Multiple Sclerosis Flashcards
1
Q
Define multiple sclerosis
A
- Inflammatory, autoimmune, demyelinating disease of the CNS
- Characterized by multiple lesions in the CNS called sclerotic plaques caused by the body’s immune system attacking & stripping the myelin sheath of nerves
- It blocks or impairs neural transmission resulting in various kinds of impairments: motor & sensory loss, weakness/fatigue, coordination problems, pain, cognitive problems
- Since multiple body systems may be involved, need multi-disciplinary approach for optimal care: disease of variabilities
2
Q
What are the general 4 types of progression
A
- Relapsing-remitting MS (RRMS)
- Secondary progressive MS (SPMS)
- Primary progressive MS (PPMS)
- Progressive relapsing MS (PRMS)
3
Q
Describe relapsing-remitting MS
A
- Most common type (85% of new cases)
- Defining a relapsing attack: new symptom just last at least 24 hrs & be separated from other symptoms by at least 30 days to qualify as a new attack
- 60% progress to secondary progressive type in 2 decades
- The 1st demyelinating attack may be clinically isolated attack for some it could be a single isolated event, most others could go on to have 2nd & subsequent attacks
4
Q
Incidence of MS
A
- MS is a disease of the temperate climates with highest prevalence in Scotland and Scandinavia
- Very rare in Japan and Africa
- Age of onset is 20-50 yrs
- Females > males
- Men transmit disease to children more than women
- Pregnancy reduces relapse rates
5
Q
Etiology of MS
A
- Exact cause is unknown but has genetic & environment factors
6
Q
Genetic factors related to MS
A
- Child of MS parent has 5 fold increased risk
- Increased presence of gene for HLA-DR2 (immune system protein)
- Absence of inhibitory KIR2DL3 is associated with MS
- Majority with MS also have other autoimmune diseases: Hashimoto thyroiditis, psoriasis, IBD, RA
- Families with Hx of MS also have other autoimmune diseases: MS develops on a background of increased susceptibility to autoimmune disorders
7
Q
Environmental factors related to MS
A
- Vitamin D deficiency: may explain higher occurrence rates in northern & southern hemispheres
- Viral infections are also thought to trigger MS; more than 1/3 relapses are preceded by infections: EB virus, Measles virus, Herpes virus, Retrovirus
8
Q
Describe the primary pathology of MS
A
- Primary pathology is demyelination of CNS nerve fibers
- Immune system erroneously attacks myelin protein, confusing it with herpes viral protein
-Demyelination causes initial abnormalities in nerve conduction and correlate with immediate functional impairments after attacks
9
Q
Describe the pathogenesis of MS
A
- Myelin loss starts around small vessels
- Plaques appear as focal lesions in white matter of cerebral hemispheres, brainstem, spinal cord, and white matter around ventricles (PWM), optic nerves, corpus callous, and also in grey matter areas
- Inflammation of myelinated areas -> demyelination of nerves -> axonal loss
10
Q
What is the primary cause of long term disability in MS
A
- Although demyelination may cause relapses, long term disability is primarily caused by irreversible axon loss & cell death
11
Q
Describe the cellular pathogenesis level of MS
A
- Starts with inflammatory process against myelin by the immune system
- Cell mediated immune reaction: T-cells are activated against myelin antigen & cross BBB
- Activated T-cell changes the BBB to allow more T-cells to cross
- Activated T-cell release pro-inflammatory cytokines like interleukins & TNF alpha which dilates BBB
- Dilated BBB allows more types of immune cells (B-cells & macrophages)
- Activated T-cells also release other inflammatory cells (microglia, reactive astrocytes)
- B-cells mark myelin basic protein (MBP) with antibodies to be then attacked by phagocytosis cells
- Demyelinated areas appear as sclerotic plaques
- W/o myelin, axons start to malfunction, can correlate to relapsing periods early in MS
- Regulatory T-cells temporarily stop inflammatory process (remission)
- Demyelination capacity reduces leading to axonal loss through inflammatory attack
- Disease progression & long term disability occurs
12
Q
What stage of MS does remission happen better
A
- Remission happens better during the early stages of MS
13
Q
Describe plaques
A
- Plaques are filled by macrophages, T-cells, immunoglobulins, & microglia
- New plaques appear pink w/faint borders exhibiting intense inflammatory activity
- Old inactive plaques appear gray with sharp edges
- New lesions frequently appear at the sites of previous lesions which contribute to failed remyelination
14
Q
What regions in the CNS are plaques frequently found
A
- Periventricular
- Juxtacortical
- Infratentorial region
- Spinal cord
15
Q
Describe general clinical manifestations of MS
A
- In most individuals MS is characterized by progressive disability over time but amount of accumulated disability varies widely “disease of variability”
