Module 12.1 - Multiple Sclerosis

Question 1

What is multiple sclerosis?

Answer 1

An immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) which is characterized pathologically by multifocal areas of demyelination

Question 2

Describe the etiology of multiple sclerosis

Answer 2

• Highly variable progression and many atypical forms
• Diagnosed primarily clinically
• Women have a 2 – 3 times higher incidence than men.
• Onset of disease is earlier in women than men.
• Caucasians have higher incidence than African Americans.
• Onset occurs in 20s-40s for up to 80% of patients
• No clear etiology, but thought to be multifactorial in cause
  
  • Viral infection as precursor
  • No clear genetic association

Question 3

What are the 5 types of multiple sclerosis?

Answer 3

A. Relapsing-Remitting (RRMS) – 85-90% of cases at onset; characterized by clearly defined relapses with full recovery, or with residual deficit upon recovery. Minimal disease progression during periods between relapses; most individuals will eventually enter a secondary progressive phase

B. Secondary Progressive (SPMS) – occurs 10-20 years after disease onset; characterized by initial RRMS course followed by gradual worsening with or without occasional relapses

C. Primary Progressive (PPMS) – represents about 10% of cases at disease onset; characterized by progressive accumulation of disability from disease onset with occasional plateaus, and relapses

D. Malignant MS – occurs in approx. 6% of patients; usually older at diagnosis; aggressive, rapid progressive course leading to significant disability in a relatively short amount of time after disease onset

E. Benign MS – occurs in about 15% of patients; a retrospective diagnosis made when the individual remains fully functional 10-15 years after disease onset; a single demyelinating event followed by no relapse

Question 4

What are some subjective findings associated with multiple sclerosis?

Answer 4

• Motor weakness, spasticity or stiffness
• Sensory alterations – numbness, burning, tingling in 1 or more limbs, facial numbness
• Brain stem symptoms- double vision, dysphasia, vertigo
• Visual deficits- decreased acuity, impaired color perception, field deficits, double vision/blurred vision
• Cerebellar symptoms- gait ataxia, tremor, uncoordinated movements
• Cognitive dysfunction – short term memory, slowed processing, difficulty in higher level problem solving
• Fatigue – 90% Of patients
• Sleep Disorders
• Bladder, bowel and sexual dysfunction
• Seizure
• Tonic spasms

Question 5

What are some physical exam findings associated with multiple sclerosis?

Answer 5

• Sensory disturbances 20-50% Of patients
• Decreased vibratory sense, position sense, pinprick perception and temperature sensation
• Reflexes- abnormal DTRs, positive Babinski and Hoffman, spastic limb weakness
• Brain Stem disorders – nystagmus, hearing loss, tinnitus
• Cerebellar disorders – ataxia, tremor, lack of coordination
• Visual disorders- 25% of patients initially present with optic neuritis; visual field defect, trigeminal neuralgia
• Frontal Lobe – cognitive dysfunction, emotional lability

Question 6

What lab/diagnostic tests are used to diagnose multiple sclerosis?

Answer 6

A. Complete neurological exam with noted deficits

B. MRI Findings: white matter lesions in brain, lesions in spinal cord, T2 weighted lesions in periventricular white matter of brain and spinal cord, cerebral atrophy

C. CSF Findings: elevated IgG with oligoclonal bands in CSF but not serum; 70% of patients with bands in CSF (not conclusive)

D. Evoked Potentials: slowed conduction or prolonged evoked response, not conclusive

E. McDonald Diagnostic Criteria: developed in 2001, latest revision 2010; core requirement of the diagnosis is the objective demonstration of dissemination of CNS lesions in both space and time, either clinically alone or a combination of clinical and MRI findings.

• Dissemination in space: MRI shows 1 or more T2 lesions in at least 2 of 4 MS typical regions of the CNS OR by the clinical development of attack of a different CNS site
• Dissemination in time: MRI shows the simultaneous presence of asymptomatic gadolinium enhancing and non-enhancing lesions at any time or a new T2 or gadolinium enhancing lesion on follow-up MRI irrespective of its timing with reference to baseline scan. OR the development of a second clinical attack.

F. Other

• No other explanation for MRI findings, CSF findings, or abnormal evoked potentials

Question 7

How do you manage a patient with multiple sclerosis?

Answer 7

A. Neurology consult

B. Mild acute exacerbations- not always requiring treatment if no functional decline present

C. Acute intervention for relapse:

• Glucocorticoids, oral of IV: High dose (500-1000mg/day) ;usually Methylprednisolone; duration dependent on clinical response

Question 8

What is the role of Disease modification medications in multiple sclerosis?

Answer 8

Reduces relapse rate, delays disability; initiate early in course of disease to slow progression of disease

• Fingolimod (Gilenya)- 0.5mg po daily; observe for bradycardia
• Interferon beta-1b: Betaseron or Extavia used in relapsing form of MS; SQ administration every other day; watch for depression/suicidality; injection site necrosis
• Interferon beta-1a : Avonex- used in relapsing MS; IM weekly dosage; watch for flu like symptoms, fatigue depression, myalgias

Question 9

What are important symptoms to control in patients with multiple sclerosis?

Answer 9

Spasticity, fatigue, mood disorders, immobility, seizures, incontinence, cognitive effects, gait disturbances, sexual dysfunction