Multiple Sclerosis

Question 1

EPIDEMIOLOGY

Answer 1

• 0.1%
• lower prevalence in tropical climates
• first degree relative
• peak age of onset 25-35y
• women(1.5:1)

Question 2

DIAGNOSIS

Answer 2

• 2 separate episodes of CNS demyelination separated in time and space

Question 3

CLINICAL FEATURES

Pattern:

Answer 3

1. a) Relapsing-remitting: relapse followed by recovery. can go on to produce secondary progressive pattern(65% of patients with relapsing-remitting disease within 15 years of diagnosis, usually gait and bladder disorders).
   - most common(85% of patients)
   - attacks for 1-2 months with periods of remission
   b) Primary progressive pattern: deterioration from onset. 10% of patients. more common in older people

Question 4

SYMPTOMS AND SIGNS:

1. Sensory
2. Visual
3. Motor
4. Spinal cord(Myelitis)
5. Brainstem and cerebellum
6. Higher function and mood
7. Sphincter and sexual disturbance
8. Others;

Answer 4

1. • Most common presentation, first symptom in up to 40% patients.
     - Numbness, coldness, pins and needles, swelling/tightness, can be radicular.
     - Trigeminal neuralgia
     - onset over few days, resolution in weeks to months
     - vibration and propioception commonly affecteed
2. • optic neuritis is a common initial presentation.
     - onset over a few days with complete/incomplete recovery over months
     - affects central vision and colour perception
     - central scotoma, relative afferent pupillary defect
     - pain upon eye movement
     - can be followed by optic atrophy
     - optic disc usually normal but can appear swollen in papillitis
     - Uhtoff’s phenomenon, decrease in visual acuity with temperature rise
3. -usually an early symptom and usually affects legs
   - progressive paraparesis is a usual pattern of primary progressive MS
   - paraplegia with spasticity, hyperreflexia and extensor plantars
4. Incomplete(Brown-Sequard syndrome/hemicord lesion) or Complete(Transverse myelitis)
5. • Diplopia is common early symptom
     - Skew deviation, lateral gaze palsies, Internuclear ophthalmoplegia(most characteristic)
     - Dizziness
     - Nystagmus
     - Ataxia(usually during acute relapse) and cerebellar tremor usually in later disease
6. Minor cognitive deficits, associated depression and anxiety
7. • Urgency, frequency
     - Detrusor sphincter dyssynergia leading to urinary retention and incomplete emptying which can lead to repeated infections and overflow incontinence
     - Impotence
8. • Lhermitte’s phenomenon where electric shock down back and arms and legs when bending neck
     - Epilepsy more common(3%)
     - Fatigue

Question 5

PRECIPITATING FACTORS:

Answer 5

1. Commonly after infections
2. Trauma(Evidence not as good)
3. Reduction during pregnancy and slight increase afterwards

Question 6

SIMPLIFIED KURTZKE EXPANDED DISABILITY STATUS SCALE

Answer 6

0 Normal
1 Signs but no disability
2 Minimal disability
3 Moderate disability, able to walk
4 Relatively severe disability, able to walk up to 500m; up to 12h/day
5 Walking limited to 200m; not able to do full day’s work without special help
6 Uses walking aid; limited to 100m
7 Wheelchair-bound; can transfer in and out of chair
8 Bed-bound, some arm function
9 Helpless and bed bound
10 Dead

Question 7

MCDONALD CRITERIA FOR DIAGNOSING MULTIPLE SCLEROSIS

- Evidence of damage to the central nervous system disseminated in time and in space

Answer 7

1. ≥2 relapses; objective clinical evidence of ≥2 lesions; objective clinical evidence of 1 lesion together with historical evidence of a previous relapse.
2. ≥2 attacks; objective clinical evidence of 1 lesion AND Dissemination in space: ≥1 MRI detected lesions typical of MS OR Await further relapse that demonstrates activity in another part of the CNS.
3. 1 attack; objective clinical evidence of ≥2 lesions AND Dissemination in time: MRI evidence showing an active(current) and non-active(previous) lesion OR MRI evidence of new lesion since previous scan OR await further relapse
4. 1 attack; objective clinical evidence of 1 lesion AND Dissemination in space: ≥1 MRI detected lesions typical of MS OR Await further relapse demonstrating activity in another part of the CNS. Dissemination in time: MRI evidence showing both active(current) and non-active(previous) lesion OR MRI evidence of new lesion since previous scan OR await further relapse.
5. Insidious neurological progression suggestive of MS(Primary progressive MS) AND Continued progression for 1 year(determined by looking at previous symptoms or by ongoing observation) + any 2 of: ≥1 MRI detected lesions in the brain typical of MS; ≥2 MRI detected lesions in the spinal cord; Positive tests on CSF

