Paralisis Periodik

Pendahuluan

Kelompok heterogen penyakit otot yang diketahui sebagai paralisis periodik ditandai dengan
episode kelemahan otot yang flasid dengan interval yang ireguler. Kondisi paling banyak
adalah herediter dan kondisi episodik lebih banyak dibanding periodik. Paralisis periodik
terbagi menjadi kelainan primer dan sekunder.

Karakteristik umum dari PP primer yaitu: (1) herediter; (2) kebanyakan dihubungkan dengan
alterasi pada level serum kalium; (3)kadang terdapat miotonia; dan (4) myotonia dan PP
dihasilkan dari defektif ion-ion channels.

Patofisiologi

PP terdiri dari bentuk hipokalemik, hiperkalemik, dan paramiotonik

Sodium channel Hyperkalemic PP (HyperPP)

Hypokalemic PP (HypoPP2)
Paramyotonia congenita
Potassium-aggravated myotonia
Calcium channel Hypokalemic PP (HypoPP1)
Potassium channel Andersen-Tawil syndrome
Hyperkalemic PP or hypokalemic PP
Sodium channel Hyperkalemic PP (HyperPP)
Hypokalemic PP (HypoPP2)
Paramyotonia congenita
Potassium-aggravated myotonia
Calcium channel Hypokalemic PP (HypoPP1)
Potassium channel Andersen-Tawil syndrome
Hyperkalemic PP or hypokalemic PP

Dasar fisiologik dari kelemahan flasid yaitu ineksitabilitas dari membran otot. Alterasi
level kalium serum bukan merupakn defek yang prinsipal dari PP primer; alterasi
metabolisme kalium merupakan hasil dari PP.pada PP tirotoksik dan primer, paralisis flasid
terjadi dengan perubahan kecil yang relatif pada level kalium serum, dimana pada PP
sekunder, level kalium serum terlihat abnormal.

Tidak ada mekanisme tunggal yang responsible untuk kelompok kelainan ini. Kelemahan
biasanya bersifat general namun dapat terlokalisir. Cranial musculature dan otot pernapasan
biasanya terkena. Serabut otot secara elektrik dapat tereksitasi selama serangan.

Voltage-sensitive ion channels closely regulate generation of action potentials (brief and
reversible alterations of the voltage of cellular membranes). These are selectively and
variably permeable ion channels. Energy-dependent ion transporters maintain concentration
gradients. During the generation of action potentials, sodium ions move across the membrane
through voltage-gated ion channels. The resting muscle fiber membrane is polarized
primarily by the movement of chloride through chloride channels and is repolarized by
movement of potassium. Sodium, chloride, and calcium channelopathies, as a group, are
associated with myotonia and PP. The functional subunits of sodium, calcium, and potassium
channels are homologous. Sodium channelopathies are better understood than calcium or
chloride channelopathies. All forms of familial PP show the final mechanistic pathway
involving aberrant depolarization, inactivating sodium channels, and muscle fiber
inexcitability.

Discussion in this article primarily addresses the sodium, calcium, and potassium
channelopathies as well as secondary forms of periodic paralyses (PP). Chloride
channelopathies are not associated with episodic weakness and are discussed in more detail in
the articles on myotonic disorders.

Muscle sodium channel gene

The sodium channel has an alpha subunit and a beta subunit. The alpha subunit of the sodium
channel is a 260-kd glycoprotein comprising about 1800-2000 amino acids. This channel is
highly conserved evolutionarily from Drosophila to human. It has 4 homologous domains (I-
IV) that fold to form a central pore, each with 225-325 amino acids. Each domain consists of
6 hydrophobic segments (S1-S6) traversing the cell membrane. The main functions of the
channel include voltage-sensitive gating, inactivation, and ion selectivity. The extracellular
loop between S5 and S6 dips into the plasma membrane and participates in the formation of
the pore. The S4 segment contains positively charged amino acids at every third position and
functions as a voltage sensor. Conformation changes may occur during depolarization,
resulting in activation and inactivation of the channel. The cellular loop between domain III-
S6 and domain IV-S1 acts as an inactivating gate.

