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Multiple Sclerosis

NDT Ch. 19 MS

Definition of MS Chronic inflammatory, demyelinating disease of CNS
S/sx of MS Paralysis; Cardinal symptoms: Intention tremor, scanning speech, & nystagmus
Charcot's Triad Intention Tremor, Scanning Speech, Nystagmus
Incidence of MS Young adults 20-40; Typically 15-50, peaks at 30; Women > Men 2:1; Mostly white populations
Etiology of MS Unknown
Autoimmune Disease Theory Autoimmune disease induced by a viral/other infectious agent (Herpes, Chlamydial Pneumonia, Increased immunoglobulin & oligoclonal bands in CSF in 65-95%)
Viral infection has been shown to precipitate ____% of relapses 33%
Genetic Factor in MS 15% have (+) family hx; Inherit genetic susceptibility to immune system dysfxn; Major histocompatibility complex proteins on chromosome 6 have been linked to antibody production & MS
Pathogenesis Immune response triggers production of T-lymphocytes, macrophages & immunoglobulins (antibodies); In turn, antigen is activated, producing autoimmune cytotoxic effects w/in CNS
Pathogenesis continued... BBB fails & myelin-sensitized T-lymphocyte cells enter & attack myelin sheath that surrounds nerve
Myelin Insulator; Speeds conduction along nerves b/t nodes of Ranvier; Conserves energy b/c depolarization occurs ONLY at nodes
Demyelination Disruption of myelin sheath; Slowing neural transmission; Causes nerves to fatigue rapidly; With severe disruption, causes conduction block with disruption of fxn
Pathogenesis continued... Local inflammation, edema & infiltrates surround acute lesion & can cause mass effect, further interfering with conductivity
Oligodendrocytes Produce myelin; Early stage, survive initial insult & can re-myelinate; Incomplete process; Eventually involved w/ dx progression & can't repair myelin
Which type of MS is associated exclusively with dx of oligodendrocytes? Primary-Progressive
Demyelinated areas fill with what & undergo what process? Fibrous astrocytes; Gliosis (proliferation of neuroglial tissue w/in CNS & results in glial scars/plaques)
Demyelination: Mild & Severe forms Mild: 10-20% loss; Severe: up to 80% loss
Lesions in advanced cases Acute & Chronic of varying size scattered throughout CNS; Primarily affect white matter early; Lesions of gray matter in more advanced dx
Areas of Predilection in Advanced Cases Optic Nn; Periventricular white matter; SC (CST, posterior white columns) & cerebellar peduncles
Benign MS Best possible; Mild; <20% of cases; Pt is functional in all neuro systems 15 yrs after onset
Malignant MS (Marburg's Variant) Worst possible; Relatively rare; Rapid onset & continual progression leading to significant disability/death within relatively short time after onset
Relapsing-Remitting (RRMS) Most common ~70%; Clearly defined relapses (acute worsening of neuro fxn) followed by remissions; 80% progress to 2ndary progressive; Relapses w/ full recovery OR some remaining neuro s/sx & residual deficit w/ recovery; Between relapses-no dx progression
Secondary Progressive (SPMS) Initial relapsing-remitting course followed by progression with or without occasional relapses, minor remissions and plateaus
Primary-Progressive (PPMS) Rare; 10% of cases; Continuous disease progression from onset, w/o relapses; Some do have occasional plateaus/temporary minor improvements; Typically later onset >40; Permanent neuro disability results from incomplete remissions, dx progression, or both
Early MS Initial Sx Categories- most common? Corticospinal
Early MS Initial Sx Categories- CN 3-12 at the root, nuclear or bulbar level? Brainstem
Early MS Initial Sx Categories- None listed Cerebellar
Early MS Initial Sx Categories- Optic N. & Cerebral Hemis Cerebral
What is classified as a relapse? New & recurrent MS symptoms that last at least 24 hours & are unrelated to another etiology
