Multiple Sclerosis

Question 1

Multiple sclerosis presentation

Answer 1

This 30‐year‐old woman complains of double vision and incoordination with previous episodes of weakness. Please perform a neurological examination.

Question 2

Clinical signs of Multiple Sclerosis

Answer 2

1. Inspection: ataxic handshake and wheelchair
2. Cranial nerves: internuclear ophthalmoplegia (frequently bilateral in MS), optic atrophy, reduced visual acuity, and any other cranial nerve palsy
3. Peripheral nervous system: Upper‐motor neurone spasticity, weakness, brisk reflexes and altered sensation
4. Cerebellar: ‘DANISH’ (see cerebellar syndrome section)

Question 3

Medial longitudinal fasciculus (MLF)

Answer 3

1. Medial longitudinal fasciculus (MLF): is a pair of tracts that allows for crosstalk between CN VI and CN III nuclei.
2. Coordinates both eyes to move in same horizontal direction.
3. Highly myelinated (must communicate quickly so eyes move at same time).
4. Lesions may be unilateral or bilateral (latter classically seen in multiple sclerosis).

Question 4

Internuclear ophthalmoplegia

Answer 4

• Internuclear ophthalmoplegia (INO) = Lesion in MLF, a conjugate horizontal gaze palsy.
• Lack of communication such that when CN VI nucleus activates ipsilateral lateral rectus, contralateral CN III nucleus does not stimulate medial rectus to fire.
• Abducting eye gets nystagmus (CN VI overfires to stimulate CN III).
• Convergence normal.
• When looking left, the left nucleus of CN VI fires, which contracts the left lateral rectus and stimulates the contralateral (right) nucleus of CN III via the right MLF to contract the right medial rectus.
• Directional term (e.g., right INO, left INO) refers to which eye is paralyzed. so the other eye will have nystagmus

Question 5

Diagnostic criteria of Multiple Sclerosis

Answer 5

Central nervous system demyelination (plaques) causing neurological impairment that is disseminated in both time and space.

Question 6

Cause of Multiple Sclerosis

Answer 6

Unknown, but both genetic – (HLA‐DR2, interleukin‐2 and ‐7 receptors) and environmental factors (increasing incidence with increasing latitude, association with Epstein–Barr virus infection) appear to play a role.

Question 7

Investigation of Multiple Sclerosis

Answer 7

Clinical diagnosis plus

1. CSF: oligoclonal IgG bands
2. MRI: periventricular white matter plaques
3. Visual evoked potentials (VEPs): delayed velocity but normal amplitude (evidence of previous optic neuritis)

Question 8

Other clinical features of Multiple Sclerosis

Answer 8

1. Higher mental function: depression, occasionally euphoria
2. Autonomic: urinary retention/incontinence, impotence and bowel problems
   ==> Uthoff’s phenomenon: worsening of symptoms after a hot bath or exercise
   ==> Lhermitte’s sign: lightening pains down the spine on neck flexion due to cervical cord plaques

Question 9

Treatment of Multiple Sclerosis

Answer 9

1. Multidisciplinary approach
2. Disease modifying treatments
3. Symptomatic treatments

Question 10

Multidisciplinary approach in Multiple Sclerosis

Answer 10

1. Specialist nurse,
2. physiotherapist,
3. occupational therapist,
4. social worker and
5. physician.

Question 11

Disease modifying treatments for Multiple Sclerosis

Answer 11

1. Interferon‐beta and Glatiramer reduce relapse rate but don’t affect progression.
2. Monoclonal antibody therapy potentially offers greater benefits; reducing disease progression and accumulated disability, e.g.
   ===> Alemtuzumab (anti‐CD52) – lymphocyte depletion,
   ===> Natalizumab (anti‐α4 integrin) – blocks T‐cell trafficking.
   »» Toxicity may limit their use.

Question 12

Symptomatic treatments for Multiple Sclerosis

Answer 12

1. Methyl‐prednisolone during the acute phase may shorten the duration of the ‘attack’ but does not affect the prognosis.
2. Anti‐spasmodics, e.g. Baclofen.
3. Carbamazepine (for neuropathic pain).
4. Laxatives for bowel disturbance.
5. Intermittent catheterization/oxybutynin for bladder disturbance.

Question 13

Prognosis of Multiple Sclerosis

Answer 13

Variable: The majority will remain ambulant at 10 years.

Question 14

Multiple Sclerosis and pregnancy

Answer 14

1. Reduced relapse rate during pregnancy
2. Increased risk of relapse in postpartum period
3. Safe for foetus (possibly reduced birth weight)

Question 15

Impairment, disability and handicap in Multiple Sclerosis

Answer 15

1. Arm paralysis is the impairment
2. Inability to write is the disability
3. Subsequent inability to work as an accountant is the handicap
   » Occupational therapy aims to help minimize the disability and abolish the handicap of arm paresis.

Question 16

Causes of Lhermitte’s sign

Answer 16

1. Multiple sclerosis
2. Cervical myelopathy
3. Cervical cord tumors
4. Subacute combined degeneration of the cord

lightening pain down the spine on neck flexion due to cord lesions

Question 17

Causes of Internuclear Ophthalmoplegia.

Answer 17

1. Multiple Sclerosis (Most Common)
2. Brainstem lesions (infarction, tumors, aneurysms)
3. Wernicke’s Encephalopathy
4. SLE
5. Miller Fischer Syndrome
6. Drug Overdose (TCA, Phenytoin, and Barbiturates)

Question 18

What are the causes of CSF oligoclonal bands?

Answer 18

1. Multiple sclerosis (oligoclonal IgG bands)
2. Neurosarcoidosis
3. Neurosyphilis
4. Neuromyelitis optica (Devic’s disease)
5. Meninoencephalitis
6. CNS lymphoma
7. SLE
8. Bechet’s disease
9. Subarachnoid haemorrhage
10. Guillain-Barre syndrome
11. Acute disseminated encephalomyelitis (Post-infectious encephalomyelitis)
12. Subacute sclerosing panencephalitis ( slow and persistent viral infection related to measles)
13. Progressive multifocal leucoencepahalopathy (Viral infection (polyomavirus JC))