Myasthenia gravis

What is it?
-Disorder of the neuromuscular junction leading to
lower motor neuron signs
-congenital vs. acquired

What form of M.G. is more common?

-Acquired: generalized vs focal vs fuliminating

Congenital M.G
-signalment: 3-8 wo puppies>>kittens>> 1 mo
Brahman calves
-breeds: springers, fox terriers, JRT, Siamese, DSH
-pathogenesis: disorder of the acetylcholine receptor
(structural vs not enough), may be inherited
-90% of megaesophagus but regurgitation less likely

Acquired M.G.: signalment and breed predisposition

-signalment: dogs>cats; adults
-predisposed breeds: Akitas, German Shorthaired
Pointers, Newfies, Great Danes, Abyssinian, Somali
-most commonly affected breeds: Goldens and Labs

Acquired M.G. pathogenesis

1. antibodies bind the nicotinic acethylcholine receptor
located at the post-synaptic NMJ, motor end plate
2. the entire receptor is internalized into the muscle
until a new receptor is made
3. acetylcholine released from the terminal axon has
nothing to bind to
***clinical signs directly correlate to the number of
receptors bound by antibodies
http://thebrain.mcgill.ca/flash/i/i_06/i_06_m/i_06_m_mo
u/i_06_m_mou.html

Generalized M.G.
*All skeletal muscle diffusely impacted
-hx: weak after exercise but then gets better once
being rested for 30-60 minutes, regurgitates food,
dyspnea, drooling, eyelid and lip paresis
-mentation: normal
-gait: short strided, paresis pelvic limbs-> thoracic
limbs if they keep exercising
-posture: kyphotic, flexed neck, +/- collapse
-spinal reflexes: normal

Fulminating M.G.
*Acute and rapid onset of generalized
-hx: recumbent, can't move
-gait: flacid paralysis
-posture: lateral
-cranial nerves: slight facial paresis
-spinal reflexes: diffuse atonia and areflexia, positive
nociception, normal anal tone
-prognosis: grave (respiratory arrest)
-prevalence: 16% of MG cases in dogs

Focal M.G.
*Only single skeletal muscle group impacted
-hx: regurgitates food>>>; dyspnic; dysphagic,
dysphonic; eyelid and lip paresis
-mentation: normal
-gait: normal
-posture: normal
-cranial nerves: facial paresis

Cat vs Dog M.G.

-Dogs: ~80% have megaesophagus; 3% have

thymoma
-Cats: ~30% have megaesophagus, 25-50% have
thymoma, ventroflexion due to thinner nuccal ligament
compared to dogs

Diagnosis
TENSILON TEST:
-anticholinesterase edrophonium chloride
- best for generalized form
-low sen/spe
ACHR AUTOANTIBODIES
-gold standard for acquired M.G.; will be negative for
congenital M.G.
-in general, highest levels in fulminate cases, lowest
levels in focal cases
-2% seronegative
MUSCLE BIOPSY
-quantifies AchR receptor
-submit external intercostal biopsy
THORACIC RADIOGRAPHS
-megaesophagus->aspiration pneumonia
-thymoma
THYROID PANEL
-high incidence of hypothyoid dogs with M.G.

Tenislon test steps

1. Exercise patient until LMN paresis obvious
2. Administer Tensilon 0.1-0.2mg/kg dog; 0.250.5mg/kg cat IV
3. In 5 seconds the paresis should get better (lasts 2-3
minutes)
***have atropine on hand in case they have a
cholinergic crisis (esp. cats)

Treatment
ANTICHOLINESTERASE
1. Pyridostigmine bromide (Mestinon): 0.5-3.0 mg/kg
(dog); 0.25 mg/kg (cat) PO q8-12 hr. Start low, work up.
2. Neostigmine: use if can't give oral med; 0.04 mg/kg
IM q6hr
**Toxic signs: paralysis (nicotinic effects); SLUDS
(muscarinic); tx with atropine
IMMUNOSUPPRESSANTS
1. Prednisone: start at 0.5mg/kg (dog) 1-4mg/kg (cat)
q12 hr
2. Azathiprine: 1 mg/kg q 12 hr
SUPPORTIVE CARE
1. aspiration pneumonia: broad spectrum abx, be
aggressive
2. esophagitis: sulcralfate, PPI
3. nutritional support

Prognosis
-some have spontaneous recovery - 80% dogs, rarely
for cats (20-30%)
-reoccurance possible
-life-long management of ME +/- aspiration pneumoa
-long-term management often necessary due to
Myasthenia Gravis
a neuromuscular disease that leads to fluctuating
muscle weakness and fatigue.

MG diagnosis
Diagnose with combination of Tensilon,
EMG and acetylocholine receptor antibodies.


MG
- Autoimmune Disorder of NMJ (Neuromuscular
Junction).
- Post-synaptic anatomic locus.
- Predominant symptoms are of bulbar character

MG most common caused by?

circulating antibodies that block acetylcholine
receptors at the postsynaptic neuromuscular junction,
inhibiting the excitatory effects of the neurotransmitter
acetylcholine on nicotinic receptors at neuromuscular
junctions.

MG epidemiology
- Young women, mature men.
- Age range; neonatal to 93.
- Associated autoimmune diseases;
- Thyroiditis, Pernicious Anemia, RA, Vitiligo, Ovarian
failure.
- Thymoma
- Hyperthyroidism
- Drug induced; penicillamine.

