Inflammatory/Demyelinating Diseases Flashcards
Basic subtypes of MS
- Relapsing-Remitting (RRMS)
- Primary Progressive (PPMS)
- Secondary Progressive (SPMS)
- Relapsing-Progressive (RPMS)
- Clinically Isolated Syndrome (CIS)
- Radiologically Isolated Syndrome (RIS)
- 4 immunopathological subtypes
Characteristics of Relapsing-Remitting MS
- 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
Characteristics of Primary Progressive MS
- Progressive disease @ outset, without true relapses
- 15% of cases
Characteristics of Secondary Progressive MS
- RRMS which converts to progressive disease.
- 50+% of RRMS ==> SPMS
Characteristics of Relapsing-Progressive MS
- patient has relapses w/ongoing progression
Characteristics of Clinically Isolated Syndrome (CIS)
- first attack of apparent demyelination
Characteristics of Radiologically Isolated Syndrome (CIS)
- pt. scanned for non-MS symptoms
- MRI shows apparent MS changes
Epidemiology of MS (age, gender, ethniticity, location, incidence)
- 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
Basic diagnostic criteria for MS
- 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.
Early clinical symptoms of MS
- 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
Late clinical symptoms of MS
- multifocal + more general sx
- fatigue
- sexual and cognitive dysfunction
- depression
- pain syndromes
- dysphagia
- secondary problems (skin breakdown, infections, immobility)
Neurologic exam abnormalities in MS (corticospinal, sensory, visual)
- Asymmetric, especially early. Mixed signs
- Corticospinal: weakness, spasticity, increased reflexes
- Sensory: loss/added sensation, cord level
- Visual: acuity loss, eye movement abnormalities
Neurologic exam abnormalities in MS (cerebellar, mood, cognitive)
- Cerebellar: ataxia, tremor, dysarthria (poor articulation)
- Mood: depression, emotional lability
- Cognitive impairment: short term memory, word finding, visual-spacial function, hand/eye coordination
MRI results in MS
- 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
CSF analysis results in MS
- 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
Evoked potential results in MS
- Prolonged conduction = demyelination
- Can test visual, brainstem, somatosensory
- High inter-operator variability
- Now, rarely used.
Treatment approach in MS: symptoms & acute attacks
- treat sx individually
- acute attack tx:
- high dose steroids
- plasma exchange if neccesary
Overall goals/treatment approach in MS
- 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
Characteristics of natalizumab
- monoclonal Ab against T4 integrin ==> T cell release
- causes increased risk for PML (progressive multifocal leukoencephalopathy), which is fatal.
Neuropathology of MS
- 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
Immunopathogenesis in MS
- Activated T cells express adhesion molecules penetrate BBB
- interact with microglia and B cells
- pro-inflammatory reactions with Th1/Th17 ==> damage axons