Prognosis

See the list below:

Hyperkalemic periodic paralyses and paramyotonia congenita
- When not associated with weakness, these usually do not interfere with ability to work.
- Myotonia may require treatment.
- Life expectancy is not known to be affected.
Hypokalemic periodic paralyses
- Untreated patients may experience fixed proximal weakness, which may interfere with activities.
- Several deaths have been reported, mostly related to aspiration pneumonia or inability to clear secretions.

Patient Education

See the list below:

Periodic Paralysis Resource Center (PPRC): This is the official Web site of the Periodic Paralysis Association.
Periodic Paralysis (PP): A Web site of the Muscular Dystrophy association. Articles from Quest magazine provide information regarding PP. The Research Digest link provides references on the causes and treatments.

Questions

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Sokolov S, Scheuer T, Catterall WA. Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemicperiodic paralysis. ProcNatlAcadSci USA. 2008. 105:19980-5.
Matthews E, Labrum R, Sweeney MG, Sud R, Haworth A, Chinnery PF, et al. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology. 2009 May 5. 72(18):1544-7. [QxMD MEDLINE Link]. [Full Text].
Arzel-Hezode M, McGoey S, Sternberg D, Vicart S, Eymard B, Fontaine B. Glucocorticoids may trigger attacks in several types of periodic paralysis. Neuromuscul Disord. 2009 Mar. 19(3):217-9. [QxMD MEDLINE Link].
Donaldson MR, Yoon G, Fu YH, Ptacek LJ. Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity. Ann Med. 2004. 36 Suppl 1:92-7. [QxMD MEDLINE Link].
Ryan DP, da Silva MR, Soong TW, et al. Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell. 2010 Jan 8. 140(1):88-98. [QxMD MEDLINE Link]. [Full Text].
Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, et al. Review of the Diagnosis and Treatment of Periodic Paralysis. Muscle Nerve. 2018 Apr. 57 (4):522-530. [QxMD MEDLINE Link].
Chalissery AJ, Munteanu T, Langan Y, Brett F, Redmond J. Diverse phenotype of hypokalaemic periodic paralysis within a family. Pract Neurol. 2018 Feb. 18 (1):60-65. [QxMD MEDLINE Link].
Siddiqui FA, Sheikh A. Muscle paralysis in thyrotoxicosis. BMJ Case Rep. 2015 May 29. 2015:[QxMD MEDLINE Link].
Chaudhry MA, Wayangankar S. Thyrotoxic Periodic Paralysis: A Concise Review of the Literature. Curr Rheumatol Rev. 2016. 12 (3):190-194. [QxMD MEDLINE Link].
Dias Da Silva MR, Cerutti JM, Arnaldi LA, Maciel RM. A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. J Clin Endocrinol Metab. 2002 Nov. 87(11):4881-4. [QxMD MEDLINE Link].
Assadi F. Diagnosis of hypokalemia: a problem-solving approach to clinical cases. Iran J Kidney Dis. 2008 Jul. 2(3):115-22. [QxMD MEDLINE Link].
Streib EW. AAEE minimonograph #27: Differential diagnosis of myotonic syndromes. Muscle Nerve. 1987 Sep. 10(7):603-15. [QxMD MEDLINE Link].
Fournier E, Arzel M, Sternberg D, et al. Electromyography guides toward subgroups of mutations in muscle channelopathies. Ann Neurol. 2004 Nov. 56(5):650-61. [QxMD MEDLINE Link].
Keveyis (dichlorphenamide) [package insert]. Hawthorne, NY: Taro Pharmaceuticals. August 2015. Available at [Full Text].
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Matthews E, Portaro S, Ke Q, et al. Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype. Neurology. 2011 Nov 29. 77(22):1960-4. [QxMD MEDLINE Link]. [Full Text].
Junker J, Haverkamp W, Schulze-Bahr E, Eckardt L, Paulus W, Kiefer R. Amiodarone and acetazolamide for the treatment of genetically confirmed severe Andersen syndrome. Neurology. 2002 Aug 13. 59(3):466. [QxMD MEDLINE Link].
Pellizzón OA, Kalaizich L, Ptácek LJ, Tristani-Firouzi M, Gonzalez MD. Flecainide suppresses bidirectional ventricular tachycardia and reverses tachycardia-induced cardiomyopathy in Andersen-Tawil syndrome. J Cardiovasc Electrophysiol. 2008 Jan. 19(1):95-7. [QxMD MEDLINE Link].
Elbaz A, Vale-Santos J, Jurkat-Rott K. Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families. Am J Hum Genet. 1995 Feb. 56(2):374-80. [QxMD MEDLINE Link].
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Lin SH, Lin YF, Chen DT, et al. Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med. 2004 Jul 26. 164(14):1561-6. [QxMD MEDLINE Link].
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Media Gallery

Mutations in periodic paralysis.