MG Initial Clinical Features

- Bulbar predominance.
- Ptosis / diplopia most common 1st symptom.
- Proximal > distal sometimes asymetric distribution.
- Respiratory distress common late but rarely may be
presenting illness.

MG Clinical
- Ocular presentation most common with ptosis and
diplopia.
- Lower bulbar symptoms may be initial manifestation;
dysphagia, dysarthria.
- Uncommon presentations: Proximal weakness and
floppy head.

MG Differential Diagnosis of Ocular Presentation

3rd nerve palsy:
- posterior communicating aneurysm.
- diabetic, hyperthyroidism.
- leptomeningeal disease, Horner's syndrome
- Lambert eaten syndrome.
Internuclear ophthalmoplegia: multiple sclerosis
Intermittent diplopia: TIA.

MG Differential Diagnosis of Lower Bulbar Presentation

TIA, bulbar stroke.
Brain tumor.
Leptomeningeal infiltration.
Motor neuron disease (primary bulbar palsy).
Miller-Fisher variant of GBS.
LEMS
Polymyositis.

MG Differential Diagnosis Extremity Weakness

LEMS
Polimyositis, dermatomyositis.
Inclusion body polymyositis.
Periodic paralysis.
Endocrinopathies.
Congenital myopathies.
Dystrophies. FSH, myotonia dystrophica.

MG Diagnostic Studies

- Tensilon Test
- EMG: Post synaptic vs. presynaptic. To rule out other
motor unit disorders.
- Acetylocholine receptor antibodies, TSH.
- Single fiber EMG.
- Chest CT.

What is tensilon test?

- Injection of edrophonium chloride used to diagnosis
myasthenia gravis
- Tensilon is the trade name for edrophonium chloride
- Tensilon blocks the action of acetylcholinesterase
- By blocking the action of acetylcholinesterase,
Tensilon prolongs the muscle stimulation, and
temporarily improves strength.
- Increased strength following an injection of Tensilon
strongly suggests a diagnosis of MG.
- differentiate between MG, cholinergic crisis and
lambert eaten syndrome

MG Diagnosis: Antibodies
Types: Binding, modulating, blocking.
Actions at AChR:
- Accelerated degradation, crosslinking, endocytosis.
- Functional blockade.
- Complement mediated lysis of end-plates

Sero-Negative MG
- Frequency = 12-17% generalized MG.
- No clinical differences from Ab + cases. - Low titers with complete binding by endplate.
- Antibodies different main AChR binding site.
- Brief MG duration, or prior immuno-therapy.
- Favorable response to Tensilon.
- Similar response to anti-immune Rx.

MG EMG diagnosis
- SNAPs normal.
- CMAPs normal to low amplitude.
- NCV and distal latencies narmal.
- RMNS: = 10-15% decrement after 2-3Hz.
- RMNS: 10" exercise=<10% facilitation.
- RMNS: 60" exercise=> decrement @ 4m
- MUPs; fluctuating amp leads to SFEMG +.

MG Therapeutic Options
- Mestinon (reversible choline esterase inhibitor)
- Plasmapheresis
- Intravenous immunoglobulin
- Prednisone
- Imuran (= azathioprine)

MG general therapeutic options: patient education

- Pace activities, reasonable rest.
- Diet = potassium supplementation.
- Minimize infections, flu immunization.
- Control exposure to heat, and overexertion.
- Search for other autoimmune: TSH, B12.
- Beware drug exacerbation (beta- blockers, cholesterol
lowering agents)
- Catamenial exac: long act progesterone.

MG Anticholineterase Therapy
- Initial treatment = Pyridostigmine (Mestinon).
- Mestinon at bedtime.
- Cholinergic crisis now rare.
- Problem = symptomatic treatment only.

Mye graving for lage pyrimider, da blir du en mester!

MG Azothioprine Therapy
- Indications: Poor response, intolerance to, or frequent
relapses with prednisone. (Try AChEI and steroids
first!!!)
- Idiosynchratic side effects: 10% patients.
- Gastrointestinal, flu like clear on own.
- Bone marrow suppression.
- Effectiveness delayed onset 6-18 months, but
eventually 70-80%.

MG Prednisone Therapy
- Action: Effects activated T&B cells and antigenpresenting cells.
- Exacerbation may occur as dose decreased.
- 70-80% response with careful treatment adjustment

MG Therapy surgery
Thymectomy

Myasthenic Crisis
- Definition: Respiratory Distress requiring ventilatory
support, pheresis, IVIg.
- Up to 16% patients need ICU
- Today treatment prevents most crisis
- Survival: <6%
- Cholinergic crisis: Exceedingly rare.
- Treatment: Withdrawl of anticholinesterse therapy.

MG Medication Exacerbation
Calcium channel and Beta blockers.
Quinidine.
Procainamide.
Botulinum toxin.
Aminoglycosides.
Magnesium salts.
Muscle relax; curare.
Penicillamine.
Early Corticosteroids.
Radiographic contrast.

Lambert-Eaton Myasthenic Syndrome

a rare autoimmune disorder that is characterized by
muscle weakness of the limbs. It is the result of an
autoimmune reaction in which antibodies are formed
against presynaptic voltage-gated calcium channels,
and likely other nerve terminal proteins, in the
neuromuscular junc

Lambert-Eaton Myasthenic Syndrome

- Proximal weakness is primary complaint.
- Areflexia classic but reflexes may be retained.
-Bulbar symptoms but often mild.
- Autonomic dysfunction (diminished potens). may be
initial presentation in men
- VQ 65(+). Voltage Gated Calcium Channel Antibody.
- Chest MRI /CT if routine chest radiograph ok.

