Here’s Dr. Adal with today’s Morning Report!
Differential diagnosis for generalized weakness
Neuromuscular (UMN and LMN)
Amyotrophic Lateral Sclerosis: Degeneration of the motor neuron
Botulism: Toxin prevents release of Ach at neuromuscular junction
Ciguatoxin: Toxin causes cell membrane excitability and instability
Cord compression
Cord infarction
CVA: Ischemic vs hemorrhagic
Diabetic neuropathy
Diptheria: Toxin causes a LMN neuropathy
Electrolyte imbalance: Myopathy
Gullian-Barre: Immune mediated LMN polyneuropathy
Myasthenia Gravis: Decreased number of functioning Ach receptors due to blockade
Multiple Sclerosis: Inflammatory disease causing loss of Myelin
Organophosphate/Carbamate poisoning: Cholinergic crisis – inhibition of acetylcholine by irreversibly binding to it
Polio
Polymyositsis: Autoimmune myopathy
Tetanus: Toxin blocks release of inhibitory transmitters, i.e. GABA
Tick paralysis: Toxin reduces MN potential and ACH action
Transverse Myelitis: UMN Neuropathy with axonal demyelination
Non-neuromuscular
Cardiovascular: Arrhythmia, Blood loss, Dehydration
Drugs: CCB, BB, etc
Endocrine/Metabolic: Hypo/Hyperthyroidism, Hyper/hypoglycemia, Poor nutritional status
Infectious: Sepsis, etc
Toxicologic
Myasthenia Gravis
A rare disease, with a prevalence of approximately 20 per 100,000. Bimodal distribution: ages 20-40 and 50-70, with women having a higher incidence in the former group and men in the latter.
Results from autoantibodies directed towards the Ach receptor in the neuromuscular junction. This decreases the total number of available Ach receptors by complement mediated destruction of receptors, and competition with Ach for remaining receptors. With repeated stimulation of muscles, fewer receptor sites become available, and muscle strength decreases.
The autoimmune response is believed to be due to either dysfunction of the thymus gland or immune response against exogenous infectious agents.
Most patients present to the Emergency Department with an established diagnosis; it is rare to make a new diagnosis. However, patients most commonly have ocular manifestations as an initial symptom. These symptoms include ptosis, diplopia, and blurred vision that get worse at the end of the day. Other symptoms include weakness of the proximal muscle groups, neck extensor muscles, facial, and bulbar muscles.
Myasthenic crisis is defined by the presence of weakness of the respiratory muscles, resulting in respiratory failure. Weakness of the bulbar muscle group is an alarm for looming respiratory failure.
Clinical diagnosis
Suggested by weakness of the muscle groups mentioned above. Ask patient about non-compliance with medications, recent infections, stress, temperature (external and internal), new medications such as
- Antibiotics: Macrolides, fluoroquinolones, aminoglycosides, tetracycline, chloroquine
- Antidysrhythmic agents: Beta blockers, calcium channel blockers, quinidine, lidocaine, procainamide, trimethaphan
- Miscellaneous: Phenytoin, lithium, chlorpromazine, muscle relaxants, levothyroxine, adrenocorticotropic hormone (ACTH), and paradoxically corticosteroids
Diagnosis can be confirmed with edrophonium testing, ice bag tests, which can be performed in the ED. Other tests include electromyographic testing or serum testing for AChR antibodies. Edrophonium is a short acting acetylcholinesterase that increases Ach at the synaptic cleft.
Edrophonium testing is performed by administering increasing doses of Edrophonium every 90 seconds. Sequentially increasing the doses at 1 or 2mg, 3mg, then 5mg with a maximum dose of 10mg. During this test, patients should be monitored closely and Atropine should be at the bedside, because Edrophonium can cause significant bradycardia, and potentially heart block and asystole. The test should be used with caution in patients with COPD and Asthma as it can potentially increase airway secretions. Edrophonium testing has a sensitivity range from 65-85% for ocular testing and specificity of approximately 85%.
Ice bag testing works on the principle that cool temperature decreases symptoms, while heat exacerbates symptoms. Ice bag testing has a sensitivity of approximately 77% and specificity of approximately 98%. It is performed by measuring the distance between the upper and lower eyelids before and after applying a bag of ice for two minutes.
In a Myasthenic crisis, the most important test to perform is pulmonary function testing. Parameters to measure include the vital capacity (VC) and the maximal inspiratory force (MIF). Both tests reflect the functioning of the inspiratory and expiratory muscle groups. These tests should be performed by the respiratory therapist. Serial measurements should be taken every 2-4hours. A VC less than 20ml/KG or a MIF <30 cmH2O can suggest the need of an elective intubation.
ED Management
1. Evaluate patient for respiratory failure
Respiratory failure can develop suddenly, and it is important to closely monitor these patients and make the decision for elective intubation. Signs and symptoms that suggest respiratory failure include:
– Dyspnea that occurs or worsens when supine
– Severe dysphagia with difficulty clearing secretions
– Hypophonia
– Speaking in incomplete sentences
– Tachypnea
– Accessory muscle use
– Retractions
– Poor pulmonary function testing results
Rapid sequence intubation medications need to be adjusted in patients with myasthenia gravis, due to the lack of Ach receptors. Since succinylcholine is a depolarizing agent, higher doses are required. Non-depolarizing paralytics are more effective and can be given at lower doses. However, these agents typically have a longer duration of action in comparison to depolarizing agents. The use of both types of paralytic agents can have varied effects in these individuals. As such, some authors advocate the avoidance of these agents and support the use of etomidate, fentanyl or propofol instead.
There have been preliminary studies that suggest the the possibility of BiPAP in a monitored setting to prevent intubation in these patients. In one of these studies, hypercapnia was shown to predict failure of BiPAP, and the need to proceed directly to intubating the patient.
2. Treat any precipitating factors
– Diagnose and treat any underlying infections. Though do not give any antibiotics that can precipitate infections
-Remove offending drugs
-Antipyretics if febrile
3. Neurology consultation
Will make the decisions to give intravenous gamma globulin or plasmapheresis.
4. ICU consultation
Intubated patient and discussing the possibility of BiPAP.
4. Consider an anticholinesterase inhibitor
Patients who are mildly ill and are currently taking these medications, can receive their usual dose. Up to 120 mg can be given. The usual doses are 60 – 120 mg q 4 hours.
5. Consider glucocorticoids
Can be associated with a transient worsening of symptoms about five to ten days after initiated, that can last for about five or six days. Benefits usually begin two to three weeks after initiation, and have been shown to have a synergistic affect with IVIG and plasma exchange.
Inpatient Management
1. Plasmapheresis
Directly removed acetylcholine receptor antibodies from the circulation. Clinical benefit usually seen within a week and lasts on average three weeks. Receptor antibodies rebounds if not given with concurrent immunotherapy.
2. IVIG
Has a immunomodulatory affect in Myasthenia Gravis that is unclear. Dose is 2g/Kg over two to five days. Benefits are usually seen within two weeks and can last up to several months.
3. Thymectomy
Associated with clinical improvement in 85%. Though up to 35% have a relapse.
Chronic outpatient management
1. Immunomodulatory therapy
Glucocorticoids, azathioprine, tacrolimus, rituximab, methotrexate, etanercept, cyclophosphamide
Jay Khadpe MD
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