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European Journal of Neurology Jul 2022Demyelinating events are listed as adverse events with tumor necrosis factor alpha inhibitors (TNFi), but epidemiological studies have provided partly conflicting risk... (Observational Study)
Observational Study
BACKGROUND AND PURPOSE
Demyelinating events are listed as adverse events with tumor necrosis factor alpha inhibitors (TNFi), but epidemiological studies have provided partly conflicting risk estimates. Furthermore, studies examining long-term outcomes of demyelinating events associated with TNFi are rare.
METHODS
This was a retrospective, observational study comprising validation and tracking of long-term outcomes in patients referred to a tertiary neurology referral center for suspected neurological complications associated with TNFi.
RESULTS
Of 48 patients evaluated, only 14 showed signs of demyelinating disease on magnetic resonance imaging, where six fulfilled criteria for a clinically isolated syndrome (CIS) and eight were diagnosed with multiple sclerosis (MS). However, 13 patients had received an International Classification of Diseases code for MS at some stage. Mean follow-up from referral was 13 and 10.5 years among subjects with MS and CIS, respectively. Continued disease activity was recorded among several of those fulfilling MS criteria, and two ultimately underwent autologous hematopoietic stem cell transplantation. In contrast, subjects with CIS showed no progression after cessation of TNFi.
CONCLUSIONS
Our findings suggest that only a minority of those with suspected demyelinating disease following TNFi fulfill diagnostic criteria for MS and that MS diagnoses among those not fulfilling MS criteria may contribute to inflated epidemiological risk estimates. Nevertheless, in those fulfilling MS criteria, initiation of disease-modulating therapy, with escalation as needed, was important to suppress further disease activity.
Topics: Demyelinating Diseases; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Nervous System Diseases; Retrospective Studies
PubMed: 35262993
DOI: 10.1111/ene.15318 -
Journal of Neuroimmunology Jun 2017We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell...
OBJECTIVE
We aimed to evaluate clinical and diagnostic features of central and peripheral immune-mediated demyelinating disease (CPID) in allogeneic hematopoietic stem cell transplantation (aHSCT) recipients.
BACKGROUND
CPID refers to the late-onset, immune-mediated neurological complications following aHSCT, when other frequent differential diagnoses have been ruled out, and when symptoms and signs of systemic GvHD manifestations are absent.
METHODS
Case records at the University of Tuebingen, between 2001 and 2015, were screened to identify patients with CPID after aHSCT.
RESULTS
Seven patients who developed CPID after aHSCT were identified. The average time interval from aHSCT until onset of CPID was 2.6 (±2.8) years (mean±SD). The most prevalent manifestations of CPID were optic neuritis and/or myelitis and polyneuropathy. Cerebrospinal fluid analyses involved elevated protein concentration and lymphocytic pleocytosis, while oligoclonal bands in CSF, but not in serum, were detected in 28% of cases. Aquaporin-4-antibodies were consistently absent. MRI studies showed features suggestive of demyelination processes, with cerebral and/or spinal cord white-matter involvement, and features compatible with cerebral vasculitis. Corticosteroids, Immunoglobulins, Cyclophosphamide, Rituximab and Interferon beta-1a showed marginal treatment responses, whereas plasma exchange resulted in marked clinical improvement in two treated patients. A chronic disease-course with persisting neurological deficits was prevalent.
CONCLUSIONS
CPID may comprise a rare complication of aHSCT, which manifests as optic neuritis and/or myelitis and is accompanied by sensorimotor polyneuropathy. A concomitant systemic manifestation of GvHD is not mandatory for CPID diagnosis. Usually, CPID exhibits a chronic, persisting disease course. Thus, clinical awareness is required, as early diagnosis and aggressive treatment may be prognostically advantageous.
Topics: Adult; Central Nervous System; Databases, Bibliographic; Demyelinating Diseases; Female; Hematopoietic Stem Cell Transplantation; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Peripheral Nervous System; Retrospective Studies; Transplantation, Homologous
PubMed: 28495143
DOI: 10.1016/j.jneuroim.2017.04.005 -
Expert Review of Neurotherapeutics May 2017Neurologists are frequently consulted for patients who have white matter lesions discovered incidentally on their brain MRI, performed for reasons other than suspecting... (Review)
Review
Neurologists are frequently consulted for patients who have white matter lesions discovered incidentally on their brain MRI, performed for reasons other than suspecting a demyelinating disease. The referring physician will question if the person has multiple sclerosis (MS). If the MRI is typical for MS but there are no clinical symptoms or signs suggestive of a demyelinating disorder, patients are diagnosed as having a Radiologically Isolated Syndrome (RIS). Areas covered: This is a timely review on RIS with a focus on treatment considerations. Expert commentary: Multiple studies have tried to identify common predictive factors for conversion of RIS to clinical MS, the strongest thus far being an asymptomatic cervical spinal cord lesion. Treatment of RIS is highly controversial, but early treatment in carefully selected patients might improve long term outcome.