The sodium channel has 2 gates (activation and inactivation) and can exist in 3 states. At rest
with the membrane polarized, the activation gate is closed and the inactivation gate is opened.
With depolarization, the activation gate opens, allowing sodium ions to pass through the ion
channel and also exposing a docking site for the inactivation gate. With continued
depolarization, the inactivation gate closes, blocking the entry of sodium into the cell and
causing the channel to enter the fast-inactivation state. This inactivation of the channel allows
the membrane to become repolarized, resulting in a return to the resting state with the
activation gate closed and the inactivation gate opened. Two inactivation processes occur in
mammalian skeletal muscle: Fast inactivation involves terminating the action potential and
acts on a millisecond time scale. Slow inactivation takes seconds to minutes and can regulate
the population of excitable sodium channels.

Sodium channel mutations that disrupt fast and slow inactivation are usually associated with
a phenotype of HyperPP and myotonia, where as mutations that enhance slow or fast
inactivation producing loss of sodium channel function cause HypoPP.

Mutations of the sodium channel gene (SCN4A) have several general features. Most of the
mutations are in the "inactivating" linker between repeats III and IV, in the "voltage-sensing"
segment S4 of repeat IV or at the inner membrane where they could impair the docking site
for the inactivation gate. The clinical phenotype differs by specific amino acid substitution
and, while some overlap may occur between hyperkalemic PP, paramyotonia congenita (PC),
and potassium-aggravated myotonias (PAM), the 3 phenotypes are generally distinct (as
described below). Nearly all mutant channels have impaired fast-inactivation of sodium
current. Most patients are sensitive to systemic potassium or to cold temperature.

Two populations of channels exist, mutant and wild-type; the impaired fast-inactivation
results in prolonged depolarization of the mutant muscle fiber membranes and can explain the
2 cardinal symptoms of these disorders, myotonia and weakness. In hyperkalemic PP, a gain
of function occurs in mutant channel gating, resulting in an increased sodium current
excessively depolarizing the affected muscle. Mild depolarization (5-10 mV) of the myofiber
membrane, which may be caused by increased extracellular potassium concentrations, results
in the mutant channels being maintained in the noninactivated mode. The persistent inward
sodium current causes repetitive firing of the wild-type sodium channels, which is perceived
as stiffness (ie, myotonia).

If a more severe depolarization (20-30 mV) is present, both normal and abnormal channels
are fixed in a state of inactivation, causing weakness or paralysis. Thus, subtle differences in
severity of membrane depolarization may make the difference between myotonia and
paralysis. Temperature sensitivity is a hallmark of PC. Cold exacerbates myotonia and
induces weakness. A number of mutations are associated with this condition, 3 of them at the
same site (1448) in the S4 segment. These mutations replace arginine with other amino acids
and neutralize this highly conserved S4 positive charge. Mutations of these residues are the
most common cause of PC. Some of the possible mechanisms responsible for temperature
sensitivity include the following:

Temperature may differentially affect the conformational change in the mutant

channel.
Lower temperatures may stabilize the mutant channels in an abnormal state.
Mutations may alter the sensitivity of the channel to other cellular processes, such as
phosphorylation or second messengers.

Most cases of hyperkalemic PP are due to 2 mutations in SCN4A, T704M, and M1592V.
Mutations in the sodium channel, especially at residues 1448 and 1313, are responsible for
paramyotonia congenita. A small proportion of hypokalemic periodic paralysis cases are
associated with mutations at codons 669 and 672 (HypoPP2). In HypoPP2, sodium channel
mutations enhance inactivation to produce a net loss of function defect.

Calcium channel gene

The calcium channel gene (CACNL1A3) is a complex of 5 subunits (alpha-1, alpha-2, beta,
gamma, and delta). The skeletal muscle dihydropyridine (DHP) receptor is located primarily
in the transverse tubular membrane. The alpha-1 subunit has binding sites for DHP drugs and
conducts the slow L-type calcium current. It also participates in excitation-contraction (EC)
coupling and acts as a voltage sensor through its linkage with the ryanodine receptor of
sarcoplasmic reticulum (ie, calcium release channel). Any changes in the membrane potential
are linked to intracellular calcium release, enabling EC coupling. Point mutations in DHP
receptor/calcium channel alpha-1 subunit cause hypokalemic PP (HypoPP1). Two mutations
of CACNA1S gene, R528H and R1239H, are responsible for most cases of hypokalemic PP.

The physiological basis of disease is still not understood, but is more likely due to a failure of
excitation rather than a failure of EC coupling. However, hypokalemia-induced
depolarization may reduce calcium release, affecting the voltage control of the channel
directly or indirectly through inactivation of the sodium channel. Insulin and adrenaline may
act in a similar manner. Mutations of the calcium channel gene have some similarities to
SCN4A mutations. Mutations modify channel inactivation but not voltage-dependent
activation. Recordings from myotube cultures from affected patients revealed a 30%
reduction in the DHP-sensitive L-type calcium current. Channels are inactivated at low
membrane potentials.

