Individuals can be deemed to have radiologically isolated syndrome (RIS) if they have incidental demyelinating-appearing lesions in their brain or spinal cord that are highly suggestive of multiple ...sclerosis but their clinical history does not include symptoms consistent with multiple sclerosis. Data from international longitudinal cohorts indicate that around half of people with RIS will develop relapsing or progressive symptoms of multiple sclerosis within 10 years, suggesting that in some individuals, RIS is a presymptomatic stage of multiple sclerosis. Risk factors for progression from RIS to clinical multiple sclerosis include younger age (ie, <35 years), male sex, CSF-restricted oligoclonal bands, spinal cord or infratentorial lesions, and gadolinium-enhancing lesions. Other imaging, biological, genetic, and digital biomarkers that might be of value in identifying individuals who are at the highest risk of developing multiple sclerosis need further investigation. Two 2-year randomised clinical trials showed the efficacy of approved multiple sclerosis immunomodulatory medications in preventing the clinical conversion to multiple sclerosis in some individuals with RIS. If substantiated in longer-term studies, these data have the potential to transform our approach to care for the people with RIS who are at the greatest risk of diagnosis with multiple sclerosis.
Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and ...restricted to the CNS, and rarely to the PNS."Primary angiitis of the CNS" is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.
Myelopathy in Behçet's disease: The Bagel Sign Uygunoglu, Ugur; Zeydan, Burcu; Ozguler, Yesim ...
Annals of neurology,
August 2017, 2017-Aug, 2017-08-00, 20170801, Letnik:
82, Številka:
2
Journal Article
Recenzirano
Objective
To describe the clinical and distinctive imaging features of myelopathy associated with Behçet's disease (BD).
Methods
We evaluated the records of patients meeting the following criteria: ...(1) fulfillment of the International Study Group criteria for BD; (2) clinically suggestive of myelopathy; (3) simultaneous spinal cord and brain magnetic resonance images (MRIs) within 1 month of acute worsening of myelopathy; and (4) follow‐up duration ≥ 1 year after initial MRI evaluation. Patients not fulfilling all inclusion criteria and having MRIs with poor quality or missing sequences were excluded.
Results
In 11 patients (9 men, 2 women), we studied 14 MRIs during distinct myelopathy episodes and nine follow‐up MRIs. Two distinct MRI patterns of spinal cord involvement were described according to T2‐weighted (T2W) axial images: (1) “Bagel Sign” pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and (2) “Motor Neuron” pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed in 1 of 14 MRIs. Of the 13 MRIs with Bagel Sign long myelopathy (n = 9), both long and short myelopathy (n = 2) and short myelopathy (n = 2) was observed. All patterns cleared with some residual lesions after steroid use and immunomodulation with associated clinical recovery in patients.
Interpretation
The signal characteristics of the Bagel Sign potentially represent venous engorgement and/or acute blood products within the spinal cord. To our knowledge, Bagel Sign has not been observed in other forms of longitudinal myelopathy outside of BD, including neuromyelitis optica. Ann Neurol 2017;82:288–298
Behçet syndrome (BS) is an idiopathic chronic relapsing multisystem vascular-inflammatory disease of unknown origin. As the disease affects many organs and systems and shows a wide range of clinical ...manifestations and presentations, it is prefereable to call Behçet's a syndrome (BS) rather than a disease. Nervous system involvement, known as "neuro-BS" (NBS), is seen in about 5-10% of all cases. Clinical and imaging evidence suggests that primary neurologic involvement in BS may be subclassified into two major forms: the first, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system disease with focal or multifocal parenchymal involvement, mostly presenting with a subacute brainstem syndrome and hemiparesis (intra-axial NBS); the other, which has few symptoms and a better neurologic prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension (extra-axial NBS), occurring in 10-20% of the cases. These two types are rarely seen in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a vascular type headache is relatively common and independent from neurologic involvement. Neurologic complications secondary to systemic involvement of BS, as well as neurologic complications related to BS treatments are considered as secondary neurologic involvement of the syndrome. The core histopathologic phenomenon seems to be a vasculitic involvement in some cases, and low-grade chronic nonspecific inflammation in others. As the neurologic involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and its response to treatment. Currently, treatment options for NBS are limited to attack therapies with high-dose intravenous methylprednisolone followed by a prolonged oral taper, symptomatic management, and generally the use of azathioprine, cyclophosphamide, interferon-α and anti-TNF agents for long-term preventive treatment, although there no evidence for their efficacy.
Objective
The radiologically isolated syndrome (RIS) represents the earliest detectable pre‐clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in ...preventing first symptom manifestation at this stage in the disease spectrum.
Methods
We conducted a multi‐center, randomized, double‐blinded, placebo‐controlled study involving people with RIS. Individuals without clinical symptoms typical of MS but with incidental brain MRI anomalies consistent with central nervous system (CNS) demyelination were included. Within 12 MS centers in the United States, participants were randomly assigned 1:1 to oral dimethyl fumarate (DMF) 240 mg twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event within a follow‐up period of 96 weeks. An intention‐to‐treat analysis was applied to all participating individuals in the primary and safety investigations. The study is registered at ClinicalTrials.gov, NCT02739542 (ARISE).
Results
Participants from 12 centers were recruited from March 9, 2016, to October 31, 2019, with 44 people randomized to dimethyl fumarate and 43 to placebo. Following DMF treatment, the risk of a first clinical demyelinating event during the 96‐week study period was highly reduced in the unadjusted Cox proportional‐hazards regression model (hazard ratio HR = 0.18, 95% confidence interval CI = 0.05–0.63, p = 0.007). More moderate adverse reactions were present in the DMF (34 32%) than placebo groups (19 21%) but severe events were similar (DMF, 3 5%; placebo, 4 9%).
Interpretation
This is the first randomized clinical trial demonstrating the benefit of a disease‐modifying therapy in preventing a first acute clinical event in people with RIS. ANN NEUROL 2023;93:604–614
This multi‐center, randomized, double‐blinded trial by Okuda, et al. assessed the impact of dimethyl fumarate (DMF) in the time to onset of first clinical symptoms attributable to a central nervous system (CNS) demyelinating event within a follow‐up period of 96 weeks. Treatment with DMF resulted in over 80% risk reduction relative to placebo in the prevention of a first acute clinical event related to multiple sclerosis. A significant reduction in new and/or newly‐enlarging T2‐weighted hyperintense lesions was also observed.
Background
Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited ...data on the long‐term clinical outcomes of these patients. This study aimed to compare the long‐term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation.
Methods
A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow‐up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non‐rebound group. Clinical and demographic data and 5‐year clinical outcomes of both groups were prospectively examined.
Results
At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non‐rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5‐year follow‐up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non‐rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow‐up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non‐rebound group (52.4%, p = 0.05).
Conclusion
When rebound activity is well‐monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long‐term follow‐up.
Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical ...utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD).
Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1).
Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples.
The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.
Abstract
Objective
To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the ...management of BS.
Methods
A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included.
Results
We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A.
Conclusion
The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.
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