Berkala Paralyses

Author: Naganand Sripathi, MD, Director, Neuromuscular Clinic, Department of Neurology, Henry Ford Hospital Pengarang: Sripathi Naganand, MD, Direktur, Klinik neuromuskular, Departemen Neurologi, Rumah Sakit Henry Ford Contributor Information and Disclosures Kontributor Informasi dan Pengungkapan Updated: Nov 25, 2010 Diperbarui: Nov 25, 2010

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Introduction Pengantar
Background Latar belakang
The heterogeneous group of muscle diseases known as periodic paralyses (PP) is characterized by episodes of flaccid muscle weakness occurring at irregular intervals. Kelompok heterogen penyakit otot yang dikenal sebagai melumpuhkan periodik (PP) yang ditandai dengan episode kelemahan otot lembek terjadi pada interval yang tidak teratur. Most of the conditions are hereditary and are more episodic than periodic. Sebagian besar kondisi keturunan dan lebih episodik dari periodik. They can be divided conveniently into primary and secondary disorders. Mereka dapat dibagi dengan mudah menjadi gangguan primer dan sekunder. General characteristics of primary PP include the following: (1) they are hereditary; (2) most are associated with alteration in serum potassium levels; (3) myotonia sometimes coexists; and (4) both myotonia and PP result from defective ion channels. Karakteristik umum PP primer meliputi: (1) mereka turun temurun; (2) kebanyakan berhubungan dengan perubahan kadar kalium serum, (3) myotonia kadang berdampingan, dan (4) baik myotonia dan hasil PP dari saluran ion rusak.

Pathophysiology Patofisiologi
A clinically useful classification of primary periodic paralyses, shown in Table 1, includes hypokalemic, hyperkalemic, and paramyotonic forms. Sebuah klasifikasi klinis yang berguna

melumpuhkan periodik primer, ditunjukkan pada Tabel 1, termasuk bentuk hipokalemik, hyperkalemic, dan paramyotonic. Table 1. Tabel 1. Primary Periodic Paralysis Primer Kelumpuhan Berkala Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Sodium channel Sodium channel Calcium channel Kalsium channel Potassium channel Kalium saluran

Hyperkalemic PP (HyperPP) Hyperkalemic PP (HyperPP) Hypokalemic PP (HypoPP2) Hipokalemik PP (HypoPP2) Paramyotonia congenita Paramyotonia congenita Hypokalemic PP (HypoPP1) Hipokalemik PP (HypoPP1)

Andersen-Tawil syndrome Andersen-Tawil syndrome Hyperkalemic PP or hypokalemic PP* Hyperkalemic PP atau PP hipokalemik * *The deficit was described in 2 small families and has not been substantiated by others. 1 , 2 * Defisit tersebut dijelaskan dalam 2 keluarga kecil dan belum dibuktikan oleh orang lain. 1 , 2 Sodium channel Sodium Hyperkalemic PP (HyperPP) Hyperkalemic PP (HyperPP) channel Hypokalemic PP (HypoPP2) Hipokalemik PP (HypoPP2) Paramyotonia congenita Paramyotonia congenita Calcium channel Kalsium Hypokalemic PP (HypoPP1) Hipokalemik PP (HypoPP1) channel Potassium channel Kalium Andersen-Tawil syndrome Andersen-Tawil syndrome saluran Hyperkalemic PP or hypokalemic PP* Hyperkalemic PP atau PP hipokalemik * *The deficit was described in 2 small families and has not been substantiated by others. 1 , 2 * Defisit tersebut dijelaskan dalam 2 keluarga kecil dan belum dibuktikan oleh orang lain. 1 , 2 The physiologic basis of flaccid weakness is inexcitability of the muscle membrane (ie, sarcolemma). Dasar fisiologis dari kelemahan lembek adalah inexcitability dari selaput otot (yaitu, sarcolemma). Alteration of serum potassium level is not the principal defect in primary PP; the altered potassium metabolism is a result of the PP. Perubahan kadar serum kalium bukanlah cacat utama dalam PP primer; metabolisme kalium berubah adalah hasil dari PP tersebut. In primary and thyrotoxic PP, flaccid paralysis occurs with relatively small changes in the serum potassium level, whereas in secondary PP, serum potassium levels are markedly abnormal. Dalam PP primer dan thyrotoxic, flaccid paralysis terjadi dengan perubahan yang relatif kecil di tingkat kalium serum, sedangkan di PP sekunder, kadar kalium serum yang nyata abnormal. No single mechanism is responsible for this group of disorders. Tidak ada mekanisme tunggal bertanggung jawab untuk kelompok gangguan. Thus, they are heterogeneous but share some

