Inflammatory/Demyelinating Diseases

Question 1

Basic subtypes of MS

Answer 1

• Relapsing-Remitting (RRMS)
• Primary Progressive (PPMS)
• Secondary Progressive (SPMS)
• Relapsing-Progressive (RPMS)
• Clinically Isolated Syndrome (CIS)
• Radiologically Isolated Syndrome (RIS)
• 4 immunopathological subtypes

Question 2

Characteristics of Relapsing-Remitting MS

Answer 2

• sporadic episodes of new or worsened symptoms and signs (over 2-10 days) + variable improvement over 1- 6 months
• 85% present in this manner
• “Relapse” = “Attack” = “Exacerbation”
• may convert to SPMS

Question 3

Characteristics of Primary Progressive MS

Answer 3

• Progressive disease @ outset, without true relapses
• 15% of cases

Question 4

Characteristics of Secondary Progressive MS

Answer 4

• RRMS which converts to progressive disease.
• 50+% of RRMS ==> SPMS

Question 5

Characteristics of Relapsing-Progressive MS

Answer 5

• patient has relapses w/ongoing progression

Question 6

Characteristics of Clinically Isolated Syndrome (CIS)

Answer 6

• first attack of apparent demyelination

Question 7

Characteristics of Radiologically Isolated Syndrome (CIS)

Answer 7

• pt. scanned for non-MS symptoms
• MRI shows apparent MS changes

Question 8

Epidemiology of MS (age, gender, ethniticity, location, incidence)

Answer 8

• ¾ present between 15-45
• ⅔ women
• highest incidence in caucasions
• higher incidence as increase distance from equator
• 10,000 new cases/year in USA
  
  • 9000 cases in CO
  • most common inflammatory CNS disease

Question 9

Basic diagnostic criteria for MS

Answer 9

• Diagnosis: lesions disseminated in space and time in CNS.
• PPMS: minimum 12 months of progression of sx with dissemenated lesions in space.
• RRMS: 2 or more attacks 30+ days apart.

Question 10

Early clinical symptoms of MS

Answer 10

• multifocal disease process:
• parasthesias
• loss of vision (optic neuritis), diplopia
• gait problems, weakness
• lhermitte’s (tingling down spine when flex neck)
• urinary urgency and frequency
• constipation
• vertigo

Question 11

Late clinical symptoms of MS

Answer 11

• multifocal + more general sx
• fatigue
• sexual and cognitive dysfunction
• depression
• pain syndromes
• dysphagia
• secondary problems (skin breakdown, infections, immobility)

Question 12

Neurologic exam abnormalities in MS (corticospinal, sensory, visual)

Answer 12

• Asymmetric, especially early. Mixed signs
• Corticospinal: weakness, spasticity, increased reflexes
• Sensory: loss/added sensation, cord level
• Visual: acuity loss, eye movement abnormalities

Question 13

Neurologic exam abnormalities in MS (cerebellar, mood, cognitive)

Answer 13

• Cerebellar: ataxia, tremor, dysarthria (poor articulation)
• Mood: depression, emotional lability
• Cognitive impairment: short term memory, word finding, visual-spacial function, hand/eye coordination

Question 14

MRI results in MS

Answer 14

• MRI: use for diagnosis and for prognosis
• T1 holes suggesting axonal damage, enhancing lesions = BBB damage
• T2: hyperintense bright lesions, 1st and 2nd echo, FLAIR
• Atrophy: focal white and/or gray matter, global brain parenchymal fraction
• T1 holes and atrophy most predictive of disability

Question 15

CSF analysis results in MS

Answer 15

• Protein mild elevation < 110 mg/dL
• WBC < 40/mm3, modest elevation (ex. meningitis would have thousands)
• Glucose = normal
• Immunoglobins in CSF abnormal in 95% of cases (increased IgG, oligoclonal bands)
• Myelin basic protein elevated, non-specific

Question 16

Evoked potential results in MS

Answer 16

• Prolonged conduction = demyelination
• Can test visual, brainstem, somatosensory
• High inter-operator variability
• Now, rarely used.

Question 17

Treatment approach in MS: symptoms & acute attacks

Answer 17

• treat sx individually
• acute attack tx:
  
  • high dose steroids
  • plasma exchange if neccesary

Question 18

Overall goals/treatment approach in MS

Answer 18

• Delay new attacks and disability/progression with immunomodulation
• Interferon beta 1a, interferon beta 1b, glatiramer acetate
  
  • All approved for RRMS, injectable at home
  • Reduce attacks, slow progression, reduce changes in MRI’s
• immunotherapy = _natalizumab (tysabri) _
• Choose treatment based on: efficacy, side effects, frequency/ease of use, neutralizing antibodies, severity of illness, find the “right” drug for each individual

Question 19

Characteristics of natalizumab

Answer 19

• monoclonal Ab against T4 integrin ==> T cell release
• causes increased risk for PML (progressive multifocal leukoencephalopathy), which is fatal.

Question 20

Neuropathology of MS

Answer 20

• Demyelination, with perivascular lymphocytic infiltrate
• Axonal loss and formation of axon bulbs in acute and chronic lesions
• Immune-mediated damage
• Caused by genetics, environment, and autoimmunity

Question 21

Immunopathogenesis in MS

Answer 21

• Activated T cells express adhesion molecules penetrate BBB
• interact with microglia and B cells
• pro-inflammatory reactions with Th1/Th17 ==> damage axons