Neuromuscular Disorders - Southwestern Ontario...

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Neuromuscular Disorders

Wilma J Koopman RN(EC) MScN CCN(C) Nurse Practitioner

LHSC University Hospital London Ontario

March 19 2013 CNA Neuroscience Nursing Review Course

Objectives:

1. Review anatomy and function of neuromuscular disorders

2. Describe common NM diseases: ◦ Guillain Barre syndrome

◦ Muscular Dystrophies

◦ Myasthenia Gravis

3. Discuss treatments and nursing management of common NM diseases

ANATOMY AND FUNCTION

Peripheral Nervous system :

Anterior Horn cells (ALS) , Peripheral nerve (GBS) , Neuromuscular Junction (MG), muscle ( DMD)

Pathophysiology maybe anatomical, metabolic, inflammatory, immunological and idiopathic

Anatomy and Function

Lower motor neurons

Peripheral nerves

Neuromuscular Junction

Muscle

Lower Motor Neurons (LMN) Cell body in the anterior gray column of the spinal cord (eg

polio , ALS)

Nerve fibre extends to the muscle

Includes cranial nerves and spinal nerves of the PNS

Peripheral Nerves (PN) PN carry input to CNS via sensory ganglia (afferent fibers)

with output to muscles and autonomic ganglia via motor (efferent) fibers.

Are mixed nerves-motor, sensory, or autonomic

CELL BODY

Myelin sheath

Schwann cell

Node of Ranvier

Synaptic terminals

Dendrites Nucleus Synapses

Nerve Physiology

Action potential generated in cell body moves along the nerve as the membrane depolarizes

Opening Na channels

Depolarization and impulse propagation of impulse are saltatory (ie moves from one node to another

node in myelinated axons)

Autonomic Nervous System

contains motor neurons that regulated activities of visceral organs

Effect smooth and cardiac (involuntary) muscles and glands

ANS – sympathetic, parasympathetic

Sympathetic: fight or flight ◦ Heart rate and BP increases, bowel and bladder function reduced

Parasympathetic – homeostasis

decreases heart rate , increases gastrointestinal and bladder activity

MUSCLE

Skeletal and cardiac muscle is striated

Smooth muscle (ie GI tract, urinary system) unstriated

Muscle is surrounded by connective tissue and a rich blood supply

Contains important proteins, and the energy system for muscle contraction

Eg Muscular dystrophies or mitochondrial diseases

Neuromuscular Junction (connection between motor axon and muscle fibers )

Guillain Barre Syndrome (GBS)

Acute immune mediated polyneuropathies are

classified under the eponym GBS

Heterogenous condition, many variants

Most often presents as an acute monophasic

paralyzing illness provoked by a preceding

infection

63 yr old male

URI 8 days and diarrhea 2 days pre admission

Paresthesia hands and feet and abnormal taste

one day pre admisssion

Followed by imbalance and leg weakness

(proximal > distal) presenting to ER

Hypertension

Intentional 30 lb wt loss

ER exam

Cardiac, resp, GI systems normal

Cranial Nerves normal

Mild proximal >distal weakness

UE Proximal 4/5 distal 5/5)

LE Proximal 4-/5 distal 4+/5

DTRs absent except right triceps

Sens dec vib jps toes, dec pp fingers

Course in Hospital

24 hrs after admission ICU ..intubation,

tracheostomy, G-J tube

Paralyzed (including craniobulbar ) except for

plantar flexion

Treated with IVIG

4 months in ICU

Neurology floor

Sept to Nov ..multiple complications…infections (UTI, RESP), Right subclavian DVT, Right thigh hematoma. Pain

Power improved

Facial 4;Shoulder abductors 2;biceps, triceps, 1, wrist extensors 0, Finger flexors 2, intrinsics, finger extensors, 0