What could be associated with a relapse? Viral/bacterial infections (cold, flu, URI, sinusitis); Diseases of major organ systems (Hepatitis, Pancreatitis, Asthma attack); Modest link b/t stress & acute attacks; Major life stress & minor stresses affect immunity & already compromised CNS
What is a pseudoexacerbation? Temporary worsening of MS symptoms, usually within 24 hours
What is Uthoff's Symptom? Adverse rxn to heat; Anything that raises body temp can cause psueoattack
Uthoff's Symptom- External Heat Stressors? Sun exposure, Hot muggy environment, Hot Bath
Uthoff's Symptom- Internal Elevations? Fever, Prolonged Exercise
Uthoff's Symptom- gradual or immediate? How long does it last? Immediate & dramatic- reduced fxn & increased fatigue; Most resolve w/in 24 hours of cooling &/or end of fever
Early Symptoms of MS Minor visual disturbances (double vision); Paresthesias progressing to numbness; Weakness; Fatiguability
Advanced Stages of MS Multiple s/sx with varying involvement; Onset develop rapidly over course of minutes/hours OR insidious over period of weeks to months (less common)
Sensory Issues Usually paresthesia; Anesthesia rare; Focal deficits can produce limited areas of diminished ssn; Altered ssns more common (inc. paresthsias [pins/needles] or numbness of face, body, extremities)
Proprioception & Vibration Sense Position sense is disturbed; LE impairment of vibratory sense
Pain Dysesthesias, Hyperpathia, Trigeminal Neuralgia, L'Hermitte's Sign, Chronic Neuropathic Pn
What % experience pain? 80%, clinically significant pain 55%, almost 1/2 experience chronic pain
What type of pain is experienced? Sharp, Shooting, Electric, Burning
Trigeminal Neuralgia (Tic Douloreux) Demyelinated ssy division of CN 5 innervating face, cheek, jaw; Eating, shaving, touching face can trigger
L'Hermitte's Sign Common symptom of posterior column damage in SC; Neck flexion produces electric shock ssn down spine into LEs
Paroxysmal Limb Pain Abnormal burning/aching (dysesthesias) that can affect any pt of body but more common in LEs; MOST COMMON type of pain in MS; Worse at night & post-exercise; Can be aggravated by increased temp
Hyperpathia Hypersensitivity to minor ssy stimuli (light touch/pressure can cause severe pain rxn)
Headaches More frequent in MS than general population; Migraine/Tension-type
Chronic Neuropathic Pain From demyelinating lesions in ST tracts or in ssy roots; More common in pts w/ minor disability; Burning pain similar to pain from disc herniation
Musculoskeletal Pain Associated with mm & ligament strain developed from mechanical stress, abnormal postures & immobility; Results of weak muscles, powerful spasticity & tonic spasms
What 2 common things can worsen pain s/sx? Anxiety & Fear
What visual impairments may an MS patient have? Optic Neuritis; Scotoma; Light Reflexes; Nystagmus; Eye Problems
What % of patients have visual impairments? 80%
What is the cause of altered visual acuity? Optic N. involvement
Is blindness common? No
Optic Neuritis Common; Ice pick pn behind eye w/ blurring/graying of vision or blindness in 1 eye; Rarely affected both eyes; Self-limiting
What is a scotoma? Dark spot in center of visual field that improves within 4-12 weeks
Light Reflexes- Marcus Gunn pupil Shine bright light into healthy eye-> Reflex contraction in both eyes (consensual light reflex), then shining light into affected eye -> Paradoxical widening/dilation of both pupils
Nystagmus From cblr/central vestibular pathway lesions; Involves involuntary cyclical mvmts of eye that develop when pt looks to side/vertically or when pt moves head
Internuclear Ophthalmoplegia (INO) Incomplete eye adduction (lateral gaze palsy) on affected side & nystagmus of opposite abducting eye with gaze to 1 side
What causes INO? Demyelination of pontine MLF
Problems with conjugate gaze & control of eye movements caused by? BS lesions affecting CN 3, 4, 6 or MLF
Diplopia Double vision when mm of eye not well-coordinated
