Myasthenia Gravis - Clinicals, Diagnosis, and Management

Neurology

Clinicals - History

Fact Explanation
Drooping of eyelids It may be unilateral or bilateral but is usually asymmetrical initially. More pronounced in the evening or after exertion.

Anti-Acetylcholine receptor antibodies cause destruction of nicotinic receptors at neuromuscular junction, this interferes with post synaptic transmission.

When the above process occurs in levator palpebrae superioris, it result in ptosis.
Drooping of eyelids
It may be unilateral or bilateral but is usually asymmetrical initially. More pronounced in the evening or after exertion.

Anti-Acetylcholine receptor antibodies cause destruction of nicotinic receptors at neuromuscular junction, this interferes with post synaptic transmission.

When the above process occurs in levator palpebrae superioris, it result in ptosis.
Double vision Fatigue of extra-ocular muscles results in diplopia. Double vision
Fatigue of extra-ocular muscles results in diplopia.
Difficulty in chewing Involvement of muscles of mastication. Difficulty in chewing
Involvement of muscles of mastication.
Difficulty in swallowing This may occur due to fatigue of the bulbar muscles due to anti-Acetylcholine receptor antibodies but even if they are absent there can be anti- MuSK (Muscle Specific Kinase) antibodies which also results in bulbar muscle involvement. Difficulty in swallowing
This may occur due to fatigue of the bulbar muscles due to anti-Acetylcholine receptor antibodies but even if they are absent there can be anti- MuSK (Muscle Specific Kinase) antibodies which also results in bulbar muscle involvement.
Difficulty in lifting objects and standing from seated position. Shoulder and pelvic girdle involvement. Difficulty in lifting objects and standing from seated position.
Shoulder and pelvic girdle involvement.
Difficulty in breathing Occurs due to a myasthenic crisis that is due to severe weakness of oropharyngeal muscles, diaphragm and accessory muscles of breathing. Difficulty in breathing
Occurs due to a myasthenic crisis that is due to severe weakness of oropharyngeal muscles, diaphragm and accessory muscles of breathing.

Clinicals - Examination

Fact Explanation
Positive peek sign Patient "peeks" after sustained closure of eyes.
Orbicularis occuli fatigue
Positive peek sign
Patient "peeks" after sustained closure of eyes.
Orbicularis occuli fatigue
Positive Cogan lid twitch sign After sustained downward gaze, which relaxes the levator palpebrae superioris(LPS), if the patient looks straight ahead, there would be an excessive contraction of LPS thus an upward twitch Positive Cogan lid twitch sign
After sustained downward gaze, which relaxes the levator palpebrae superioris(LPS), if the patient looks straight ahead, there would be an excessive contraction of LPS thus an upward twitch
Paradoxical reversal of ptosis caused by edrophonium Edrophonium administration alleviates ptosis, relaxing compensatory contraction (according to Hering's law of equal innervation) of LPS in the unaffected eye causing it to droop. Paradoxical reversal of ptosis caused by edrophonium
Edrophonium administration alleviates ptosis, relaxing compensatory contraction (according to Hering's law of equal innervation) of LPS in the unaffected eye causing it to droop.
Enhanced ptosis Elevation of the ptotic eyelid manually results in drooping of the contralateral eye

Due to same reason as above. (Removal of compensatory elevation of "normal" eyelid)
Enhanced ptosis
Elevation of the ptotic eyelid manually results in drooping of the contralateral eye

Due to same reason as above. (Removal of compensatory elevation of "normal" eyelid)
Deteriorating voice on counting Due to weakness of the bulbar muscles involved in phonation. Deteriorating voice on counting
Due to weakness of the bulbar muscles involved in phonation.
Wasting of muscles In long standing disease due to chronic acetylcholine depletion. Wasting of muscles
In long standing disease due to chronic acetylcholine depletion.
Normal reflexes But on repetitive elicitation may fatigue Normal reflexes
But on repetitive elicitation may fatigue

Investigations - Diagnosis

Fact Explanation
Serum anti-Acetylcholine receptor and anti-MuSK antibodies 90% of patients with generalized myasthenia gravis and 75% with ocular myasthenia have anti-Acetylcholine receptor antibody ; 39-49% of patients with generalized myasthenia yet without Acetylcholine receptor antibodies have anti-MuSK antibodies. Serum anti-Acetylcholine receptor and anti-MuSK antibodies
90% of patients with generalized myasthenia gravis and 75% with ocular myasthenia have anti-Acetylcholine receptor antibody ; 39-49% of patients with generalized myasthenia yet without Acetylcholine receptor antibodies have anti-MuSK antibodies.
Repetitive nerve stimulation (RNS) Positive RNS features are; decrement in compound muscle action potential amplitude, post-tetanic potentiation and post-exercise exhaustion.
Decrement pattern is only positive in 50% of ocular myasthenia and 75% of generalized myasthenia.
Repetitive nerve stimulation (RNS)
Positive RNS features are; decrement in compound muscle action potential amplitude, post-tetanic potentiation and post-exercise exhaustion.
Decrement pattern is only positive in 50% of ocular myasthenia and 75% of generalized myasthenia.
Single fibre electromyography (SFEMG) The most sensitive test for myasthenia. More than 95% positive in both generalized & ocular myasthenia.
It simultaneously records potentials of two muscle fibers innervated by an individual axon and measures this variability called "Jitter".
Single fibre electromyography (SFEMG)
The most sensitive test for myasthenia. More than 95% positive in both generalized & ocular myasthenia.
It simultaneously records potentials of two muscle fibers innervated by an individual axon and measures this variability called "Jitter".
Positive Tensilon test Admission of edrophonium results in transient improvement in symptoms.