common traits. Dengan demikian, mereka heterogen namun berbagi beberapa ciri umum. The weakness usually is generalized but may be localized. Kelemahan biasanya umum tetapi bisa dilokalisasi. Cranial musculature and respiratory muscles usually are spared. Cranial otot dan pernapasan otot biasanya diselamatkan. Stretch reflexes are either absent or diminished during the attacks. Stretch refleks baik tidak ada atau berkurang selama serangan. The muscle fibers are electrically inexcitable during the attacks. Serat otot elektrik inexcitable selama serangan. Muscle strength is normal between attacks but, after a few years, some degree of fixed weakness develops in certain types of PP (especially primary PP). kekuatan otot adalah normal antara serangan tetapi, setelah beberapa tahun, beberapa derajat kelemahan tetap berkembang di beberapa jenis PP (PP terutama primer). All forms of primary PP (except Becker myotonia congenita [MC]) are either autosomal dominant inherited or sporadic (most likely arising from point mutations). Semua bentuk PP primer (kecuali myotonia congenita Becker [MC]) baik autosomal dominan warisan atau sporadis (yang paling mungkin timbul dari mutasi titik). Voltage-sensitive ion channels closely regulate generation of action potentials (brief and reversible alterations of the voltage of cellular membranes). saluran ion Voltage-sensitif erat mengatur potensi generasi tindakan (perubahan singkat dan reversibel dari tegangan membran selular). These are selectively and variably permeable ion channels. Ini adalah selektif dan variabel saluran ion permeabel. Energy-dependent ion transporters maintain concentration gradients. transporter ion Energi-tergantung mempertahankan gradien konsentrasi. During the generation of action potentials, sodium ions move across the membrane through voltage-gated ion channels. Selama generasi potensial aksi, ion natrium bergerak melintasi membran melalui saluran tegangan-gated ion. The resting muscle fiber membrane is polarized primarily by the movement of chloride through chloride channels and is repolarized by movement of potassium. Membran serat otot istirahat terpolarisasi terutama oleh pergerakan klorida melalui saluran klorida dan repolarized oleh pergerakan kalium. Sodium, chloride, and calcium channelopathies, as a group, are associated with myotonia and PP. Natrium, klorida, dan kalsium channelopathies, sebagai kelompok, yang berhubungan dengan myotonia dan PP. The functional subunits of sodium, calcium, and potassium channels are homologous. Sub-unit fungsional natrium, kalsium, dan saluran kalium yang homolog. Sodium channelopathies are better understood than calcium or chloride channelopathies. Sodium channelopathies lebih baik dipahami daripada channelopathies kalsium atau klorida. All forms of familial PP show the final mechanistic pathway involving aberrant depolarization, inactivating sodium channels, and muscle fiber inexcitability. Semua bentuk PP keluarga menunjukkan jalur depolarisasi mekanistik akhir melibatkan menyimpang, menonaktifkan saluran natrium, dan inexcitability serat otot. Discussion in this article primarily addresses the sodium, calcium, and potassium channelopathies as well as secondary forms of PP. Pembahasan dalam artikel ini terutama alamat natrium, kalsium, dan kalium channelopathies serta bentuk sekunder PP. Chloride channelopathies are not associated with episodic weakness and are discussed in more detail in the articles on myotonic disorders. channelopathies Klorida tidak berhubungan dengan kelemahan episodik dan dibahas secara lebih rinci dalam artikel di gangguan myotonic. Muscle sodium channel gene Otot saluran natrium gen