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Disease	Gene	Protein	Inheritance	Mutation
HyperPP	SCN4A	Nav1.4	Dominant	Gain
NormoPP				Gain (ω-pore)
Paramyotoniacongenita				Gain
HypoPP Type II				Gain (ω-pore)
HypoPP Type I	CACNA1S	Cav1.1	Dominant	Gain (ω-pore)
ThyrotoxicPP	KCNJ18	Kir2.18	Dominant	Loss
Andersen-Tawil syndrome	KCNJ2	Kir2.1	Dominant	Loss

Syndrome	Age of Onset	Duration of Attack	Precipitating Factors	Severity of Attacks	Associated Features
Hyper-kalemic periodic paralyses	First decade of life	Few minutes to less than 2 h (mostly less than 1 h)	Low carbohydrate intake (fasting) Cold Rest following exercise Alcohol Infection Emotional stress Trauma Menstrual period	Rarely severe	Perioral and limb paresthesias Myotonia frequent Occasional pseudo-hypertrophy of muscles
Hypo-kalemic periodic paralyses	Variable -Childhood to third decade Majority of cases before 16 years	Few hours to almost a week Typically no longer than 72 h	Early morning attacks after previous day physical activity High-carbohydrate meal, Chinese food, alcohol Cold, change in barometric pressure or humidity Fever, upper respiratory tract infections Lack of sleep, fatigue Menstrual cycle	Severe Complete paralysis	Occasional myotonic lid lag Myotonia between attacks rare Unilateral, partial, monomelic Fixed muscle weakness late in disease
Potassium- associated myotonia	First decade	No weakness	Cold Rest after exercise	Attacks of stiffness can be mild to severe	Muscle hypertrophy
Para-myotonia congenita	First decade	2-24 h	Cold	Rarely severe	Pseudo-hypertrophy of muscles Paradoxical myotonia Fixed weakness rare
Thyrotoxic periodic paralyses	Third and fourth decades	Few hours to 7 d	Same as hypokalemic PP Hyper-insulinemia	Same as hypokalemic PP	Fixed muscle weakness may develop Hypokalemia during attacks

Hypokalemic	Hyperkalemic
Urinary potassium-wasting syndromes Hyperaldosteronism Conn syndrome Bartter syndrome Licorice intoxication
Alcohol	Addison disease Chronic renal failure Hyporeninemic Hypoaldosteronism
Drugs - Amphotericin B, barium	Ileostomy with tight stoma
Renal tubular acidosis	Potassium load
GI potassium-wasting syndromes Laxative abuse Severe diarrhea	Potassium-sparing diuretics

Urine K/C Ratio	Acid Base Status	Other Associated Features	Medical Conditions
< 1.5	Metabolic acidosis		Lower GI loss – Laxative abuse, diarrhea
< 1.5	Metabolic alkalosis	Normal BP	Surreptitious vomiting
>1.5	Metabolic acidosis		DKA, type 1 or type 2 distal RTA
>1.5	Metabolic alkalosis	Normal BP	Diuretic use, Bartter syndrome, Gitelman syndrome
≥1.5	Metabolic alkalosis	Hypertension	Primary aldosteronism, Cushing syndrome, renal artery stenosis, congenital adrenal hyperplasia, apparent mineralocorticoid excess, Liddle syndrome

	Hypokalemic PP	Hyperkalemic PP
Serum potassium	Mildly depressed; may reach 1-5 mEq/L	Increases from baseline but may not increase beyond normal range
Serum CPK	Moderately elevated during attacks	Mildly elevated during attacks
ECG	Bradycardia Flat T waves, U waves, ST-segment depression	Tall T waves

	Para- myotonia Congenita	Hyper- kalemic Periodic Paralysis	Hypo- kalemic Periodic Paralysis
Electrophysiological pattern	I	IV	V
Channel mutations	Sodium T1313M, R1448C	Sodium T704M	Calcium R528H
Short Exercise Test:
Post exercise myotonic potentials	Yes	No	No
CMAP amplitude change after First trial	Increase or decrease	Increase	No
CMAP amplitude change after second and third trial	Gradual increase	Gradual increase	No
Long Exercise Test:
Immediate change of CMAP amplitude	Decrease	Increase	No
Late change of CMAP amplitude	Decrease	Decrease	Decrease
Modified from Fournier et al, 2004.^[15]

Periodic Paralyses Follow-up

Prognosis

Patient Education

References

Tables

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