Edrophonium is a short acting acetylcholinesterase inhibitor leading to accumulation of acetylcholine thus transient improvement in symptoms.
Positive Tensilon test
Admission of edrophonium results in transient improvement in symptoms.

Edrophonium is a short acting acetylcholinesterase inhibitor leading to accumulation of acetylcholine thus transient improvement in symptoms.
Positive ice test Placing ice on the ptotic eyelid, relieves ptosis
Thought to be due to reduced temperature reducing the efficacy of anticholinesterase, resulting in reduced breakdown of acetylcholine, thus accumulation of it, improving the weakness.
Positive ice test
Placing ice on the ptotic eyelid, relieves ptosis
Thought to be due to reduced temperature reducing the efficacy of anticholinesterase, resulting in reduced breakdown of acetylcholine, thus accumulation of it, improving the weakness.
Mediastinal CT Sixty five percent of patients with myasthenia have thymic hyperplasia, 10-28% have thymoma and rest have normal or involuted thymus. Mediastinal CT
Sixty five percent of patients with myasthenia have thymic hyperplasia, 10-28% have thymoma and rest have normal or involuted thymus.
CPK/ESR - normal Needed in the evaluation of a patient with muscle weakness. CPK and ESR would be raised in myopathies that can cause symptoms similar to myasthenia. CPK/ESR - normal
Needed in the evaluation of a patient with muscle weakness. CPK and ESR would be raised in myopathies that can cause symptoms similar to myasthenia.

Investigations - Management

Fact Explanation
Forced vital capacity (FVC) In concordance with other signs and symptoms helps to decide timing of intubation and ventilation. Forced vital capacity (FVC)
In concordance with other signs and symptoms helps to decide timing of intubation and ventilation.
Bed side single breath count Reducing count indicates deteriorating illness. Ventilatory support may be necessary. Bed side single breath count
Reducing count indicates deteriorating illness. Ventilatory support may be necessary.
Spirometry If patient is undergoing thymectomy along with other preoperative investigations spirometry should be done, since myasthenic patients may have respiratory depression complicating general anaesthesia. Spirometry
If patient is undergoing thymectomy along with other preoperative investigations spirometry should be done, since myasthenic patients may have respiratory depression complicating general anaesthesia.
Chest CT To stage thymoma, if present. Chest CT
To stage thymoma, if present.

Management - Supportive

Fact Explanation
Find the cause for relapse and treat the cause or remove triggers. Infections - Pneumonia/upper-respiratory infection.
Drugs - Aminoglycosides, Magnesium sulfate enemas, Propranolol, Morphine, Barbiturates, Procainamide, Quinidine.
Stress - pain, sleep deprivation, emotional and physical stress, extreme heat/ cold, menstruation, pregnancy, childbirth.
Find the cause for relapse and treat the cause or remove triggers.
Infections - Pneumonia/upper-respiratory infection.
Drugs - Aminoglycosides, Magnesium sulfate enemas, Propranolol, Morphine, Barbiturates, Procainamide, Quinidine.
Stress - pain, sleep deprivation, emotional and physical stress, extreme heat/ cold, menstruation, pregnancy, childbirth.
Intubation and ventilation. Patient should be continuously monitored and decision to artificially ventilate should be taken preemptively when adequate. Intubation and ventilation.
Patient should be continuously monitored and decision to artificially ventilate should be taken preemptively when adequate.

Management - Specific

Fact Explanation
Oral anti-Cholinesterases Eg: Pyridostigmine 60 mg qds. Provide symptomatic relief by prolonging the availability of Acetylcholine at neuromuscular junction but do not interfere with the immune processes.
The dose should be titrated according to treatment outcome and side effects (abdominal cramps, nausea, vomiting, diarrhea,excessive salivation).
Oral anti-Cholinesterases Eg: Pyridostigmine 60 mg qds.
Provide symptomatic relief by prolonging the availability of Acetylcholine at neuromuscular junction but do not interfere with the immune processes.
The dose should be titrated according to treatment outcome and side effects (abdominal cramps, nausea, vomiting, diarrhea,excessive salivation).
Immunosuppressants: Prednisolone, Azathioprine, Mycophenolate. In treatment relapse and if there is no response to oral anti-Cholinesterases. Immunosuppressants: Prednisolone, Azathioprine, Mycophenolate.
In treatment relapse and if there is no response to oral anti-Cholinesterases.
Thymectomy Improves prognosis, particularly in women less than 50 years of age.
Presence of thymoma has worse prognosis.
Thymectomy
Improves prognosis, particularly in women less than 50 years of age.
Presence of thymoma has worse prognosis.
Plasmapheresis and IV Immunoglobulin Used during exacerbation/Myasthenic crisis to rapidly remove the antibodies.
Plasma exchange is more efficient than IV immunoglobulin, but has higher risk.
Plasmapheresis and IV Immunoglobulin
Used during exacerbation/Myasthenic crisis to rapidly remove the antibodies.
Plasma exchange is more efficient than IV immunoglobulin, but has higher risk.

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