Hip flexion 2, Hamstrings 4, quadriceps 0, ADF 2-2+;APF 5

Decreased PP to wrist and ankles, Vib mildly impaired

DTR returned

Transferred to Rehab

GJ tube and trach in place

AIDP-Guillain Barre Syndrome

(GBS) Most common cause of acute flaccid paralysis in western Countries

Incidence 1-2/100, 000

All age groups-both sexes

Monophasic paralytic illness

Variable progression and severity

1/3 require mechanical ventilation:median 27 days

Progression 2-4 weeks, recovery in 6-24 months

Favorable prognosis, residual deficits in 20%, mortality rate 5-8%

GBS- Pathophysiology Auto-immune

Develop auto-antibody and cell-mediated immune response against myelin/gangliosides -local inflammatory reaction-segmental demyelination+/-axonal degeneration

Immune responses towards infecting organisms cross-react with neural tissues

In ~10% of cases immune response is directed against ganglioside epitopes in axonal membrane(molecular mimicry)

animal model disease; EAN –experimental allergic neuritis

Pathogenesis of GBS

Demyelination (90%) > axonal (10%)

Immune-mediated - molecular mimicry – 2/3 have preceding infection

• Campylobacter, mycoplasma, herpes viruses (CMV, VSV, Mono etc)

– Campylobacter and gangliosides

Humoral (cytokines and antibodies) and cellular attack on myelin antigens

Hartung, Willison, Kieseier

Curr. Opin. Neurol 2002

Diagnostic Features of GBS

Progression over days to a few weeks

Relative symmetry

Mild sensory signs or symptoms

Cranial nerve involvement

Onset of recovery 2-4 weeks after halt of progression

Autonomic dysfunction

Initial absence of fever

Elevated CSF protein after I week of symptoms

Abnormal results of electrodiagnostic studies with slowed conduction or prolonged F waves

GBS: Clinical Features

Progressive, fairly symmetric muscle weakness

Depressed or absent deep tendon reflexes

Pts present days to a week after onset of sx

Variable course - mild walking difficulty to

complete paralysis of all limbs, face, respiratory

and facial muscles

Clinical Features (cont‘d)

Onset: Usual – proximal legs: 10% arms and

facial muscles

Ventilation 30%

Facial, oropharyngeal weakness 50%

Oculomotor 15%

Paresthesias:hands and feet with weakness in

> 80%, but abnormalities on exam mild

Clinical Features (cont‘d)

Prominent severe pain in lower back

Dysautonomia 70%

-tachycardia (Most common), bradycardia, other

arrythmias

-urinary retention, ileus

-hypertension / hypotension; orthostatic

hypotension

-loss of sweating

Unusual features

Papilledema

Facial myokymia

Hearing loss

Meningeal signs

Vocal cord paralysis

Mental changes ( hallucinations, delusions, REM

sleep abn)

Clinical Course

Progresses for two weeks,

By 4 weeks, 90% have reached nadir

Disease progression > 8 weeks consistent with a

diagnosis of Chronic Inflammatory

Demyelinating Polyneuropathy (CIDP)

Diagnostic Tests

Lumbar Puncture (CSF)

Electrophysiology (EPS)

Antibodies (Ab)

MRI Spine ( only with clinical suspicion)

Other:

Viral studies

Laboratory Features

Lumbar Puncture

CSF protein elevated-normal WBC (albuminocytologic dissociation) present in 80-90% by one week post symptom onset

Electrophysiology ( EMG and NCS)

Demyelination, conduction block

Axonal features (later or in axonal variants)

• Antibodies

eg GQ1b 85-90% Miller Fisher Variant

GBS-Post-Infectious Illness

Triggering bacterial or viral illness –2/3 of pts-either gastroenteritis or URTI

Latency to neuropathic symptoms 1-4 weeks

Most frequent antecedent pathogens:

-Campylobacter jejuni-30%(40-60% in Japan & China)

-Cytomegalovirus-20%

-Epstein Barr virus 5-10%

Classification of GBS

AIDP – acute inflammatory demyelinating

polyneuropathy

MFS - Miller Fisher Syndrome

AMAN- acute motor axonal neuropathy

AMSAN -acute motor/sensory axonal

neuropathy

Common GBS Variants

AIDP (GBS) most common in NA (85-90 % of

cases)

MFS –opthalmoplegia ataxia, and areflexia (5%)

AMAN, AMSAN – axonal forms (5-10 %) more

frequent in China, Japan and Mexico

Variant:AIDP (GBS)