Are visual disturbances permanent? No, they frequently remit & seldom are the primary cause of disability
What should be monitored if pt has visual disturbances? Effects on balance and movement
Motor Impairments S/sx UMN; Spasticity in LE > UE (leads to indirect impairments: pn, contractures, abnormal posturing, skin problems)
Spasticity Fluctuates daily, increases with extremes of temp & humidity, infections, tight clothes & certain anti-depressants; Doesn't abate during spontaneous remissions
Weakness- CST Lesions UMN s/sx; Paresis, spasticity, brisk reflexes, involuntary flexor/extensor spasms, clonus, Babinski's, exaggerated cutaneous reflexes, Loss of precise autonomic contron
Weakness- Movements Slow, stiff, weak; results of loss or orderly recruitment & reduced firing rate modulation of motornns
Weakness Reduced strength, power & endurance along with impaired synergistic relationships are evident
Weakness in pts with cblr lesions Asthenia or generalized mmw eakness along with ataxia
Weakness secondary to inactivity Range from mild paresis to total paralysis
Fatigue Subjective lack of physical &/or mental energy perceived by the individual/caregiver to interfere with usual & desired activities
Fatigue Occurrence Daily event in 75-95%; 50-60% report as most troubling symptom; Interferes with physical fining, overall role performance, & perceived health status; Comes on abruptly, w/o warning & resembles an overwhelming flu-like exhaustion
Is disease severity related to fatigue severity? NO
Fatigue results from what? Failure of central activation & excitation-contraction coupling
Fatigue Precipitation Factors Physical exertion, Exposure to heat & humidity; Depression; Sleep disorders; Low self-esteem; Mood disorders; Medical conditions; Secondary complications (respiratory impairment, infection)
Side Effects of Meds can also impact fatigue Analgesics, Anti-convulsants, Anti-depressants, Anti-histamines, Anti-HTN agents, Anti-inflammatories
What is a strong psychosocial predictor? Environmental Mastery (sense of control)
How common is spasticity? Very: ~80%; Range from mild to severe depending on progression of disease; UE & LE
Clinical Indications of Spasticity Impaired voluntary control of mvmt (abnormal co-contraction); Increased DTRs, clonus, flexion or extension synergy patterns; Decreased ROM
Spasticity results in what? Increased fatigue; Impaired functional mobility; Impaired ADLs; Can cause pain, disabling contractures, abnormal posturing & problems w/ skin
Fluctuation of Spasticity Daily & exacerbated w/ fatigue, stress, extremes of temp & humidity, infections, tight clothes (noxious stimuli) & certain anti-depressant (serotonin-reuptake inhibitors); Does not abate during spontaneous remissions
Spasticity in Advanced MS Quite disabling, Difficult to Manage
Balance & Coordination Demyelinating lesions in cblm & cblr tracts common producing cblr s/sx
Clinical S/sx Balance & Coordination- Ataxia Uncoordinated mvmts, progressive of trunk & LEs; Dysmetria, Dyssynergia, Dysdiadochokinesia
Clinical S/sx Balance & Coordination- Tremor Postural; Intention (cblm can't dampen motor mvmts); Vary fine to gross; Severe tremors impose significant limitations infxnal activities; Exacerbated by stress, excitement & anxiety
Clinical S/sx Balance & Coordination- Sensory Ataxia Severe numbness of feet -> Difficulty standing/walking
Clinical S/sx Balance & Coordination- Dizziness from lesions affecting cblm/central vestibular pathways Disequilibrium (difficulties with balance); Vertigo; Nausea; Worse w/ head/eye mvmt; Paroxysmal attack brought on by period of hyperventilation
Ambulation & Mobility Difficulty walking; 1/2 of pts with RRMS require some form of assistance within 15 yrs
What does gait look like? Staggering, uneven steps, poor foot placement, uncoordinated limb mvmts, frequent LOB
What causes speech & swallowing dysfunction? Muscle weakness, spasticity, tremor, ataxia; 40%