Lambert-Eaton diagnostic study of choice

EMG

gravis
myasthenia _______ is an autoimmune transmission
disorder --> causes weakness of voluntary muscles,
affects communication btwn a motor neuron & muscle

cell (at neuromuscular junction); has no effect on

sensation or coordination

T
myasthenia gravis is probably caused by sensitized ___
helper cells that cause an autoantibody-mediated
attack on the acetylcholine receptors --> decreased
amount of receptor-rich areas, decreased number of
receptors, and widened synaptic space --> impaired
transmission of signals across neuromuscular junction

thymic
the antibodies that attack in myasthenia gravis are
present in 80-90% of people with MG. These people
usually have either ______ hyperplasia or a ______
tumour (probably d/t the fact that antibodies are
produced in the thymus gland)

ptosis
symptoms of myasthenia gravis include ______
(drooping eyelid), diplopia (double vision), and later
maybe generalized weakness of all extremities,
respiratory muscles (affecting vital capacity), and the
face and throat (affecting swallowing, chewing, speech,
and facial expressions)

increases
myasthenia gravis' weakness and fatigue ________ with
continued activity because each time acetylcholine is
released from the presynaptic membrane, the endplate
potential (depolarization) decreases even more

nerve
myasthenia gravis Dx includes Hx and physical exam,
the anticholinesterase test, _____ stimulation tests, and
an investigation of acetylcholine receptor antibodies

anticholinesterase
__________ test - acetylcholine breakdown is prevented
by the anticholinesterase agents (enzyme inhibitors)
--> acetylcholine levels increase

stimulation
nerve __________ tests record the targeted muscle's
electrical activity after stimulation. Pts with myasthenia
gravis have a 15% decrease in successive action
potentials.

MRI
the third way to diagnose myasthenia gravis is by
administering an ____. In 90% of cases, the MRI shows
enlargement of the thymus gland (a site of
acetylcholine receptor antibody production)

antibodies
management of myasthenia gravis includes improving
Fx, and reducing & removing circulating ________ by
administering anticholinesterase agents,
immunosuppressive therapy, plasmapheresis, and
thymectomy.

plasmapheresis
aka plasma exchange - used to treat exacerbations of
myasthenia gravis; removal, separation of blood cells
and plasma, tx, and replacement of plasma with a
plasma substitute --> temporary decrease in the
concentration of circulating antibodies (sustained by

cholinesterase inhibitors, corticosteroids,

immunosuppressive drugs or a combination)

myasthenic
________ crisis = a sudden increase in myasthenia
gravis symptoms and weakness; occurs when muscle
weakness becomes very severe - enough to cause
difficulty with ventilation and severe bulbar (face and
throat muscle) weakness.
May be d/t stress (d/t infection, emotional or physical
trauma such as surgery, pregnancy, alcohol ingestion,
cold exposure, or improper doses of Tx drugs
(anticholinesterase drugs))

Myasthenia Gravis (MG)

neuromuscular disorder characterized by fluctuating
muscle weakness and a predisposition to rapid fatigue

MG common symptoms
1. ptosis (drooping eyelids)
2. difficulty swallowing
3. skeletal muscle weakness

MG symptom with severe form

difficulty breathing --> possibly respiratory failure

neostigmine
reversible cholinesterase inhibitor

neostigmine: mechanism of action

prevents the breakdown of ACh by acetylcholinesterase
(ChE) --> will increase muscle strength

Neostigmine
lifelong therapy that will produce symptomatic relief

neostigmine: routes of administration

PO, transdermal, IM, IV, SQ

neostigmine: side effects

**Due to accumulation of ACh at muscarinic junctions
1. excessive salivation
2. increased gastric secretions
3. increased tone and motility of GI/GU tract
4. Bradycardia
5. Sweating
6. Miosis

treatment of too much neostigmine

ATROPINE!!! (use sparingly)

dosing off neostigmine

1. challenge -- use trial and error
2. start low, go slow and increase until optimal level of
muscle functioning
3. meticulous record keeping (what works, when
fatigue occurs, when are muscles too tired, etc)
4. signs of improvement (ease of swallowing and
increased ability to raise eyelids)

Under medication = myasthenic crisis

1. extreme muscle weakness due to insufficient ACh at
NMJ
2. untreated can lead to death
3. Treatment = neostigmine

Over Medication = Cholinergic Crisis

1. skeletal muscle paralysis & signs of excessive

muscarining stimulation (salivation, GI/GU motility, etc)
2. Treatment = respiratory support, atropine,
withholding neostigmine

How to distinguish b/w myasthenic crisis and

cholinergic crisis?
1. history of medication administration and sx of
excessive muscarinic stimulation
2. give challenging dose of edrophonium (Sx better =
myasthenic crisis; Sx worse = cholinergic crisis)

Neostigmine: nursing considerations

1. promote compliance
2. wear medic alert bracelet
3. be aware of myasthenic crisis
4. use atropine sparingly

Myasthenia Gravis (MG)

An autoimmune disease
Characterized by fluctuating weakness of certain
muscle groups
Course of the disease is variable: short term
remissions, stabilization, severe progression

MG: Etiology
Same as every other autoimmune disease
Antibody association

MG Risk Factors
Age 10-65
Women > men

MG Patho
Antibodies attack ACh receptors "anti-ACh-R
antibodies"
Decrease in ACh receptor sites at the NMJ
This prevents ACh molecules from attaching and
stimulating muscle contraction

MG CM
Fluctuating weakness of skeletal muscle
Strength comes back after resting
Involves eyes/eyelids, facial, speaking, and breathing
muscles

Myasthenic Crisis
Acute exacerbation of muscle weakness
Triggered by a stressor: infection, surgery, emotional
distress, pregnancy/menses, inadequate
pharmacotherapy or other drugs
Major complication is breathing muscle weakness

MG: Pharm
Immunosuppressants (steroids)
Cholinesterase Inhibitors

How do Cholinesterase Inhibitors work?

