Progressive Neuromuscular Disorders Pt 1: MS & ALS

Question 1

MS: Pathophysiology

Is a chronic neurological disorder in which the nerves of the CNS (brain & spinal cord) degenerate & derives its name from the buildup of scar tissue (___) or plaques that form during ___ (destruction of myelin sheath)

Answer 1

sclerosis; demyelinaton

Question 2

MS: Clinical manifestations

• Impaired sensation, movement, & thinking

Answer 2

• Numbness or weakness in limbs, partial or complete vision loss, tingling or pain, electric-shock sensations w/head movements, tremor, lack of coordination, or unsteady gait, fatigue, & dizziness

Question 3

• Exact cause of MS is unknown
• Both immune processes & infectious agents have been implicated in MS pathogenesis
• Demyelination is suspected to be triggered by a viral infection, probably by EBV

Answer 3

• Variety of precipitating factors can precede the onset or an exacerbation of MS like infection, physical or emotional stress, pregnancy, & fatigue

Question 4

Etiology, Incidence, & Prevalence

• Immune-mediated dz
• 2.3 mil worldwide have MS w/onset between 20-50 yrs
• Affects women > men

Answer 4

• Immune-mediated dz that affects the myelin sheath & conduction pathway of the CNS

Causes
- Immune
- Environment
- Infectious
- Genetic

Question 5

Immune

• Scientists know that there’s an abn immune-mediated response that attacks the myelin coating, CNS, & nerve fibers, but are unclear what sets this in motion

Answer 5

Environmental

• Some evidence supporting that those closer to the equator have a stronger immune system & lower chance of development; colder climates see a higher inc rate
• Smoking inc risk

Question 6

Infectious

• Exposure to viruses, bacteria, & other microbes during childhood; demyelination & inflammation occur & are a triggering factor in MS development
• Studied but no proof yet → measles, canine distemper, HSV-6, EBV, chlamydia pneumonia

Answer 6

Genetic

• MS is not hereditary but having a 1st deg relative sig inc risk
• Id’ing >100 gene variants
• Studying epigenetics aka lifestyle choices that turn off & on genes
• Some discounted causes - living w/a dog or small pet d/t canine distemper; allergies; heavy metal exposure; physical trauma; aspartame

Question 7

4 Major types of MS

• Relapsing-remitting
• Primary progressive
• Secondary progressive
• Progressive-relapsing

Question 8

?

Is characterized by frequent relapses w/partial recovery but not a return to baseline

This type is seen only in a small % of pts; progressive, cumulative sx’s & deterioration occur over several yrs

Answer 8

Progressive-relapsing (PRMS)

Question 9

?

Involves a steady & gradual neurologic deterioration w/o remission of sx’s

Pt has progressive disability w/no acute attacks

Pts w/this type of MS tend to be between 40-60 y.o. @ dz onset

Answer 9

Primary progressive (PPMS)

Question 10

?

Begins w/a relapsing-remitting course that later becomes steadily progressive

About 1/2 of all ppl w/RRMS develop ___ within 10 yrs

Current addn of dz-modifying rx’s as part of dz management may dec the development of ___

Answer 10

Secondary progressive (SPMS)

Question 11

?

Is the classic picture that occurs in most cases of MS; course of dz may be mild or moderate

Sx’s develop & resolve in a few wks to mos, & pt returns to baseline

During relapsing phase, pt reports loss of function & the cont’g development of new sx’s

Answer 11

Relapsing-remitting

Question 12

MS: Management

• No spec test & can be difficult to diagnose
• Hx, physical, & neurological exam
• No cure

Answer 12

Treatment

• Improving the speed of recovery from attacks
• Reducing the # of attacks
• Slowing the dz progression
• Rx’s used to treat clinical manifestations

Question 13

Interferon beta-1a (AVONEX or Rebif)

An immunomodulator that modifies the course of dz & also has antiviral effects

Answer 13

Interferon beta-1b (Betaseron, Extavia)

• Another immunomodulator w/antiviral properties

Question 14

Glatiramer acetate (Copaxone)

A synthetic protein that is similar to myelin-based protein

Answer 14

Mitoxantrone (Novantrone)

An anti-neoplastic anti-inflammatory agent used to resolve relapses but w/risks for leukemia & cardiotoxicity

Question 15

?