Topics: Demyelinating Diseases; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Spinal Cord; Syndrome; Watchful Waiting; White Matter
PubMed: 27830953
DOI: 10.1080/14737175.2017.1259568 -
Pflugers Archiv : European Journal of... Dec 2022The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is...
The cuprizone model is a widely used model to study the pathogenesis of multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is mainly being used to study demyelination and the mechanisms of remyelination, as well as the efficiency of compounds or therapeutics aiming at remyelination. Although early investigations using high dosages of cuprizone reported the occurrence of hydrocephalus, it has long been assumed that cuprizone feeding at lower dosages does not induce changes at the blood-brain barrier (BBB). Here, by analyzing BBB ultrastructure with high-resolution electron microscopy, we report changes at astrocytic endfeet surrounding vessels in the brain parenchyma. Particularly, edema formation around blood vessels and swollen astrocytic endfeet already occurred after feeding low dosages of cuprizone. These findings indicate changes in BBB function that will have an impact on the milieu of the central nervous system (CNS) in the cuprizone model and need to be considered when studying the mechanisms of de- and remyelination.
Topics: Animals; Mice; Cuprizone; Astrocytes; Demyelinating Diseases; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 36241864
DOI: 10.1007/s00424-022-02759-8 -
Journal of Neurology May 2024The widespread use of magnetic resonance imaging (MRI) has led to increased detection of individuals exhibiting asymptomatic brain and spinal cord lesions suggestive of... (Review)
Review
The widespread use of magnetic resonance imaging (MRI) has led to increased detection of individuals exhibiting asymptomatic brain and spinal cord lesions suggestive of multiple sclerosis (MS), defined as "radiologically isolated syndrome" (RIS). Specific criteria have been proposed and updated over time to identify individuals with RIS. Moreover, a younger age, the presence of infratentorial, spinal cord or gadolinium-enhancing lesions, as well as of cerebrospinal fluid-specific oligoclonal bands have been recognized as relevant risk factors for the occurrence of a first clinical event. Recent randomized controlled trials conducted in individuals with RIS have shown that dimethyl fumarate and teriflunomide significantly reduce the occurrence of clinical events in this population. These findings support the notion that early treatment initiation may positively influence the prognosis of these patients. However, several aspects should be taken into account before treating individuals with RIS in the real-world clinical setting, including an accurate identification of individuals with RIS to avoid misdiagnosis, a precise stratification of their risk of experiencing a first clinical event and further data supporting favorable balance between benefits and risks, even in the long term. This commentary provides an overview of the latest updates in RIS diagnosis, prognosis, and emerging treatment evidence.
Topics: Humans; Demyelinating Diseases; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 38502339
DOI: 10.1007/s00415-024-12294-4 -
Rheumatology (Oxford, England) Aug 2014Inflammatory brain diseases (IBrainDs) are a leading cause of devastating neurological deficits or neuropsychiatric syndromes in previously healthy children. The... (Review)
Review
Inflammatory brain diseases (IBrainDs) are a leading cause of devastating neurological deficits or neuropsychiatric syndromes in previously healthy children. The spectrum is expanding rapidly and new disease entities have been discovered in the last decade. IBrainD can occur as a primary disease or may occur secondary to an underlying cause. This review focuses on the clinical presentation, diagnostic features, pathology and histology characteristics and treatment of the primary childhood IBrainDs.
