ACh receptor antibodies
Assoc c thymus disorders
Pathologic fatigability of muscles.
The most common presenting symptoms are ocular (Ptosis, diplopia). If limb weakness is involved it is usually greatest in upper extremities.
Normal pupils, dtrs, and sensory exam.
Easiest is extended gaze testing.
If there is ptosis or EOM abnormalities, can perform cold testing. Cover eye c ice pack for 2 minutes and see if sx improve.
· There are reports of false positives in cases of botulism, eaton-lambert, ALS, GBS, and Cavernous sinus lesions
· Measure the distance from the upper to the lower eyelid in the most severely affected eye
· intravenous test dose of 1 to 2 mg is given first.
· If no adverse reaction is found, and the patient does not dramatically improve in 30 to 90 seconds, a second dose of 3 mg is given.
· If there is still no response, a final dose of 5 mg is given for a total maximum dosage of 10 mg.
· Potential bradycardia from edrophonium, atropine should be available at the bedside. Also, because of the potential cholinergic effect of increased airway secretions, this test should be used with caution in asthmatics and patients with COPD
Below from Jama 2005;293:1906-1914.
Box. Edrophonium Test
Establish reliable peripheral intravenousaccess
Prepare a syringe with 2 mg of atropine (available in0.4-mg/mL or 1-mg/mL ampules) to have handy
Prepare 1 mL (10mg) of edrophonium in a tuberculin syringe (edrophonium is availablein a 10-mg/mL solution in a 1-mL ampule [10 mg] or in a 10-mLvial [total of 100 mg])
Inject 2 mg (0.2 mL) slowly over 15seconds while observing for an objective improvement in target muscles
Improvement should occur within 30 seconds and disappearin 5 minutes; if no response and no significant adverse effects,administer the remaining edrophonium (8 mg [0.8 mL]) for a totaldose of 10 mg
Atropine should be injected (0.5 or 1 mg) incase of clinically significant bradycardia, respiratory distress,or syncope*
*Routine administration of atropine simultaneously with edrophonium for the purpose of diagnostic testing for myastheniagravis is not recommended. Bartley and Bullock29 recommend usinga 3-way stopcock with the edrophonium-containing syringe attachedto the direct port and the atropine-containing syringe attachedto the side port, so that atropine may be quickly injected in case of severe adverse effects
In treated pts, you must differentiate between too little ACh from myasthenic crisis (undertreatment) or Cholinergic Crisis (Overtreatment)
Often physical exam can help with cholinergics giving gastric hyperactivity, sweating, and other signs similar to organophosphate toxicity. Sometimes the safer strategy is to withdraw all cholinergic medicine, support patients respiratory status and allow the consultant to interpret the patients sx as cholinergic crisis can be superimposed on myasthenic crisis.
Assess Resp Status
Patients often look good until just before they require emergent intubation
An easy bedside assessment used to follow ventilatory status is to have the patient count from 1 to 25 with one breath. With sequential performance of this, a decline in respiratory function will be detected as the patient fails to count as high as before
Ask the patient to cough and observe the force generated
Bedside spirometry for NIF and FVC
FVC (forced vital capacity less 10-12 cc/kg or a
NIF (negative inspiratory force) <20 cmH2O may indicate the need for mechanical ventilation. These results may be thrown off by the inability of the patient to make a tight seal around the pulmonary function mouthpiece.
Need ~ 50% the dose of non-depol or
2.6 x the dose of succinylcholine
(Mt Sinai J of Med 2002;69(1):31
anticholinesterase therapy: pyridostigmine is the oral agent of choice, neostigmine can be used parenterally
immunosuppressive therapy: prednisone 60-150 mg/day
Lambert-Eaton Myasthenic Syndrome
is a rare disorder often associated with small-cell carcinoma of the lung. Autoantibodies cause an inadequate release of ACh from nerve terminals, affecting both nicotinic and muscarinic receptors. With repeated stimulation the amount of ACh in the synaptic cleft increases, leading to an increase in strength, the opposite of that seen with MG. The classic syndrome includes weakness that increases with use of muscles, hyporeflexia, and autonomic dysregulation. Management primarily focuses on treating the underlying neoplastic disorder, although plasmapheresis and immunoglobulin G (IgG) have been reported to be useful. This disease unlike MG will often spare EOM and may have autonomic dysfunction.
Clostridium botulinum, spore forming anaerobic, gram positive bacilli
Can withstand boiling for hours
Toxin mediated. Blocks ACh release at the NMJ.
12-36 hrs post-ingestion.
1st cranial nerves are effected (papillary dilation), then descending paralysis/weakness
Botulinum toxin-can be released as aerosol or spread by contaminated food. The most toxic substance known.
Prevents presynaptic release of ACh, therefore anticholinergic toxidrome, i.e.. dry mouth, ileus, and urinary retention.
Sx 1-3 days after inhalation
Starts c Bulbar palsies then descending flaccid paralysis c intact sensation and decreased reflexes
Differential-G. Barre, myasthenia, Eaton Lambert, tick paralysis, hypokalemia, CO, diphtheria, metal poisoning
Antitoxin and toxoid vaccine available in scant supply. Will probably need to demonstrate LP and EMG to exclude other diagnoses. Two antitoxins bivalent (AB) and trivalent (ABE)
Surfaces can be decontaminated c .1% bleach
Dry tongue and sore throat, ileus, urinary retention, double vision, dysarthria, hyporeflexia
Trend vital capacity to see impending resp failure.
Consider miller fisher variant of guillain barre, get LP if diagnosis is in question in botulism it will be normal
Antitoxin available from CDC
Notify CDC and other EDs
honey and corn syrup, but not necessarily any food source
check stool for toxin
Usually in IVDAs (black tar heroin)
± antitoxin, consult toxicologist
PCN 10-20 million units IV/day
Adult Onset Infantile Botulism (Undetermined)
Similiar to infant botulism, seen in adults with reduced stomach acidity or reduced gut flora which allows intraluminal growth.
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Peripheral Nerve Disorders