Question 8

DIFFERENTIAL DIAGNOSIS:

Answer 8

1. Optic nerve compression
   - More insidious onset and progression
   - MRI to rule out
2. Spinal cord syndromes
   - Spinal cord compression
   - Vitamin B12 deficiency
   - HTLV-1 myelopathy
   - familial spastic paraparesis
   - Amyotrophic Lateral Sclerosis: lack sensory signs and associated LMN signs
3. Brain stem syndromes
   - Tumours
   - Brainstem encephalitis
   - Cranial polyneuritis
   - Arnold-Chiari malformation
   - Vascular disease(especially in older patients)
   - MRI and CSF examination to differentiate
4. Multifocal CNS disease
   - SLE, Behcet’s disease, Sarcoid, Polyarteritis nodosa
   - Lyme disease, syphilis
   - Widespread multifocal demyelination in acute disseminated encephalomyelitis and post-infectious encephalomyelitis: episode disseminated in space but not in time

Question 9

INVESTIGATIONS:

Answer 9

1. MRI
   - Changes in characteristic sites within white matter ie paraventricular areas and corpus callosum
   - Similar changes also seen in cerebral ischaemia, sarcoidosis, Behcet’s syndrome, other vasculitic illnesses
2. Neurophysiological tests
   - Visual evoked responses
   - Somatosensory evoked responses
3. CSF
   - May have slight elevation of WCC(normal: <15 cells/mL)
   - Protein electrophoresis usually identifies oligoclonal bands in CSF but not in serum. Oligoclonal bands also occur in infections(eg: neurosyphilis, Lyme disease) and inflammatory diseases(eg; Behcet’s and SLE) but also found in serums for these illnesses.

Question 10

PROGNOSIS:

Answer 10

1. Life-expectancy reduced by 10-20 years
2. 15% have very benign disease with only few relapses
3. If disease mild after 5 years, severe disease develops infrequently
4. Relapsing-remitting pattern, female, and sensory/optic neuritis symptoms at onset, young age of onset(20s/30s), long interval btw first 2 relapses and complete recovery btw relapses are all good prognostic factors.

Question 11

COMPLICATIONS:

Answer 11

1. Spasticity
   - Treat with Baclofen/gabapentin(first-line), Dantrolene, Tizanidine, Physiotherapy, Botulinum toxin in selected muscles
2. Fatigue
   - Amantadine, pemoline, modafinil
3. Ataxia
   - Isoniazid(with pyridoxine)
4. Bladder problems
   - USS first to assess bladder-emptying as anticholinergics can worsen urinary retention
   - Unstable bladder, treat with oxybutynin, tolterodine
   - Uncoordinated bladder, treat with intermittent self-catheterization with oxybutynin
5. Erectile failure
   - Sildenafil
6. Constipation
   - Bulking agents and stool softeners
7. Oscillopsia(oscillating visual fields)
   - Gabapentin

Question 12

TREATMENTS:

1. Symptomatic
2. Disease-modifying

Answer 12

1. a) IV Steroids(Methylprednisolone over 5d) to shorten duration of acute relapse, poor response in progressive MS
   b) Amitriptyline/Gabapentin for neuropathic pain
   c) Carbamazepine for Lhermitte’s/trigeminal neuralgia
   d) Occassionally stereotactic thalamotomy for tremor
   e) Antidepressants and support for depression
   f) Physiotherapy, occupational therapy, speech therapy
2. a) Beta-Interferon(SC/IM)
   - decrease relapse rate by 30%, does not reduce overall disability
   - Criteria: i) Relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided. ii) Secondary progressive disease + 2 relapses in past 2 years + able to walk 10m(aided/unaided)
   b) Glatiramer acetate
   c) Natalizumab(small risk of developing fatal progressive multifocal leucoencephalopathy)
   d) Cyclophosphamide and azathioprine(minor benefits)
   e) Fingolimod