The sodium channel has an alpha subunit and a beta subunit. Saluran natrium memiliki subunit alfa dan subunit beta. The alpha subunit of the sodium channel is a 260-kd glycoprotein comprising about 1800-2000 amino acids. Subunit alfa saluran natrium adalah glikoprotein 260kd terdiri sekitar 1800-2000 asam amino. This channel is highly conserved evolutionarily from Drosophila to human. Saluran ini sangat kekal evolusi dari Drosophila ke manusia. It has 4 homologous domains (I-IV) that fold to form a central pore, each with 225-325 amino acids. Ia memiliki 4 homolog domain (I-IV) yang flip untuk membentuk pori-pori pusat, masing-masing dengan 225-325 asam amino. Each domain consists of 6 hydrophobic segments (S1-S6) traversing the cell membrane. Setiap domain terdiri dari 6 segmen hidrofobik (S1-S6) melintasi membran sel. The main functions of the channel include voltage-sensitive gating, inactivation, and ion selectivity. Fungsi utama saluran termasuk gating tegangan-sensitif, inaktivasi, dan selektivitas ion. The extracellular loop between S5 and S6 dips into the plasma membrane and participates in the formation of the pore. Loop ekstraseluler antara S5 dan S6 dips ke dalam membran plasma dan berpartisipasi dalam pembentukan pori-pori. The S4 segment contains positively charged amino acids at every third position and functions as a voltage sensor. Segmen S4 mengandung asam amino yang bermuatan positif pada setiap posisi ketiga dan fungsi sebagai sensor tegangan. Conformation changes may occur during depolarization, resulting in activation and inactivation of the channel. perubahan konformasi mungkin terjadi selama depolarisasi, mengakibatkan aktivasi dan inaktivasi saluran. The cellular loop between domain III-S6 and domain IV-S1 acts as an inactivating gate. Loop selular antara domain III-S6 dan bertindak domain IV-S1 sebagai gerbang menonaktifkan. The sodium channel has 2 gates (activation and inactivation) and can exist in 3 states. Saluran natrium memiliki 2 gerbang (aktivasi dan inaktivasi) dan dapat ada di 3 negara bagian. At rest with the membrane polarized, the activation gate is closed and the inactivation gate is opened. Saat istirahat dengan membran terpolarisasi, aktivasi gerbang ditutup dan gerbang inaktivasi dibuka. 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. Dengan depolarisasi, gerbang aktivasi terbuka, yang memungkinkan ion natrium melewati saluran ion dan juga memperlihatkan sebuah situs docking untuk gerbang inaktivasi. 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. Dengan depolarisasi melanjutkan, gerbang inaktivasi menutup, menghalangi masuknya natrium ke dalam sel dan menyebabkan saluran untuk memasuki negara cepat-inaktivasi. 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. Inaktivasi ini memungkinkan membran saluran untuk menjadi repolarized, sehingga kembali ke keadaan istirahat dengan aktivasi gerbang ditutup dan gerbang inaktivasi dibuka. Two inactivation processes occur in mammalian skeletal muscle: Fast inactivation involves terminating the action potential and acts on a millisecond time scale. Dua proses inaktivasi terjadi pada otot rangka mamalia: inaktivasi Cepat melibatkan mengakhiri potensial aksi dan bertindak pada skala waktu milidetik. Slow inactivation takes seconds to minutes and can regulate the population of excitable sodium channels. inaktivasi Lambat memerlukan beberapa detik untuk menit dan dapat mengatur populasi saluran natrium bersemangat. 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. mutasi yang mengganggu saluran Natrium inaktivasi cepat dan lambat biasanya berhubungan dengan fenotip HyperPP dan myotonia, sedangkan mutasi yang meningkatkan inaktivasi lambat atau cepat menghasilkan hilangnya fungsi saluran natrium menyebabkan HypoPP. Mutations of the sodium channel gene ( SCN4A ) have several general features. Mutasi gen saluran natrium (SCN4A) memiliki beberapa fitur umum. 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. Sebagian besar mutasi berada di linker "menonaktifkan" antara mengulangi III dan IV, di S4 segmen "tegangan-sensing" dari mengulang IV atau pada membran dalam mana mereka bisa merusak situs docking untuk gerbang inaktivasi. 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). Fenotip klinis berbeda dengan substitusi asam amino dan spesifik, sementara beberapa tumpang tindih mungkin terjadi antara PP hyperkalemic, congenita paramyotonia (PC), dan potasium-diperparah myotonias (PAM), 3 fenotip umumnya berbeda (seperti yang dijelaskan di bawah). Nearly all mutant channels have impaired fast-inactivation of sodium current. Hampir semua saluran mutan merugikan cepat-inaktivasi natrium saat ini. Most patients are sensitive to systemic potassium or to cold temperature. Kebanyakan pasien yang sensitif terhadap kalium sistemik atau suhu dingin. 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. Dua populasi saluran ada, mutan dan wild type, cepat-inaktivasi hasil terganggu pada depolarisasi berkepanjangan dari membran serat otot mutan dan dapat menjelaskan gejala kardinal 2 myotonia ini, gangguan dan kelemahan. In hyperkalemic PP, a gain of function occurs in mutant channel gating, resulting in an increased sodium current excessively depolarizing the affected muscle. Dalam PP hyperkalemic, keuntungan fungsi terjadi pada saluran gating mutan, yang mengakibatkan natrium meningkat saat ini berlebihan depolarizing otot terpengaruh. 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. Depolarisasi ringan (5-10 mV) dari membran myofiber, yang mungkin disebabkan oleh meningkatnya konsentrasi kalium ekstraseluler, hasil dalam saluran mutan dipertahankan dalam modus noninactivated. The persistent inward sodium current causes repetitive firing of the wild-type sodium channels, which is perceived as stiffness (ie, myotonia). Natrium batin terus-menerus saat ini menyebabkan pembakaran berulang-ulang dari saluran sodium wild type, yang dianggap sebagai kekakuan (yaitu, 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. Jika depolarisasi lebih parah (2030 mV) hadir, baik saluran normal dan abnormal adalah tetap dalam keadaan inaktivasi, menyebabkan kelemahan atau kelumpuhan. Thus, subtle differences in severity of membrane depolarization may make the difference between myotonia and paralysis. Dengan demikian, perbedaan yang halus dalam keparahan depolarisasi membran dapat membuat perbedaan antara