The 1st Mab approved for MS that binds to WBCs to prevent further damage to the myelin (may cause PML, a viral infection of the brain)

Monitoring near status is key; PML confirmed by MRI & CSF

! Rx also causes damage to the liver; routine LFT’s & self-monitoring req’d

Answer 15

Natalizumab (Tysabri)

Question 16

Fingolimod (Gilenya)
teriflunomide (Aubagio)
dimethyl fumarate (Tecfidera)

Are newer oral immunomodulating drugs

! May cause bradycardia, esp within the 1st 6 hrs after taking it

Answer 16

Common s/e’s are facial flushing & GI dist

Routine labs essential as this may cause dec in WBC, predisposing pt to infection

Question 17

• Medical marijuana (cannabis) also used sometimes for sx management to help reduce pain, muscle stiffness, & spasticity
• Pts need to be counseled on use as it may impair cognitive function, cause dizziness &/or intoxication, depending on form

Answer 17

• Corticosteroids (e.g., methylprednisolone (SoluMedrol), dexamethasone, or prednisone), anti-inflammatory, & immune-suppressing rx’s used short-term for exacerbation or initial onset

! Is just for an acute or initial episode; then pt is maintained on prev mentioned rx’s

Question 18

Medication Symptom Management: Spasticity

▴ muscle relaxers
* baclofen (Lioresal)
* tizanidine (Zanaflex)
* dantrolene sodium (Dantrium)

▴ benzodiazepines
* diazepam (Valium)

Answer 18

▴ Also, a potassium channel blocker may be prescribed to help walking speed & ability - dalfampridine (Ampyra)

Question 19

Other Symptoms

▴ Paresthesias - anti-epileptics & anti-depressants; e.g., carbamazepine (Tegretol); amitriptyline (Elavil)

▴ Cerebellar ataxia - may use propanolol & clonazepam

Answer 19

▴ Fatigue may utilize amantadine HCl (Symmetrel), methylphenidate (Ritalin), modafinil (Provigil)

▴ Constipation - docusate sodium [stool softeners] (Colace)

▴ Urinary retention - bethanechol (Urecholine)

▴ Urinary incontinence - oxybutynin (Ditropan)

Question 20

MS - Assessment: Recognize Cues

History
* Vision, mobility, sensory perception changes

Physical assessment/s&s
* Muscle weakness & spasticity
* Tremors
* Dysmetria
* Dysphagia

Answer 20

Psychosocial assessment
* Anger & frustration @ length of time to obtain dx

Lab assessment
* CSF

Other diagnostic assessment
* MRI brain

Question 21

?

Is a condition in which there is improper measuring of distance in muscular acts

?

Is overreaching (overstepping)

?

Is underreaching (understepping)

Answer 21

Dysmetria

Hypermetria

Hypometria

Question 22

Common clinical manifestations

▴ Muscle stiffness or spasms

▴ Paralysis, often in the legs

▴ Problems w/bladder, bowel, or sexual function

Answer 22

▴ Mental status changes - memory loss, problems concentrating, visual perception, word finding but general intellect is intact; emotions can be anger, depression, euphoria

Question 23

Complications

• B/c MS affects nerves throughout body, comp’s can vary
• May be periods of worsening & have a recovery period w/some improvement
• Radicular (nerve root) pains may be present part’ly in low thoracic & abd regions

Answer 23

• Lhermitte’s sign is electrical shocks that shoot down the spine when head is flexed forward; commonly seen in MS but also in cervical problems like spondylosis, herniation, etc. (compression of spinal cord)

Question 24

?

Refers to involuntary muscle contractions that’re very painful

1st line of treatment is exercise &/or muscle relaxants like Valium, Baclofen

Answer 24

Spasticity

Question 25

* Bladder problems can be incontinence or urinary retention. Many pts w/MS develop a neurogenic bladder & have to self-cath * General intellect, incl long-term memory, conversational skills, & reading comprehension, remains unchanged & intact

Answer 25

* Normal life expectancy if sx's are well managed. Death usually occurs as a result of infectious complications (e.g., pna), immobility, or b/c an unrelated dz

Question 26

? Is a disorder of language

Answer 26

dysphasia

Question 27

? Is a disorder of speech

Answer 27

dysarthria

Question 28

* Speech is the process of articulation & pronunciation; it involves the bulbar muscles & the physical ability to form words * Language is the process in which thoughts & ideas become spoken; it involves the selection of words to be spoken, called semantics, & the formulation of appropriate sentences or phrases, called syntax

Answer 28

Sensory ▴ numbness, tingling, blurred vision ▴ vertigo, tinnitus, dec hearing ▴ chronic neuropathic pain, Lhermitte's sign Cerebellar ▴ nystagmus, ataxia, dysphagia ▴ scanning speech - pauses between syllables of words (form of dysarthria) ▴ seizures Sexual dysfunction ▴ ED, dim libido ▴ difficulty w/orgasmic response, painful intercourse, dec lubrication

Question 29

? Is an intense burst of pain like an electric shock that runs down the back into the arms and legs when the neck is moved "barber chair" sign; can be painful, but is not life-threatening Sometimes r/t severe B12 deficiencies

Answer 29

Lhermitte's sign

Question 30

? Occurs b/c of damage to the optic nerve Interferes w/the transmission of signals between the eyes & brain Sx's incl blurry or reduced vision & it's often 1 of the 1st sx's of MS

Answer 30

Uhthoff's sign (*think hot*)

