Question

PATIENT’S CHIEF COMPLAINTS

double vision
axial limb weakness
difficulty swallowing

PAST MEDICAL HISTORY

35-year-old white female
fracture of radius at age 10

FAMILY MEDICAL HISTORY

mother diagnosed with mild osteoporosis
sister, age 29, has Type I diabetes
one daughter and two sons exhibiting no major health problems

PHYSICAL EXAMINATION

Height = 5’2”                                      
Weight = 115 lbs
Body temperature = 98.9^o F
Heart rate = 76 bpm
Blood pressure = 115/75 mm Hg
Respiratory Rate = 14 bpm

LABORATORY TESTS

Complete blood count (CBC) - normal
Standard laboratory tests - normal
EKG - normal
Chest X-ray – enlargement of upper mediastinum
Chest computed tomography (CAT scan) – smooth mass in upper mediastinum
Acetylcholine receptor antibodies elevate

What is the pathogenesis (biological mechanism that leads to a diseased state) of the disease?

Answer 1

Answer : Myasthenia gravis

The patient is a young female, who has presented with proximal (axial) muscle weakness, diplopia ( double vision), and dysphagia (difficulty in swallowing).

Chest Xray and CT scan show superior mediastinal mass, suggestive of Thymoma.

Acetylcholine receptor antibodies are elevated.

All these features are suggestive of Myasthenia gravis.

EXPLANATION

Myasthenia gravis (MG) is an autoimmune disorder where antibodies are produced against acetylcholine receptors located at motor end plates in myoneural junctions.

• Antibodies are produced by B lymphocytes that are defectively regulated by T lymphocytes.
• T lymphocyte tolerance to self-antigens is established in the thymus, but in MG this tolerance is lost that results in production of autoantibodies against acetylcholine receptors.
• Thymic hyperplasia is observed in about 65% of MG patients, and thymomas are present in about 10% of MG patients.

Clinical Features

• Age of onset is 15-50 years.
• Females are more affected than males.
• Remissions and relapses are seen during the early course of illness.
• Characteristic feature is easy fatiguability associated with paresis of muscles.
• Repeated contractions worsen the weakness.
• Rest improves the muscular strength.
• Reflexes and sensations are normal.
• Diurnal variation is present.
• Ocular muscles are most commonly affected resulting in ptosis and diplopia ( double vision).
• Involvement of bulbar muscles results in dysphagia (difficulty in swallowing), nasal regurgitation and difficulty in speaking (nasal voice).
• Limb muscle involvement is of proximal group resulting in difficulty in raising the arm above shoulder, and problems in getting up from squatting or sitting positions.
• Involvement of respiratory muscles results in myasthenic crisis and can cause death.

Investigations

Tensilon Test (Edrophonium Test)
Edrophonium is a rapidly acting acetylcholinesterase inhibitor. It has a short duration of action and reverses the muscular weakness dramatically in myasthenia. In adults, a 2-mg injection is given as a test dose (to check for tolerance) followed by another 8 mg that results in dramatic improvement in ptosis, diplopia, nasal voice, etc. within 30 seconds and persists up to 1-2 minutes. Positive test is highly suggestive of MG. Borderline or mild improvement may occur in other neuromuscular disorders. Side effects like abdominal cramps can be relieved by atropine.

Other tests
• Chest radiography and CT scan for thymic enlargement.
• Thyroid function tests (10% may have associated hyperthyroidism).
• Acetylcholine receptor antibody levels (present in >90% patients with generalised myasthenia).
• Anti-muscle-specific protein (tyrosine) kinase (anti-MuSK) antibodies in many patients who are negative for ACh receptor antibodies.
• Patients with MuSK-antibody associated MG are usually younger women who present with predominant facial, bulbar and respiratory weakness, lingual atrophy and relatively mild limb weakness.
• Electrodiagnostic studies (nerve conduction testing, repetitive nerve stimulation, exercise testing and in certain instances single-fibre EMG).
• Ice test: In a patient with ptosis a small cube of ice is placed over the eyelid for about 2 minutes. Improvement of the ptosis after this procedure suggests a disorder of neuromuscular transmission.