myotonia dan kelumpuhan. Temperature sensitivity is a hallmark of PC. sensitivitas Suhu adalah tanda dari PC. Cold exacerbates myotonia and induces weakness. Dingin memperparah myotonia dan menginduksi kelemahan. A number of mutations are associated with this condition, 3 of them at the same site (1448) in the S4 segment. Sejumlah mutasi yang terkait dengan kondisi ini, 3 dari mereka di tempat yang sama (1448) di segmen S4. These mutations replace arginine with other amino acids and neutralize this highly conserved S4 positive charge. Mutasi ini mengganti arginine dengan asam amino lain dan menetralisir muatan positif yang sangat lestari S4. Mutations of these residues are the most common cause of PC. Mutasi residu ini merupakan penyebab paling umum PC. Some of the possible mechanisms responsible for temperature sensitivity include the following: Beberapa mekanisme yang mungkin bertanggung jawab untuk sensitivitas temperatur antara lain meliputi:

Temperature may differentially affect the conformational change in the mutant channel. Diferensial suhu dapat mempengaruhi perubahan konformasi dalam saluran mutan. Lower temperatures may stabilize the mutant channels in an abnormal state. Turunkan suhu dapat menstabilkan saluran mutan dalam keadaan normal. Mutations may alter the sensitivity of the channel to other cellular processes, such as phosphorylation or second messengers. Mutasi dapat mengubah sensitivitas saluran ke proses seluler lain, seperti fosforilasi atau utusan kedua.

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. Kebanyakan kasus PP hyperkalemic disebabkan oleh 2 mutasi dalam SCN4A, T704M, dan M1592V. Mutasi di saluran natrium, terutama pada residu 1448 dan 1313, bertanggung jawab untuk congenita paramyotonia. A small proportion of hypokalemic periodic paralysis cases are associated with mutations at codons 669 and 672 (HypoPP2). Sebagian kecil dari hipokalemik kasus paralisis periodik berhubungan dengan mutasi pada kodon 669 dan 672 (HypoPP2). In HypoPP2, sodium channel mutations enhance inactivation to produce a net loss of function defect. Dalam HypoPP2, natrium meningkatkan saluran inaktivasi mutasi untuk menghasilkan rugi bersih sebesar cacat fungsi. Calcium channel gene Kalsium channel gen The calcium channel gene ( CACNL1A3 ) is a complex of 5 subunits (alpha-1, alpha-2, beta, gamma, and delta). Saluran kalsium gen (CACNL1A3) adalah kompleks dari 5 subunit (alpha-1, alfa-2, beta, gamma, dan delta). The skeletal muscle dihydropyridine (DHP) receptor is located primarily in the transverse tubular membrane. The dihydropyridine otot rangka (DHP) reseptor terletak terutama di membran tubular melintang. The alpha-1 subunit has binding sites for DHP drugs and conducts the slow L-type calcium current. The alfa-1 subunit memiliki situs mengikat bagi obat DHP dan melakukan kalsium L-tipe lambat saat ini. It also participates in excitationcontraction (EC) coupling and acts as a voltage sensor through its linkage with the ryanodine receptor of sarcoplasmic reticulum (ie, calcium release channel). Hal ini juga berpartisipasi dalam eksitasi-kontraksi (EC) kopling dan bertindak sebagai sensor tegangan melalui keterkaitan dengan reseptor ryanodine dari retikulum sarkoplasma (yaitu, kalsium saluran pelepasan). Any changes in the membrane potential are linked to intracellular calcium release, enabling EC coupling. Setiap perubahan dalam potensial membran terkait untuk melepaskan kalsium