Calcium channel mutations cause a loss of function manifested as a reduced current density
and slower inactivation. How this inactivation is related to hypokalemia-induced attacks is
not understood. At least in R528H mutation, a possible secondary channelopathy occurs, tied
to a reduction in the ATP-sensitive potassium current from altered calcium homeostasis. The
lower currents associated with CACNL1A3 mutations could slightly alter intracellular calcium
homeostasis, which could affect the properties and expression of K+ channels, particularly
KATP (ATP-sensitive potassium channel) belonging to inward rectifier class of channels.
Insulin also acts in HypoPP by reducing this inward rectifier K+ current.

Voltage sensor charge loss accounts for most cases of HypoPP. Sodium and calcium channels
have homologous pore-forming alfa subunits. Point mutations in CACNL1A3 and SCN4A
affect argentine residues in the S4 voltage sensors of these channels. Arginine mutations in
S4 segments are responsible for 90% of HypoPP cases.3

Glucocorticosteroids cause HypoPP by stimulating Na+ K+ ATPase mediated by insulin and

amylin.4

Potassium channel gene

Potassium channel mutations are seen in Andersen-Tawil syndrome. The triad of dysmorphic
features, periodic paralysis, and cardiac arrhythmias characterizes Andersen-Tawil syndrome.
This syndrome is associated with mutations in the KCNJ2 gene.5 The KCNJ2 gene encodes
the inward-rectifying potassium channel Kir2.1. Potas sium channel mutations in KCNE3 are
reported to cause hypokalemic PP, but this has not been substantiated.

Frequency

United States

The frequencies of hyperkalemic periodic paralysis, paramyotonia congenita (PC), and

potassium-aggravated myotonias (PAM) are not known. Hypokalemic periodic paralysis has
a prevalence of 1 case per 100,000 population.

International

Not known

Race

Thyrotoxic PP is most common in males (85%) of Asian descent with a frequency of

approximately 2%.
Clinical
History

Semua paralisis periodik ditandai dengan episode kelemahan. Kekuatan otot normal di antara
serangan. Perbaikan kelemahan akan terjadi dalam berbagai bentuk. Kebanyakan pasien
dengan PP primer timbul gejala sebelum dekade ketiga.