Progressive symmetric muscle weakness absent / reduced reflexes

Myelin of peripheral nerve is site of immune attack

Inflammatory demyelination starts at level of nerve roots leading to conduction block

Multifocal patchy widespread peripheral nerve demyelination

Reversal of conduction block and remyelination can occur rapidly over weeks to months

Secondary axonal degeneration delays and may result in incomplete recovery

Variant: Miller Fisher Syndrome

Opthalmoplegia, ataxia, areflexia

I/3 may have extremity weakness

Anti GQ1B Ab present in 85-89 %

Ab linked to oculomotor nerves

EPS absent sensory responses without sensory

conduction slowing

If weak may also have motor nerve abnormalities

Variant: AMAN

Most preceded by campylobacter jejuni infection

Freq in Japan, China in young people

Summer predilection

DTR preserved

Sensory nerves not affected

EPS-selective motor and axonal involvement

Variant: AMSAN

More severe form of AMAN with sensory involvement

Marked axonal degeneration, incomplete recovery

EPS -axonal both sensory and motor nerves

AMAN and AMSAN strongly associated with Ab to the gangliosides GM1, GD1a, GD1b, GalNac all present in peripheral nerve axons

These Ab can be induced by campylobacter jejuni infection

Pathophysiology is that of antibody and complement mediated axonal nerve damage

Diagnostic Criteria

National Institute of Neurological Disorders and Stroke

(NINDS) (Annals of Neurology 1978)

Required Features:

Progressive weakness of one limb, ranging from minimal to

total paralyis of all four limbs, trunk, bulbar, and facial

muscles and external opthalmoplegia

Areflexia (hyporeflexia at knees and biceps acceptable)

Diagnostic Criteria (NINDS)

Supportive Features:

Progressive symptoms over days to 4 weeks

Relative symmetry

Mild sensory signs or symptoms

Cranial nerve involvement, especially bilateral facial involvement

Recovery starting 2-4 weeks after progression halts

Autonomic dysfunction

No fever at onset

Elevated CSF protein with cell count <10 mm3

Electrodiagnostic abnormalities consistent with GBS

Diagnosis Doubtful if:

Sensory level (decrement or loss of sensations

per neurologic examination

Marked persistent asymmetry of weakness

Severe and persistent bowel and bladder

dysfunction

> 50 WBC in CSF

Differential Diagnosis

Other acute polyneuropathies:

-acute arsenic poisoning, n-hexane (in glue-sniffing neuropathy

-vasculitis

-Lyme Disease

-Tick paralysis ( (mostly in children)

-Porphyria

-Sarcoidosis

-Leptomeningeal disease

-Paraneoplastic disease

-Critical illness

Spinal Cord Disorders (SCD):

Acute myelopathies due to spinal cord

compression, and acute transverse myelitis can

be confused as DTRS depressed in acute stage

of spinal cord disease

Acute bowel and bladder dysfunction and a

sensory level point to SCD .

MRI---focal spinal cord lesion

Neuromuscular Junction Disorders

Botulism, Lambert Eaton myasthenic syndrome

May present with acute weakness, sensory S&S

absent

Differential Diagnosis for Miller

Fisher Syndrome

Brainstem Stroke (acute vs gradual onset)

Wernicke‘s Encepahlopathy (mental status,

nystagmus)

Brainstem encephalitis (mental status)

Myasthenia gravis (EPS)

Prognostic Factors

Associated with poorer prognosis:

Older age

Rapid onset (<7 days ) to presentation

Need for ventilation

Average distal motor response amplitude reduction to <

20% of normal

Preceding diarrheal illness

Long term outcome

At 6 months 65% able to walk independently

80% recover completely or have minor deficits

5-10% have a prolonged course with several months of ventilator dependency and very delayed and incomplete recovery

3% remain wheelchair bound

5% die (if ventilator dependent 20% die)

Causes of Death:

Acute respiratory distress syndrome, sepsis, PE, unexplained cardiac arrest

Acute Treatment & Management

of the GBS patient

Acute Treatment

Plasma exchange or Intravenous

Immunoglobulin can be used

Both are equally effective

IVIG is easier to administer and therefore used

more commonly

Costs of both Rx are similar (approx. $10,000

per course)

IVIG is a blood product and requires consent

Side effects may include headache & flu-like symptoms (approx 50%), aseptic meningitis.

