Myasthenia gravis

Background

Pathophys

thymus abnl in most - thymoma, thymitis, B cells sensitized to Ach receptors here.

Epi

1. mostly women in 20s
2. peak incid in men is 60-70s

DDX

1. Toxin Induced
   1. Botulism
   2. Tick Paralysis
   3. Envenomation (coral snake, black widow spider), paralytic shellfish
2. Autoimmune - Eaton Lambert
3. Drug-Induced - aminogly, dilantin, procainamide, chloroquine
4. Poisoning - Organophosphates, Carbamates
5. Miller Fisher Variant Guillen Barre
6. Causes of oculomotor palsy - DM, MS, aneurysm

Botulism

1. toxin binds to presyn prevents AcH release. Wound may be benign in appearance
2. GI source - neuro sxs w/in 72 hrs of ingestion usually. Aticholinergic effects include dry mouth, mydriasis, ileus, urine retention then fluctuating but rapidly progressive weakness
3. send cx blood, food, stool or wound
4. only 33% of food borne source have positive blood cx
5. may actually see pos Tensilon test in botulism.
6. Wound Botulism - high dose PCN & debridement.

Eaton Lambert

1. rare, defect in release of AcH from presynapse
2. Usually paraneoplastic (part. small cell Ca of lung)
3. Clinically proximal weakness of limb muscles, hyporeflexia, dry mouth, impotence.
4. Extraocular & facial muscles usually spared.

Tick Paralysis

1. acsending flaccid paralysis caused by neurotoxin block acH release
2. late spring, summer in Rockies & NW
3. female wood tick or common dog tick
4. paralysis progresses over 1-2 days to involve bulbar, extraocular muscles.
5. Resp paralysis can follow
6. Ataxia may be early finding
7. normal sens exam usually
8. DTRs decreased markedly as in GB
9. fatal in 10% if tick not removed
10. CHECK for ticks in someone you think has Guillen Barre

=Diagnosis

History

1. pts report worse sxs as day progresses.
2. insidious onset, can develop over wks to months.
3. precipitated by stress, preg, infec

Symptoms

1. diplopia, ptosis (later in day)
2. weakness in eye closure, swallowing muscles of facial expression, difficulty chewing, dysarthria, dysphagia.

Physical Exam

1. Provocative tests - ptosis with prolonged upward gaze, hold arms up, clench tongue blade, dysarthria w/ loud counting
2. sensation, reflexes usually normal
3. always eval tidal volume, FEV & ability to handle secretions

Testing

1. Always test FEV, consider ABG, Look for infections (resp) or meds, electrolyte problems that may have induced problem.
2. Edrophonium - use caution in trying to test for crisis vs. cholinergic crisis
3. Ach receptor antibodies - found 90%
4. CT of thymus, TFTs, search for other immun dz

Treatment

1. Plasmapherisis or plasma exchenge in acute setting
2. Anticholinesterase agent such as Pyridostigmine 60 mg tid
3. Corticosteroids produce good results in >80% but are reserved for those who don't respond to anti-cholinesterases and thymectomy due to adverse effects. Decreases levels of antiAch receptor Ab. Also may initially aggravate muscle weakness so usually begun in hosp & at low doses

1. don't treat Myasthenic with meds that may exacerbate weakness
2. search for source of infection or electrolyte problem w/ weakness

Myasthenic Crisis vs. Cholinergic

1. Cholinergic - usually present w/ signs of cholinergic overactivity (miosis, sweats, salivation, GI distress-musc) & cramps, fasciculations (nicotinic)
2. Myasthenic - more common, caused by noncompliance, drug interaction, infection, stress
   1. aminoglycosides, flouroquinolones, clinda, sulfas, erythro, ampicillin, Dilantin, phenobarb, B blockers, Ca channel Blk, procainamide, steroids, lithium, phenothiazines, MSO4, benzos, antihistamines

VERY DANGEROUS & UNRELIABLE to use Tensilon Test to distinguish between the two.

Source

Harwood Nuss p.1002