Prevent inactivation of Ach by cholinesterase
Intensify the effects of Ach released from motor
neurons - increases muscle strength

Are cholinesterase inhibitors a cure or symptomatic

relief?
Symptomatic relief

Neostigmine/Prostigmin

Cholinesterase Inhibitor
Given for MG

Muscarinic receptors
Affect glands

Nictonic receptors
Affect muscles

Effects of Atropine
Dry mouth
Urinary retention
Pupil dilation (mydriasis)
Bronchodilation

Cholinergics
Increased motility, diarrhea
Increased secretions
Urinary urgency
Bradycardia
Bronchial Constriction
Miosis (constriction)

Anticholinergics
Decreased motility, constipation
Dry mouth
Urinary retention
Tachycardia
Bronchodilation
Mydriasis (dilation)

Neostigme AE
Muscarinic: Increased secretions, GI motility, urinary
urgency, bradycardia, bronchial constriction, miosis,
near-sightedness
Neuromuscular: Therapeutic doses increase muscle
contraction, toxic doses reduce contraction, toxicity
could lead to cholinergic crisis

Cholinergic Crisis
Extreme muscle weakness or paralysis
S/S of excessive muscarinic stimulation
Tx: Mechanical ventilation & intubated, antidote is
atropine
Patient should wear medic-alert bracelet at all times!

Myasthenic Crisis
Muscle weakness
No excessive muscarinic stimulation
Test dose of an ultra-short acting cholineterase
inhibitor (Edrophonium) alleviates symptoms
Treat with mechanical ventilation and plasmapheresis

Cholinergic Crisis
Muscle weakness
Excessive muscarinic stimulation
Test dose of an ultra-short acting cholineterase
inhibitor (Edrophonium) makes symptoms worse
Treat with mechanical ventilation and atropine

What is myasthenia gravis?

A chronic, progressive autoimmune disorder; manifests
as weakness and abnormal fatigability of skeletal
muscles

What neurotransmitter is severely reduced in MG?

Acetylcholine

What are the causes of MG?

Insufficient secretion of acetylcholine
Excessive secretion of cholinesterase
Unresponsiveness of muscle fibers to acetylcholine

What is the purpose of the Tensilon test?

also know as the Edrophonium test
- Diagnoses myasthenia gravis
- Differentiates between cholinergic crisis and
myasthenic crisis

What is a positive Tensilon test?

the injection of edrophonium; marked improvement in
muscle strength is a positive finding of MG*

When is the Tensilon test negative?

the client does not show signs of muscle improvement;
the client's strength may even deteriorate (indicative
of cholinergic crisis)

What is the antidote for a negative Tensilon test?

atropine

Name other possible diagnostics

EMG - electromyography
thyroid test
CT scan of thymus

Do remissions and exacerbations occur with MG?

Yes

Co-morbidities/Associations with MG
Rheumatoid Arthritis
SLE - lupus
Pernicious anemia
Ulcerative colitis
Hyperthyroidism
Hyperplasia of thyroid gland
Polymyostitis
Sjogren syndrome

T/F: MG is more common in women

True; 3:2

What are triggers of myasthenia gravis?

infection
stress
Fatigue
cathartics (laxatives?)
Heat - saunas, hot tub, sunbathing

What is the clinical presentation of MG?

- Progressive weakness and fatigue of skeletal muscles
that worsens as the day progresses*
- Inability to maintain position without support
- Ptosis, diplopia, inability to maintain upward gaze
- Dysphagia
- Respiratory compromise*

What are signs of fulminating MG? (severe)

Early respiratory dysfunction
Cholinergic/myasthenic crisis

Rapid onset with severe weakness*

Response is poor :(

With fulminating MG, high morality rate is associated

with..?
respiratory failure or aspiration

What causes a cholinergic crisis?

Overmedication with anticholinesterase

Signs of a cholinergic crisis

Abdominal cramps
Nausea and vomiting, diarrhea
increased respiratory secretions
Blurred vision
Pallor
Facial muscle twitching
hypotension
pupillary miosis

What causes a myasthenia crisis?

infection, stress, fatigue
inadequate amount of medication
(tolerance/exacerbation of disease)

Signs of myasthenia gravis

increased Pulse, respirations, BP
Dyspnea, anoxia, cyanosis
Bowel/bladder incontinence
Decrease UO
absent cough/gag reflex

What medication is given to improve MG?

pyridostigmine

What therapeutic procedures manage MG?

Irradiation
plasmapharesis
respiratory support

What medications are used for MG?

Cholinesterase inhibitor ---> pyrdiostigmine
corticosteroids ----> prednisone
immunosuppressive drugs ---> azathioprine
IVig

What is the first line of therapy for MG?

cholinesterase inhibitors

Client instruction for pyridostigmine

Take with food to minimize adverse GI effects
Advise client to eat within 45 minutes of taking the
medication to strengthen chewing/reduce aspiration
risk

Nursing care for a client with MG

Assess for a patent airway
Assess swallowing to prevent aspiration
Allow for frequent rest periods

What type of diet should be advised for a client with

MG?