Paralisis periodik hiperkalemi

o Onset usia yaitu pada usia kurang dari 10 tahun. Pasien biasanya memiliki keluhan
kelemahan atau kekakuan otot. Kelemahan dimulai pada paha dan kemudian
menyebar ke lengan dan leher. Kelemahan proksimal lebih dominan; otot distal
dilibatkan setelah latihan berat.
o Pada anak-anak, gejala paling awal yaitu ptosis. Paralisis komplit jarang dan kadang
menghasilkan gejala sisa. Otot pernapasan jarang terkena. Serangan berlangsung
kurang dari 4 jam dan pada kebanyakan kasus, kurang dari 1 jam. Spingter tidak
terlibat; disfungsi usus dan vesica urinaria terjadi karena kelemahan otot abdomen.
o Kelemahan terjadi selama istirahat setelah periode latihan berat dan selama puasa.
Juga dipicu oleh kalium, dingin, etanol, atau stres. Selain itu juga dapat dipengaruhi
oleh latihan ringan yang berlangsung lama atau intake karbohidrat. Pasien juga
sering merasakan nyeri otot dan parestesia. Di antara serangan, miotonia elektrikal
dan klinikal terjadi pada kebanyakan pasien. Beberapa kelompok tidak terdapat
myotonia. Secara klinik, miotonia yang nyata terlihat pada kurang dari 20% pasien,
tetapi miotonia elektrikal mungkin ditemukan pada 50-70%. Kelemahan Interictal,
jika terjadi, tidak seberat PP hipokalemi.
Paralisis periodik Hipokalemik
o Kasus berat terjadi pada awal masa kanak-kanak dan kasus ringan terjadi setelah
dekade ketiga. Sebagian besar kasus terjadi sebelum umur 16 tahun. Serangan yang
berat dimulai pada pagi hari, sering dengan latihan yang kuat atau diet karbohidrat
yang tinggi. Kadang-kadang, waktu antara gejala mulai terlihat sampai terjadi
serangan hanya beberapa menit. Serangan juga dipicu oleh stres, termasuk infeksi,
menstruasi, gangguan tidur, dan obat-obatan seperti beta-agonists, insulin, dan
corticosteroids). Patients wake up with severe symmetrical weakness, often with
truncal involvement.
o Mild attacks are frequent and involve only a particular group of muscles, and may be
unilateral, partial, or monomelic. This may affect predominantly legs; sometimes,
extensor muscles are affected more than flexors. Duration varies from a few hours
to almost 8 days but seldom exceeds 72 hours. The attacks are intermittent and
infrequent in the beginning but may increase in frequency until attacks occur almost
daily. The frequency starts diminishing by age 30 years; it rarely occurs after age 50
years.
o Urinary output is decreased during the attack because water accumulates
intracellularly in muscles. In HypoPP1 patients, the age of onset is earlier (10 y), the
symptoms lasts longer (20 h), and the fixed proximal weakness is more frequent
(about 70%), compared with HypoPP2 patients (16 y, 1 h, none).
o Permanent muscle weakness may be seen later in the course of the disease and may
become severe. Hypertrophy of the calves has been observed. Proximal muscle
wasting, rather than hypertrophy, may be seen in patients with permanent
weakness.
Potassium-aggravated myotonia
 o These autosomal dominant inherited disorders have been divided into 3 categories,
myotonia fluctuans, myotonia permanens, and acetazolamide-responsive MC.
o Weakness is rare in these disorders, but episodic muscle pain and stiffness due to
myotonia is present in myotonia fluctuans and acetazolamide-responsive MC, while
it is continuous in myotonia permanens.
o Attacks begin at rest soon after exercise in myotonia fluctuans but are more
common with exercise in acetazolamide-responsive MC. Potassium and cold
aggravate the myotonia in all 3 disorders.
Paramyotonia congenita
o In this autosomal dominant inherited disorder, myotonia worsens with activity
(paradoxical myotonia) or cold temperatures.
o Symptoms are most pronounced in the face.
o Episodic weakness also may develop after exercise or cold temperatures and usually
lasts only a few minutes, but may last as long as days.
o Potassium loading usually worsens the symptoms, but in some cases, lowering the
serum potassium level precipitates the attacks.
Thyrotoxic periodic paralyses
o Thyrotoxicosis periodic paralyses (TPP) are the most common secondary
hypokalemic PP. TPP is most common in adults aged 20-40 years. Hyperinsulinemia,
a carbohydrate load, and exercise are important in precipitating paralytic attacks.
Weakness is proximal and, if severe, may involve respiratory or bulbar muscles.
Attacks last hours to days.
o The prevalence of TPP in patients with thyrotoxicosis is estimated to be 0.1-0.2% in
Caucasians and 13-14% in Chinese. Ninety-five percent of TPP cases are sporadic. As
TPP is more common in Asians, a genetic predisposition is strongly suspected.
Familial clustering of TPP indicates unmasking of an inherited disease (which is
sporadic) by thyrotoxicosis. A mutation in KCNE3 potassium channel gene was
identified in one series.6
Andersen-Tawil syndrome
o Andersen-Tawil syndrome is characterized by variable expression of the triad of
dysmorphic features, periodic paralysis, and cardiac arrhythmias. Patients may have
short stature, hypertelorism, low-set ears, micrognathia, fifth finger clinodactyly,
and scoliosis. Episodic weakness lasting a few hours to several days may arise
spontaneously but usually follows physical activity. The periodic paralysis is not
associated with myotonia.
o Prolonged QT interval and ventricular arrhythmias are the most common cardiac
manifestations. Other ECG abnormalities include PVCs, ventricular bigeminy,
supraventricular and ventricular tachycardias, prominent U waves, and torsades de
pointes. Bidirectional ventricular tachycardia, which is characterized by beat-to-beat
alternating QRS axis polarity, is unique to a subset of patients. Patients may be
completely asymptomatic. Patients may experience palpitations, syncopal episodes,
and cardiac arrest. Sudden cardiac death is less frequent in ATS when
compared with the other long QT syndromes.

