Summary

Multiple Sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the Central Nervous System (CNS) characterised by Dissemination in Space and Time – multiple lesions affecting different areas of the brain and spinal cord at different times. MS primarily affects young adults (Peak onset 20-40 years) with a 2:1 female predominance. The aetiology involves a complex interplay of genetic susceptibility and environmental factors (Vitamin D deficiency, EBV infection, Smoking) leading to autoimmune-mediated demyelination and axonal damage. Clinical presentations are highly variable and include Optic Neuritis, Sensory Symptoms, Motor Weakness, Ataxia, Bladder Dysfunction, and Cognitive Impairment. MS is classified into subtypes: Relapsing-Remitting MS (RRMS) (~85% at onset), Secondary Progressive MS (SPMS), and Primary Progressive MS (PPMS) (~10-15%). Diagnosis is based on McDonald Criteria 2017 (Clinical + MRI + CSF). Disease-Modifying Therapies (DMTs) reduce relapse frequency and slow disability progression in RRMS/Active SPMS. Symptomatic management addresses specific deficits. [1,2,3]

Clinical Pearls

"Dissemination in Space and Time": The hallmark of MS. Lesions in multiple CNS locations at different points in time.

"Young Adult, Female, Neuro Symptoms That Come and Go": Classic demographic and pattern for RRMS.

"Optic Neuritis = Think MS": Often the first presentation. Painful vision loss in one eye.

"MRI is Key": Periventricular, Juxtacortical, Infratentorial, Spinal cord lesions. Dawson's fingers.

MS Subtypes

Definitions

"Escalation vs Induction." The landscape of MS treatment has exploded. There are two philosophies:

1. Escalation Therapy: Start safe/mild, step up if breakthroughs occur.
   • Examples: Interferons, Glatiramer, Teriflunomide.
   • Pros: Safety. Long-term data.
   • Cons: Brain atrophy continues. Time lost is brain lost.
2. Induction Therapy (Flipping the Pyramid): Hit hard and early with high-efficacy drugs.
   • Examples: Alemtuzumab (Lemtrada), Cladribine (Mavenclad), HSCT (Stem Cell).
   • Pros: Can induce "NEDA" (No Evidence of Disease Activity) for years drug-free.
   • Cons: High risk of autoimmune side effects (Thyroid, ITP) or Infection.
   • Ocrelizumab/Ofatumumab (Anti-CD20): Highly effective, safe, becoming first-line.

"The Intrathecal Pump." When oral Baclofen causes sedation but spasticity remains severe.

• The Problem: Oral Baclofen crosses the BBB poorly. You need massive doses (sedation) to get a tiny amount to the spinal cord.
• The Solution: Intrathecal Baclofen (ITB) Pump.
  • Procedure: Pump implanted in abdominal wall. Catheter tunneled to intrathecal space (spine).
  • Dose: Micrograms, not Milligrams (1/1000th the oral dose).
  • Effect: Powerful muscle relaxation without cognitive side effects.
  • Risk: Catheter kink/pump failure -> Baclofen Withdrawal (Life threatening emergency: Seizures, Hyperthermia, Rhabdomyolysis).

Differentiation in Space (DIS):

• $\geq$ 1 lesion in $\geq$ 2 of 4 MS-characteristic areas:
  1. Periventricular.
  2. Cortical or Juxtacortical.
  3. Infratentorial (Brainstem/Cerebellum).
  4. Spinal Cord.

Differentiation in Time (DIT):

• Use of Gadolinium (Enhancing + Non-enhancing lesions simultaneously).
• OR new lesion on follow-up MRI.
• OR Oligoclonal Bands in CSF (New in 2017: OCBs can substitute for DIT!).

" The One-Off?"

• 25-year-old female. Optic Neuritis right eye.
• MRI Brain: 2 periventricular lesions (Demyelination).
• Is it MS?
• Not yet (No Dissemination in Time). Diagnosis: CIS.
• Risk: 80% chance of converting to MS within 20 years.
• Action: Start DMTs now? (Yes, evidence supports early treatment to delay onset of CDMS - Clinically Definite MS).

Keeping them safe on DMTs.

1. Natalizumab (Tysabri): PML Risk

• PML (Progressive Multifocal Leukoencephalopathy): Fatal brain infection by JC Virus.
• Risk Factors:
  1. JCV Antibody Positive.
  2. Prior Immunosuppression.
  3. Treatment Duration > 2 years.
• Monitoring: JCV Titer every 6 months. MRI every 3-6 months.

2. Alemtuzumab (Lemtrada): The "Monthly Bloods"

• Risk: Autoimmune Thyroid Disease (40%), ITP (3%), Goodpasture's (Rare).
• Monitoring: FBC, U&E, LFT, TFTs monthly for 4 years after LAST dose.

