What is the diagnostic workup and treatment for a young to middle-aged adult presenting with relapsing-remitting neurological symptoms suggestive of multiple sclerosis?

Multiple Sclerosis: Symptoms and Diagnostic Workup

Clinical Presentation

MS typically presents in young adults aged 20-30 years with acute neurological symptoms developing over several days, most commonly affecting the optic nerve, spinal cord, brainstem, or causing sensory disturbances. 1

Common Presenting Symptoms

• Optic neuritis: Unilateral vision loss with pain on eye movement 1, 2
• Partial myelitis: Motor weakness, sensory level, bowel/bladder dysfunction 1
• Brainstem syndromes: Internuclear ophthalmoplegia, diplopia, vertigo 1, 2
• Sensory disturbances: Numbness, paresthesias in limbs or trunk 3, 4
• Lhermitte sign: Electric shock sensation down spine with neck flexion 4
• Motor symptoms: Weakness, spasticity, impaired gait, incoordination 3, 4

Temporal Pattern Recognition

The time course is characteristic and diagnostically important: symptoms worsen over days, plateau for 1-2 weeks at nadir, then improve over weeks with potentially incomplete recovery 3. This pattern distinguishes inflammatory demyelination from other etiologies.

Diagnostic Workup Algorithm

Step 1: Clinical Assessment

Obtain detailed history specifically asking about prior episodes of neurological symptoms that may have resolved spontaneously, as patients often fail to report transient past events. 3 Perform comprehensive neurological examination looking for objective clinical signs—symptoms alone are insufficient for diagnosis 5.

Step 2: MRI Imaging (Primary Diagnostic Tool)

Brain and spinal cord MRI with gadolinium is the most sensitive and specific paraclinical examination and must be performed using high-quality, state-of-the-art technology. 6, 5

Required MRI sequences include: 5

• T1-weighted pre- and post-gadolinium
• T2-weighted
• FLAIR (fluid-attenuated inversion recovery)
• Diffusion-weighted imaging (DWI)

Look for lesions in characteristic locations: 5

• Periventricular (adjacent to lateral ventricles)
• Juxtacortical (involving U-fibers)
• Infratentorial (brainstem, cerebellum)
• Spinal cord

Step 3: Cerebrospinal Fluid Analysis

CSF analysis showing oligoclonal bands is particularly useful when imaging is atypical or insufficient, and is essential for diagnosing primary progressive MS. 6, 5 CSF should demonstrate evidence of inflammation and immune abnormality, including elevated IgG index or oligoclonal bands not present in serum 5.

Step 4: Visual Evoked Potentials

Visual evoked potentials provide additional diagnostic support, especially in cases with few MRI abnormalities or when documenting dissemination in space 6.

Applying Diagnostic Criteria Based on Clinical Presentation

Two or More Attacks with Objective Clinical Evidence of Two Lesions

Diagnosis: MS - No additional testing required if clinical presentation is typical 5

Two or More Attacks with Objective Evidence of One Lesion

Must demonstrate dissemination in space using: 5

• MRI showing multiple lesions in characteristic locations, OR
• At least two brain lesions or one brain plus one spinal cord lesion consistent with MS, coupled with abnormal CSF analysis 5

One Attack with Objective Evidence of Two or More Lesions

Must demonstrate dissemination in time: 5

• MRI showing new lesion at least 3 months after clinical event (this 3-month interval reduces risk of misdiagnosing acute disseminated encephalomyelitis), OR
• Occurrence of second clinical attack 5

One Attack with Objective Evidence of One Lesion (Clinically Isolated Syndrome)

Requires demonstration of both dissemination in space AND time: 5

• Space: MRI lesions in characteristic locations OR at least two brain lesions plus positive CSF
• Time: New MRI lesion ≥3 months after clinical event OR second clinical attack affecting different site 5

Insidious Progressive Neurological Deterioration Without Relapses

For primary progressive MS diagnosis, the following are essential: 5

• Abnormal CSF with evidence of inflammation and immune abnormality (mandatory)
• Dissemination in space (MRI or abnormal VEP)
• Dissemination in time (MRI or continued progression for 1 year)

This presentation is diagnostically challenging with less published follow-up data, requiring stringent criteria 5.

Critical Diagnostic Pitfalls and Red Flags

Mandatory Exclusion Principle

Even if clinical and paraclinical evidence strongly suggests MS, there must be no better explanation for the abnormalities than MS for a secure diagnosis. 5 This is non-negotiable.

Conditions Requiring Careful Exclusion

Before diagnosing MS, actively exclude: 5

• Vascular disorders: Phospholipid antibody syndrome, lupus, CADASIL, cerebral vasculitis 5
• Infections: HTLV-1, Lyme disease, neurosyphilis 5
• Other demyelinating diseases: Neuromyelitis optica spectrum disorders (check serum anti-AQP4 antibodies), MOG antibody disease, acute disseminated encephalomyelitis 5
• Monophasic syndromes: Do not diagnose MS unless new symptoms/signs or imaging abnormalities appear >3 months after clinical onset 5

Atypical Presentations Requiring Extra Caution

Exercise extreme caution and obtain additional CSF and VEP testing when patients present with: 5

• Age <10 or >59 years at presentation
• Progressive onset without clear relapses
• Unusual features: dementia, epilepsy, aphasia
• Symptoms not typical for MS

MRI Quality Considerations

Accurate diagnosis requires highest quality imaging with proper repositioning and coregistration of scans to determine if lesions are truly new. 5 When quality cannot be assured, extreme care must be taken using results as diagnostic evidence 5.

Disease Course Classification

• Relapsing-remitting MS (RRMS): Most common form with relapses at onset and stable disability between episodes 1
• Secondary progressive MS: Steadily increasing disability following initial relapsing course, may occur after several years 3, 1
• Primary progressive MS: 10-15% of cases with slow deterioration from onset without relapses 3, 7
• Clinically isolated syndrome: First attack meeting criteria for possible MS but not yet fulfilling full diagnostic criteria 2, 4

Prognostic Indicators

Favorable prognostic factors include: 3

• Female sex
• Onset with optic neuritis or sensory symptoms (rather than weakness or ataxia)
• Long interval between initial relapses