Multiple Sclerosis

Question 1

What is MS?

Answer 1

Chronic Autoimmune T-cell mediated Inflammatory Disorder; Multiple Plaques of
Demyelination occurs throughout Brain and Spinal Cord (Space) and sporadically over the
years (Time); Major cause of Disability in young adults

Question 2

Who does MS affect?

Answer 2

Most common Neurological Disorder in the UK (1.2 per 1000); >2F:M
o Typically presents 20 – 40yrs; >60yrs is rare
o More common in White, with increasing prevalence further from the Equator –
Prevalence varies widely with geographic and ethnicity (environment and genes)
o Migrants develop a higher risk of MS if they move further from equator, implying
environmental factors

Question 3

Aetiology of MS

Answer 3

• Assoc other Autoimmune disorders and FMH; Complex Polygenic Inheritance pattern; Much increased risk if first-deg relatives (3-5% Lifetime risk); Genes mostly associated with Immune
Function and Regulation (HLA and MHC polymorphisms)
• Viral Infections believed to precipitate MS relapse; Exposure at critical times may trigger
o Evidence to believe EBV (Higher seropositivity in MS patients), HHV6 as well;
Exposure in childhood might be protective (Hygiene Hypothesis)

Question 4

MRI Prognosis

Answer 4

Prognosis unpredictable, but high MRI lesion load a presentation, High relapse rate and Male gender are poor prognostic features; Life expectancy reduced by 7yrs on average

Question 5

Pathological features of MS

Answer 5

• Demyelination Plaques 2 – 10mm in size are cardinal; Occur anywhere within CNS, with Predilection for Optic
Nerves, Periventricular Regions, Corpus Callosum, Brainstem, Cerebellar Connections and Cervical
Cord (CST and Dorsal Column)
• Most Inflammatory Plaques are Asymptomatic; Peripheral Myelinated Nerves are not directly affected in MS
• Acute Relapses due to Focal Inflammation causing Myelin Damage and Conduction Block; Recovery
follows as Inflammation subsides and Remyelination
o Severe Damage – Secondary Permanent Axonal Destruction occurs; Progressive Axonal Damage seen in Progressive forms of MS

Question 6

Clinical Features of MS

Answer 6

• Wide variety of possible symptoms based on location of Demyelination; Three main clinical patterns of MS based on time course and evolution
• Optic Neuritis, Brainstem Demyelination (Diplopia, Vertigo, Facial Numbness/Weakness,
Dysarthria, Dysphagia, Pyramidal Signs), Cord Lesions (Paraparesis over days or weeks leading
to difficulty in walking and Numbness with Tingling)
o Lhermitte’s sign – Electrical sensation running down Back into LL

Question 7

Clinical Features of MS: Sensory Changes

Answer 7

• Visual Changes, Sensory Symptoms (Presenting in 40% of patients; Reduced Vibration Sense and Proprioception among most common on examination), Temperature Sensitivity
o Temporary worsening of Pre-existing Symptoms when increase in body temperature
(=Uhthoff’s Phenomenon)
• Clumsiness/Useless Hand or Limb – Loss of Proprioception; Unsteadiness/Ataxia

Question 8

Clinical Features of MS: Urinary Symptoms

Answer 8

Bladder Hyperreflexia causing Urgency and Frequency

Question 9

Clinical Features of MS: Other features

Answer 9

Neuropathic Pain, Fatigue, Spasticity, Depression, Sexual Dysfunction

Question 10

Pathognomic signs of MS

Answer 10

Bilateral Internuclear Ophthalmoplegia or Tonic Spasms of one limb are Pathognomonic of
Multiple Sclerosis; Epilepsy and Trigeminal Neuralgia more common in MS

Question 11

Late Stages of MS

Answer 11

Spastic Tetraparesis, Ataxia, Optic Atrophy, Nystagmus, Brainstem Signs, Pseudobulbar Palsy, Urinary Incontinence, Cognitive Impairment, Frontal Lobe involvement
o Median time to requiring walking aids is 15yrs, Time to wheelchair use 25yrs