Small, frequent high-calorie meals

What lab should be monitored for nutritional status of

MG?
Albumin

T/F: Pain is not usually a problem with MG

True

what causes demyelination of MS

autoimmune activity

where is the highest geographic prevalence of MS

in europe, new zealand, southern australia, northern
US and southern canada

primary drug for MS

interferon beta

side effects of interferon beta medications

flulike symptoms, potential liver damage, fetal
abnormalities and depression

what is the medication that reduces the rate of relapse

in RR course of MS and is administered subcutaneously
daily
Copaxone

the key agent in treating acute relapse in the RR

course, shortens the duration of relapse but has not
been found to have long term benefit. exerts anti
inflammatory effects by acting on T cells and cytokines
IV methylprednisolone

what is IV methylprednisolone followed by

oral taper of prednisone

side effects of IV methylprednisolone

mood swings, weight gain, electrolyte imbalances

what does the medication mitoxantrone (novantrone)

do
adminstered by IV every 3 months and reduces the
frequency of clinical relapses in patients with
secondary progressive or worsening RR MS.

side effects of novantrone

cardiac toxicity

an autoimmune disorder affecting the myoneural

junction is characterized by varying degrees of
weakness of the voluntary muscles
myasthenia gracis

initial manifestations of myasthenia gravis

diplopia and ptosis, weakness of muscles of face and
throat, voice impairment (dysphonia) and dysphgia

what test diagnoses myasthenia gravis

acetylcholinesterase inhibitor test

first line drug for myasthenia gravis

mestinon (anticholinesterase medication) AKA
pyridostigmine bromide

adverse effects of anticholinesterase medications

fasciculations, abdominal pain, diarrhea, increases

oropharyngeal secretions

other than pharmacological treatment for myasthenia

gravis what else can be done
thymectomy

exacerbation of the disease process characterized by

severe generalized muscle weakness and respiratory
and bulbar weakness leading to respiratory failure
myasthenic crisis

what can cause a myasthenic crisis

respiratory infection, medication change, surgery,
pregnancy

autoimmune attack on the peripheral nerve myelin

gullain barre sundrome

clincal manifestations of guillain barre syndrome

muscle weakness, diminished reflexes of the lower
extremities, neuromuscular respiratory failure

Guillain Barre
Pathophysiology
-Progressive ascending paralysis
-Segmental demyelination of peripheral nerves
-Frequently preceded by a viral illness, vaccination, or
surgery
-Believed to be an autoimmune disorder
-Remyelination and recovery occurs in >80% of
patients afflicted
-potentially fatal b/c of paralysis to respiratory so on
mechanical vent

Clinical Manifestations
Rapidly progressing ascending flaccid paralysis with
loss of DTRs
-Muscles of respiration frequently involved
-Pain and paresthesias are common, may be
accompanied by sensory loss
slight touch could be super painful
-If cranial nerves are involved patient will have facial
weakness, dysphagia and difficulty with EOMs.
EYE MOVEMENTS

Clinical Manifestation
Autonomic dysfunction is common
-May have SIADH associated with autonomic
dysreflexia (uncontrolled hypertension) no full
bladders, no constipation. leads to cardiac block,
severe diuresis, facial flushing
-Risk for infection
-Complications of immobility

Phases of Illness
ACUTE - Continues until no new symptoms or
deterioration occurs
PLATEAU - Symptoms remain but do not worsen

RECOVERY Condition begins to improve, often to full

recovery

Expected Outcomes: Physiological

-Adequate ventilation
-Avoidance of aspiration
-Maintenance of adequate nutrition
-Avoidance of infection
-Avoidance of injury
-Adequate bowel and bladder emptying
-Maintenance of adequate cardiac output
-Avoidance of complications of immobility
-Adequate pain control

Expected Outcomes: Functional

-Maintenance of baseline muscle strength and ROM
-Maintenance of adequate means of communication
-Return to usual physical functioning

Expected Outcomes: Mental

-Fear is minimized
-Family and social support is adequate
-Sensory deficits are minimized

Diagnostic Testing
Diagnosis based on history and clinical presentation
No specific diagnostic test
CSF analysis: elevated protein with normal cell count
(albuminocytologic dissociation) is highly suggestive
-EMG and nerve conduction studies will eventually
show profound slowing

Assessments
Frequent monitoring of neurological functioning during
acute stage (how is it progression, is it getting to
respiratory muscles)
SIADH (urinary output would decrase, concentratin
would be higher, sodium would hyponatremia)
FREQUENT MONITORING OF RESPIRATORY STATUS
Careful monitoring for signs of autonomic dysreflexia
including cardiac monitoring if indicated (KNOW SIGNS,
flushing, profuse sweating, bradycardia, blurred vision,
hypertension!!! problem is occuring know this shit
Ongoing monitoring for complications of immobility
(DVT, PE, watch skin, pneumonia)

Symptom Management: Morbidity Reduction

Measures to prevent and manage autonomic
dysfunction (atropine for bradycardia, HOB elevated,
reduce noxious stimuli, no full bladder, constipation,
vasopressor for bradycardia, volume expanders if blood

is low, if SIADH then fluid restriction)

Measures to maintain muscle tone and prevent
contractures
Measures to maintain skin integrity
DVT prevention
Non pharmacological pain management

Skills and Technologies

Mechanical ventilation
Nutritional support (swallowing, maybe feeding tube)
Maintenance of airway (drooling) vital
capacity,ominous sign is drooling
Management of bowel and bladder dysfunction
(suppositories, maybe. avoid foley catheters b/c of
foley, but if need it use it)
PLASMAPHERESIS (Removal of abnormal circulating
antibodies through plasma exchange)
only of vavlue if you can do it early on in disease
process.