Serious but rare side effects include anaphylaxis, DVT/PE, or stroke

The total dose is usually 2g/Kg and is divided into 2 – 5 days (depending on patients ability to tolerate the volume)

Requires frequent monitoring (VS @ pre, 15

minutes then q 1h)

Start slowly then increase if tolerated

If severe reaction – Stop and call MD

If mild reaction – try slowing the rate down

May take 3-10 days to work

Plasmapheresis

PLEX or Plasma Exchange

Essentially, each PLEX exchange removes 60% of the antibodies in the system

– 1st Rx 60%

– 2nd Rx 84%

– 3RD Rx 93%

– 4th Rx 97%

– 5th Rx 99%

Acute Management - Autonomic

Cardiac/Hemodynamic

Serious and potentially fatal, and occur in approximately 20% of patients

Severe bradycardia or heart block possibly causing asystole and may require pacemaker

Dysrythmias (Afib, VFib) may require intervention

Swings in BP

Nursing Care

Monitor VS – be concerned with changes or fluctuation eg. HR 60 and then 85, or SBP 150 then 100

– Abrupt swings in BP may herald a sudden arrhythmia

More significant changes in VS may require intervention (eg. brady – atropine)

Severe bulbar dysfunction and quadraplegia – more likely to have cardiovascular instability

Nursing Care

Monitor ECG

In beginning stages of the disease, monitor these with position changes and mobilizing (eg. standing up). IF there are changes, maintain bedrest

Acute Management – Autonomic

Bowel and Bladder

Constipation is common

50% develop paralytic ileus (some had Ogilvie‘s

Syndrome develop)

Urinary retention may develop

Acute Management – Autonomic

Nursing Care

Assess bowels daily

Aggressive bowel regime to maintain BMs q1-2

days (especially if on narcotics)

Urinary catheterization intermittently if urinary

retention present. May need indwelling catheter

for hemodynamic monitoring in acute phase

Acute Management - Respiratory

30% GBS patients require ICU for respiratory

support

Respiratory compromise may be caused by 2

mechanisms

– Neuromuscular weakness of diaphragm

– Bulbar dysfunction causing difficulty with secretion

management

Nursing Care

Monitor for respiratory decline (tachypnea,

sweating, orthopnea, paradoxical breathing,

accessory muscle use)

O2 satn and gases will only change in later

stages

FVC – look for trend downwards (not just

absolute value to be > 1 litre), look for difference

sitting to supine

Nursing Care

If intubated, PFTs done at 2 weeks are best

predictor for need for ongoing ventilator support

Tracheostomy should not be performed prior to

this unless on an individual basis.

Acute Management - Pain

Often one of the first symptoms – back pain

May also develop neuropathic pain over time

(burning, numbness/tingling)

NSAIDS, tylenol, and narcotics are helpful

If Neuropathic pain – gabapentin, amitriptyline

may also be useful

Acute Management – Prevention of

Complications

Prevent secondary nerve injury - protect elbows

(ulnar nerve) and behind knees (peroneal nerve)

with foam pads

Prevent DVT & PE – ensure LMWH or heparin

ordered for non-ambulatory patients

Prevent skin breakdown – ensure adequate

nutrition (if not taking p.o. need for NG), and

position changes/pressure relief bed

Acute Management - Psychosocial

Patient & family need education, support, &

reassurance. Pt. may need to go to ICU

(remember 30%)

If pt. is deteriorating, reassure them that this

disease most commonly improves!

Pts not needing ICU – excellent recovery

Pts needing ICU – a review of 20 yrs GBS pts

admitted to ICU at LHSC demonstrated that 63%

returned to walking independantly

Acute Management –

‗Pearls‘ to Remember

The earlier in the course of the disease, the

more likely pt. will deteriorate (eg. Pt admitted 3

days after symptom onset vs. 9 days)

The quicker the weakness worsens (eg. shift to

shift) = the more likely the patient will develop

respiratory compromise and require ICU

Acute Management –

‗Pearls‘ to Remember

If quick changes, keep on bedrest (more likely to

have autonomic problems)