Speech Dysarthria Slur/poorly articulated speech with low volume, unnatural emphasis & slow rate
Dysphonia Changes in quality- harshness, hoarseness, breathiness or hypernasal sounds
Dysphagia Poor coordinatoin of tongue & oral mm, difficulty swallowing
Signs of Dysphagia Trouble chewing & maintaining lip seal, inability to swallow & spitting or coughing during/after meals; Can have poor nutritional intake & dehydration
Aspiration Pneumonia- What is it? S/sx? Serious complicatoin that can develops if food/liquid inhaled into trachea; Wet voice quality with gurgling or sounds of congestion & fever
Cognitive Impairments Common (~50%); 10% severe enough to affect ADLs; Related to the specific distribution of the lesions rather than to overall severity, its course or disability status
Changes in cognitive function Impaired attention & concentration (esp. alternating & divided attn); Slowed info processing; Impaired recent memory; Impaired executive fxns; Focal frontal lobe lesions can produce cognitive inflexibility
Significant Mental deterioration (Global Dementia) Rare but may be seen in rapidly progressing disease (malignant MS) or in pts with significant cerebral lesions; Level of cognitive fxn major factors in determining QOL, social fxning, employment, fxn in ADLs
How common is depression? @ Least 50%
Symptoms of Depressoin Feeling of hopelessness/despair; Diminished interest/pleasure in activities; Change in appetite & significant wt changes; Insomnia/Hypersomnia; Feelings of lethargy/worthlessness, fatigue, loss of energy; Decreased concentration; Thoughts of death/suicide
Depression Can be direct result of MS lesions, as a side effect of drugs or as a psych rxn to stresses of dx; Anxiety, denial, anger, aggression or dependency can also occur; Learned helplessness & low self-efficacy also common
How common are affective changes? ~10%
Pseudobulbar Affect Sudden loss of emotional control on multiple occasions that is typically unrelated to external circumstances, depression or underlying mood; Assoc w/ more progressive disability & greater intellectual impairment
Euphoria Exaggerated feeling of well-being, sense of optimism incongruent w/ pt's incapacitating disability; Found primarily in pts w/ advanced dx
Affective Changes Bipolar Disorders can occur; Symptoms have been linked to diffuse, bilateral cerebral involvement (esp pre-frontal cortex & corticobulbar tract involved in emotional control)
CV Dysautonomia ANS involvement; Problems w/ cardioacceleration/reduction in BP response during exercise; May have attenuated or absent sweating responses also
How common is bladder dysfunction? ~80%
Bladder Dysfunction Loss in volitional & synergistic control of micturition reflex; Produced by demyelinating lesions affecting the lateral & posterior spinal tracts unmasking the sacral reflex arc
Types of Bladder Dysfunction- Small, Spastic Failure to store
Types of Bladder Dysfunction- Flaccid, Big Failure to Empty
Types of Bladder Dysfunction- Dyssynergic Problem with coordination b/t bladder contraction & sphincter relaxation
S/sx Bladder Dysfunction Urinary urgency & frequency; Hesitancy in starting urination; Nocturia; Dribbling; Incontinence; Severity associated with severity of other neuro s/sx (particularly pyramidal tract involvement)
Bladder Dysfunction Emptying dysfunction with large residual urine volume increases risk of recurrent UTI & kidnsey damage from frequent UTIs
Bowel Dysfunction Constipation most common; From lesions affecting control of gastrocolic reflex; Presence of spasticity of pelvic flor mm & frequent consequence of inactivity, lack of fluid intake, poor diet & bowel habits, depression, med SE's
Sexual Dysfunction Common (91% men, 72% women)
Sex Dysfxn- Women Changes in sensation; Vaginal Dryness; Trouble reaching orgasms; Loss of libido
Sex Dysfxn- Men Impotence; Decreased sensation; Difficulty/inability to ejaculate; Loss of libido
