MS

Question 1

Define: demyelinating disorders

Answer 1

Characterised by inflammation and selective destruction of CNS myelin. The peripheral nervous system is spared, and most patients have no evidence of an associated systemic illness

Question 2

Define: multiple sclerosis (MS)

Answer 2

It is characterised by the triad of inflammation, demyelination and gliosis; the course can be replapsing-remitting or progressive
Lesions of MS typically occur at different times and in different CNS locations

Question 3

What is the anatomomical pathogenesis of MS

Answer 3

• inflammation: acute MS lesions are characterised by periventricular cuffing with inflammatory mononuclear cells, predominately T cells and macrophages, which also infiltrate and surround white matter
• demyelination: in more than half of cases myelin-specific autoantibodies promote demyelination and stimulate macrophages and microglial cells that scavenge the myelin debris
• gliosis: as lesions evolve, astrocytes proliferate

Question 4

What is the physiologial pathogenesis of MS

Answer 4

Nerve conduction in myelinated axons occur in saltatory manner; with nerve impulse and jumping from one node of Ranvier to another. This produces considerably faster conduction velocities than slow velocities produced by continuous propagation in unmyelinated nerves. Conduction block occurs when nerve impulses are unable to transverse the demyelinated segment

Question 5

What is the immunological pathogenesis of MS

Answer 5

• myelin basic protein is an important T cell antigen in experimental allergic encephalomyelitis and probably also in human MS> activated MBP-reactive t cells are often found in blood or CSF of MS patients and occasionally also in MS lesions
• autoantibodies, directed against myelin antigens such as myelin oligodendrocyte glycoprotein, probably act in concert with pathogenic T cell response to cause the demyelinating lesions in many patients

Question 6

What is the microbiological pathogenesis of MS

Answer 6

MS risk also correlates with high socioeconomic status, which may reflect improved sanitation and delayed initial exposures to infectious agents. By anolagy, some viral infections produce neurologic sequale more frequently when age of initial infection is delayed

Question 7

Epidemiology of MS

Answer 7

x3 in women
age of onset is typically between 20-49 (later in men than woman
prevelance increases with increasing distance from equator. Vitamin D deficiency is assocaited with increased risk of MS

Question 8

Clinical manifestations of MS

Answer 8

onset may be abrupt or insidious. People may wait months or years before seeking medical attention
**symptoms vary according to location and severity of lesions within the CNS
- weakness
- spasticity
- visual blurring
- visual symptoms: periorbital pain, diplopia, bilateral INO
- sensory symptoms
- ataxia
- vertigo
- bladder dysfunction
- cognitive dysfunction
- depression
- fatigue

Ancillary symptoms:
- heat sensitvity
- Lhermitte’s symptoms
- paroxysmal symptoms

Question 9

what is Lhermitte’s syndrome

Answer 9

describes an electric shock-like sensation that occurs on flexion of the neck. This sensation radiates down the spine, often into the legs, arms, and sometimes to the trunk

Question 10

What are the 4 clinical types of MS (read up on each one)

Answer 10

1. relapsing/remitting MS
2. secondary progressive MS
3. primary progressive MS (PPMS)
4. Progressive/relapsing MS (PRMS) `

Relapsing/remitting: discrete attacks that evolve over days to weeks. Complete recovery in ensuing weeks/months. When ambulation is severely impaired during an attack, over half will fail to improve. Neurologically stable between attacks
Secondary progressive MS: secondary to RRMS. Steady deterioration in function unassociated with acute attacks.
Primary progressive MS: no attacks; only a steady functional decline from disease onset. Disease onset is later in life and disability develops faster
Progressive/relapsing MS: overlaps with PPMS and SPMS.

Question 11

What diagnostic tests are done for MS

Answer 11

1. MRI: lesions perpendicular to ventricular surface corresponding to pathologic pattern of perivenous demyelinations (Dawson’s fingers)
   - lesions are multifocal within the brain, brainstem and spinal cord
   - lesions >6mm loated in the corpus callosum, periventricular white matter, brainstem, cerebellum or spinal cord are particularly helpful
   - breakdown of BBB –> leakage of intravenous gadolinium into parenchyma
2. CSF: mononuclear cell pleocytosis and increased level of intrathecally synthesised IgG
   - measurement of oligoclonal banding in CSF also asseses the intrathecal producation of IgG
3. Evoked potentials: assesses function in afferent or efferent CNS pathways

Question 12

How is MSA treated

Answer 12

• treatment of acute attacks as they occur
  -treatment with disease-modifying agents that reduce the biological activity of MS
• symptomatic therapy

Question 13

What disease modifying therapies for relapsing forms of MS can be utilised

Answer 13

• interfeuron B
• IFN-B-1a
• Glatiramer
• natalizumab
• mitoxantrone

Question 14

What symptomatic therapy can be carried out for MS

Answer 14

• Ataxia/tremor is often intractable. Clonazepam, 1.5-20mg/d; Propranolol, 40-200 mg/d may
  help.
• Spasticity and spasms may improve with physical therapy, regular exercise, and stretching.
  Avoidance of triggers (e.g., infections, faecal impactions, bed sores) is extremely important.
  Effective medications include Lioresal (20-120 mg/d) and diazepam (2-40 mg/d).
• Pain is treated with anticonvulsants (carbamazepine, 100-1000 mg/d; gabapentin, 300-3600
  mg/d)
• Urinary tract infections should be treated promptly. Prevention by urine acidification (with
  cranberry juice or vitamin C) inhibits some bacteria.
• Fatigue may improve with assistive devices, help in home, or successful management of
  spasticity. Primary MS fatigue may respond to amantadine (200mg/d)
• Cognitive problems may respond to cholinesterase inhibitor donepezil hydrochloride
  (10mg/d).