Clinical Features of Demyelinating Diseases

Question 1

What are common MS symptoms at onset?

Answer 1

1. Sensory disturbance (34%)
2. Weakness (22%)
3. Visual loss (13%)
4. Ataxia (11%)
5. Diplopia (8%)
6. Vertigo (4.3%)
7. 2% or less=fatigue, facial pain, headache, bladder dysfunction, facial weakness, dysarthria, hearing loss, cramps, los of consciousness, psychiatric symptoms, poor memory, dysphagia, loss of taste

Question 2

List the top 4 MS Symptoms during entire disease course:

Answer 2

• Weakness (89%)
• Sensory disturbance (87%)
• Ataxia (82%)
• Bladder dysfunction (71%)

Question 3

How can the clincal course of MS be described (4)?

Answer 3

1. Relapsing-remitting MS (RRMS)
2. Secondary progressive MS (SPMS)
3. Primary progressive MS (PPMS)
4. Progressive relapsing MS (PRMS)

Question 4

Describe the RRMS course:

Answer 4

• Relapses (“Flares”, “attacks”, “exacerbations”): acute/subacute symptoms caused by plaque formation
• Remissions: periods of recovery of neurologic function
• Approximately 85% of patients

Question 5

Describe the SPMS course:

Answer 5

• 60-85% of patients with RRMS develop SPMS
• Median time from initial flare to secondary progression = 19 years (highly variable)
• Relapses can still occur; frequency declines (eventually stop in most patients)

Question 6

Describe the PPMS and PRMS courses:

Answer 6

• PPMS
  
  • 10% of patients
  • Progressive from onset without relapses/remissions
• PRMS
  
  • 5% of patients
  • Progressive symptoms from onset and also rare relapses

Question 7

How is MS diagnosed?

Answer 7

• No specific test
• Relies largely on clinical history and documentation of consistent signs on neurologic exam
  
  • “Dissemination in time and space”

Question 8

McDonald Criteria

Answer 8

McDonald Criteria

Question 9

• What is Clinically Isolated Syndrome (CIS)?
• What is the risk of developing MS?

Answer 9

• Clinically Isolated Syndrome (CIS) = the first clinical demyelinating event that is suggestive of MS
  
  • Some patients with CIS will go on to have further attacks (and therefore develop MS) while others will have no further attacks (and therefore won’t develop MS)
• Risk of developing MS after CIS (after 14 years):
  
  • 88% if there are any lesions on initial MRI
  • 19% if there are 0 lesions on initial brain MRI

Question 10

How is MS treated?

Answer 10

• No cure currently
• Available treatments are only partially effective in reducing MS symptoms and disability
• Available treatments are approved for relapsing MS:
  
  • Interferon ß (SC and IM preparations)
  • Glatirameracetate (SC)
  • Natalizumab(IV)
  • Fingolimod(PO)
  • Teriflunomide(PO)
  • Dimethyl fumarate(PO)

Question 11

What is the most common inflammatory optic neuropathy?

Answer 11

Demyelinating Optic Neuritis (DON)

• Association with MS

Question 12

What are the demographics of DON?

Answer 12

• Mean age = 31.8
• F>M (3:1)
• More common in Caucasians

Question 13

How is DON diagnosed?

Answer 13

Clinical diagnosis

Question 14

What are the characteristic symptoms of DON?

Answer 14

• Acute-subacute vision loss
• Pain (92%) typically worse with eye movements
• Decreased color vision
• Phosphenes (lights, sparkles, shifting squares)

Question 15

What are the characteristic signs of DON?

Answer 15

• Optic neuropathy
  
  • Decreased visual acuity (any level)
  • Dyschromatopsia
  • Visual field defect
  • Decreased contrast sensitivity
  • Relative afferent defect

Question 16

• What is the recovery time of DON?
• How is DON treated?
• What is the long term prognosis?

Answer 16

• Recovery typically fairly prompt and nearly complete
  
  • begins within 1 month, with slower recovery over 12-18 months
• IV steroids increase the rate at which vision recovers
  
  • Oral prednisone increased risk of recurrent optic neuritis
  • Long-term visual prognosis same with or without steroids​
• Excellent long-term prognosis

Question 17

How is DON related to MS?

Answer 17

• IV steroids may impart a short-term protective effect against MS
  
  • Protective effect lost beyond 2 years
• Long-term MS risk stratification based on brain MRI
• Other risk factors:
  
  • CSF OCBs, CSF IgG synthesis, abnormal SSEPs, abnormal VEPs

Question 18

Acute Disseminated Encephalomyelitis (ADEM):

• Definition:
• Onset:
• Demographics:
• Patients are often ….