Medication Management
Intravenous immune globulin (IGIV)
-cause renal failure, MI, hypovolemia, fluid overload,
infection. not really helpful.
Heparin prophylaxis
Augmentation of cardiac output as needed
-vasopressors and volume expanders if BP low
Short acting antihypertensive agents
Corticosteroids and ACTH
-stimulate body to produce own corticosteroids.
Artificial tears
-protect cornea, lubircate eye shield
Analgesics
-major focus for parasthesias
Antianxiety agents
-lots of anxiety with this disorder
Stool softeners, bulking agents

Social Interventions
Maintaining communication Minimizing sensory deficits
Measures to decrease anxiety
Guillan Barre Path
lesions at nerve roots!!!!! Autoimmune acute
inflammatory causing demylelinization and axonal
damage. Inflammation is proximal PNS; slows or stops
signals; must take 4 weeks to peak disability to be GBS

Causes of GB
lesions at nerve roots! immune mediated, infections,
toxins, diabetes, post-surgery, immunization,

More Path

lesions at nerve roots! demyelinating inflammatory

polyradiculoneuropathy, patchiness of myelin loss, 4
weeks until plateau, function comes 6 months to a year
back through remylenination and possibly re-nervation

Prognosis
85% recover, bad prog if quad, no signs of recovery
within 3 weeks plateau, respiratory dependence, rapid
onset, 5% die: weak anterior tib, hand intrinsics, quad
and glutes

Medical
stabilize respiration, prevent infections/complications,
steroids, plasmaphoresis, IV immunoglobulin

Symptoms
Distal to proximal, symmetrical leg weakness first:
Early LE weaknesss and tenderness of muscles,
stocking glove distribution, hypotonia, atrophy, LMN
symptoms, 50% cranial nerve involved, pain in back
and legs, 50% autonomic problem = BP, trophic,
regional pain syndrome, =

Phase 1 acute
respiratory, maintain structural mobility ensure joint
integrity

Phase 2 rehab
increase strength with submax resistive exercise, avoid
overwork, eval mm strenth every day monitor vitals,
reduce discomfort and pain, improve posture,
breathing training, endurance

The peripheral nervous system problems found with

Guillain-Barr syndrome (GBS) include:
loss of reflexes & flaccid paralysis of skeletal muscles.

Under microscopic inspection, the skeletal muscle

nerves of a Guillain-Barre patient show the following:
edema. Inflammation. Demyelination.

The major pathologic or structural changes of the lungs

associated with ventilator failure accompanying
Guillain-Barr syndrome include:
alveolar consolidation, airway distortion and dilation,
atelectasis.

Guillain-Barr syndrome most likely occur

Caucasian male53 years of age

When a person has Guillain-Barr syndrome, how are

peripheral nerves affected?
The myelin sheath is removed.

Common noncardiopulmonary manifestations

associated with Guillain-Barr is (are):
1.difficulty swallowing. 2. leg pain. 3. distal
paresthesia. 4. absent deep tendon reflexes.

The diagnosis of Guillain-Barr syndrome is based on

all of the following:
abnormal electromyography results. cerebrospinal fluid
shows elevated protein level clinical history.

Clinical indications that a patient has impending acute

ventilatory failure include:

1. pH 2. vital capacity (VC) 3. PaCO2 >45 mm Hg.

A patient with Guillain-Barr is paralyzed and on

mechanical ventilatory support. Which of the following
pulmonary complications is most likely to occur as the
result of prolonged immobilization?
Thromboembolism or a PE

Which of following has been shown to shorten the

course of a severe case of Guillain-Barr syndrome?
Plasmapheresis

Typical chest assessment findings in a patient with

Guillain-Barr syndrome include:
1. diminished breath sounds. 2. crackles.

A Guillain-Barr syndrome patient has autonomic

nervous system dysfunction which can result in all of
the following:
tachycardia hypotension & urinary retention.

A patient with Guillain-Barr syndrome developed

atelectasis. His chest radiograph findings would be
expected to show:
increased opacity as a result of increased secretions

Approximately what percentage of patients with GBS

develop respiratory muscle paralysis
10% to 30%

In the United States and Europe, what is the most

common subtype of GBS?
Acute inflammatory demyelinating polyneuropathy
(AIDP)
Multiple Sclerosis
Multiple Sclerosis
partial destruction of myelin shealths around the spinal
cord, brain and optic nerve

Multiple Sclerosis Etiology

Invasion of external dampness, diet, excessive sexual
activity, shock

Damp phlegm with spleen deficiency Rx

swollen with teeth marks and a yellow sticky coating

and forceful pulse
Si Miao San

Ren 12, Ub 20, Sp 9, Sp 6, St 40

Kidney and Liver Deficiency

Tonify liver and kidney and strengthen bones and
tendons
Progressive weakness of the legs, weak back and
knees, dizziness, poor memory, blurred vision,
hesitancy or urgency urination

Kidney and Liver Deficiency Rx

Tonify liver and kidney and strengthen bones and

tendons
Liu We Di Huang Wan
K 3, Ren 4, UB 23, Sp 6, Lv 8, Ub 18, Si 3, Ub 62, Lv 3,
GB 20
Scalp: Voluntary movement leg motor and sensory area

