A Young Man With Episodic Weakness

An 18-year-old man was evaluated for intermittent muscle weakness that occurred mainly in the mornings after eating pizza the previous night. This started about 6 months earlier. A recent attack prompted him to make an emergency room visit, where he had a potassium level of 3.0 mEq/L (normal, 3.5–5.0 mEq/L) and was treated with an oral potassium supplement.

Past medical history was unremarkable. His father had complained of similar problems with weakness following rest after exercise and heavy meals. There was no other family history. He was a college student who did not drink alcohol or smoke.

Examination revealed normal mentation and cranial nerves. Muscle strength was normal. Reflexes were normal and symmetrical, and there were no Babinski signs. Sensation and coordination were normal. There was no clinical myotonia. The neurological examination was otherwise normal.

What is the Differential Diagnosis?

This patient presented with intermittent weakness. Myasthenia gravis is a consideration, but the weakness did not include cranial nerves and was episodic and related to heavy meals, and it did not fluctuate during the day as in that disease; the patient was otherwise completely normal between attacks.

A mitochondrial myopathy is also a possibility, as those patients can present with intermittent weakness and fatigue; however, this occurs mainly during exercise, and they also usually have other manifestations. In other metabolic myopathies there are exercise-induced muscle pains.

The history was rather suggestive of a periodic paralysis. The clinical presentation, symptoms in his father, and his low serum potassium during an attack are characteristic of hypokalemic periodic paralysis (HypoPP). Tables 78-1 and 78-2 describe the various periodic paralyses.

Table 78-1

Characteristics and Treatment of Hypokalemic Periodic Paralysis (HypoPP)

Reprinted with permission from Moxley R. Channelopathies affecting skeletal muscle: myotonic disorders including myotonic dystrophy and periodic paralysis. In: Jones HR, DeVivi DC, Darras BT, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach . Boston, MA: Butterworth-Heinemann; 2003:787.

	Periodic Paralysis With Cardiac Arrhythmia	Calcium Channel Periodic Paralysis	Sodium Channel Periodic Paralysis	Potassium Channel Periodic Paralysis	Periodic Paralysis With Thyroid Disease
Clinical Features	Andersen Syndrome With Normo-, Hypo-, or Hyperkalemic Periodic Paralysis	HypoPP 1	HypoPP 2	HypoPP	Hypokalemic Thyrotoxic Periodic Paralysis
Inheritance	Dominant	Dominant	Dominant	Dominant	Sporadic; occasionally dominant
Gene defect	Chromosome 17; affects Kir2.1 potassium channel	Chromosome 2; affects skeletal muscle calcium channel	Chromosome 17; affects skeletal muscle sodium channel	Chromosome 11; affects MiRP2 subunit of potassium channel	Unknown
Age of onset; myopathy infrequent	First or second decade typical; also short stature; dysmorphic features; prolonged QT interval on ECG; ventricular arrhythmias	First to third decade; moderate common late; vacuoles frequently seen on biopsy	First to third decade; not yet determined	Second to third decade; not yet determined	Third decade (males 20:1)
Myotonia; provocative stimuli	No Rest after exercise, oral glucose	No High-carbohydrate meals, rest after exercise, cold; emotional stress/excitement	No High-carbohydrate meals, rest after exercise, cold; emotional stress/excitement	No Usually by strenuous exercise followed by rest; less consistent provocation after high carbohydrate intake	No High-carbohydrate meals, rest after exercise, acetazolamide
Therapy for symptoms	Mild exercise, glucose, high sodium intake, acetazolamide	Acetazolamide, dichlorphenamide, potassium, spironolactone	Potassium, spironolactone	Acetazolamide	Propranolol, restoration of euthyroid state, oral potassium, spironolactone

ECG , Electrocardiography.

Table 78-2

Characteristics and Treatment of Hyperkalemic Periodic Paralysis

Reprinted with permission from Moxley R. Channelopathies affecting skeletal muscle: myotonic disorders including myotonic dystrophy and periodic paralysis. In: Jones HR, DeVivo DC, Darras BT, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach . Boston, MA: Butterworth-Heinemann; 2003:788.

	Sodium Channel Myotonia with Periodic Paralysis			Sodium Channel Periodic Paralysis without Myotonia
Inheritance Gene defect	Dominant Chromosome 17; affects skeletal muscle sodium channel	Dominant Chromosome 17; affects skeletal muscle sodium channel	Dominant Chromosome 17; affects skeletal muscle sodium channel	Dominant Chromosome 17; affects skeletal muscle sodium channel
Age of onset Myopathy Myotonia	First decade Very rare Especially paradoxical myotonia of the eyelids and grip	First decade Rare Especially paradoxical myotonia of the eyelids and grip	First decade Infrequent Especially paradoxical myotonia of the eyelids	First decade Infrequent No
Provocative stimuli	Cold exposure followed by exercise leads to focal paralysis; occasionally exercise provokes stiffness	Oral potassium load, rest after exercise mainly in morning (hyperkalemic weakness), cold exposure followed by exercise (focal paralysis)	Rest after exercise, cold, and oral potassium	Rest after exercise, cold, and oral potassium
Therapy for symptoms	Mexiletine, mild exercise, keep patient warm	Mild exercise, thiazides, mexiletine, and tocainide	Thiazides, acetazolamide, dichlorphenamide, and sodium restrictions	Thiazides, acetazolamide, dichlorphenamide, and sodium restrictions