The early diagnosis and treatments in multiple sclerosis

So Young Huh

doi:10.7180/kmj.2017.32.2.151

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Huh: The early diagnosis and treatments in multiple sclerosis

Review Article

Kosin Medical Journal 2017;32(2):151-163.

Published online: 19 January 2017

DOI: https://doi.org/10.7180/kmj.2017.32.2.151

The early diagnosis and treatments in multiple sclerosis

So Young Huh

Department of Neurology, College of Medicine, Kosin University, Busan, Korea

Corresponding Author: So Young Huh, Department of Neurology, College of Medicine, Kosin University, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-6461 Fax: +82-51-990-3077 E-mail: caccu@naver.com

Received 6 April 201717 April 2017 Accepted 19 April 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system that leads to neurological disability. The diagnosis of MS relies on the MRI criteria, which can demonstrate dissemination in space and time. Exclusion of other demyelinating mimics is essential because there are no specific biomarker for MS and MRI criteria are still have imperfect. There is incremental improvements in MS treatment option that have contributed to the delay of disease progression. The early initiation of DMT may ameliorate the neurological disability. In this review, we discusses the new diagnostic MS criteria and summarize the evidences supporting the early treatment in the course of MS.

Keywords: Diagnosis, Multiple sclerosis

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Fig. 1.

Example of lesion for multiple sclerosis MRI Criteria of dissemination in space (A) periventricular lesions; (B) juxtacortical lesions; (C) infratentorial lesions; (D) spinal cord lesion; (E) optic nerve lesion. Gadolinium-enhancing lesion in T1 gadolinium weighted image; (F) are visible in the patient with MS.

Table 1.

CIS clinical features and likelihood of signaling an MS diagnosis⁴

CIS features typically seen in MS	Less common CIS features which may be seen in MS	Atypical CIS features not expected in MS
Optic nerve
Unilateral optic neuritis Pain on eye movement Partial and mainly central visual blurring Normal disc or mild disc swelling	Bilateral simultaneous optic neuritis No pain No light perception Moderate to severe disc swellingwithno hemorrhages Uveitis (mild, posterior)	Progressive optic neuropathy Severe, continuous orbital pain Persistent complete loss of vision Neuroretinitis (optic disc swelling with macular star) Uveitis (severe, anterior)
Brain stem/cerebellum
Bilateral internuclear ophthalmoplegia Ataxia and multidirectional nystagmus Sixth nerve palsy Facial numbness	Unilateral internuclear ophthalmoplegia, facial palsy, facial myokymia Deafness One-and-a-half syndrome Trigeminal neuralgia Paroxysmal tonic spasms	Complete external ophthalmoplegia; verticalgaze palsies Vascular territory syndrome, e.g., lateramedullary Third nerve palsy Progressive trigeminal sensory neuropathy Focal dystonia, torticollis
Spinal cord
Partial myelopathy Lhermitte’s symptom Deafferented hand Numbness Urinary urgency, incontinence, erectile dysfunction Progressive spastic paraplegia (asymmetrical)	Complete transverse myelitis Radiculopathy, areflexia Segmental loss of pain andtemperature sensation Partial Brown-Sequard syndrome (sparing posterior columns) Faecal incontinence Progressive spastic paraplegia (symmetrical)	Anterior spinal artery territory lesion (sparing posterior columns only) Cauda equina syndrome Sharp sensory level to all modalities andlocalized spinal pain Complete Brown-Sequard syndrome Acute urinary retention Progressive sensory ataxia (posterior columns)
Cerebral hemispheres
Mild subcortical cognitive impairment Hemiparesis	Epilepsy Hemianopia	Encephalopathy (obtundation, confusion, drowsiness) Cortical blindness

Table 2.

2010 McDonald criteria and 2016 MAGNIMS Diagnosis criteria⁸

	2010 McDonald criteria	2016 MAGNIMS criteria
Dissemination in space	≥2 of 4 characteristic location ≥1 periventricular lesion ≥1 juxtacortical lesion ≥1 asymptomatic brainstem lesion ≥1 asymptomatic spinal cord lesion	≥2 of 5 characteristic location ≥3 periventricular lesion ≥1 cortical/juxtacortical lesion ≥1 brainstem lesion ≥1 spinal cord lesion ≥1 optic nerve lesion *If a patient has a brainstem or spinal cord syndrome, or optic neuritis, the symptomatic lesion (or lesions) are not excluded from the criteria and contribute to the lesion count. †This combined terminology indicates the involve- ment of the white matter next to the cortex, the involvement of the cortex, or both, thereby expanding the term juxtacortical lesion.
Dissemination in time	- Simultaneous presence of asymptomatic Gd-en- hancing and non-enhancing lesion at any time - A new T2 and/or Gd-enhancing lesion on follow-up MRI irrespective of timing of baseline scan	- Simultaneous presence of asymptomatic Gd-en- hancing and non-enhancing lesion at any time - A new T2 and/or Gd-enhancing lesion on follow-up MRI irrespective of timing of baseline scan - Clinical symptoms should be associated with radiologically isolated syndrome

Table 3.