Answer 18

• Acute or subacute polysymptomatic onset that affects multifocal areas of the CNS and must include encephalopathy (behavioral change or alteration in consciousness)
• Typically monophasic, but may be recurrent or multiphasic
• More common in children
• Patients are often very ill (coma common)

Question 19

1. ADEM usually follows ….
2. What does MRI show?
3. What is seen in the CSF?

Answer 19

1. Often follows an acute infectious illness or vaccination
   
   • Believed to be induced by an immune reaction directed at a cross-reacting myelin antigen
2. MRI usually shows multiple/extensive lesions
   
   • Usually both cerebral hemispheres
   • Involvement of deep gray matter common (more so than in MS)
   • Optic nerves and spinal cord may be involved
3. CSF usually shows increased WBCs

Question 20

How is ADEM diagnosed?

Answer 20

Diagnosis of exclusion

Question 21

ADEM

• Brain Biopsy:
• Treatment:
• Prognosis:

Answer 21

• Brain Biospy: perivenous demyelination, typically distributed in sleeves surrounding areas of perivascular inflammation
• Treatment: high-dose IV corticosteroids
• Prognosis: generally favorable

Question 23

Define Transverse Myelitis:

Answer 23

• Syndrome of acute or subacute myelopathy accompanied by indicators of inflammation (either radiologically or based on spinal fluid)
• Heterogeneous collection of disorders
  
  • May occur as a stand-alone syndrome (idiopathic), a relapse of MS or NMO, a component of ADEM, or a nondemyelinating syndrome (ex. infectious, granulomatous)

Question 24

What are the clinical s/s in transverse myelitis?

Answer 24

• Most patients present with a combination of sensory, motor, and bladder/bowel-related symptoms
• Lhermitte Sign: electrical or dysesthetic sensation in the spine or limbs elicited by neck flexion
• Paroxysmal tonic spasms: repeated, brief (30-90 sec) stereotyped attacks of painful limb or truncalmuscle spasms, often triggered by limb movements

Question 25

How is transverse myelitis classified and what can the classes suggest?

Answer 25

1. Complete = relatively symmetric moderate-severe loss of motor and sensory modalities caudal to the level of the lesion
   
   • Suggests a monophasic disorder or relapsing NMO
2. Incomplete = partial or patchy involvement of at least one spinal segment with mild to moderate weakness and asymmetric or dissociated sensory symptoms
   
   • More likely to herald MS, with high risk for future relapses

Question 26

What is the treatment and prognosis of transverse myelitis?

Answer 26

• Treatment (non-infectious):
  
  • High dose IV corticosteroids
    
    • optional oral prednisone taper
  • Severe attacks: Plasma exchange
• Prognosis: depends on etiology
  
  • Partial cord syndromes in MS are typically mild to moderate, plateau after days to 4 weeks, and patients typically recover well
  • Complete cord syndromes are more likely to result in substantial residual deficits

Question 27

Define Central Pontine Myelinolysis:

• What is the most common cause?

Answer 27

Demyelinating condition due to severe osmotic stress

• Most commonly caused by overly-rapid correction of hyponatremia in patients with conditions predisoposingto nutritional/electrolyte stress

Question 28

What are the symptoms of central pontine myelinolysis?

Answer 28

• Neuropsychiatric
  
  • emotional lability, disinhibition, bizarre behaviors
• Neurologic
  
  • ​confusion, impaired cognition, dysarthria, dysphasia, gait instability, weakness/paralysis, seizures
• Demyelination can occur outside of the pons (“extra-pontine myelinolysis”)

Question 29

Define Neuromyelitis Optica(NMO, “Devic disease”):

Answer 29

Severe demyelinating disease which preferentially involves the optic nerves and spinal cord

Question 30

How does NMO present?

Answer 30

• **Typical presentation **= Acute optic neuritis preceded or followed by myelitis
• Vision loss often severe, 20% bilateral
• Periorbital pain less common than in idiopathic ON
• May be monophasic or relapsing (70%)

Question 31

NMO

• Optic disc may appear ….
• What is typically seen on MRI?
• What is shown on spinal MRI?
• What is seen in the CSF?

Answer 31

• Optic disc may appear:
  
  • normal or swollen acutely
  • pallor chronically
• MRI typically shows scattered areas of demyelination,
  
  • concentrated in the optic nerves, chiasm, spinal cord
• Spinal MRI:
  
  • lesions are longitudinally extensive
  • ≥3 vertebral segments
• CSF:
  
  • may be moderate pleocytosis (>50 cells)
  • OCBs in 20-30% (70-90% in MS)

Question 32

How is NMO diagnosed?

Answer 32

• No definitive diagnostic test
• Aquaporin-4 IgG autoantibody (73% sensitivity, 94% specificity serum)
  
  • Antibody targets aquaporin channel located in astrocyticfoot processes of the BBB