3. Fingolimod (Gilenya): Cardiac First Dose

• Risk: Bradycardia / AV Block. Macular Edema.
• Monitoring: First dose observation (6 hours) with ECGs. OCT scan for eyes at baseline and 4 months.

Beyond being in a wheelchair.

• Bladder:
  • Failure to Store (Urgency): Anticholinergics (Solifenacin).
  • Failure to Empty (Retention): Intermittent Self Catheterisation (ISC). Ideally avoid indwelling catheters.
• Bowel: Constipation is universal. Movicol/Laxido.
• Sexual Dysfunction:
  • Men: Phosphodiesterase inhibitors (Sildenafil).
  • Women: Lubricants, vibratory stimulation (for sensory loss).
• Fatigue: Energy conservation (Pacing). Cooling vests (Uhthoff's). Amantadine (Off-label).

Key Guidelines

Key Trials

What is Multiple Sclerosis?

MS is a condition where the immune system mistakenly attacks the protective covering (Myelin) of nerves in the brain and spinal cord. This causes scars (Sclerosis) that disrupt nerve signals.

What are the symptoms?

Symptoms vary widely depending on which nerves are affected:

• Vision problems (Blurry, Painful).
• Numbness or tingling.
• Weakness in arms or legs.
• Balance problems.
• Bladder issues.
• Fatigue.
• Difficulty thinking clearly.

Symptoms often come and go in "Relapses".

What causes MS?

The exact cause is unknown. It involves:

• Immune system attacking the brain/Spinal cord.
• Genetics play a role.
• Environment: Low vitamin D, Prior EBV infection, Smoking.

How is it treated?

• Relapses: High-dose steroids speed recovery.
• Disease-Modifying Drugs (DMDs): Reduce the number of relapses and slow progression.
• Symptom Management: Medications and therapies for specific symptoms (Spasticity, Pain, Bladder, Fatigue).
• Rehabilitation: Physiotherapy, OT, Support services.

What is the outlook?

MS is a lifelong condition. With modern treatments, Many people live active lives for many years. Early treatment is important. Some people experience significant disability over time.

Common Exam Questions

1. McDonald Criteria: "What is required for Dissemination in Space?"
   • Answer: ≥1 T2 lesion in ≥2 of 4 locations: Periventricular, Juxtacortical/Cortical, Infratentorial, Spinal cord.
2. Classic Sign: "What is Lhermitte's sign?"
   • Answer: Electric shock sensation down the spine on neck flexion. Indicates cervical cord demyelination.
3. CSF Finding: "What is the characteristic CSF finding in MS?"
   • Answer: Oligoclonal Bands (Present in CSF, Absent in serum).
4. DMT for PPMS: "Which DMT is licensed for PPMS?"
   • Answer: Ocrelizumab (Ocrevus).

Viva Points

• Dawson's Fingers: Periventricular lesions perpendicular to ventricles.
• INO (Bilateral): Highly suggestive of MS in young adult.
• Uhthoff's Phenomenon: Symptoms worsen with heat.
• RRMS → SPMS: Most RRMS patients transition over 15-20 years.
• High-Efficacy Early: Trend towards earlier use of high-efficacy DMTs.

Common Exam Questions

1. MRCP / PLAB:

• Q: A 32-year-old woman with MS presents with internuclear ophthalmoplegia (INO). Where is the lesion?
• A: Medial Longitudinal Fasciculus (MLF). If the Right eye cannot adduct (look left), the lesion is in the Right MLF.

2. Neurology Rotation:

• Q: A patient on Natalizumab develops confusion, hemiparesis, and visual field defects. MRI shows non-enhancing white matter lesions. CSF PCR is positive for JC Virus. Diagnosis?
• A: Progressive Multifocal Leukoencephalopathy (PML). Stop drug immediately. Consider Plasma Exchange.

3. General Practice:

• Q: A patient with MS complains of electric shock sensations down her back when she bends her neck forward to read. What is this sign?
• A: Lhermitte's Sign. Indicates cervical cord demyelination.

Viva Points

• "Space and Time": The mantra of diagnosis. Never diagnose MS on a single scan without clinical or radiological evidence of lesions occurring at different times (or OCBs).
• "The Pseudo-Relapse": Worsening of old symptoms due to infection/fever (Uhthoff's). Not a new relapse. Treat the UTI, don't give steroids.
• "Clinically Isolated Syndrome (CIS)": The first attack. High risk of converting to MS if MRI is abnormal (80%). Low risk if MRI normal (<20%).

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.