Periodic Paralysis, Emergency Medicine

Basics

Description

Periodic paralysis (PP): Disorder of muscle metabolism usually inherited that leads to flaccid extremity weakness. Exacerbated by hyperkalemia, hypokalemia, thyrotoxicosis
Primary: Familial AD mutation skeletal muscle calcium, sodium, or potassium channel
Secondary: Thyrotoxic, hypokalemia, hyperkalemia

Epidemiology

Incidence and Prevalence Estimates

Hypokalemic PP (HypoPP):
- MC, 1:100,000 prevalence
- 1/3 new AD mutations
Hyperkalemic PP (HyperPP):
- 1:200,000 prevalence
- 90% of people with mutation will have clinical symptoms
Thyrotoxic PP (ThyroPP):
- Incidence 2% in patients with thyrotoxicosis
- Higher in Asians
- Subset of HypoPP, clinically identical
Andersen " “Tawil:
- Subset of HypoPP
- Rare
- Prevalence unknown

Etiology

Mutation of skeletal muscle Na channel gene:
- SCN4A
- HypoPP, HyperPP:
  - AD inheritance
  - Spontaneous mutation
Mutation of skeletal muscle calcium channel gene CACN1AS:
- HypoPP
Mutation of KCNJ2 gene:
- Andersen " “Tawil:
  - AD inheritance
  - 50% spontaneous
M>F
Age of onset:
- HypoPP:
  - 1st or 2nd decade
- HyperPP:
  - 1st decade
- Andersen " “Tawil:
  - 1st or 2nd decade
- ThyroPP:
  - 2nd " “5th decade

Diagnosis

Signs and Symptoms

History

Intermittent weakness:
- Can be isolated
- Rapid onset
- Common for attacks to recur and for weakness to persist between attacks
- Frequency from single isolated to daily attacks
Type of attack:
- Spontaneous
- At night or early morning
- Provoked:
  - History of thyroid disease
  - Recent carbohydrate rich meal
  - Rest after strenuous exercise
  - Illness
  - Lack of sleep
  - Medications: Insulin, epinephrine, corticosteroids, ˇ ²-agonists, diuretics
  - Cold environment
  - Menstruation
  - Reduced sleep
  - Pregnancy
  - Medications that induce thyroid disease
Length of attack:
- HypoPP: 1 hr " “days
- HyperPP: 15 min " “4 hr
- ThyroPP: Same as HypoPP
- Andersen " “Tawil: Variable
Family history of episodes of weakness

Physical Exam

General:
- ThyroPP:
  - Hyperthermia
HEENT:
- HypoPP and HyperPP:
  - Lid lag: Rare
  - Difficulty swallowing: Rare
- ThyroPP:
  - Exophthalmos
  - Goiter
- Andersen " “Tawil:
  - Dysmorphic features: Short stature, low set ears, broad based nose, micrognathia
Cardiac:
- HypoPP and HyperPP:
  - Dysrhythmias possible
- ThyroPP:
  - Tachycardia, dysrhythmia
- Andersen " “Tawil:
  - Cardiac dysrhythmia
Pulmonary:
- HypoPP:
  - Can affect respiratory muscles, rare
- Severe hypokalemia
M/S:
- HypoPP, HyperPP, ThyroPP:
  - Symmetrical muscle weakness in 1 or more extremity
  - Legs > arms
- Andersen " “Tawil:
  - Periodic flaccid muscle weakness <1 hr
  - Proximal > distal
Neuro:
- Alert, conscious
- Sensation intact
- DTR reduced or absent
- Skeletal muscle weakness, symmetrical
- Sphincter normal
Skin:
- ThyroPP:
  - Warm, moist

Essential Workup

Lab tests and EKG ‚

Diagnosis Tests & Interpretation

EKG:
- HypoPP:
  - Sinus bradycardia
  - Flattened T-wave
  - ST-segment depressions
- HyperPP:
  - Rarely peaked T-waves
- ThryoPP:
  - Tall P-waves, wide QRS, decreased T-wave, AV block, ventricular fibrillation or asystole
- Andersen " “Tawil:
  - Long QT, ventricular arrhythmias
  - U-waves, prolonged T-wave downslope
  - Differentiates Andersen syndrome from other long QT syndromes
Electrolytes:
- Potassium:
  - HyperPP: Normal or increased
  - HypoPP: Normal or decreased
  - ThryoPP: Decreased during attacks
  - Andersen " “Tawil: Decreased, normal, or increased
- Calcium:
  - ThryoPP: Decreased during attacks
- Phosphorus:
  - ThryoPP: Decreased during attacks
Thyroid Studies:
- ThyroPP:
  - TSH: Low
  - T4: Elevated

