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Periodic Paralysis, Emergency Medicine

Basics

Description

- Thyrotoxic PP (ThyroPP): - Incidence 2% in patients with thyrotoxicosis - Higher in Asians - Subset of HypoPP, clinically identical

- Mutation of skeletal muscle Na channel gene: - SCN4A - HypoPP, HyperPP: - AD inheritance - Spontaneous mutation

- 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

- General: - HEENT: - HypoPP and HyperPP: - Lid lag: Rare - Difficulty swallowing: Rare

- M/S: - HypoPP, HyperPP, ThyroPP: - Symmetrical muscle weakness in 1 or more extremity - Legs > arms

- Neuro: - Alert, conscious - Sensation intact - DTR reduced or absent - Skeletal muscle weakness, symmetrical - Sphincter normal

- EKG: - HypoPP: - Sinus bradycardia - Flattened T-wave - ST-segment depressions

- 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

- Hyperkalemia: - Drugs: Spironolactone, ACE inhibitors, NSAIDs, heparin - Hereditary: 21-hydroxylase deficiency, McArdle disease - GI: - Ileostomy with tight stoma

- 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

- 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

  • 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 prevalence1/3 new AD mutations
  • Hyperkalemic PP (HyperPP):1:200,000 prevalence90% of people with mutation will have clinical symptoms
  • Thyrotoxic PP (ThyroPP):Incidence 2% in patients with thyrotoxicosisHigher in AsiansSubset of HypoPP, clinically identical
  • Andersen " “Tawil:Subset of HypoPPRarePrevalence unknown

Etiology

  • Mutation of skeletal muscle Na channel gene:SCN4AHypoPP, HyperPP:AD inheritanceSpontaneous mutation
  • Mutation of skeletal muscle calcium channel gene CACN1AS:
  • Mutation of KCNJ2 gene:Andersen " “Tawil:AD inheritance50% spontaneous
  • M>F
  • Age of onset:HypoPP:HyperPP:Andersen " “Tawil:ThyroPP:

Diagnosis

Signs and Symptoms

History

  • Intermittent weakness:Can be isolatedRapid onsetCommon for attacks to recur and for weakness to persist between attacksFrequency from single isolated to daily attacks
  • Type of attack:SpontaneousAt night or early morningProvoked:History of thyroid diseaseRecent carbohydrate rich mealRest after strenuous exerciseIllnessLack of sleepMedications: Insulin, epinephrine, corticosteroids, ˇ ²-agonists, diureticsCold environmentMenstruationReduced sleepPregnancyMedications that induce thyroid disease
  • Length of attack:HypoPP: 1 hr " “daysHyperPP: 15 min " “4 hrThyroPP: Same as HypoPPAndersen " “Tawil: Variable
  • Family history of episodes of weakness

Physical Exam

  • General:
  • HEENT:HypoPP and HyperPP:Lid lag: RareDifficulty swallowing: RareThyroPP:Andersen " “Tawil:Dysmorphic features: Short stature, low set ears, broad based nose, micrognathia
  • Cardiac:HypoPP and HyperPP:ThyroPP:Andersen " “Tawil:
  • Pulmonary:HypoPP:Can affect respiratory muscles, rareSevere hypokalemia
  • M/S:HypoPP, HyperPP, ThyroPP:Symmetrical muscle weakness in 1 or more extremityLegs > armsAndersen " “Tawil:Periodic flaccid muscle weakness <1 hrProximal > distal
  • Neuro:Alert, consciousSensation intactDTR reduced or absentSkeletal muscle weakness, symmetricalSphincter normal
  • Skin:

Essential Workup

Lab tests and EKG ‚

Diagnosis Tests & Interpretation

  • EKG:HypoPP:Sinus bradycardiaFlattened T-waveST-segment depressionsHyperPP:ThryoPP:Tall P-waves, wide QRS, decreased T-wave, AV block, ventricular fibrillation or asystoleAndersen " “Tawil:Long QT, ventricular arrhythmiasU-waves, prolonged T-wave downslopeDifferentiates Andersen syndrome from other long QT syndromes
  • Electrolytes:Potassium:HyperPP: Normal or increasedHypoPP: Normal or decreasedThryoPP: Decreased during attacksAndersen " “Tawil: Decreased, normal, or increasedCalcium:ThryoPP: Decreased during attacksPhosphorus:ThryoPP: Decreased during attacks
  • Thyroid Studies:

Imaging

Not necessary for diagnosis ‚

Diagnostic Procedures/Surgery

None in ED but specialists may consider the following: ‚

  • EMG:HypoPP:HyperPP:Andersen " “Tawil
  • Muscle biopsy
  • Provocative testing:HyperPP:Potassium and epinephrineHypoPP:

Differential Diagnosis

Other causes of hypokalemia or hyperkalemia ‚

  • Hyperkalemia:Drugs: Spironolactone, ACE inhibitors, NSAIDs, heparinHereditary: 21-hydroxylase deficiency, McArdle diseaseGI:Ileostomy with tight stomaRenal:Endocrine:
  • Hypokalemia:Drugs:Tocolytics, amphotericin B, diuretics, reduced potassium intake, malignant hyperthermiaGI:VomitingCeliac and tropical sprueShort bowel syndromeRenal:Conn syndromeBartter/Gitelman syndromeAcute tubular necrosisRenal tubular acidosisNeuromuscular:Andersen " ”TawilMyasthenia gravisEndocrine:ThyrotoxicosisHyperaldosteronismDKA

Treatment

Pre-Hospital

Initial Stabilization/Therapy

  • Supportive care
  • HyperPP:Many attacks brief and do not need treatmentIV calcium gluconate may end attack
  • HypoPP:Potassium:Preferred: Oral potassium 40 mEqIV potassium 10 mEq 1 or 2 doses onlyWatch for overcorrectionIV hydration can help correct potassium
  • Andersen " “Tawil:Potassium unpredictable:Could be helpful in hypokalemia
  • ThyroPP:Treat thyroid abnormalities:Tachycardia: Nonselective ˇ ²-blockerTreat underlying abnormalities:Same as in HypoPPSee 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