Case Index

PATIENT CASE STUDIES
Case 13 2/24/99 Myasthenia Gravis


Case discussion

A 24 year old right handed white male of chinese extraction, a medical intern at UCDMC, presented to the emergency room with a five day history of progressive weakness in all four extremities. He initially noticed difficulty with his golf swing while on vacation in Hawaii. By the following day he was unable to run. Standing from sitting and walking becausme difficult and by the time of admission he was unable to get out of bed unassisted and had marked difficulty with use of his upper extremities. There was no shortness of breath, diplopia, swallowing difficulty, pain, sensory symptoms, or urinary or bowel incontinence. He had suffered mild trauma to the low back while playing basketball two days prior to the onset of the weakness. He also had a history of mild intermittent diarrhea associated with 5 lbs of weight loss over the previous six months. He was not on medication and he had no known allergies. His father had well controlled insulin dependent diabetes mellitus. His mother was in good health. Prior to going on vacation a week before he had finished the first six months of a busy and stressful medical internship.

On examination his temperature was 37° C, pulse rate was 120/min regular, BP 145/95, respiratory rate was 20/min. On general examination he appeared anxious. He was not dyspneic. He was awake, alert, attentive and fully oriented. Speech was fluent with good naming, comprehension and repetition. Eyes were mildly proptotic. Fundoscopy was normal and visual fields were full to confrontation. Visual acuity was 20/20 bilaterally. Pupils were round, equal and reactive. Ptosis was present bilaterally. Extraocular movements were full with binocular diplopia at right lateral gaze. Face was symmetric with mild decrease of nasolabial folds. He was not hoarse, dysphonic or dysarthric. Tongue was midline with normal strength and without atrophy. Neck flexion and extension was mildly weak (4/5). Motor examination of the extremities revealed normal bulk and tone. He had a fine tremor of outstretched hands. He had generalized weakness with strength symmetrically in upper and lower extremities weaker proximally (3/5) than distally (4/5). Deep tendon reflexes were 1 through out and symmetric. Plantar reflexes were flexor. Cerebellar examination revealed accurate finger to nose testing. Primary sensory modalities were intact. He was unable to stand and walk unassisted.

  1. Summarize the Case in 1-2 sentences.

    2. 24 years old white male of chinese descent presents to the ED with a 5 day Hx of progressive muscle weakness in all 4 extremities, and a 6 month Hx of mild intermittent diarrhea and weight loss with no SOB, diplopia, dysphagia, sensory symptoms, pain nor urinary or bowel incontinence. Significant physical findings include tachycardia, tachypnea, hypertension, anxiety, tremor, exopthalmus, DTR’s are present but diminished and there is muscle weakness of extraocular, facial, and peripheral muscles.

    good summuary of course and findings, but on the long side: This is a 24 yr old male with a subacute progressive course over 5 days of generalized weakness with ptosis and exophthalmoplegia with preserved DTRS and normal sensation and 6 months of diarrhea and weight loss. He is also tachycardic, tachpneic, hypertensive, anxious with tremor, and exophthalmos.

  2. Discuss lesion localization on the basis of the physical examination.

    3. good

  3. Discuss underlying pathogenesis on the basis of clinical course.

    4. The patient’s subacute-crescendo course presenting in young adult hood combined with his global muscle weakness exclude congenital, traumatic, neoplastic and vascular etiologies. The patients symptoms are most consistent with an immunological disease with acute exacerbating factors.

    subacute course suggests inflammatory or immunological or metabolic

  4. Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses.

    5. Thyrotoxicosis Periodic Paralysis.

    Alternative Dx: Myasthenia gravis, GBS, muscular dystrophy

    good, thyrotoxic periodic paralysis with hypokalemia

  5. Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis.

