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
What is the therapy protocol in MS?
• Main goal is Life-Long Brain Health
• Behavioral changes
○ Sleep, exercise (strength, balance, aerobic), don’t smoke, vitamin D supplements, low salt diet
• Agressively treat co-morbidities
○ HTN, diabetes, spine disease, hip and knee disease, primary sleep disturbances
• Treatment of acute attacks
○ High dose corticoseroides
○ Solumedrol with prednisone taper
○ Plasma exchange for severe demyelination unresponsive to steroids
• Symptomatic therapy
○ All the therapy specialties
○ Symmetrel, modafanil, armodafanil, prozac, ritalin for fatigue (if not from other source)
○ Pharm treatmens for urinary dysfucntion, spasticity,sexual dysfunction, neuropathic pain, depression, etc.
• Disease Modifying Therapy (immunotherapy)
What cells are not approved for targeted destruction with immunomodulating drugs but seem to be helping in trials of MS?
- Anti-CD20 B-cell killers
- Kill circulating B cells and the progression of lesions is reduced
- Expensive expensive expensive
What tends to be a huge issue in MS immunotherapy?
- When to take what drugs
- The older, less efficacious or aggressive are known comodoties and “safer”
- Start often with first line then if patient wants you can step it up to the newer stuff
- Money money money, and insurance companies dictate when you can step up the treatment
What type of MS can immunomodulation help?
pretty good success in RRMS, but PPMS…not really effective at all