Physical

Most of the patients with a periodic paralysis (PP) have similar clinical features, which are as
follows:

Interictal lid lag and eyelid myotonia - May be the only clinical signs in hyperkalemic PP
Normal sensation
 Fixed proximal weakness - May develop in patients with either hyperkalemic or hypokalemic
PP
Diminished stretch reflexes during attacks

Table 2. Distinguishing Features Among the Common Forms of Periodic Paralyses

Open table in new window

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Table

Syndrom Age of Onset Duration of Precipitating Severity of Associated Features

e Attack Factors Attacks

Hyperkal First decade Few minutes Low Rarely severe Perioral and
emic of life to less than 2 carbohydrat limb
periodic h (mostly less e intake paresthesias
(fasting) Myotonia
paralyses than 1 h)
Cold frequent
Rest Occasional
following pseudohypert
exercise rophy of
Alcohol muscles
Infection
Emotional
stress
Trauma
Menstrual
period

Hypokale Varia Few Early Severe Occasional

mic ble - hours morning Compl myotonic lid
periodic Childh to attacks after ete lag
ood almos previous day paralys Myotonia
paralyses
to ta physical is between
third week activity attacks rare
decad Typica High- Unilateral,
e lly no carbohydrat partial,
Major longer e meal, monomelic
ity of than Chinese Fixed muscle
cases 72 h food, weakness late
befor alcohol in disease
e 16 Cold,
years change in
barometric
pressure or
humidity
Fever, upper
respiratory
 tract
infections
Lack of
sleep,
fatigue
Menstrual
cycle

Potassiu First decade No weakness Cold Attacks of Muscle hypertrophy

m- Rest after stiffness can
associate exercise be mild to
d severe
myotonia

Paramyot First decade 2-24 h Cold Rarely severe Pseudohypert

onia rophy of
congenit muscles
Paradoxical
a
myotonia
Fixed
weakness rare

Thyrotoxi Third and Few hours to Same as Same as Fixed muscle

c periodic fourth 7d hypokalemic hypokalemic weakness
paralyses decades PP PP may develop
Hyperinsulin Hypokalemia
emia during attacks

Syndrom Age of Onset Duration of Precipitating Severity of Associated Features

e Attack Factors Attacks

Hyperkal First decade Few minutes Low Rarely severe Perioral and
emic of life to less than 2 carbohydrat limb
periodic h (mostly less e intake paresthesias
(fasting) Myotonia
paralyses than 1 h)
Cold frequent
Rest Occasional
following pseudohypert
exercise rophy of
Alcohol muscles
Infection
Emotional
stress
Trauma
Menstrual
period

Hypokale Varia Few Early Severe Occasional

mic ble - hours morning Compl myotonic lid
periodic Childh to attacks after ete lag
paralyses ood almos previous day paralys Myotonia
to ta physical is between
third week activity attacks rare
decad Typica High- Unilateral,
e lly no carbohydrat partial,
Major longer e meal, monomelic
ity of than Chinese Fixed muscle
cases 72 h food, weakness late
befor alcohol in disease
e 16 Cold,
years change in
barometric
pressure or
humidity
Fever, upper
respiratory
tract
infections
Lack of
sleep,
fatigue
Menstrual
cycle

Potassiu First decade No weakness Cold Attacks of Muscle hypertrophy

m- Rest after stiffness can
associate exercise be mild to
d severe
myotonia

Paramyot First decade 2-24 h Cold Rarely severe Pseudohypert

onia rophy of
congenit muscles
Paradoxical
a
myotonia
Fixed
weakness rare

Thyrotoxi Third and Few hours to Same as Same as Fixed muscle

c periodic fourth 7d hypokalemic hypokalemic weakness
paralyses decades PP PP may develop
Hyperinsulin Hypokalemia
emia during attacks

Causes
Refer to Pathophysiology and Table 2 and Table 3.