If patient further into course of disease with little

change in weakness, consider slow mobilization

BUT monitor position changes (VS, ECG, and

symptoms)

Muscular Dystrophy (MD)

Inherited group of progressive muscle disorders

Result from defects in a number of genes

required for normal muscle function

Some of the genes have been identified

Muscle weakness is the primary symptom

Muscular Dystrophy

OVERVIEW

Clinical Features

Diagnosis

Management and Treatment

Clinical Vignettes

Pediatric MD

Most common childhood form of MD is

Duchenne (DMD)

Others include:

Becker (BMD)

DMD and BMD are caused by a mutation in the

dystrophin gene …..dystropinopathies

Muscle fiber degeneration is the primary pathologic

process

Adult MD

Most common is Myotonic Muscular Dystrophy

Facioscapulohumeral MD

Limb Girdle MD (types 1A, 1B, 1C etc)

Genetics and MD

X-linked:

Duchenne and Becker MD

Autosomal recessive:

Limb Girdle MD 2A, 2B, 2C, etc

Autosomal dominant:

Myotonic Dystrophy 1

Facioscapulohumeral MD

Limb Girdle 1A 1B 1C etc

X-Linked Recessive Inheritance

X-linked recessive disease usually occurs in males who have inherited a recessive X-linked mutation from their mother.

Rarely, the disease may be seen in females who have inherited mutations in the same gene X-linked from both parents.

More typically, the mother is a carrier and is unaffected,

Female carriers of X-linked disorders may have mild clinical manifestations related to the disorder —

Clinical Characteristics

DMD is associated with the most severe clinical

symptoms

Occurs in 1/3500 live male births (prevalence 3

per 100,000)

BMD has a similar presentation to DMD but a

relatively milder course

Rarer---1/30,000 male births

Genetics and Pathogenesis

DMD is caused by a defective gene located on the X chromosome that is responsible for the production of dystrophin

Dystrophin is located on the cytoplasmic face of the plasma membrane of muscle fibers, functioning as a component of a large, tightly associated glycoprotein complex

Dystrophin gene

Dystrophin

Dystrophin normally stabilizes the complex

therefore shielding it from degradation

In the absence of dystrophin the glycoprotein

complex is digested by proteases.

Loss of these membrane proteins may initiate

the degeneration of muscle fibers resulting in

muscle weakness

Dystrophinopathies

Duchenne MD: caused by an absence of

dystrophin

Becker MD: caused by a deficiency of dystrophin

Caused by mutations in dystrophin gene in the X

chromosome at Xp21

This large gene expresses dystrophin

It is present in the heart, striate and smooth

muscle and brain

Treatment

Management has improved, treatment elusive

Over 30 different drugs have been tried

Only steroids (prednisone, prednisilone,

deflazacort) appear to slow progression

Looking at molecular therapy…DNA gene

transfer, …..stem cell therapy

Clinical Overview of DMD

First descriptions in mid 1800‘s

―clinical picture of slowly progressive muscle wasting disease marked by symptoms that develop before age 5‖

Early on affects proximal hip and shoulder girdle muscles, anterior neck and abdominal muscles

If only receiving supportive care...limited to a wheelchair in late childhood, early teens and usually die of complications of respiratory insufficiency and/or cardiomyopathy in their late teens or early twenties

Historical descriptions

Meryon 1852 (Duchenne, 1861)

Meryon..4 brothers….described one

In infancy the child was a dead weight

Throughout early childhood..never jumped

At age 8 trouble climbing stairs

Age 11 couldn‘t stand

Age 14 extremeties very weak

Age 16 died

Further Historical Highlights

Erb (1891) studied 29 DMD pts

Described the clinical and muscle pathologic

features that typify DMD

1930-1970 resports of increased CK in DMD

and female carriers

Late 1980‘s gene discovery

Mutations in dystrophin gene …diagnostic

testing

Diagnosis

History physical exam

CK (10X n early on)

DNA testing

Rarely EMG , muscle biopsy

Other Clinical manifestations

Respiratory Insufficiency

If not receiving corticosteroids: between ages 11-20 yrs

FVC declines to <60-70% of N. (2L)