Question 31

MS - Analysis: Analyze Cues & Prioritize Hypotheses * Impaired immunity d/t the dz & rx therapy for dz management * Dec or impaired mobility d/t muscle spasticity, intentional tremors, &/or fatigue * Dec visual acuity & cognition d/t dysfunctional brain neurons

Answer 31

Diagnostic Testing * MRI shows presence of multiple plaques * Electrophoresis of CSF * Evoked potential studies * Neuropsychological test (assess cognitive impairment)

Question 32

90% of ppl w/MS have been found to have elevated amounts of an antibody protein called ___ in their CSF to a greater deg than is present in their blood serum

Answer 32

IgG

Question 33

? Are the electrical signals generated by the nervous system in r/t sensory stimuli Auditory, visual, & somatosensory stimuli are used commonly for clinical studies (DELAYED in persons w/MS) Can help define the extent of the dz; are used for clinical dx in pts w/neurologic dz

Answer 33

Evoked potentials

Question 34

MS - Planning & Implementation: Generate Solutions & Take Action * Managing impaired immunity * Improving mobility - exercise will help to preserve function * Managing dec visual acuity & cognition

Answer 34

MS - Care Coordination & Transition Management * Home care management * Self-management education - MS affects the whole family & is often unpredictable & uncertain in terms of dz course - Healthcare resources (e.g., National MS Society)

Question 35

Amyotrophic Lateral Sclerosis (ALS) * Lou Gehrig's dz * Sx's usually develop >age 50 (40-60) * Prevalence 3.9 per 100,000 people * Death d/t resp failure within 3-5 y.o. sx onset * Affects voluntary muscle control & men > women; no treatment course & considered 100% fatal * Both upper & lower neurons degenerate & die

Answer 35

* Unable to function, muscles gradually weaken, atrophy, & twitch (fasciculation); progressive degeneration leads to death of cells, resulting in brain losing ability to initiate & control muscle movement * Eventually all voluntary muscles are affected & pts are paralyzed but doesn't impair senses or ability to think

Question 36

ALS: Clinical Manifestations * Muscle cramps or stiffness, muscle weakness, slurred speech, & difficulty swallowing * Upper motor neuron damage assoc w/spasticity * Lower motor neuron damage assoc w/flaccidity

Answer 36

Question 37

Not-so-Diagnostic testing ❐ No single test can be used to dx ALS ❐ CT scan &/or MRI of neck & head to r/o other cond that can mimic ALS like spinal cord tumors, herniated discs, spondylosis, MS, etc. ❐ LP for CSF protein/cytology ❐ Ck will be elevated

Answer 37

❐ EMG shows fibrillations or fasciculation; US can show these in deep muscles & can lead to early dx's ❐ Repeated muscle strength testing to look for loss ❐ Swallow evals to r/o risk for aspiration

Question 38

❐ RPR for neurosyphilis ❐ ANA for general autoimmune screen ❐ TSH for hypothyroid ❐ Serum protein electrophoresis for protein disorders

Answer 38

❐ Rheumatoid factors ❐ ESR as a general inflammatory screen ❐ Creatine phosphokinase (CPK) for muscle injury ❐ Electrolytes for imbalances ❐ CBC's for leukemias/plasma cell dyscrasias

Question 39

❐ Anti-MAG & anti-GM1 antibodies for other neuromuscular diseases ❐ Parathormone for deficiency ❐ UA/24 hr urines for heavy metals

Answer 39

❐ Serum lead, acid maltase, & hexosaminidase lvls for other metabolic-neuromuscular diseases

Question 40

Management - Symptomatic Treatment ▻ benzothiazole (Riluzole, Rilutek) ▻ Muscle relaxants for antispasmodics - baclofen for muscle spasms ▻ Laxatives (Miralax, MOM) for constipation

Answer 40

▻ Analeptics (Provigil or Doxapram) for fatigue ▻ TCAs (e.g., amitriptyline) for excessive salivation, pain, & depression ▻ Antimuscarinics, anticholinergics to help secretions

Question 41

benzothiazole (Riluzole, Rilutek) ▻ Decreases the glutamate lvls, an amino acid that affects the nerves that send msgs from the brain to the muscles S/e's * hepatic injury * neutropenia * interstitial lung dz

Answer 41

* Drug trials w/Gilenya (an MS drug) but not appvd for ALS * IPLEX - under investigational new drug application; used to treat growth failure in children w/severe primary IGF-1 deficiency or w/GH gene deletion who have developed neutralizing antibodies to GH

Question 42

* Treatment includes rx's for symptomatic relief, such as baclofen for muscle cramps, laxatives & stool softeners for constipation, analeptics (CNS stimulants) for fatigue & weakness, & TCA's for excessive salivation, pain, & depression

Answer 42

Nursing Care * Maintain patent airway * Facilitate effective communication * Make appropriate referrals * Assess coping & depression * Assess swallow reflex * Nutritional needs * Utilize conservation measure(s) * Address possible advance directive **Remember** - *the psychological effects of intact cognitive ability in the face of progressive paralysis & wasting*