What are the clinical features and management options for multiple sclerosis?

Clinical Features of Multiple Sclerosis

Disease Subtypes and Natural History

Relapsing-Remitting MS (RRMS) is the predominant initial presentation, affecting approximately 85% of patients at onset, characterized by acute inflammatory episodes with symptom development over hours to days, followed by periods of remission where nerve conduction improves but cumulative myelin damage and progressive neuronal loss occur over time 1.

Primary Progressive MS (PPMS) affects approximately 15% of patients, presenting with steadily increasing neurological disability from onset without distinct relapses or remissions, often manifesting as progressive myelopathy 1, 2.

Typical Clinical Presentations

Common Neurological Symptoms

The characteristic clinical features include 1, 2:

• Optic neuritis - typically unilateral vision loss with characteristic pain on eye movement, developing over several days 1, 3, 4
• Sensory disturbances - numbness, tingling, or paresthesias 1, 3, 5
• Motor symptoms - weakness, often asymmetric or affecting one side of the body 1, 3
• Diplopia and internuclear ophthalmoplegia - failure of ipsilateral eye adduction with contralateral eye abduction nystagmus due to medial longitudinal fasciculus lesions 1, 4
• Myelopathy - partial transverse myelitis with motor, sensory, and bladder dysfunction 1, 3
• Balance and gait dysfunction - incoordination, imbalance, and ataxia 1, 5

Temporal Pattern of Symptoms

True MS relapses are characterized by 1, 2:

• New or worsening neurological symptoms lasting at least 24 hours 1, 2
• Symptoms develop over hours to days, typically stabilize, and often resolve spontaneously 1, 2
• New inflammatory demyelinating activity, often showing new or enhancing lesions on MRI 2

Red Flags Suggesting Alternative Diagnoses

Atypical features that should prompt additional investigation and consideration of alternative diagnoses include 1, 6:

• Subacute onset over weeks with progressive evolution without stabilization 1
• Dementia, epilepsy, or aphasia as presenting features 1, 6
• Bilateral sudden hearing loss 1, 6
• Sudden onset of focal neurologic symptoms such as headache, confusion, or focal weakness suggesting stroke 6

Progressive Multifocal Leukoencephalopathy (PML) Distinction

PML presents distinctly from MS with 1:

• Aphasia, behavioral/neuropsychological changes 1
• Retrochiasmal visual deficits 1
• Hemiparesis and seizures 1
• Progressive course over weeks without stabilization 1

MRI Characteristics

Classic MS Lesion Features ("Green Flags")

Typical MS lesions demonstrate focal, periventricular location with sharp edges, ovoid or flame-shaped morphology, and orientation perpendicular to the ventricles (Dawson's fingers) 7, 1.

Additional characteristic features include 7, 1:

• Lesions in corpus callosum and spinal cord 1
• Three or more periventricular lesions required to demonstrate dissemination in space 1
• Additional diagnostic locations: juxtacortical, infratentorial, and spinal cord regions 1
• T2-weighted hyperintensities and gadolinium-enhancing lesions on T1-weighted sequences 6, 3

Emerging MRI Features

Advanced imaging features that may improve diagnostic specificity include 7:

• Central vein sign - lesions centered around small veins 7
• Subpial demyelination 7
• Lesion rims indicating chronic active inflammation 7

MRI Red Flags

Atypical MRI patterns suggesting alternative diagnoses include 7:

• Ischemic lesion patterns 7
• Peculiar patterns of contrast enhancement 7
• Age-related periventricular capping on T2-weighted images 7
• Distinctive features of neuromyelitis optica spectrum disorders (NMOSD) or anti-MOG-IgG disease 7

Age-Specific Considerations

Typical Diagnostic Age Range

The McDonald criteria apply best to individuals between 10-59 years of age, with mean age of onset between 20-30 years 7, 1, 6, 3.

Pediatric Considerations

In children under 11 years, special diagnostic care is needed 7, 6:

• Presence of at least one black hole (hypointense lesion on T1-weighted MRI) 7, 6
• At least one periventricular lesion at baseline helps distinguish MS from monophasic demyelination 7, 6

Older Adults

In patients older than 50 years or with vascular risk factors, more stringent criteria should be applied, requiring a higher number of periventricular lesions abutting the lateral ventricles 7, 6.

Diagnostic Essentials

Core Requirements

Diagnosis requires evidence of CNS lesions disseminated in both time and space, at least one clinical event consistent with acute demyelination, and exclusion of alternative diagnoses 1, 2, 6, 3, 5.

The clinical syndrome should be typical of demyelination, with symptoms developing over hours to days 7.

Supportive Paraclinical Findings

Additional diagnostic support includes 1, 6:

• Oligoclonal bands specific to CSF (not present in serum) 1, 6, 3
• Visual evoked potentials showing delayed conduction 1

Critical Differential Diagnoses

Key conditions requiring exclusion include 1, 6:

• Neuromyelitis optica spectrum disorder (NMOSD) - more severe visual loss with preferential altitudinal field loss, chiasmal and tract lesions 1, 6, 4
• Cerebrovascular disease - multifocal areas of cerebral ischemia or infarction 1, 6
• Infectious diseases - HTLV1, Lyme disease 1, 6
• Paraneoplastic disorders 1, 6
• Monophasic demyelinating diseases - acute disseminated encephalomyelitis (ADEM) 1, 6
• Chronic relapsing inflammatory optic neuropathy (CRION) 4
• Leber's hereditary optic neuropathy - painless, subacute bilateral optic nerve involvement in young males 4

Technical MRI Requirements

MRI studies should be of adequate quality with minimum field strength of 1.5 T, using 3D acquisitions or 2D with 3-mm thick slices and no gap between slices 7.

Key MRI sequences include 7:

• T2-weighted imaging of brain and spinal cord 7
• T1 post-gadolinium imaging of brain and spinal cord 7
• Fat-suppressed MRI of optic nerves in atypical cases 7
• Cervical, thoracic, and lumbar spine imaging as MS lesions can occur anywhere in the CNS 7

Diagnostic Pitfalls

Common pitfalls to avoid 7, 6:

• Do not diagnose MS solely on MRI findings - at least one clinical event consistent with acute demyelination remains the cornerstone 6
• Diagnosis should be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments 6
• Application of diagnostic criteria in atypical clinical presentations increases misdiagnosis risk 7
• In patients with small numbers of lesions or comorbidities (migraine, cerebrovascular disease), careful lesion characterization is crucial 7