Liver wind due to kidney and liver deficiency

Subdue liver wind
pale thin tongue with wiry thready pulse

Damp phlegm with spleen deficiency

Nourish the heart, ease the mind, strengthen the
spleen and kidney

tremor, spasms, paraplegia, difficulty in balancing

difficulty in urination, cerebellar disturbance with
ataxic gait, spastic muscles, pale thin tongue with wiry
thready pulse

swollen with teeth marks and a yellow sticky coating

and forceful pulse

numbness feeling of heaviness of legs, tingling,

dizziness tiredness, hot sensation in soles of feet with
desire to expose them to coolness, swollen with teeth
marks and a yellow sticky coating and forceful pulse

Liver wind due to kidney and liver deficiency Rx

Subdue liver wind
pale thin tongue with wiry thready pulse

Lui Wei Di Huang Wan

T2: spinal fluid hyperintense, bright

Lv 3 Gb 20

FLAIR: remove spinal fluid

-makes lesions more enhanced
-pictured: multiple old lesions adj to ventricles

cervical spinal cord MRI in MS

-flame shaped lesion

chronic small vessel ischemic dz

-small strokes that have happened over time
-not oval or oriented outward
-non enhancing, can't say they happened at the same
time

what is MS
-lesions of CNS disseminated in time and space
-MC bw age 15-45 yo, women >> 4:1
-85% w relapsing-remitting MS (RRMS)
--50% untx will develop secondary progressive MS
(SPMS)--> disability in 10yrs
-demyelination in random, various locations throughout
CNS
-genetic predisposition, something happens to trigger
(viruses, vit D)

economic/social impact
->450,000 in US and 2.5 million worldwide
-duration= 30 ys
-30% w severe disability
-70% unemployed
-$9.6 billion/yr, care is $34,000/yr NOT including DMT
-farther from equator--> less sun--> larger impact
-suppl vit D might help dz?

what causes MS?

-immunologic/autoimmune: molecular, Vit D
-microbial: viral (EBV, HHV-6), chlamydia
-oligodendrogliopathy
-vascular: small vessel, CCSVI
-toxic/environmental

dx criteria
2 or more attacks:
-objective clinical evidence of 2+ lesions , or 1 lesion w
evidence of previous attack
-obj evidence of 1 lesion + DIS or await another attacks
1 attack:
-obj clinical evidence of 2+ lesions + DIT or wait
second clinical attack
-obj clinical evidence of 1 lesion + DIS, OR await
further attack implicating different CNS site and DIT,
OR 2nd clinical attack
0 attacks, no progression: 1 yr of dz progression AND
(2): DIS in brain, DIS in spinal cord

classic MRI white matter lesion characteristics in MS

-asymmetric, ovoid, >3mm
-periventricular and perpendicular to lateral ventricles
-pons, cerebellar peduncle, and white matter
cerebellum
-enhancing and non enhancing: most initially enhance-> chronic residual T2 (T1)
-cervical >> thoracic cord lesions
-residual- abn, need other MRI imaging

MRI findings
-classic periventricular lesion
-large, oval lesion, oriented outwards
relapse: sx >24 hrs
disseminated in time and space--> findins on MRI
suggestive >1 event

T2 vs FLAIR

-pictured: juxtamedullary, periventricular

clinical subtypes of MS
-relapsing-remitting MS RRMS
-progressive relapsing MS PRMS (recently eliminated)-categorize as PPMS w activity (relapses)
-secondary progressive MS SPMS
-primary progressive MS: PPMS, slow progression, no
relapse

new disease courses

CIS: clinically isolated syndrome
-first attack of inflamm demyelinating dz consistent w
MS
-first sx, >24 hrs, isolated in time
RIS: radiographic isolated syndrome
-MRI consistent w MS absent any clinical episodes
-incidental finding
-not an MS phenotype

core MS phenotypes
-relapsing and progressive
-important modifiers:
--assessment of dz activity measured by clinical
relapse or CNS lesion activity
--ongoing progression of disability

MS phenotype descriptions: progressive disease

(revisions)

mechanism of worsening MS
clinical:
-incomplete recovery from exacerbations in relapsing
forms
-gradual, progressive worsening independent of
relapses
path: inflamm dz, degeneration
no tx for progressive component
-neurodegeneration: progress is separate from relapses
-initial demyelinating event- CIS

why tx MS?
-progressive dz--> acquire significant disability over
time
-50% will need unilat aid to walk in 15 yrs
-help dec relapses/yr

current MS therapies (FDA approv)

- interferons
-Glatiramer acetate
-Natalizumab
-Fingolimod
-Teriflunomide
many emerging tx

immunomodulatory tx
-signaling proteins
-recombinant proteins injected
IFNB-1a IM weekly- prob least effective

Natalizumab (Tysabri)
PROS:
-highly effective, well tolerated, IV q4 weeks (monthly)
-70% dec relapse
CONS:
-progressive multifocal leukoencephalopathy
(PML) (an often lethal brain infection, assoc w JC virus)
-3 hrs in infusion center every 4 weeks
-rebound activity 3-4 months after stopping
usu aggressive dz

Fingolimod (Gilenya)
PROS:
-mod-high efficacy, 50% better than weekly IFNB-1a
-once daily oral capsule
CONS:
-limited exp, potential infection (PML), but much lower
concern than Natalizumab
-CVS deaths: HR monitored closely after 1st dose
-macular edema
-baseline eval + monitoring required
-melanoma?
-it's a pain to start!!!

managing Fingolimod pts

BEFORE tx: get baseline
-CBC and hepatic panel
-ophtho exam
-cardiac status via EKG
-varicella immune status
-derm exam
at INITIATION: 6 hr observation for bradycardia
when on TX:
-CBC, hepatic panel
-ophtho exam at 3-4 months (check for macular
edema), derm annually (melanoma)
-check BP

Teriflunomide (Aubgagio)
PROS:
-mod effective, good safety record
-once/day
-ONLY drug w signif dec disability progression
CONS:
-mod effective
-monthly liver monitoring
-mild hair loss
-pregnancy category X!

