Myasthenia Gravis - Neuro

Question 1

Myasthenia Gravis

Answer 1

-anautoimmune disease
-Caused by antibodies to acetylcholine receptors at neuromuscular junction
-fatigue and exhaustion of the muscular system, often with fluctuating severity.
-No sensory disturbance or atrophy.
dysarthria, dysphagia and ocular muscle weakness occur
-Onset F 20-40yo and both sexes 50-70yo
-It is a fluctuating skeletal muscle weakness
-Concurrent autoimmune disease including hyperthyroidism, rheumatoid arthritis, scleroderma, and lupus is common.
-About 15-20% of patients will experience a myasthenic crisis. 75% experience this within 2 years of diagnosis

Question 2

Myasthenic crisis

Answer 2

respiratory muscles paralysis, mechanical ventilation required.
Causes:
-surgical intervention
-Pregnancy
-Childbirth
-tapering of immunosuppressive medications.
-Spontaneous
-MEDICATIONS!
-Most medication common offenders:
antibiotics (aminoglycosides, erythromycinand azithromycin),
-cardiac drugs (beta-blockers, procainamide, and quinidine)
magnesium.

Question 3

Causes

Answer 3

• We don’t know all of the causes.
• In most cases, antibodies against the acetylcholine receptor (AChR) bind to and block the muscle fiber end plate receptors or destroy the receptor.
• Acetylcholine is released from the nerve cell, but insufficient amounts are able to bind to the muscle to stimulate a contraction. Over time, the muscle membrane may be destroyed.
• About 6% of patients without AChR antibodies have antibodies against MuSK, a muscle-specific kinase that is needed for the development and clustering of AChR. The pathogenic role of the anti-MuSK antibodies remains unclear.

Question 4

thymus

Answer 4

• There are a number of theories that the acetylcholine receptor antibody formation is promoted by the thymus.
• 60-70% of MG patients who are AChR antibody positive have thymic hyperplasia.
• 10–15% of patients with MG have a thymoma and, conversely, 30–45% of patients with thymomas have MG.

Question 5

symptoms

Answer 5

• Weakness of the voluntary (skeletal) muscles. The muscle weakness worsens with activity and improves with rest.
• Chewingor swallowing difficulty, gagging,choking, ordrooling
• Difficulty climbing stairs, lifting objects, rising from seat
• Dysarthria
• Drooping head
• Facial muscle weakness
• Fatigue
• Hoarseness, voice change
• Diplopia
• Eye strain
• Ptosis
• Breathing difficultybecause of weakness of the chest wall muscles

Question 6

Physical Exam Findings

Answer 6

• Eyelid weakness results in ptosis. Patients may furrow their foreheads, using the frontalis muscle to compensate for this weakness. A sustained upward gaze (have pt look up x 30 seconds) exacerbates the ptosis; closing the eyes for a short period (or applying ice) alleviates it.
• When seen, nystagmus becomes coarser on sustained lateral gaze as the medial rectus of the abducting eye fatigues. (Have patient look to side x 30 seconds, may induce nystagmus or diplopia.)
• • • Peek sign: Try to open eyes as patient squeezes them shut. If patient cannot resist your force and eyes open, they have a “+ peek.”
• Test any affected muscle group, allow pt to rest and or apply ice, and test again.
• looking at the feet while lying on the back for 60 seconds
• keeping the arms stretched forward for 60 seconds
• ten deep knee bends
• walking 30 steps on both the toes and the heels
• five situps, lying down and sitting up completely

Question 7

Diagnostic Testing

Answer 7

-Most common is the anti–acetylcholine receptor (AChR) antibody (Ab) test -Highly specific
-90% + in generalized MG
-Only 50-70% in purely ocular MG
-Half of patients with negative for anti-AChR Ab (seronegative MG) have positive test results for antibody to muscle-specific kinase (MuSK)
Edrophonium/Tensilon test : An infusion blocks the degradation of acetylcholine increasing the amount available at neuromuscular synapse and temporarily relieves weakness.
-Electoromyography (EMG): Detect impaired nerve-to-muscle transmission
-Pulmonary function testing: measures breathing strength, helps to predict whether respiration may fail and lead to a myasthenic crisis.
-Where diagnosis is uncertain, CT or MRI of the brain and/or orbits may be utilized.

Question 8

Work-Up

Answer 8

-When an MG diagnosis is confirmed, CT or MRI of the chest will be performed to evaluate for thymoma and/or thymic hyperplasia

Question 9

Treatment

Answer 9

-Acetylcholine esterase (AChE) inhibitors and immunomodulating medications are the mainstays of treatment.
-Pyridostigmine bromide/Mestinon and neostigmine bromide/Prostigmin (AChE) retard the hydrolysis of acetylcholine at synapses, increasing acetylcholine concentration and effect.
-GI complaints common
Increased bronchial and oral secretions problematic
-Overdosage can lead to weakness and even precipitate Myasthenic Crisis
-Prednisone will improve or resolve symptoms in 75% of patients and is often used initially.
-Azathioprine, cyclosporine, or mycophenolate mofetil decrease symptoms by suppressing the immune system response.
-Although there are risks, thymectomy is always considered in MG and may result in improvement or even resolution of disease.
-Plasmapheresis (plasma exchange):
-Removes circulating antibodies and immune complexes from the circulation.
-Used primarily in crisis and in preparation for surgery
-Long-term regular plasmapheresis qw, qm prn.
Intravenous Immune Globulin (IVIG)
-IVIg is effective in moderate or severe MG worsening into crisis
-More cost-effective than plasmapheresis.
-In theory, down-regulates antibodies directed against AChR
-Used in autoantibody-positive patients
Respiratory Ventilation:
-May be required for days, rarely weeks in Crisis.