Imaging- MRI Detects acute & chronic lesions, small & large with high resolution; Scans distinguish new with active inflammation that occurred during preceding 6 wks
Imaging- MRI Lesions seen as "bright spots"
What types of scans detect more long-term disease activity? T2; lesions seen as "black holes"; Darker the lesion = more extensive tissue damage
What % of pts with clinically defined MS have well-defined MRI changes? ~95%; excessive MRI activity = 3+ enhancements on repeat scans separated by at least quarterly intervals; Silent attacks > attacks that cause active s/sx such as paralysis/vision loss by 10:1
Current Neurology Guidelines MRIs to be performed at pre-defined intervals to document dx progression & response to dx-altering meds
CSF Elevated total immunoglobulin in spinal fluid & the presence of oligoclomal IgG bands; Pts with PPMS have higher immunoglobulin levels in CSF than pts w/ RRMS
Evoked Potentials Up to 90% demo abnormal evoked potentials; Presence of demyelinating lesions on visual, auditory, somatosensory or motor pathways produce slows/abnormal condition
Is life expectancy reduced? Not usually; Only small % die from dx; Only minority are in workforce 10 yrs post-onset; 75% survive 25 yrs after sx onset
At how many years will what % require use of AD to walk? 15; 50%
At how many years will what % require WC? 20; 50%
Prognostic Factors- Symptoms onset with only 1 symptom is one of strongest indicators of favorable prognosis
Prognostic Factors- Course of Disease Benign & RRMS are associated with better prognosis whereas PPMS is generally considered more ominous
Prognostic Factors- Age Young onset more favorable than onset >40 (associated w/ PPMS course & increased disability)
Prognostic Factors- Neuro findings at 5 years One of most important prognostic factors; Significant pyramidal & cblr s/sx w/ involvement at multiple sites associated w/ poorer prognosis & more severe disability
Prognostic Factors- MRI Findings Favorable px factors: Low total lesion burden, Low action lesion formation, Negligible myelin/axon loss
For most pts receiving dx-modifying drugs, tx only partially effective in controlling dx Some show reduced relapses; Reduced severity of attack (acquired neuro deficits); Fewer & smaller damaged areas on MRI; Slower rate of dx progression
Frequent relapses/excessive MRI activity may indicate need to switch drug therapy to higher doses & more frequently administered beta-interferons/combination therapies Agents can't reverse existing deficits; Drugs not indicated for PPMS
Common Adverse Effects of Interferon Drugs Injection-site skin run (sore, rd, pain, bruising, swelling); Flu-like s/sx post-injection (Fever, Chills, Sweating, Mm ache, Fatigue); Injection sites vary to reduce AEs; Depression; Allergic rxn; Liver rxn
Common AEs for Copaxone Similar injection site rxns; Initial flushing rxn immediately after injection (anxiety, chest pain, palpitations, SOB); Does NOT cause flu-like s/sx or depression
Problems with adherence using what? Immunomodulating agens
Management of Relapses & Symptoms Prompt mgmt of flare-ups & symptomatic & supportive rx are ESSENTIAL
Corticosteroid Therapy Rx acute dx relapses, shortening episode duration; Powerful anti-inflammatory & immunosuppressive effects, diminishing swelling within CNS & temporarily repairing BBB; May prevent circulating toxins from entering CNS; Don't modify dx course/recovery
Adverse SE's of Corticosteroids Agitation, nervousness, & insomnia; Increased sweating, appetite & susceptibility to infection; GI distress including heartburn & diarrhea/constipation
ACTH (Adrenocorticotropic Hormone) Long-term immune suppression
ACTH SE's Suppression of blood production by marrow; Bleeding Disorders; Increased risk of infection
Management of Spasticity Mm relaxants; Oral baclofen, tizanidine, dantrolene, diazepam (valium)