Question 12

Relapsing Remitting MS

Answer 12

Relapsing-Remitting MS (RRMS) in 85 – 90%; Symptoms occur in attacks with onset over days and partial or complete recovery within weeks
o One relapse per year on average; Occasionally, many years may separate relapses
(=Benign MS; 10% of patients)
o Patients accumulate disability over time if incomplete recovery

Question 13

Secondary Progressive MS

Answer 13

Secondary Progressive MS – Late stage of gradually worsening disability over years; 75% of patients with RRMS will eventually evolve into Secondary Progressive by 35yrs
o Relapses may sometimes occur in this progressive phase (=Relapsing-
Progressive MS)

Question 14

Primary Progressive MS

Answer 14

Primary Progressive MS in 10 – 15%; Gradual worsening disability without Relapse or Remission; Presents later, associated with fewer Inflammatory Changes on MRI

Question 15

Clinically Isolated Syndrome

Answer 15

• Patients with first episode of Neurological symptoms suggestive of Neuroinflammation
• Up to 70% show multiple clinically-silent lesions; This confers 85% chance of developing MS
(50% if first presentation was Optic Neuritis)
• Second clinical event indicative of new lesions allows MS diagnosis confirmed; Also, Repeat
MR at least 1/12 later showing new lesion can confirm diagnosis even if asymptomatic

Question 16

Investigation of MS

Answer 16

• Diagnosis requires ≥2 attacks (time) affecting different parts of the CNS (space); History plus
Investigations (E.g. MRI Head);
o Typical MR Lesions are Oval, up to 2cm Diameter, often Perpendicular to Lateral
Ventricles; Tumefactive (Swelling) lesions can be seen o Acute lesions show Gadolinium enhancement for 6 – 8/52
• CSF often unnecessary if MRI suggestive and compatible clinical picture; Will demonstrate Oligoclonal IgG bands >90% of cases, but not specific for MS; Raised CSF cell count
• Evoked Responses – E.g. Visual in Optic Nerve lesions might demonstrate clinically-silent lesions; Less important in Diagnosis vs MRI
• Blood tests – To rule out other Inflammatory Disorders – Sarcoidosis, SLE; Or other causes of Paraparesis – Infections, B12 Deficiency

Question 17

Management of MS

Answer 17

• No cure – Immunomodulatory Treatments have modified course of Inflammatory phase
• Education, Provision of Materials, MDT support; Treatment of Pain, Urinary Symptoms (Anticholinergics or Botox), Spasticity (E.g. Baclofen), Fatigue (Amantadine, Modafinil,
Psychological Therapy); PT/OT; Immunisations are safe

Question 18

How are acute relapses managed?

Answer 18

Steroid Course Steroids (IV Methylpred 1g/day/3days or high-dose oral)
o Speeds recovery but does not influence long-term outcome

Question 19

How are relapse rates reduced?

Answer 19

• β-Interferon (INF-β1b and 1a), Glatiramer acetate reduce Relapse Rate by 1/3 and serious relapses by half in RRMS
o Glatiramer – Random polymer of four amino acids found in Myelin; May act as decoy for the immune system
o Administered SC or IM; SE: Flu-like symptoms, Injection site irritation
o Offered to patients who are Ambulant, with ≥2 Significant relapses over 2yr period, or
after Major Disabling relapse
o May reduce the conversion rate from CIS to Definite MS; Not effective in Primary
Progressive or Secondary Progressive MS

Question 20

When can monoclonal antibodies be used?

Answer 20

• Monoclonal Antibodies (Natalizumab – Anti-VLA4, Alemtuzumab – Anti T cell, Fingolimod) –High efficacy at preventing relapses in Aggressive RRMS; May have serious SE, generally used when Beta interferon or Glatiramer unsuccessful