results and histology of a biopsy specimen obtained endoscopically. Upon examination of the cerebrospinal fluid, oligoclonal bands were detected. Although his symptoms and radiological findings improved following steroid pulse treatment, they worsened dramatically almost 1 year after the first surgery and even after an additional steroid pulse treatment. Prompted by the clinical course, a second biopsy was performed, and a pathological examination of the specimen showed a two-cell pattern. The diagnosis was changed to intracranial germinoma. After chemotherapeutic treatment with etoposide and cisplatin, the patient's symptoms and radiological findings dramatically improved. We conclude that it is very challenging to distinguish germinomas with a granulomatous reaction due to other inflammatory diseases, especially when only small specimens can be obtained. Stereotactic or endoscopic biopsies should be performed using samples from several different points even if the lesions are associated with eloquent brain regions.
Topics: Adolescent; Brain Neoplasms; Demyelinating Diseases; Diagnosis, Differential; Germinoma; Humans; Male; Pulse Therapy, Drug
PubMed: 26811911
DOI: 10.1159/000439028 -
Journal of Neuroinflammation Sep 2012Theiler's virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS). IL-1 plays an...
BACKGROUND
Theiler's virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS). IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE) and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease.
METHODS
Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO) were infected with Theiler's murine encephalomyelitis virus (1 x 106 PFU). Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry.
RESULTS
Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6) mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence.
CONCLUSIONS
These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of inhibitory cytokines and regulatory molecules. Therefore, the balance of IL-1 signaling appears to be extremely important for the protection from TMEV-induced demyelinating disease, and either too much or too little signaling promotes the development of disease.
Topics: Animals; Demyelinating Diseases; Disease Models, Animal; Female; Interleukin-1beta; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Multiple Sclerosis; Poliomyelitis; Signal Transduction; Theilovirus
PubMed: 22985464
DOI: 10.1186/1742-2094-9-217 -
Archives of Neurology Jun 1999Administration of high-dose intravenous immunoglobulins has become one of the most successful new treatment regimens for demyelinating diseases. In a decade of molecular... (Review)
Review
Administration of high-dose intravenous immunoglobulins has become one of the most successful new treatment regimens for demyelinating diseases. In a decade of molecular medicine, it came as a surprise that a natural blood product would prove effective in several disorders, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and, probably, multiple sclerosis. Many experimental studies, both in vivo and in vitro, have shown that intravenous immunoglobulins can interfere with the immune system at several levels. In addition, intravenous immunoglobulins may promote remyelination in demyelinating disease associated with viral infections. At present, no single mode of action has been identified as the crucial mechanism, which leads us to suggest that multiple effects may act in concert.
Topics: Antibodies, Anti-Idiotypic; B-Lymphocytes; Complement System Proteins; Cytokines; Demyelinating Diseases; Humans; Immunoglobulins, Intravenous; Multiple Sclerosis; Polyradiculoneuropathy; Receptors, Fc; T-Lymphocytes
PubMed: 10369303
DOI: 10.1001/archneur.56.6.661