Adverse Effects of Mm Relaxants Sedation, weakness, fatigue; PT must be alert to these changes & communicate w/ MD to achieve optimal dosing for rehab; Recognize that at time spasticity can enhance fxn, substituting for lack of strength
Carbamezapine effective in reducing what? Paroxysmal (Sudden, sharp onset) spasms
Pts who don't adequately respond to conservate rx (intractable spasticity/spasms) may benefit from? Intrathecal baclofen into CSF of L-spine; Significant reduction in spasticity & spasms in LEs & trunk with less improvement reported in UEs
Adverse Effects of Intrathecal Baclofen Pump failure; Infection; Lead displacement
Surgical Interventions indicated more for? Severe spasticity; Spastic paralysis for many yrs resulting in non-functional limb & serious complications (contractures/skin breakdown)
Surgical Techniques Severing tendons (tendinotomy), Nerves (neurectomy) or Nerve roots (Rhizotomy)
Phenol Nerve Blocks Reduce spasticity (6+ month effective); Botox can temporarily block nerve/mm
Extensor Spasticity good for? Assist standing during stand-pivot xfer
Paroxysmal Pain Mgmt Reponds best to carbamezapine, amitriptyline, Gabapentin
Dysesthesia Mgmt Low doses of amitriptyline, imipramine, desipramine
Pain/Discomfort from Spasms/Spasticity Mgmt OTC/Prescription Anti-Inflammatories
Pain & Numbness Mgmt Brief course of corticosteroids
Narcotic Analgesics Problematic, not typically prescribed
Symptomatic Rx of Fatigue Amantadine HCl: 1st line therapy is anti-viral & dope agonist that has significant impact on lessening fatigue; Modafinil; Premoline (CNS stimulant with undesirable SE of anorexia, irritability, insomnia)
Mgmt of Dizziness & Vertigo Anti-Nausea drugs; Severe cases may require administration of short course corticosteroids
Severe Tremor Treatment Surgery (Thalamotomy) or Deep brain stimulation that involves implanting electrodes into thalamus; DBBS is experimental for MS still
Agents approved by FDA for Alzheimer's Rx Slow cognitive decline; Moderate benefits in memory deficits have been observed
Depression Mgmt Anti-depressants, in which some can also help lessen fatigue
How to treat pts with pseudobulbar affect? Anti-depressant amitriptyline
What non-medicinal way can pts do to help cope with stresses? Professional counseling & participation in support groups; Active lifestyle also helps reduce depression & anxiety
Overactive/Spastic Bladder Mgmt Anticholinergics; Oxybutynin; Imipramine
Adverse Effects of Overactive/Spastic Bladder drugs Dry mouth, Tachycardia; Accommodation disturbances
Dietary Recommendations when taking spastic bladder meds 8 glasses water/day; Limit caffeine/alcohol intake
Flaccid Bladder- Alternate Techniques for emptying Crede Maneuver- manual downward pressure over lower abdomen; Intermittent self-catheterization
Flaccid Bladder- Dietary Recommendations Limit intake of citrus juices; Drink cranberry juice daily
Dyssynergic Bladder (combined dysfunction ) Mgmt Alpha-adrenergic blocking agents; Prazosin; Temsulosin; Anti-spasticity agents
In the rare occasion where bladder s/sx can't be controlled with meds/ISC, what do you do? Continuous cath or surgical urinary diversion
What results from retention of urine in bladder & from catheterization procedures? UTIs; Antibiotics used to treat
How to manage constipation? Dietary changes: increased fluid & fiber, bulk-forming supplements, stool softeners
What is not recommended for management of constipation? Regular/continuous use of stimulant laxatives & enemas
Incontinence Management Dietary: avoid irritants (caffeine, alcohol); Adjust meds used to reduce spasticity (can contribute to problem); Add meds to control bowel spasms
Progressive-Relapsing (PRMS) Progressive disease from onset but without clear acute relapses, +/- some recovery or remission; Common in people who develop disease after 40
Created by: 1190550002



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