Multiple Sclerosis - Corboy Flashcards
In addition to demyelination, what other pathological process occurs in MS?
Key Point: Demyelination leading to axonal transection and loss is the common feature of MS lesions and is a consequence of an immune-mediated inflammatory process.
What are the different presentations of MS?
What differentiates each type?
RRMS = Relapsing Remitting (85%) PPMS = Primary Progressive (15%) SPMS = Secondary Progressive (RRMS-->SPMS) CIS = Clinically Isolated Symptoms (first attack) RIS = Radiologically Isolated Symptoms (imaging looks like MS w/o symptoms)
What is the basic epidemiology of MS?
2/3 patients are women, most are Caucasian, most present between 15-45 y/o (75%)
Prevalence is increasing, and is highest away from the equator
The most common inflammatory CNS disease.
What happens to the relapse rate (attack rate) over time?
Attack rate decreases with each decade (relapse/inflammation), however, disability progression continues over the same time period.
What genetic factors may contribute to MS? What are the most important risk factors? What is protective?
HLA DR2 is a risk factor (Odds Ratio 1.1)
Obesity, smoking
1st degree relatives is a 10-20 fold increase.
Increased risk in twins Monozygotic (30%) dizygotic (10%)
No EBV infection is 10-20 fold protective decrease.
What might the initial presentation of a patient with MS look like? How will this likely change over time?
MS often starts with a single lesion, which will lead to more focal clinical findings (eg numbness/gait/loss of vision) and spread to more general findings as multiple lesions appear over time (malaise/incontinence/cognitive dysfunction/etc)
Likely symptoms in these systems? CORTICOSPINAL SENSORY VISUAL CEREBELLAR MOOD COGNITIVE IMPAIRMENT SEXUAL
CORTICOSPINAL – weakness, spasticity, inc reflexes
SENSORY – loss/”added” sensation; cord level
VISUAL – acuity loss, eye movement abnormalities
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 or libido
What MRI findings might be seen in MS?
T1 - dark holes (axonal damage), bright with contrast (which usually should not be able to enter brain, BBB disruption
T2 - scars, atrophy (accurate prognostic indicator)
What are “Dawson’s Fingers”?
HYperintense bands of white (on FLAIR MRI) that run parallel alongside the lateral ventricles, and radiate dorsally into the cerebrum.
What MRI finding is pathognmonic for MS?
Thinning of the corpus callosum (saggital).
What is a very bad prognostic factor for someone with CIS?
More than 1 lesion on MRI. Predicts an 80% chance the disease will progress.
How are acute attacks treated?
Steroids (Methylprednisolone)
Plasma exchange if unresponsive to steroids
What immune-modulating drugs can be used? How effective are these, and are they still used today?
Interferon
Overall: modest efficacy, good long term safety, poorly tolerated
[Key Point: Currently, an important aspect of MS that can be treated is inflammation.
Immunomodulatory agents (IMAs) target the early process of MS pathology, inflammation. Although they are not curative, IMAs represent disease-modifying therapies1]
What is the modern concept of therapy? WHich drugs are used first?
Since the highest risk of immune flare is early in the disease progression, the best drugs should be used first. One drug mentioned in the lecture is natalizumab.