More on Periodic Paralyses

Overview: Periodic Paralyses

Differential Diagnoses & Workup: Periodic Paralyses

Treatment & Medication: Periodic Paralyses

Follow-up: Periodic Paralyses

References

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References
1. Miller TM, Dias da Silva MR, Miller HA, et al. Correlating phenotype and genotype
in the periodic paralyses. Neurology. Nov 9 2004;63(9):1647-55. [Medline].
2. Venance SL, Cannon SC, Fialho D, et al. The primary periodic paralyses: diagnosis,
pathogenesis and treatment. Brain. Jan 2006;129(Pt 1):8-17. [Medline].
3. 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. May 5 2009;72(18):1544-7. [Medline].
4. 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. Mar 2009;19(3):217-9. [Medline].
5. 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. [Medline].
6. 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. Nov 2002;87(11):4881-4. [Medline].
7. Assadi F. Diagnosis of hypokalemia: a problem-solving approach to clinical
cases. Iran J Kidney Dis. Jul 2008;2(3):115-22. [Medline].
8. Streib EW. AAEE minimonograph #27: Differential diagnosis of myotonic
syndromes. Muscle Nerve. Sep 1987;10(7):603-15. [Medline].
9. Fournier E, Arzel M, Sternberg D, et al. Electromyography guides toward subgroups
of mutations in muscle channelopathies. Ann Neurol. Nov 2004;56(5):650-
61. [Medline].
10. Levitt JO. Practical aspects in the management of hypokalemic periodic paralysis. J
Transl Med. Apr 21 2008;6:18. [Medline].
11. 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. Feb 1995;56(2):374-80. [Medline].
12. Engel AG, Lambert EH, Rosevear JW, Tauxe WN. Clinical and electromyographic
studies in a patient with primary hypokalemic periodic paralysis. Am J
Med. Apr 1965;38:626-40. [Medline].
13. Griggs RC. Evaluation and Treatment of Myopathies. 1995. Philadelphia: FA
Davis; 318-354.
14. Hoffman EP, Lehmann-Horn F, Rudel R. Overexcited or inactive: ion channels in
muscle disease. Cell. Mar 10 1995;80(5):681-6. [Medline].
15. Junker J, Haverkamp W, Schulze-Bahr E, et al. Amiodarone and acetazolamide for
the treatment of genetically confirmed severe Andersen syndrome. Neurology. Aug
13 2002;59(3):466. [Medline].
16. Koch MC, Steinmeyer K, Lorenz C. The skeletal muscle chloride channel in
dominant and recessive human myotonia. Science. Aug 7 1992;257(5071):797-
800. [Medline].
17. Lin SH, Lin YF, Chen DT, et al. Laboratory tests to determine the cause of
hypokalemia and paralysis. Arch Intern Med. Jul 26 2004;164(14):1561-6. [Medline].
18. McManis PG, Lambert EH, Daube JR. The exercise test in periodic paralysis. Muscle
Nerve. Oct 1986;9(8):704-10. [Medline].
19. Meola G, Sansone V. Treatment in myotonia and periodic paralysis. Rev Neurol
(Paris). May 2004;160(5 Pt 2):S55-69. [Medline].
20. Ptacek L. The familial periodic paralyses and nondystrophic myotonias. Am J
Med. Jul 1998;105(1):58-70. [Medline].
21. Ptacek LJ, Johnson KJ, Griggs RC. Genetics and physiology of the myotonic muscle
disorders. N Engl J Med. Feb 18 1993;328(7):482-9. [Medline].
22. Ruff RL. Slow inactivation: slow but not dull. Neurology. Mar 4 2008;70(10):746-
7. [Medline].
23. Tricarico D, Barbieri M, Mele A, et al. Carbonic anhydrase inhibitors are specific
openers of skeletal muscle BK channelof K+-deficient rats. FASEB
J. Apr 2004;18(6):760-1. [Medline].
24. Zhang J, George AL, Griggs RC. Mutations in the human skeletal muscle chloride
channel gene (CLCN1) associated with dominant and recessive myotonia
congenita. Neurology. Oct 1996;47(4):993-8. [Medline].

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Further Reading
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Keywords
periodic paralysis, hypokalemia, hyperkalemia, myotonia, paramyotonia congenita,
potassium-aggravated myotonia, voltage-sensitive ion channels, voltage-gated ion channels,
channelopathy, calcium channels, sodium channels, chloride channels, thyrotoxicosis,
periodic paralyses, PP

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Contributor Information and Disclosures
Author

Naganand Sripathi, MD, Director, Neuromuscular Clinic, Department of Neurology, Henry

Ford Hospital
Naganand Sripathi, MD is a member of the following medical societies: American Academy
of Neurology, American Medical Association, Michigan State Medical Society, and New
York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Paul E Barkhaus, MD, Professor, Department of Neurology, Medical College of Wisconsin;

Director of Neuromuscular Diseases, Milwaukee Veterans Administration Medical Center
Paul E Barkhaus, MD is a member of the following medical societies: American Academy of
Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and
American Neurological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Managing Editor

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of

Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St
Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of
Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and
Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program,

Departments of Neurology and Neurosurgery, University of South Florida School of
Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy
of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology
Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology
Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha
and American Academy of Neurology
Disclosure: Nothing to disclose.

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