MS diagnosis and treatment Flashcards
What are the dysmyelinating disorders?
- Don’t focus on these, just recognize their names
- Krabbe
- Metachromatic leukodystrophy
- Pelizaeus-merzbacher
- Sudanophilic leukodystrophies
- Alexnder’s
- Canavan’s
- Adrenoleukodystrophy/adrenomyeloneuropathy
What are the causes of demyelination?
• Metabolic
○ B12
○ Subacute combined degeneration
• Viral
○ JC virus - Progressive multifocal leukoencephalopathy
○ HIV - myelin pallor in AIDS dementia complex
○ Human Herpes Virus 6 (HHV6)
• Post-infectious and post-vaccine
○ Measles, rubella, chicken pox infection
○ Smallpox, old rabies, mumps, influenza vaccination
○ We think the infection response triggers an autoimmune reaction
○ Acute disseminated encephalomyelitis (ADEM)
○ Hemorrhagic leukoencephalitis
• Unknown
○ MS
What are the nomenclature differences in MS presentation?
• RRMS - relapsing-remitting
○ 85% of patients
○ Sporadic episodes of new or worsened symptoms and signs over 2-10 days with variable improvement over 1-6 months
• PPMS - primary progressive
○ Slow progression, not any relapses
○ More of the diagnosed later in life people
○ 15% of patients
• SPMS - secondary progressive
○ When RRMS converts to a progressive disease that doesn’t have relapses but steadily shows worse lesions
What is the epidemiology of MS (learning objective)
- Age - 3/4 present between 15-45
- Sex - 2/3 or more are women, and increased prevalence recently shows women predominance
- Race - primarily caucasians? (recent data suggests shared more equally)
- Geography - higher further from equator, highest in UK, iceland, canada, Australia, US
- Incidence - 10,000 new cases per year in USA
- Prevalence - 400,000 total cases in USA
- Colorado and wyoming have 1/500 residents prevalance which is HIGH
- MOST COMMON CAUSE of CNS inflammatory disease
What are the important points of MS neuropathology?
- Demyelinating disorder of CNS, but it looks more like a diffuse process with distinct CNS consequences of immunological deposition
- Demyelination with perivascular lymphocyte, macrophage, antibody and complement in active lesions
- Relative sparing of the axons, though aconal loss and axon bulbs in both acute and chronic lesions
- Immune-mediated damage (more commonly held presumption)
- 4 different types of immunopathology known. Lesions and types vary between MS patient BUT within one patient there is only one type of immunopathology
MS is a mix of environmental and genetic causes/factors. What are the particular genes you should recognize as contributing to the risk of MS?
- HLA DR2, 3x risk
- IL-7 and IL-2 receptor alpha chain mutations
- Some familial link as well
What are some environmental risk factors for MS to be aware of?
- Vitamin D deficiency
- Viral infection (EBV, HHV-6)
- Smoking
- Obesity in young adult women
- High salt diet
Formal criteria for dx of MS is known as what?
• McDonald Criteria
• Multiple lesions of the CNS disseminated in time and space
○ Time = 2 or more sets of symptoms lasting at least 24 hours, 30+ days apart for RRMS or 12mo for PPMS
○ Space = 2 separate locations in brain/spinal cord
§ Abnormalities noted on examination without any other cause identified
What is the late common history of the MS patient?
- Multifocal symptoms, really a coalescence of symptoms in multiple distributions
- Same as early PLUS:
- Fatigue
- Sexual dysfunction
- Depression
- Cognitive dysfunction
- Pain
- Dysphagia
- Seizures and hearing loss
- Immobility-related problems like infection, pressure sores and DVT
What is the early common history of the MS patient?
• Early - often unifocal paresthesias,
- monocular loss of vision,
- gait problems,
- weakness,
- diplopia (double vision),
- Lhermitte’s sign (paresthesias down spine with neck flexion),
- urinary urgency/frequency,
- constipation
What are the neurologic exam findings in MS?
• Usualy asymmetric
• Upper motor neuron/pyramidal tract signs
○ Weakenss, spasticity, babinski sign
• Decreased visual acuity
• Optic atrophy and afferent upillary defect
• Eye moevemtn abnormalities such as nystagmus
• Internucler opthalmoplegia
• Sensory loss
• Cerebellar signs such as ataxia, tremor, dysarthria
• Labile affect (emotional lability)
• Cognitive dysfunction
What is the igG index?
- igG index = (IgG-csf/IgG-serum)/(Alb-csf/Alb-serum)
* Comparing igG in csf to ablumin, which is a control protein
What laboratory studies are often ordered to arrive at MS dx?
• The first point is to rule out other causes
• MRI, with and without contrast
• CSF analysis
• Evoked potentials
○ Prolonged conduction points to MS lesions (demyelination)
• Optical coherence tomography (OCT)
○ See optic nerve, good for prognosis not diagnosis
• CBC with diff - rule out infections
what are the MRI things you look for in MS?
• MRI, with and without contrast
○ With FLAIR images to see lesions in periventricular regions, corpus callosum, juxtacortical spinal cord and brainstem/cerebellum
○ T1 = “holes” are bad long term prognostic marker with axonal damage
○ T1 - contrast-enhancing lesions - show BBB breakdown and typically seen early in evolution of lesion, enhancement only 2-6 weeks (bad short term prognostic)
○ T2 - hyperintense/bright lesion is seen with acute and chronic lesions and includes FLAIR (fluid attenuated inversion recovery which makes CSF dark)
○ Atrophy
what are you specifically looking for in CSF analysis in the MS patient?
• CSF analysis
○ Protein usually normal or mild elevation
○ WBC usually normal with mild elevation b/c of lymphocytes
○ Glucose is ALWAYS normal
○ Evidence of abnormal IgG production through increased IgG index
○ Evidence of abnormal IgG by seeing oligoclonal bands (gel running technique)
○ Myelin basic protein elevation
