Multiple Sclerosis Flashcards
Definition: a chronic inflammatory disease of the CNS characterized by ___ __ or __ neurologic symptoms due to __, __ and __ degeneration
Epi: average age of onset is 32, (which gender is affected more?), worldwide 1:3000; Canada 1:400
Definition: a chronic inflammatory disease of the CNS characterized by relapsing remitting or progression neurologic symptoms due to inflammation, demyelination and axonal degeneration
Epi: average age of onset is 32, F>M, worldwide 1:3000; Canada 1:400
Recall that non-pain neurons are more myelinated than pain neurons. Therefore, this demyelinating disease is more likely to affect myelinated axons, indicating that motor skills tend to be more affected in MS than pain.
MS is a __ and ___ disorder. The continuous __ of ___ and neurons is believed to be the principal contributor to progression of disability in MS.
How does inflammation play a role in the degeneration process of MS
DEMYELINATING and DEGENERATIVE disorder. The continuous loss of axons and neurons is believed to be the principal contributor to progression of disability in MS.
INFLAMMATION CAUSES PLAQUES
Inflammatory: immune cells (T-cells primarily) activated in periphery enter the CNS to destroy oligodendrocytes + myelin (demyelinating). The immune cells enter the CNS through post-capillary venules, meninges and choroid plexus
Inflammation of both white and gray matter drives neuropathology
The MS lesions= plaques (loss of oligodendrocytes + myelin)
In addition to inflammatory cells, glutamate, free radicals, mitochondrial dysfunction/energy insufficiency, iron toxicity, proteases, hypoxia also contribute to mechanisms of injury
In addition to inflammation, what other factors contribute to the neuropathology of MS?
In addition to inflammatory cells, glutamate, free radicals, mitochondrial dysfunction/energy insufficiency, iron toxicity, proteases, hypoxia also contribute to mechanisms of injury
Classic sign on CT that may indicate MS
Active Plaque: where demyelination is ongoing in the presence of cellular infiltrates (inflammatory cells, T cells, macrophage and microglia)–> may see central vein sign: specific for MS and can be seen in active lesions
Protective factors and risk factors of MS
Risk Factors: smoking, later in life EBV exposure, vit D def, high BMI in adolescence, lack of exercise in childhood, concussion in adolescence, night shift work, changes in the microbial composition of the intestinal compartments.
Protective: sunlight, vit D, coffee/fish intake
Which gene confers the highest signle risk of MS
- Environment: see risk factors above
- Genetics: accounts for 30% of risk. If identical twin 1:3; fraternal 1:15, sib 1:25
Over 200 genetic loci implicated, _HLA-DRB1 *1501 confers highest single risk._
First (and possible only attack) in a person’s life time–> what kind of subtype?
clinically isolated syndrome
(almost always has ocular manifestations)
diagnostic criteria and gender that relapsing remitting MS causes
Relapsing remitting (RRMS): 85% of all new cases, requires 2 attacks to diagnose, 3F:1M
Is there a gender difference in cases of primary progressive symptoms
Primary progressive (PPMS): 10% of all new cases, F=M, average age 45yo
“No relapses,” only steady progression of disability.
T/F there are relapses in PPMS
false. this is primary progressive– it just continues to get worse. there are no relapses or good/bad days
secondary progressive is the “second step “ that 50-70% of __ cases become
50-70% of relapsing remitting cases become SPMS
DDx for MS
vascular: multiple strokes
migraines
infections: HIV, lyme
tumor: space occupying lesions
metabolic: vit B12 def, hypothyroid
inflammatory: acute demyelinating encephalomyelitis, sarcoid, SLA, neuromyelitis optica spectrum
DDx for MS
vascular: multiple strokes
migraines
infections: HIV, lyme
tumor: space occupying lesions
metabolic: vit B12 def, hypothyroid
inflammatory: acute demyelinating encephalomyelitis, sarcoid, SLA, neuromyelitis optica spectrum
Symptoms of MS are broad because symptom presentation depends on lesion location. some can even be clinically silent. Some symptoms include numbness, visual disturbance, weakness, spasticity, diplopia, impaired gait, vertigo, bladder dysfunction
E|Which two condition/symptoms can happen in 80% oc ases?
bladder dysfunction and eye movement abnoramlities can haooen in 80% of cases.
- optic nueritis can happen in 50% in the first 5 years.
Is MS UMN or LMN
it often causes lesion in the BRAIN so it can manifest a lot in UMN
Spasticity can happen in 90% of cases
Compare and contrast acute and chronic MS pain
acute MS pain: trigeminal neuralgia, optic neuitis, injection sites reaction
chronic MS pain: neuropathic pain (burning, electric, shooting), band-like tightness, deep aching pain (spasticity)
Mcdonald criteria for diagnosing RRMS
symptoms need a dissemination in time and space
Dissemination in time: 2 attacks at two different points in time
§ 2nd episode must occur >30d after 1st relapse
§ New lesion must appear on MRI >30d after 1st relapse
Dissemination in space: 2 different clinical symptoms due to lesions in 2 CNS locations
§ MRI lesions must be characteristic location for an MS lesions
Mcdonald criteria for diagnosing PPMS
McDonald Criteria: for diagnosing PPMS
1 year of progressive symptoms with at least 2 of…
>2 spinal cord lesions
>1 lesion in the brain in a characteristic location
Oligoclonal bands/increased protein in the CSF
demyelinating plaques appear as ___ lesions on T2 weight MRI.
What are characteristics locations of MS lesions?
What are characteristics of MS lesions in general?
appear as HYPERDENSE LESIONS on T2 weigth MRI
- MS lesions are usually located periventricular, Juxtacortical/cortical, brainstem, cerebellum, spinal cord
Characteristics of MS lesions: ovoid, well-circumscribed, oritented perpendicular to lateral ventricles.
What two characteristics of CSF analysis would indicate PPMS
oligocloncal pans and elevated protein
anti-aquaporin4 antibodies are characteristic of ___ ____ spectrum disorder
neuromyeltiis optica spectrum disorder
general labs for MS
Labs: ANA, ENA, ESR, HIV, TSH, vitB12, CSF analysis (elevated protein and oligoclonal bands), anti-aquaportin4 antibodies (for neuromyelitis optica spectrum disorder)
T/F you should wait for symptoms to get to a certain point before you treat MS
false. treatment shoud be started ASAP.
TREAT EARLY→ steroids (1250 prednisone q2d x5) or IVIG (if steroids are not tolerated)
Treatment shortnes time to recovery, but no evidence to suggest it changes extent of recovery.
CIS: minocycline→ conversion from CIS to MS was lowered from 61% to 33% by minocycline
key medication that has been seen to have effects in CIS
TREAT EARLY→ steroids (1250 prednisone q2d x5) or IVIG (if steroids are not tolerated)
Treatment shortnes time to recovery, but no evidence to suggest it changes extent of recovery.
CIS: minocycline→ conversion from CIS to MS was lowered from 61% to 33% by minocycline
1st, 2nd and 3rd line prevention
1st line: vitamin D, smoking cessation, disease modifying theapy (teriflunomide, interferon-beta, glatiramer acetate)
2nd line: natalizumab, fingolimod
Avoid EBV
what medication class might help with cognition to improve short term memory?
L-amphetamines
Factors in addition to MS that can contribute to brain atrophy
Control atrophy from other causes: cardiovascular disease, diabetes, poor sleep, obesity, depression, alcohol use, dehydration
Mediterranean tired found decreased rate of relapses and decrease in T2 lesions.
MIND diet: leady greens, nuts, berries, beans, whole grains, fish, poultry, olic oil and wine.