- 20% may show benign course with 1 or a few relapse attacks followed by complete remission
16
Q
What does the type and extent of disability in MS depend on
A
- Type of MS
- CNS area affected
- Capacity of the brain to adapt to lesions
- Individual’s threshold of appearance of symptoms
17
Q
What is the most common presentation of primary progressive type
A
- Myelopathy (spasticity, paraparesis, pain, gait impairments, balance problems)
- Progressive sensory loss & motor weakening
- Pain
18
Q
Describe optic neuritis
A
- One of the 1st manifestations of MS
- Optic nerve is part of CNS tracts and is subject to demyelination
- Typically unilateral painful decrease in vision: usually temporary during relapse, pain in periocular area, good healing with remission
- Decreased color vision, changes in pupillary light reflex, reduced clarity, blurry vision, visual field defects
19
Q
Ocular problems associated with MS
A
- Gaze palsies
- Nystagmus
- Inability to fix gaze: caused by lesions in the pons, vestibular nuclei of brainstem, or cerebellum
20
Q
Describe fatigue as a clinical manifestation of MS
A
- Single most common & disabling symptom in MS
- Often precedes diagnosis by years
- Presents as severe tiredness along with mental fatigue/fuzziness
21
Q
Describe central fatigue
A
- Due to demyelination
- Nerve fibers start to short circuit after repetitive firing when called upon to do repetitive task
- Repetitive exercises w/o rest could lead to feeling of increased weakness and should be avoided
22
Q
Unique characteristics of MS fatigue
A
- Simple ADLs can cause fatigue
- May occur early in the morning even after a restful night’s sleep
- Generally occurs on a daily basis
- Tends to worsen as the day progresses
- Tends to be aggravated by heat & humidity
- Unpredictable: comes on easily & suddenly
- Generally more severe than normal fatigue
23
Q
Describe cognitive problems associated with MS
A
- AKA “Cog fog”
- Occurs in 50% of MS patients
- Memory loss: forgetfulness
- Attention deficits
- Depression can occur either bc of actual changes in brain or due to knowledge of disease
- Medications can cause cognitive problems like sedation, confusion, or depression
24
Q
Common sensory changes related to MS
A
- Somatosensory symptoms: hypoesthesia, parasthesia, or dysesthesia
- Loss of sense of vibration, position, 2-point discrimination: which all could lead to balance problems
- May begin in part of one extremity, face, trunk, or perineum
- Symptoms may not be substantiated by objective findings as remission might have happened by the time patient shows up for examination
25
Weakness/paresis related to MS
- Result of decreased neuromuscular firing secondary to demyelination & axonal loss
- Loss of orderly recruitment of motor units
- Disrupted agonist-antagonist relationships
- Heat increases weakness due to conduction block
- Cooling improves strength & function
26
Spasticity related to MS
- UMN lesion very common with MS
- More common in LE
- Severity can vary from non-existent to severe in same person from time to time making it challenging to manage with meds
- Noxious stimuli can exacerbate spasticity
- Often Ms patients can use their spasticity to walk, transfer, & manage ADLs
- Spasms may accompany spasticity: more severe at night
- Clonus, Babinski's sign
27
Cerebellar symptoms related to MS
- Axonal loss and/or atrophy
- Incoordination, tremor, and ataxia in extremities or trunk
- May be symmetric or asymmetric
- Dysarthria: scanning speech
- Occur mostly during progressive phases
28
Balance, coordination, & dizziness problems related to MS
- Due to impairments in any/all balance regulating systems: sensory, motor, & cognitive
- Due to excessive fatigue, raise in body temperature, or lesions in brainstem, cerebellar structures, or from BPPV
29
Cranial nerve dysfunction related to MS
- when lesions are in brainstem affecting CN nuclei
- CNs 3-12 at the nuclei level
- Trigeminal neuralgia/Tic Douloureux (CN 5)
- Spasms or weakness of facial muscles (CN 7)
- Vertigo, N/V, balance problems if vestibular nuclei are affected
- Dysarthria/dysphagia (CN 9-10)
30
Pain related to MS
- Common in MS (50%)
- Usually neuropathic type pain (burning, stabbing, sharp) may occur with dysesthesias (like squeezing sensations)
- Distribution may/may not follow any sensory pattern of involvement
- Fairly constant with nocturnal worsening
- Pain meds offer minor relief
- Trigeminal neuralgia: shock like pain in face, characteristic in young person
- Lhermitte sign: momentary electric shock like sensation evoked by flexing neck or cough; more likely to occur when fatigued or overheated
31
Bladder and bowel symptoms related to MS
- Urge incontinence: spastic small (fail to store) bladder, frequent night time urination (nocturia)
- Stress incontinence: weakened pelvic floor muscle