-accelerated elimination: charcoal!! get it out,

otherwise stays for months-yr

Dimethyl Fumarate (Tecfidera)

PROS:
-mod-high effectiveness
-safety for psoriasis
-oral med
CONS:
-2x/day
-tolerability probs: GI, flushing
-PML case

Alemtuzumab (Lemtrada)
-a lot of SE!
-need appropriate setting in case of anaphylaxis or
serious infusion rxn
-inc risk malig: thyroid, melanoma, lymphoproliferative
-CBC, BMP, UA monthly, thyroid studies Q3 months x
48 months
-annual skin exam

how to choose tx
is dz aggressive? -- mutliple relapse, a lot of brain
activity on MRI

neuromyelitis optica NMO

-not MS but in spectrum, demyelinating + acquired
CNS disorder
--inflamm and demyelination of optic nerve and spinal
cord
-Delvic's dz
-different prognosis, tx (MS tx doesn't work on NMO)
-AQP4 Ab likely pathogenic: levels may correlate w
activity
-can be assoc w SLE, Sjogren, celiac, myasthenia
gravis, sarcoidosis

MS sx management
-fatigue: MC
-spasticity
-mobility: cane, walker
-bladder dysfunction
-pain, paroxysmal sx
-depression, pseudobulbar affect (uncontrollable
laugh/cry)

fatigue in MS
-probs MC sx
-tx factors: insomnia, anxiety/depression, spasticity,
pain, urinary freq, RLS type sx

pharm approaches
-amantadine: antiviral, dopamine agonist,
antiglutamate
-1/3 report improvement short term
-100mg bid-- a drug holiday 2 days/wk prolongs effect
-SE: nausea, light headed, confusion, hallucination, dry
mouth, livedo reticularis (skin condition), periph edema

Modafinil (Provigil)
-orig "wake promoting agent"
-like CNS stimulant- daytime wakefulness w fewer SE,
less abuse potential
-up to 200 mg bid
-take before 1pm

-interference w OCP (birth control)

-drug holidays maintain sensitizations

clinical signs of spasticity

-hyperactive reflexes
-musc spasms, clonus
-pain
-weakness- spastic

exercise and therapy

-stretching, ROM, weight bearing
-inhibitory casting
-pool therapy, aerobics
-EMG biofeedback, electric stim
--early rehab/PT referrals even in mild dz

managing spasms and stiffness

-Baclofen
-Tizanidine
-Clonazepam
-Gabapentin
-Dantrolene
-dopamine agonist

issues w mobility
-weak, spastic, ataxia, fatigable, pain alt gait
-device: cane, crutch, walker, orthotic, wheelchair
-tx: conditioning programs, adaptive exercises,
orthotics, stabilizers, transfer training

pharm tx of mobility impairment-- dalfampridine

-Dalfampridine
-improve walking in 35-43% (25 foot walk test)
-well tolerated (10mg bid)
-SE: mild dizziness, GI, agitation, wakefulness
-inc risk at higher doses ~20-40 mg bid (sz)

bladder dysfunction
sx based pathophysio:
-storage deficit: spastic bladder
--urgency, urge incontinence, frequency, nocturia and
eneuresis
-emptying deficit: hypotonic bladder
--hesitancy, double voiding, poor force stream, bladder
insensitivty

interventions for voiding dysfunction

-alpha 1 antag
-relaxation techniques
-double voiding
-intermittent cath, indwelling cath
-surg- diversion

tx for pain/paroxysmal sx
-anticonvulsants: Carbamazepine, gabapentin,
levetiracetam, topiramate, pregabalin, zonisamide,
lamotrigine
-antidepressants: duloxetine, tricyclic
antidepressants
-IV methylprednisone 1000mg x 3-5 days
-oral steroids
-topical analgesics: lido
-Baclofen 5mg tid to 10-20mg tid
(spasticity/neuropathic pain)
-trigeminal rhizotomy or instillation of glycerol
-trigeminal decompression

depression in MS
-mood disorders are common in MS
-unpredictability of MS
-depression from dz itself or rxn to dx and lifestyle
changes
-may be SE of interferon therapy
-mood changes inc MS sx

pseudobulbar affect (PBA) in MS

-inappr episodes of crying, laughing sudden, freq,
involuntary
-pts w MS, ALS, stroke, TBI
-possible loss frontal control/disinhibition

tx of pseudobulbar affect
-SSRIs
-dextromethorphan hydrobromide/quinidine
sulfate
-significant reduction in freq and severity of PBA
episodes
-twice daily dosing

cognitive screening and eval

-regular screening: modify activity to dec risk of injury
--adjust expectations
-consider primary MS processes as well as secondary
processes
--fatigue, drug therapy, depression, comorbidities
--tx fatigue, depression, sleep
-limit sedative drugs, modify environment,
anticholinergic

stress
-makes sx of any neuro dz worse, but no evidence it
makes actual dz worse
-pseudo exacerbations vs true
-unavoidable, adapt
-counsel, biofeedback, mindfulness