demyelinating dz Flashcards
- Be able to describe the basic subtypes of MS
Relapsing-Remitting (RRMS): Sporadic episodes of new or worsened symptoms (over 2-10 days), with variable improvement over 1- 6 months. Primary Progressive (PPMS): slow progression, without relapses. Secondary progressive MS: Start with relapsing course, but goes on to become progressiv. Relapsing-Progressive (RPMS): combo of relapses and progression from outset. Clinically isolated syndrome: first attack. Radiologically isolated syndrome: MS on MRI but without clinical attack.
Which MS subtype is most common overall
relapsing remitting (85%).
How many RRMS convert to SPMS?
50%
tumefactive lesions
> 2cm, mimic tumors
which MS subtype is most common in young adults? Middle age?
The majority of young adults are diagnosed with Relapsing-Remitting MS. Primary progressive is most common in middle age
- Be able to describe the basic epidemiology of MS (ie age, sex, ethnicity, geography)
A. Age: up to 3/4 present between ages 15-45. B. Sex: at least 2/3+ are women; increased prevalence over last several decades primarily seen in women. C. Highest incidence in Caucasians, tho recent data questions this. D. Geography: incidence increases with distance from equator; highest in UK, Iceland, Canada, Australia, USA
MS pathology
demyelination, perivascular lymphocytic infiltrate, Axonal loss and formation of axon bulbs in both acute and chronic lesions, gray matter lesions, brain and/or spinal lesions,
compare immunopathology btw MS patients
At least four types of immunopathology in white matter have now identified. Between patients, immunopathology is variable, while within a single patient, immunopathology does not vary. Gray matter lesions are classified based on location, NOT immunology
Pathogenesis of MS
T cell activation in blood or lymph nodes by APC with antigen > T cells activate matrix metalloproteinases > BBB becomes leaky > T cells, B cells, macrophages, complement enter through BBB > B cells present antigen and secrete Abs > cytokine release in CNS causes further BBB breakdown > myelin and oligodendrocyte damage
Discuss white matter immunopathology and MS subtypes
All Type IV are PPMS. Types I/II correlate with encephalomyelitis. Types III/IV correlate with oligodendrocyte dystrophy
MS genetics
–Risk linked to HLA DR2; Link to IL-7 receptor, IL-2 receptor mutations; now >200 genes linked, most at odds ratios of about 1.1. Increased risk in family memebers
MS and environmental causes
Risk factors include viruses (EBV), chlamydia, pneumoniae, smoking, Vitamin D deficiency (risk of developing dz and higher risk of relapse), obesity in young women, high salt diet (risk of worse MS)
How is MS diagnosed
- Multiple CNS lesions disseminated in space (2 separate locations in CNS) and time (RRMS – 2 or more clinical attacks 30+ days apart. PPMS - Minumum 12 months of progression of Sx) 2. Abnormal exam without other identified cause. 3. Primarily clinical diagnosis, but MRI/CSF can help define dissemination in time/space. 4. Dx afer single attack and single scan if certain MRI features seen
MS early symptoms
Often unifocal at first, paresthesias (numbness and tingling), monocular loss of vision (optic or retrobulbar neuritis), gait problems, weakness, diplopia (double vision), Lhermitte’s (paresthesias down spine with neck flexion), urinary urgency/frequency, constipation
Often unifocal at first, paresthesias (numbness and tingling), monocular loss of vision (optic or retrobulbar neuritis), gait problems, weakness, diplopia (double vision), Lhermitte’s (paresthesias down spine with neck flexion), urinary urgency/frequency, constipation
Often unifocal at first, paresthesias (numbness and tingling), monocular loss of vision (optic or retrobulbar neuritis), gait problems, weakness, diplopia (double vision), Lhermitte’s (paresthesias down spine with neck flexion), urinary urgency/frequency, constipation
MS late symptoms
Multifocal and more general: early symptoms plus fatigue, sexual dysfunction, depression, cognitive dysfunction, pain, dysphagia; rarely, seizures and hearing loss; problems related to immobility
MS exam- corticospinal, sensory, visual
Often assymmetric, especially early. Mixed signs over time, as lesions accumulate. CORTICOSPINAL – weakness, spasticity, inc reflexes (upper motor neuron signs). SENSORY – loss/”added” sensation; cord level. VISUAL – acuity loss, eye movement abnormalities
MS exam - cerebellar, mood, cognition, sexual
CEREBELLAR – ataxia, tremor, dysarthria (“Charcot’s triad”), balance, coordination. MOOD – depression, emotional lability. COGNITIVE IMPAIRMENT - ST memory, word-finding, visual-spatial function, hand-eye coordination. SEXUAL – impaired sensation
Labs to diagnose MS
MRI, CSF analysis, Evoked potentials, optical coherence tomography, blood
MS- MRI T1 results
a. T1 “holes”, bad long-term prognostic sign consistent with axonal damage, often felt consistent with more chronic lesions, but can be seen early. b. T1 with contrast-enhancing lesions = Blood-Brain-Barrier breakdown, and typically seen early in evolution of lesion, with enhancement only lasting 2-6 weeks. Enhancement means leakage of the dye is seen. Bad short-term prognostic sign
MS- MRI T2 results
T2 hyperintense/bright lesion, seen with acute and chronic lesions, and includes FLAIR (fluid attenuated inversion recovery – makes CSF dark). There are many causes of bright dots on the T2 and FLAIR images, not just MS, so the pattern of lesions is RELATIVELY specific for MS. “Burden of Disease”, ie volume of lesions, seen even on first scan is predictive of disability over time.
MS- MRI non contrast
atrophy: white and/or gray matter focal atrophy and brain parenchymal fraction global atrophy
Long-term bad Prognostic Factors for MS
1) Atrophy, especially gray matter 2) High Burden of T1 holes 3) High Burden of T2 lesions 4) Posterior Fossa lesions 5) Spinal cord lesions
nonspecific brain MRI changes
migraine, HTN and aging can all show up as microvascular ischemic dz
MS- CSF analysis (protein, WBC, glucose, Igs, myelin basic protein)
Protein less than 110 mg/dl , WBC rarely more than 40/mm3, Glucose always normal, Immunoglobulins in CSF abnormal about 95% (elevated IgG index and/or oligoclonal bands >5), MBP elevation non specific