- Overflow incontinence (less common): large (fail to empty) bladder, higher risk of UTI, spasticity/dyssynergia b/w bladder & urinary sphincter
- Bowel incontinence (diarrhea) or constipation: occurs less frequently
32
What is used to diagnosed MS
- McDonald criteria
33
Define dissemination in space and dissemination in time
- Space: presence of >1 lesions in different CNS regions in an MRI scan
- Time: simultaneous presence of active (inflammatory) & inactive (old) lesions in different CNS regions in an MRI scan; done using contrast enhancing technique
34
Describe ADEM (acute disseminating encephalomyelitis)
- Acute attack during childhood
- Characterized by inflammatory attack of the brain & spinal cord that damages myelin with features of encephalitis (fever, headache, seizures, & coma)
- Usually occurs just once
- Could convert to MS later with relapses
35
Describe diagnosis of MS using imaging
- Plaques & brain atrophy seen in MS brain
- During early stages or in relapsing-remitting type plaques correlate with clinical picture but not much during chronic stages or with progressive types of MS
- Correlation b/w periods of clinical worsening & total number of plaques/lesions, # of new lesions, & total area of gadolinium contrast enhancement
36
What is the hallmark of progressive forms of MS
- Cortical demyelination
- For both primary & secondary progressive types & provide better indication of disease progression & disability
37
Diagnosis of progressive forms of MS
- Measures of brain atrophy using MRI imaging volume quantification of grey & white matter areas can provide better correlations with functional disability & disease progression than white matter lesion (plaque) activity
38
Grey matter atrophy is partly related to what
- Neuropsychological impairment
- Impairments in verbal memory, euphoria, & disinhibition
39
Describe treatment for MS
- Goal is to stop the destructive inflammatory process by the activated immune system
- Disease modifying drugs can significantly decrease relapse rates, new cortical lesions, cortical atrophy progression, disability progression, & transition to secondary progressive MS
- Disease modifying drugs (DMDs): (the ABCs) Avonex, Betaseron, Copaxone
- Interferons modify or interfere with the immune response
40
List non-interferon DMDs
- Mitoxantrone
- Natalizumab
- Fingolimod
- reduce relapses, secondary progression, & long term increase in disability
- Dalfampridine: improve conduction by blocking potassium leaks
41
Other drugs that provide symptomatic management for MS
- Muscle relaxants (Baclofen, Botox injections) for spasticity
- Gabapentin for pain
- Stimulants (Modafinil, Amantadine) for fatigue
- Sedatives (Diazepam) for inducing sleep
- Corticosteroids: 1st line Tx against acute exacerbations; can alter all aspects of inflammation
42
Describe typical prognosis of MS
- Life expectancy is modestly reduced
- Average number of attacks is 1 per year
- If untreated 50% of MS cases will require AD to walk after 15 yrs & 50% will be w/c bound at 20 yrs
- Physical rehab improves functional independence but cognitive problems & ataxia tend to be refractory
43
Factors that predict worse MS prognosis
- Motor & cerebellar symptoms
- Short time between attacks
- Numerous attacks within 1st year or initial years
- Rapid disability after 1st attacks
44
Factors that predict better MS prognosis
- Sensory symptoms
- Infrequent attacks
- Full recovery after a relapse
- Low level of disability after 5-7 yrs of onset
45
Implications of MS for PT
- Goal: improve/maintain functional mobility status in house & community
- Visit mostly for complaints of fatigue & weakness
- Aerobic exercise with balance training & socialization improves fitness/function in mild MS & function in moderate-severe MS
- Avoid fatigue & overheating: distributed practice might be helpful, submit aerobic training might be better
- Use MFIS to monitor level of fatigue level
46
Describe Kurtzke expanded disability status scale (EDSS)
- Documents disease severity and progression: helpful for quantifying movement disability
- Defines functional systems as follows: Pyramidal, Cerebellar, Brainstem, Sensory, Bowel and Bladder, Visual, Cerebral. Other
47
MS severity categorization using EDSS
- EDSS = 0-3.5: mild disability; full ambulatory w/o AD
- EDSS = 4-6.5: moderate disability; ambulatory to specific distances w/o or w/ AD
- EDSS = 7-9.5: severe disability; very limited ambulation even w/ aid; w/c or bed bound
48
Roles for PT related to MS
- Be involved with dosing of intrathecal baclofen to relieve spasticity
- Be involved with determining appropriate muscles for botox injections
- Need good task analysis skills, consult with team for planning of botox injections
- Submax strength training
- Balance training, gait training
- Exacerbation of sx like increased reflex activity, increased extensor tone & difficulty with flexion are also signs of increased fatigue/heat intolerance
- Cooling vests
