Diagnosis and Treatment of Multiple Sclerosis
Diagnostic Approach
MS diagnosis requires objective demonstration of CNS lesions disseminated in both time and space, integrating MRI with clinical findings and excluding alternative diagnoses. 1, 2
Core Diagnostic Requirements
- At least one clinical event consistent with acute demyelination is essential—diagnosis cannot be made on MRI alone 2
- Diagnosis applies best to individuals aged 10-59 years with typical presentations 2
- Must be made by a specialist familiar with MS, its differential diagnoses, and interpretation of paraclinical assessments 2
Clinical Presentations to Recognize
Relapsing-Remitting MS (85% of cases at onset):
- Acute neurological symptoms developing over hours to days 3, 4
- Common presentations include unilateral optic neuritis, partial myelitis, sensory disturbances, diplopia, internuclear ophthalmoplegia, and balance/gait dysfunction 4, 5
- Episodes typically stabilize and resolve spontaneously 3
- True relapses last at least 24 hours with new inflammatory demyelinating activity 3
Primary Progressive MS (15% of cases):
- Steadily increasing neurological disability from onset without distinct relapses 3, 4
- Often presents as progressive myelopathy 3
MRI Characteristics (Preferred Imaging Modality)
Classic MS lesion features: 4
- Focal T2 hyperintense lesions with sharp edges
- Ovoid/flame-shaped orientation perpendicular to ventricles
- Periventricular location (≥3 lesions required for dissemination in space) 4
- Additional diagnostic locations: juxtacortical, infratentorial, corpus callosum, and spinal cord 4
- Gadolinium-enhancing lesions indicate active inflammation 2
Supportive Laboratory Findings
- Oligoclonal bands specific to CSF (not present in serum) support diagnosis 3, 4
- Visual evoked potentials may show delayed conduction 4
Critical Red Flags Requiring Alternative Workup
These features suggest diagnoses other than MS: 2, 4
- Bilateral sudden hearing loss 2
- Sudden onset focal symptoms (headache, confusion) suggesting stroke 2
- Subacute onset over weeks with progressive evolution without stabilization 4
- Dementia, epilepsy, or aphasia as presenting features 2, 4
Key differential diagnoses to exclude: 2, 4
- Neuromyelitis optica spectrum disorder (NMOSD)—must be distinguished from MS 2
- Cerebrovascular disease (multifocal ischemia/infarction in young adults) 2
- Infectious diseases (HTLV1, Lyme disease) 2
- Paraneoplastic disorders 2
- Monophasic demyelinating diseases 2
Age-Specific Diagnostic Modifications
- Pediatric cases (under age 11): Require at least one black hole (T1 hypointense lesion) and one periventricular lesion to distinguish MS from monophasic demyelination 2
- Patients >50 years or with vascular risk factors: Apply more stringent criteria with higher number of periventricular lesions required 2
Treatment Approach
Disease-Modifying Therapies for Relapsing Forms
Nine classes of DMTs are FDA-approved for relapsing-remitting MS, clinically isolated syndrome, and active secondary progressive MS: 6, 7, 6, 5
Available DMT classes with efficacy rates (29-68% reduction in annualized relapse rates): 5
- Interferons (interferon beta-1a IM, interferon beta-1b SQ) 6, 7, 6
- Glatiramer acetate 5
- Teriflunomide 5
- Sphingosine 1-phosphate receptor modulators 5
- Fumarates 5
- Cladribine 5
- Three types of monoclonal antibodies 5
Common adverse effects to monitor: 5
- Infections
- Bradycardia and heart blocks
- Macular edema
- Infusion and injection-site reactions
- Secondary autoimmune effects (particularly autoimmune thyroid disease)
Primary Progressive MS Treatment
Ocrelizumab is the only FDA-approved DMT for primary progressive MS 8, 5
Acute Relapse Management
Treatment of acute relapses should be initiated promptly when new inflammatory demyelinating activity is confirmed 9
Symptom Management (Critical for Quality of Life)
A multimodal approach is essential since there is no cure: 10
Common symptoms requiring management: 10
- Spasticity
- Fatigue
- Sexual dysfunction
- Bladder dysfunction
- Pain
- Cognitive dysfunction
- Depression
- Bowel dysfunction
Management strategies include: 10
- Effective communication and patient education
- Physical modalities and activities
- Occupational and other therapies
- Pharmacologic interventions individualized to each patient
- Early symptom control to prevent symptom cycles from developing
Monitoring Strategy
Regular MRI monitoring is recommended to assess disease activity and treatment response, evaluating for new T2 lesions and gadolinium-enhancing lesions 2, 5
Rehabilitation plays a crucial role in maintaining function through physical therapy, occupational therapy, and cognitive rehabilitation 2