This correlates with decreased cough,..pneumonia

Decreased night time ventilation then respiratory failure

When FVC < 1.0 L and PCO2 45 mm Hg, 3-5 yr

survival

Cardiomyopathy

ECG abnormalities early on ( increased R/S amplitude in lead VI and deep Q waves in V5 V6)

Late stage of DMD atrial arrythmias

Echocardiogram reveals primary alteration in left ventricular function

Resting tachycardia common throughout each stage of DMD

Gastrointestinal Dysfunction

Involves both voluntary and smooth muscles (due to deficiency in dystrophin)

Bulbar weakness( upper voluntary skeletal muscle portion of pharyngeal-esophagael tractand lower involuntary smooth muscle portion)

Freq clearing of throat, and coughing esp at mealtime

Delayed gastric emptying

Acute gastric dilatation (diaphragmatic pressure)

Chronic intestinal dysfunction..constipation, distention hypomotilty, impaction

Management

Maintain ambulation

Optimize cognition

Anticipate complications

eg. wt gain, joint contractures, respiratory

insufficiency, scoliosis, GI hypomotility,

cardiomyopathy

Pediatric DMD Health care team

Pt, family

Primary care Dr, neurologist, orthopaedic

surgeon, cardiologist, pulmonologist, social

worker, PT, OT, school teachers

Issues over the decades

Diagnosis……..biopsy to DNA

Respiratory Failure……BIPAP

Adults living with pediatric diseases

Families of NM Adults……caregivers to distant

support

Research:science to psychology

Adult DMD

Health care team

Neurologist, APN

Respirologist, Palliative Care Consultant

Nutritionist, OT, PT, Physiatry, social work, PSW

Case 1

Transferred to adult NM clinic Oct 2004 (age 24)

Works part time, lives alone with support care of 14-16 hrs per day

DX age 6

Difficulty arising from the floor age 8

Using wheelchair age 12

BiPAP at night age 18

No Family hx of DMD (has 2 healthy brothers)

Case 1: Surveillance

P 110 beats/min

ECG : (2005) NSR, deep Q wave lead 111, AVF

Echo: normal

FVC: (2005) 0.6L FEV1 0.41L PCO2 47 PO2 78

MBS: 2006, 2007-mild oropharyngeal dysphagia

Annual flu shot, Pneumovax

Antibiotic Rx on order (Levofloxacin)

Ocular exam : early cataracts, normal intraocular pressures

Allied Health team

Physio: lower limb splints, breath stacking in

exsuflator

OT: seating, upper limb splints

Social Work

Nutrition

Speech Language Pathologist

What is MG?

Rare Autoimmune Disorder of the Neuromuscular

Junction (NMJ)

Affects Voluntary Muscles

– Fluctuating muscular weakness

– Worsening weakness with repetitive action

NMJ in MG

Three main mechanisms of dysfunction

Acetylcholine Receptors (AChRs) by muscle

autoantibodies:

– Blockade of AChRs by antibodies at the receptor

binding sites

Source: Meriggioli and Sanders,

AChR Antibodies Anti-AChR (Binding, Blocking, Modulating)

Present in 65 - 80% MG cases

Source: Macko slides

NMJ in MG

Three main mechanisms of dysfunction AChRs by

muscle autoantibodies:

binding sites

– Degradation of AChRs

Source: Meriggioli and Sanders, 2009

Neuromuscular Junction

Destruction by AChR antibodies

and complement

NMJ in MG Three main mechanisms of dysfunction AChRs by

muscle autoantibodies:

binding sites

– Degradation of AChRs

– Damage to the muscle endplate distortion of

postsynaptic membrane folds

Ach Receptors are Internalized and NMJ

simplified by antibody and complement

Auto Antibodies Found

Antibodies to AChR protein:

– 85 % of patients with generalized myasthenia

– 60% of those with ocular myasthenia

Anti-MuSK Ab

– 40% of seronegative cases

Thymus Gland

Role in autoimmune process

Thymoma or Hyperplasia in MG

– 10 - 15% of MG patients

– Greater than 80% found at early onset of disease

– Equal in Men and Women

– Occur at any age

CT of Thymus Gland

Normal vs. abnormal presentation (Thymona) in Myasthenia Gravis.

