New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

/pdf/diagnostic-criteria-for-multiple-sclerosis-2010-revisions-to-24iph50480.pdf

Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

https://www.onlinelibrary.wiley.com/doi/epdf/10.1002/ana.1032

Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1002/ana.20703

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".

The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase I11 trial of interferon beta-la. Interferon beta-la, 6.0 million units (30 μg), was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-la treatment produced a significant delay in time to sustained EDSS progression (p equals; 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-la-treated group. Patients treated with interferon beta-la also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (pvalues ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-la-treated patients. There were no major adverse events related to treatment. Interferon beta- la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the hndamen- tal course of relapsing multiple sclerosis.

Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis

Summary Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.

/pdf/a-clinical-approach-to-diagnosis-of-autoimmune-encephalitis-13ityv7sgw.pdf

A clinical approach to diagnosis of autoimmune encephalitis

From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected.

/pdf/breakdown-of-the-blood-brain-barrier-precedes-symptoms-and-pzxzu29ygr.pdf

Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis : pathogenetic and clinical implications

In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated. In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI over a 6-month period. The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced. Enhancement also occurred within and at the edge of preexisting lesions. In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced. There was no difference in the degree of clinical deterioration between the two groups over the 6-month period. These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.

Major differences in the dynamics of primary and secondary progressive multiple sclerosis.

A definitive diagnosis of multiple sclerosis cannot be made at presentation on patients with a clinically isolated syndrome of the optic nerve, spinal cord or brainstem suggestive of demyelination, as dissemination in time is not established. To determine the long-term risk of abnormalities on brain MRI for the development of multiple sclerosis and disability we performed a 10-year follow-up on 81 such patients who had T2-weighted brain MRI at presentation. Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an abnormal MRI revealed progression to clinically definite multiple sclerosis in 45 out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13 (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS < or = 3) disease. For those with a normal MRI progression to clinically definite multiple sclerosis occurred in only three out of 27 (11%), all benign. There was a significant relationship between the number of lesions at presentation and both EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001). Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.

/pdf/the-prognostic-value-of-brain-mri-in-clinically-isolated-16ooatok1x.pdf

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.

Brain MRI was performed on 12 patients with acute disseminated encephalomyelitis (ADEM). Multifocal white matter lesions indistinguishable from those seen in multiple sclerosis (MS) were found in 10. In 5 there were rather extensive symmetric abnormalities in the cerebral (2) or cerebellar white matter (2), or basal ganglia (1). Follow-up MRI after intervals of 2 wks to 18 months demonstrated partial resolution of the abnormalities, but some persisting lesions. New MRI lesions were found at follow-up in only 1 case after an interval of 2 wks. Serial MRI makes a useful contribution to the distinction between MS and ADEM.

Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis.

A 5-year follow-up study was performed on 89 patients who had undergone brain magnetic resonance imaging (MRI) at presentation with an acute clinically isolated syndrome of the optic nerves, brainstem or spinal cord of a type suggestive of multiple sclerosis. At presentation, MRI was abnormal, revealing one or more asymptomatic cerebral white matter lesions in 57 (64%), and was normal in 32 (36%). At follow-up, progression to clinically definite multiple sclerosis had occurred in 37 out of 57 (65%) with an abnormal MRI and one out of 32 (3%) with normal MRI. Human leucocyte antigen (HLA) typing was performed in 70 patients and cerebrospinal fluid (CSF) was examined at presentation in 36. The presence of HLA-DR2 antigen or cerebrospinal fluid oligoclonal IgG bands were both associated with a significantly increased risk of progression to multiple sclerosis, but MRI was much more powerful in predicting outcome. The presence of four or more MRI lesions at presentation was associated with a higher rate of progression to multiple sclerosis, more frequent development of moderate or severe disabilities and a greater number of new MRI lesions at follow-up. The results indicate that brain MRI at presentation with a clinically isolated syndrome suggestive of multiple sclerosis is a powerful predictor of the clinical course over the next 5 years. This observation, combined with an ability to detect other sometimes treatable disorders which can also cause such syndromes, suggests that MRI is the investigation of choice in evaluating this group of patients.

The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis: A 5-year follow-up study

Brian Kendall

Papers

Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis : pathogenetic and clinical implications

Major differences in the dynamics of primary and secondary progressive multiple sclerosis.

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.

Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis.

The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis: A 5-year follow-up study