Topics: Brain; Brain Diseases; Child; Demyelinating Diseases; Diagnosis, Differential; Humans; Inflammation; Sarcoidosis; Vasculitis, Central Nervous System
PubMed: 24324213
DOI: 10.1093/rheumatology/ket398 -
Tidsskrift For Den Norske Laegeforening... Feb 2017BACKGROUND Mitochondria play an important role in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease. Neurodegenerative changes occur... (Review)
Review
BACKGROUND Mitochondria play an important role in the pathogenesis of various neurodegenerative disorders, including Parkinson's disease. Neurodegenerative changes occur early in the course of multiple sclerosis (MS). This article aims to present information on a possible association between mitochondrial dysfunction and multiple sclerosis.MATERIAL AND METHOD The article is based on original and review articles selected following a literature search in PubMed, restricted to articles written in English, and concluded in May 2016. The literature search resulted in a total of 2276 articles. After a discretionary evaluation by the authors, 71 articles were read in full. Of these, 19 were used as references. In addition, we included 15 articles from reference lists and seven from the authors' own literature archive.RESULTS Mitochondrial changes have been demonstrated in affected areas of the brains of patients with MS. Although some of the changes may be attributed to mitochondrial damage that is secondary to inflammation, others may be compensatory due to the increased energy demands of demyelinated axons. The type of mitochondrial damage varies and is dependent on the pathology that triggers it.INTERPRETATION Mitochondrial damage secondary to inflammation, combined with increased energy demands secondary to demyelination, may result in a chronic energy deficiency in the central nervous system. This in turn may lead to neurodegeneration. Improved knowledge of the role of mitochondria in MS, both secondary to inflammation and possibly as a direct contributor to neurodegeneration, may provide a better understanding of the pathogenesis of the disease and perhaps contribute to new treatment options.
Topics: Demyelinating Diseases; Humans; Inflammation; Mitochondria; Multiple Sclerosis; Nerve Degeneration
PubMed: 28225235
DOI: 10.4045/tidsskr.16.0210 -
Journal of Computer Assisted Tomography 2020We aim to review the imaging appearance of fulminant demyelinating disorders of central nervous system that have different pathological features, clinical course,... (Review)
Review
We aim to review the imaging appearance of fulminant demyelinating disorders of central nervous system that have different pathological features, clinical course, clinical features, and imaging findings different from classic multiple sclerosis. Routine magnetic resonance imaging (MRI) can help in accurate localization of the lesions, detection of associated lesions, and monitoring of these patients. Advanced MRI combined with routine MRI can aid in differentiation fulminant demyelinating lesions from simulating malignancy. Tumefactive demyelination lesions are located in supratentorial white matter mainly frontal and parietal regions with incomplete rim enhancement. Baló concentric sclerosis shows characteristic concentric onion skin appearance. Schilder disease is subacute or acute demyelinating disorders with one or more lesions commonly involving the centrum semiovale. Marburg disease is the most severe demyelinating disorder with diffuse infiltrative lesions and massive edema involving both the cerebral hemisphere and brain stem.
Topics: Brain; Demyelinating Diseases; Humans; Magnetic Resonance Imaging
PubMed: 32195804
DOI: 10.1097/RCT.0000000000000997 -
Neurotherapeutics : the Journal of the... Jan 2016Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute... (Review)
Review
Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.
Topics: Child; Encephalomyelitis, Acute Disseminated; Humans; Immunologic Factors; Immunotherapy; Multiple Sclerosis
PubMed: 26496907
DOI: 10.1007/s13311-015-0396-0 -
Current Neuropharmacology 2019Demyelinating diseases of the central nervous system (CNS) comprise a group of neurological disorders characterized by progressive (and eventually irreversible) loss of... (Review)
Review
INTRODUCTION
Demyelinating diseases of the central nervous system (CNS) comprise a group of neurological disorders characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter tracts. Some of myelin disorders include: Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others. To date, the etiology of these disorders is not well known and no effective treatments are currently available against them. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology and clinical signs of these diseases. Herein, we describe the model of toxic demyelination induced by cuprizone (CPZ), a copper chelator that reduces the cytochrome and monoamine oxidase activity into the brain, produces mitochondrial stress and triggers the local immune response. These biochemical and cellular responses ultimately result in selective loss of oligodendrocytes and microglia accumulation, which conveys to extensive areas of demyelination and gliosis in corpus callosum, superior cerebellar peduncles and cerebral cortex. Remarkably, some aspects of the histological pattern induced by CPZ are similar to those found in multiple sclerosis. CPZ exposure provokes behavioral changes, impairs motor skills and affects mood as that observed in several demyelinating diseases. Upon CPZ removal, the pathological and histological changes gradually revert. Therefore, some authors have postulated that the CPZ model allows to partially mimic the disease relapses observed in some demyelinating diseases.
CONCLUSION
for five decades, the model of CPZ-induced demyelination is a good experimental approach to study demyelinating diseases that has maintained its validity, and is a suitable pharmacological model for reproducing some key features of demyelinating diseases, including multiple sclerosis.
Topics: Animals; Brain; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Oligodendroglia; Reproducibility of Results
PubMed: 28714395
DOI: 10.2174/1570159X15666170717120343