Source:

Epidemiology

Rare Disease

– 20 per 100,000 in the US population

– Age <40 yrs: Women more than men

– Age >50 yrs: Men more than women

– Equal in both sexes for puberty and >40 yrs.

Clinical Feature of MG Muscle fatigue causing weakness

– Activity exacerbates symptoms

– Fluctuates throughout the day

– Improves with rest or early morning

Involvement of specific muscle groups

Myasthenia Gravis Classification

Ocular MG (15%)

–Ptosis

–Diplopia

Generalized MG

Clinical Presentation

Ocular Muscles

Initial symptom – ocular in 85% patients:

– ptosis (32%)

– diplopia (14%)

– ptosis and diplopia (36%)

– blurred vision (3%)

Source: Grob et al., 2008

Facial & Bulbar Muscles Facial Weakness

– Eyelid closure

– Drooling

Bulbar /Oropharyngeal Weakness

– Dysarthria (nasal speech)

– Dysphagia

– Dysphonia

– Jaw weakness (chewing problems)

Neck & Limb Weakness

Neck Muscle Weakness

– Neck flexion

– Neck extension (head droop)

Limb Muscle Weakness

– Proximal symmetrical

– Arms > Legs

Respiratory Muscles Respiratory weakness of:

Intercostal muscles

Diaphragm

Emergency issues in MG

Detection of an impending crisis

Management of an impending crisis

Nursing/medical history

Medication list

Prodromal events

Patients presenting with

undiagnosed MG

Differential Diagnosis of presenting symptoms

Ocular

Bulbar

Differential diagnosis:

Ocular symptoms: Brain tumor

Bulbar: brain stem stroke, ALS

Respiratory: MI, PE

Assessment

Pts with established MG

Provocative factors:

Infection **

Idiopathic

Medications

Stress induced

Drugs reported to cause an exacerbation:

Antibiotics: macrolides, floroquinolones,

aminoglycosides

Antidysrythmic agents: beta-blockers, calcium channel

blockers, quinidine

Miscellaneous: corticosteroids

To differentiate between cholinergic or

myasthenic crises

Edrophonium: Tensilon challenge test:

Other tests

Ice pack

Electromyography-probably not available on a

emergent basis

Other tests

Pulmonary Function studies

FVC, FEV1 supine , standing

Pulse oximetry

ABG‘s

Emergent Signs and symptoms

Worsening dysphagia and dysarthria despite

taking medication

Severe choking

Emergent Signs and Symptoms

Weak breathing-breathing worsening 30 minutes

after taking pyridostigmine

Fast shallow breathing when beginning to feel tired

Weak voice

Head drop

Signs and Symptoms of Crisis

Restlessness, apprehension

Generalized muscle weakness

Dyspnea

Increased bronchial secretions, sweating

Dysarthria dysphagia

Complications of Emergent Issues

Respiratory failure

Hypoxemia and respiratory acidosis may render the

patient somnolent, and unresponsive

Pneumonia may be a cause of death

Chronic respiratory failure

Cholinergic vs Myasthenic Crises

MG Crisis

Prodrome of infection

S&S of worsening MG

12-16% of generalized MG patients experience

crisis

Cholinergic Crisis

Over medication with anticholinesterase drugs

Symptoms

Abdominal cramping/diarrhea (MUSCARINIC

Effects-slow)

Profound generalized weakness, excessive

pulmonary secretions and impaired respiratory

function (NICOTINIC Effects-rapid)

Crises

Both are medical emergencies

May require tracheal intubation and assisted

ventilation

Parameters: Negative Inspiratory Force (NIF) <-

20cm H20

FVC <15cc/kg body weight

Humidified Air and Oxygen (if PO2<70)

Cholinergic Crisis Management

Stop ChE

Intubate

Ventilate

Treat underlying cause:

Infection, electrolyte disturbance (hypokalemia,

hypocalcemia, hypermagnesium )

Resume ChE at lower dose and escalate slowly

MG Crisis Management

Intravenous immunoglobulin ( IVIg)

Blood product –safe

Modulates the immune system – how?

