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Early and accurate diagnosis of Multiple Sclerosis crucial for prompt initiation of treatment

By December 9, 2016 No Comments

While acknowledging the important advances in the diagnosis of MS, some questions still remain in the application of new diagnostic criteria in daily clinical practice, and it is important to emphasize that there is no single “fail-safe” diagnostic test

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) of presumed autoimmune aetiology characterised by localised areas of inflammation, demyelination, axonal loss and gliosis in the brain and spinal cord.
The clinical presentation and course of the disease are highly variable, but several disease types can be recognised, including relapsing-remitting, primary progressive, secondary progressive, progressive- relapsing and clinically isolated syndrome.
There is currently no single diagnostic test.
The central requirements for diagnosis of MS are dissemination in space (DIS) and dissemination in time (DIT) of lesions in the CNS, with the caveat that there should be no alternative diagnosis that better explains the clinical presentation.
The gold standard diagnosis has been the purely clinical one, with two separate attacks of symptoms (fulfilling DIT criteria) involving at least two different areas of the CNS (fulfilling DIS criteria).
In recent years, diagnostic criteria have undergone regular revisions aimed at improving disease definitions and diagnostic thresholds to facilitate and speed up the diagnostic process. A quicker and more accurate diagnosis is particularly important to enable prompt initiation of disease-modifying treatments.
In 2001, the International Panel on MS Diagnosis, chaired by Ian McDonald, developed new criteria for diagnosing MS, now known as the “McDonald criteria”. The number of diagnoses were reduced to three: “MS”, “possible MS” and “not MS”.
Further modifications of the McDonald criteria (2005, 2010) were proposed by the expert panel to facilitate the diagnostic process. The 2001 McDonald diagnostic criteria and their 2005 revision incorporated magnetic resonance imaging (MRI) criteria for DIS and DIT that provided guidance on how to diagnose MS after presentation with a clinically isolated syndrome (See Table).
MRI plays a central role in the diagnosis and management of MS providing mechanistic insights into the clinical efficacy of disease-modifying therapies. MRI allows visualisation of active inflammatory brain white matter lesions and enables indirect detection of tissue damage and diffuse degenerative processes that contribute to progressive brain atrophy.
The most recent 2010 McDonald criteria simplify requirements for DIS and DIT and may allow for an earlier diagnosis of MS from a single baseline MRI if there are both clinically silent gadolinium enhancing and non-enhancing lesions.
The expert panel have stressed that the McDonald criteria should serve as an aid and not the basis for the diagnostic process. The criteria were developed for a Western adult population whose clinical features are typical for demyelinating disease – symptoms lasting >24 hours suggesting structural damage to cerebral hemispheres, brainstem, cerebellum or spinal cord. Patients with atypical symptoms such as cognitive impairment, encephalopathy, seizures, pain, psychosis should not be assessed by these criteria. In such patients, a search for other diseases should be pursued.
There are a number of different diseases that can mimic a clinical presentation of MS and result in lesions on MRI that appear similar to MS lesions. Among these are other demyelinating conditions of the CNS such as neuromyelitis optica and acute disseminated encephalomyelitis while systemic inflammatory or infectious conditions with CNS involvement may also need to be excluded.
While acknowledging the important advances in the diagnosis of MS, some questions still remain in the application of new diagnostic criteria in daily clinical practice, and it is important to emphasise that there is no single “fail-safe” diagnostic test. Thorough clinical evaluation and judgment along with careful consideration of differential diagnosis still remain crucial in the diagnosis of MS.

Milo R and Miller A. Revised diagnostic criteria for multiple sclerosis. Autoimmune Review 2014;13 (4-5):518-24.
Gomez-Moreno M et al. Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis. Multiple Sclerosis 2012;18(1):39-44.
Selchen D et al. MS, MRI and the 2010 McDonald criteria: a Canadian expert commentary. Neurology 2012;79 (23 suppl 2):S1-15.

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