    6. Thyroid Panel: If Dx is correct we would expect a low TSH and a high T3 and T4

    Chemistry Panel: If Dx is correct we would expect to see a low K (hypokalemia)

    good

  6. Indicate complications of the disease and ancillary tests that would help evaluate them.

    7. Respiratory muscle weakness leading to respiratory failure-Pulse oxiometry Cardiac Arrhythmia-EKG Diarrhea (leading to further electrolyte imbalances) Thyroid Storm-monitor thryoid levels

    good

  7. Discuss how the underlying pathophysiology is relevant in the management of this patient.

    8. The patient is synthesizing thyroid stimulating antibodies which are causing elevated T3 and T4 hormone. This causes an increase in BMR (due to increase in Na/K ATPase), upregulation of -Adrenergic Receptors, increased blood glucose, and increased protein breakdown. This increased pump activity in addition to diarrhea lead to a condition of hypokalemia. The hypokalemia leads to global muscle weakness secondary to hyperpolarization of the muscle membrane, with proximal, facial and extraocular muscles being most greatly affected. The decrease in DTR is due to global weakness. The increased -Adrenergic activity accounts for the patients tachycardia, hypertension, tachypnea, tremor and anxiety. Ptosis and exopthalmos (proptotic) are characteristic signs of thyrotoxocosis.

    Therefore we would treat this patient with K+ to correct the hypokalemia. As for the thryotoxicosis, you could treat this patient with radioactive iodine or surgery with hormone replacement therapy.

    goood: the immune response in graves' disease is against thyrogolobulin: the exophthalmos in thyroid disease is against muscle antigens which include mitochondrial succinate dehydrogenase and calsequestrin.

Another Version:

  1. Summarize the Case in 1-2 sentences.

    2. This 24 year-old asian male medical intern presents with a 5 day history of progressive generalized proximal weakness, along with tremor, anxiety, tachycardia, ptosis and proptosis, diarrhea, and weight loss over several months, and not associated with sensory loss.

    good

  2. Discuss lesion localization on the basis of the physical examination.

    3. generalized weakness without flaccidity or UMN signs: muscle diarrhea, weight loss, tachycardia, anxiety, proptosis: thyroid

    good

  3. Discuss underlying pathogenesis on the basis of clinical course.

    4. The 5-day progressive subacute course suggests an infectious, inflammatory, or mass lesion.

    good (possibly toxic occasionally metabolic)

  4. Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses.

    5. Chronic thyrotoxicosis with thyrotoxic periodic paralysis

    Differential diagnosis
    á Metabolic: hyper/hypokalemic periodic paralysis, acute intermittent porphyria, hyperparathyroidism, hypoglycemia
    á Psychiatric: Panic disorder with conversion reaction,
    á Neurologic: myasthenia gravis, muscular dystrophy, Guillain-Barre, poliomyelitis, Lambert-Eaton syndrome
    á Drug-induced: thyrotoxicosis factitia caused by overdose of thyroid hormone, excess alcohol intake

  5. Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis.

    6. á Serum potassium level--decreased
    á Serum Thyroid panel: TSH, T3, T4--TSH very low to undetectable, T3, T4, or both elevated.

    good

  6. Indicate complications of the disease and ancillary tests that would help evaluate them.

    7. Complications of hypokalemia: cardiac arrhythmias--EKG

    good; also embolic infarcts secondary to atrial fibrillation

    Complications of chronic thyrotoxicosis: á cardiac -- hypertrophy, CHF--EKG, cardiologic evaluation
    á respiratory failure--close monitoring during attacks
    á Other: osteopenia, muscle wasting, thyroid storm, opthalmopathy--evaluated with periodic exam

    good

  7. Discuss how the underlying pathophysiology is relevant in the management of this patient.

    8. Thyrotoxic periodic paralysis occurs most commonly among Latin American and Asian men with hyperthyroidism. Its pathophysiology is not understood, but it has been found that during attacks muscle membranes become less excitable, which is thought to be due to overactivity of the Na/K pump caused by hyperthyroidism. The acute attacks are terminated by administration of KCl intravenously, and treatment of the hyperthyroidism with propylthiouracil prevents their recurrence.

    Thyrotoxic periodic paralysis is very similar in presentation to hypokalemic periodic paralysis (a.k.a. Familial periodic paralysis), which is a disorder of the calcium channel. This condition is associated with an autosomal dominant genetic defect consisting of mutations in the alpha-1 subunit of the dihydropyridine receptor, a slow voltage-gated L-type calcium channel located in T-tubules of muscle cells, resulting in reduced calcium flux through the channel. It is hypothesized that reduced calcium flux through the pore reduces Ca++ release from the sarcoplasmic reticulum, thus reducing muscle contraction. The attacks are commonly precipitated by a large carbohydrate meal or strenuous exercise. Treatment consists of increasing dietary K+ intake, and KCl for acute attacks.

    good