Benefits seen in 70%of patients within 2 weeks

Common side effects –mild

MG Crisis Management

Plasma Exchange (Plex)

Removes the antibodies which cause weakness

Benefits in 70% of patients within 2 weeks

Few serious effects

More difficult to arrange on short notice

IVIg and Plex equal in terms of efficacy

Plasmapheresis more rapid effect than

IVIG ( removes circulating antibodies

including those implicated in MG…3

days versus 2 weeks with IVIG)

IN HOSPITAL CARE

Admit to a monitored unit

Admit with pneumonia-?aspiration

Treat with Plasmaphersis, or IV Ig

Ongoing care with a neurologist

Clinical Vignettes

Interactive Review

Case 1

72 year old healthy male

Admitted to medical service

2 month history of dysphagia, difficulty handling

secretions, dysarthria, SOB

CPAP for OSA

Developed increasing SOB, unable to lay flat to

Anxious, drooling, unable to swallow

Rx: IvIg, Mestinon, Pred

Azathioprine, CPAP/BiPAP

LOS 20 days

Readmitted for 3 days

Dysphagia, dysarthria, unable to handle secretions

Rx with IVIG, treated with AZA, Pred, Mestinon

Case 2

69 year female in Northern Ontario

Dx locally with MG treated with Mestinon

Three days before admission 2 visits to local emerg

Mestinon increased to 120 mg every 2-3 hours

Transferred to UC unable to handle secretions, dysarthric,

proximal fatiguable weakness, facial weakness, constant

double vision, ptosis

Intubated within 24 hours

Mestinon stopped

Solumedrol IV 500mg BID

Complications: upper GI bleed, MI, diverticulitis-abscesses

IVIG contraindicated – renal dysfnction

Plasmapheresis-cardiac risk

Mestinon slowly reintroduced

Prednisone 50 mg every other day

Case 3

24 y.o.Female presents to the ER w/ one week worsening symptoms of

diplopia, dysphagia, dysarthria, facial weakness and fatigue which she

reports is worse during the afternoon. She states that she just got over a cold

over 2 wks ago. You noticed during the interview that she is restless, her

voice is becoming more nasal and dysarthric and she has a weak cough and

Exam: BP 130/88 P-99 RR-32 T-99F

PMH: MG diagnosed x 1.5 years limited to ocular symptoms and have been

symptom free x 3 months

Current Meds: prednisone 20 mg daily, vitamins

Impaired Communication Symptoms: Dysarthria, Dysphonia,

facial weakness

Conserve energy

Limit interview question to Yes/No answer

Find alternate way of communication—ie writing

Patient education

Potential for Aspiration r/t Bulbar

Weakness Symptoms: dysphagia, dysarthria,

weak cough,dysphonia

Keep HOB up

Assess breath sounds

Provide suction

Keep pt informed

Encourage small sips of liquid

Ineffective Respiratory Function

Symptoms: weak cough, Dyspnea

Assess and respiratory status—RR and effort

Assess gag and cough

Suction oral secretion

Check serial FVC

O2 support

Standby for ventilatory support

Provide pt education and emotional support

Altered Visual Function

Symptom: diplopia

Provide alternating eye patch

Provide pt education on energy conservation

References 1. Alshekhlee A, Miles JD, Katirji B, Preston DC, Kaminski HJ. (2009) Incidence and mortality rates

of myasthenia gravis and myasthenic crisis in US hospitals. Neurology; 72(18):1548-1554.

2. Caress JB, Hunt CH, Batish SD. (2005) Anti-MuSK myasthenia gravis presenting with purely

ocular findings. Arch Neurol; 62(6):1002-1003.

3. Goldenberg WD and Sinert RH. Myasthenia Gravis in Emergency Medicine. Medscape

Reference. 1 April 2011. <http://emedicine.medscape.com/article/793136-overview>.

4. Grob D, Brunner N, Namba T, Pagala M. (2008) Lifetime course of myasthenia gravis. Muscle

Nerve; 37:141-149.

5. Meriggioli MN and Sanders DB. (2009) Autoimmune myasthenia gravis: emerging clinical and

biological heterogeneity. Lancet Neurol; 8(5):475-490.

6. Phillips LH. (2004) The epidemiology of myasthenia gravis. Semin Neurol; 24(1):17-20.

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