Imaging
Not necessary for diagnosis ‚
Diagnostic Procedures/Surgery
None in ED but specialists may consider the following: ‚

EMG:
- HypoPP:
  - No myotonia
- HyperPP:
  - Myotonia
- Andersen " “Tawil
Muscle biopsy
Provocative testing:
- HyperPP:
  - Potassium and epinephrine
- HypoPP:
  - Insulin and glucose

Differential Diagnosis

Other causes of hypokalemia or hyperkalemia ‚

Hyperkalemia:
- Drugs: Spironolactone, ACE inhibitors, NSAIDs, heparin
- Hereditary: 21-hydroxylase deficiency, McArdle disease
- GI:
  - Ileostomy with tight stoma
- Renal:
  - Chronic renal failure
- Endocrine:
  - Addison disease
Hypokalemia:
- Drugs:
  - Tocolytics, amphotericin B, diuretics, reduced potassium intake, malignant hyperthermia
- GI:
  - Vomiting
  - Celiac and tropical sprue
  - Short bowel syndrome
- Renal:
  - Conn syndrome
  - Bartter/Gitelman syndrome
  - Acute tubular necrosis
  - Renal tubular acidosis
- Neuromuscular:
  - Andersen " ”Tawil
  - Myasthenia gravis
- Endocrine:
  - Thyrotoxicosis
  - Hyperaldosteronism
  - DKA

Treatment

Pre-Hospital

Supportive:
- ABC, IV, O2, monitor

Initial Stabilization/Therapy

Supportive care
HyperPP:
- Many attacks brief and do not need treatment
- IV calcium gluconate may end attack
HypoPP:
- Potassium:
  - Preferred: Oral potassium 40 mEq
  - IV potassium 10 mEq 1 or 2 doses only
  - Watch for overcorrection
  - IV hydration can help correct potassium
Andersen " “Tawil:
- Potassium unpredictable:
  - Could be helpful in hypokalemia
ThyroPP:
- Treat thyroid abnormalities:
  - Tachycardia: Nonselective ˇ ²-blocker
- Treat underlying abnormalities:
  - Same as in HypoPP
  - See the section on thyrotoxicosis

HypoPP should avoid volatile anesthetics and depolarizing muscle relaxants which can cause an attack or malignant hyperthermia ‚

Follow-Up

Disposition

HypoPP or HyperPP:
- Lifestyle modifications:
  - Avoid triggers: Ethanol, prolonged exercise, high potassium foods, fasting
ThryoPP:
- Depends on severity of underlying disease, if asymptomatic and controlled may consider discharge with consultation with neurologist and endocrinologist.

Admission Criteria

HypoPP or HyperPP:
- Consider if severe hypo- or hyperkalemia, still symptomatic, cardiac or respiratory compromise
Andersen " “Tawil:
- Admit, risk of sudden cardiac death high

Discharge Criteria

HypoPP, HyperPP, ThyroPP:
- Resolved symptoms, referral to neurologist, no cardiac or respiratory compromise

Issues for Referral

Neurology
Endocrinology for ThyroPP
Genetic counseling:
- 50% risk of inheriting primary PP

Follow-Up Recommendations

Neurology specialist in metabolic myopathies
Geneticist

Pearls and Pitfalls

Admit Andersen " “Tawil patients and all PP patients who remain symptomatic.
Use caution with volatile anesthetics and depolarizing muscle relaxants in patients with all forms of PP

Additional Reading

Alkaabi ‚ JM, Mushtaq ‚ A, Al-Maskari ‚ FN, et al. Hypokalemic periodic paralysis: A case series, review of the literature and update of management. Eur J Emerg Med. 2010;17(1):45 " “47.
Finsterer ‚ J. Primary periodic paralyses. Acta Neurol Scand. 2008;117(3):145 " “158.
Fontaine ‚ B. Periodic paralysis. Adv Genet. 2008;63:3 " “23.
Venance ‚ SL, Cannon ‚ SC, Fialho ‚ D, et al. The primary periodic paralyses: Diagnosis, pathogenesis and treatment. Brain. 2006;129:8 " “17.

Codes

ICD9

359.3 Periodic paralysis ‚

ICD10

G72.3 Periodic paralysis ‚

SNOMED

267607008 Familial periodic paralysis (disorder)
7409003 Secondary periodic paralysis (disorder)
278513006 Hyperkalemic periodic paralysis (disorder)
240093008 Hypokalemic periodic paralysis
30967002 Thyrotoxic periodic paralysis

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