Clinical and MRI major red flags suggestive of alternative diagnosis to multiple sclerosis⁴

Red flag	Type	Examples of alternative diagnosis
Bone lesions	Clinical	Histiocytosis; Erdheim Chester disease
Lung involvement	Clinical	Sarcoidosis; Lymphomatoid granulomatosis
Multiple cranial neuropathies or pol-yradiculopathy	Clinical	Chronic meningitis, including sarcoidosis and tuberculosis; Lyme disease
Peripheral neuropathy	Clinical	B12 deficiency; adrenoleukodystrophy; metachromatic leukodystrophy, Lyme disease
Tendon xanthomas	Clinical	Cerebrotendinous xanthomatosis
Cerebral venous sinus thrombosis	MRI	Behçet’s disease; vasculitis; chronic meningitis, antiphospholipid or anticardiolipin antibody syndromes
Cardiac disease	Clinical	Multiple cerebral infarcts; brain abscesses with endocarditis or right to left cardiac shunting
Myopathy	Clinical	Mitochondrial encephalomyopathy (e.g.,MELAS); Sjögren’s syndrome
Cortical infarcts	MRI	Embolic disease; thrombotic thrombocytopenic purpura; vasculitis
Hemorrhages/ microhemorrhages	MRI	Amyloid angiopathy; Moya Moya disease; CADASIL; vasculitis
Meningeal enhancemen	MRI	Chronic meningitis; sarcoidosis; lymphomatosis; CNS vasculitis
Extrapyramidal features	Clinical	Whipple’s disease; multisystem atrophy; Wilson’s disease
Livedo reticularis	Clinical	Antiphospholipid antibody syndrome; systemic lupus erythematosus; Sneddon’s syndrome
Retinopathy	Clinical	Mitochondrial encephalomyopathy; Susac, and other vasculitides (retinal infarction); neuronal ceroid lipofuscinosis
Calcifications on CT scans	MRI	Cysticercosis; toxoplasmosis, mitochondrial disorders
Diabetes insipidus	Clinical	Sarcoidosis; histiocytosis
Increase serum lactate level	Clinical	Mitochondrial disease
Selective involvement of the anterior temporal and inferior frontal lobe	MRI	CADASIL
Hematological manifestations	Clinical	Thrombotic thrombocytopenic purpura; vitamin B12 deficiency; Wilson’s disease (hemolytic anemia); copper deficiency
Lacunar infarcts	MRI	Hypertensive ischemic disease; CADASIL; Susac syndrome
Persistent Gd-enhancement and continued enlargement of lesions	MRI	Lymphoma; glioma; vasculitis; sarcoidosis
Mucosal ulcers	Clinical	Behçet’s disease
Myorhythmia	Clinical	Whipple’s disease
Hypothalamic disturbance	Clinical	Sarcoidosis; neuromyelitis optica; histiocytosis
Recurrent spontaneous abortion or thrombotic events	Clinical	Antiphospholipid antibody syndrome; thrombotic thrombocytopenic purpura; metastatic cancer with hypercoagulable state
Simultaneous enhancement of all lesions	MRI	Vasculitis; lymphoma; sarcoidosis
Rash	Clinical	Systemic lupus erythematosus; T-cell lymphoma; Lyme disease, Fabry disease
T2-hyperintensity in the dentate nuclei	MRI	Cerebrotendinous xanthomatosis
Arthritis, polyarthalgias, myalgias	Clinical	Systemic lupus erythematosus; Lyme disease; fibromyalgia
Amyotrophy	Clinical	Amyotrophic lateral sclerosis; syringomyelia; polyradiculpathy
Headache or meningismus	Clinical	Venous sinus thrombosis; chronic meningitis; lymphoma or glioma, vasculitis, systemic lupus erythematosus
T1-hyperintensity of the pulvinar	MRI	Fabry disease; hepatic encephalopathy; manganese toxicity
Persistently monofocal manifestations	Clinical	Structural lesion (e.g., Chiari malformation); cerebal neoplasm
Large and infiltrating brainstem lesions	MRI	Behçet’s disease; pontine glioma
Predominance of lesions at the cortical/subcortical junction	MRI	Embolic infarction; vasculitis; progressive multifocal leukoencephalopathy

CADASIL; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, MELAS; mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes syndrome

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