intraseluler, sehingga kopling EC. Point mutations in DHP receptor/calcium channel alpha-1 subunit cause hypokalemic PP (HypoPP1). Point mutasi pada reseptor DHP / kalsium alpha channel-1 menyebabkan subunit hipokalemik PP (HypoPP1). Two mutations of CACNA1S gene, R528H and R1239H, are responsible for most cases of hypokalemic PP. Dua mutasi gen CACNA1S, R528H dan R1239H, bertanggung jawab atas sebagian besar kasus PP hipokalemik. 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. Dasar fisiologis dari penyakit ini masih belum dimengerti, tapi lebih cenderung karena kegagalan eksitasi daripada kegagalan kopling EC. However, hypokalemia-induced depolarization may reduce calcium release, affecting the voltage control of the channel directly or indirectly through inactivation of the sodium channel. Namun, hipokalemia-depolarisasi induced dapat mengurangi pelepasan kalsium, mempengaruhi kontrol tegangan pada saluran secara langsung atau tidak langsung melalui inaktivasi saluran natrium. Insulin and adrenaline may act in a similar manner. Insulin dan adrenalin bisa bertindak dengan cara yang sama. Mutations of the calcium channel gene have some similarities to SCN4A mutations. Mutasi gen calcium channel memiliki beberapa kesamaan dengan mutasi SCN4A. Mutations modify channel inactivation but not voltage-dependent activation. Mutasi memodifikasi inaktivasi channel tetapi tidak tergantung pada tegangan aktivasi. Recordings from myotube cultures from affected patients revealed a 30% reduction in the DHP-sensitive L-type calcium current. Rekaman dari budaya myotube dari pasien yang terkena menunjukkan penurunan 30% dalam kalsium tipe L-DHP-sensitif saat ini. Channels are inactivated at low membrane potentials. Saluran yang tidak aktif pada potensial membran rendah. Calcium channel mutations cause a loss of function manifested as a reduced current density and slower inactivation. mutasi saluran Kalsium menyebabkan hilangnya fungsi diwujudkan sebagai densitas arus berkurang dan inaktivasi lambat. How this inactivation is related to hypokalemiainduced attacks is not understood. Bagaimana inaktivasi hal ini berkaitan dengan hipokalemiaserangan induksi tidak dipahami. At least in R528H mutation, a possible secondary channelopathy occurs, tied to a reduction in the ATP-sensitive potassium current from altered calcium homeostasis. Setidaknya dalam mutasi R528H, sebuah channelopathy sekunder yang mungkin terjadi, terkait dengan penurunan sensitif kalium ATP arus dari homeostasis kalsium diubah. 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. Arus bawah yang terkait dengan mutasi CACNL1A3 sedikit bisa mengubah homeostasis kalsium intraselular, yang dapat mempengaruhi sifat dan ekspresi K + channel, khususnya KATP (sensitif saluran-kalium ATP) milik kelas penyearah ke dalam saluran. Insulin also acts in HypoPP by reducing this inward rectifier K + current. Insulin juga bertindak dalam HypoPP dengan mengurangi penyearah ini ke dalam K + saat ini. Voltage sensor charge loss accounts for most cases of HypoPP. Tegangan sensor account rugi biaya untuk sebagian besar kasus HypoPP. Sodium and calcium channels have homologous pore-forming alfa subunits. Natrium dan saluran kalsium telah subunit alfa homolog porimembentuk. Point mutations in CACNL1A3 and SCN4A affect argentine residues in the S4 voltage sensors of these channels. mutasi Point di CACNL1A3 dan SCN4A mempengaruhi residu Argentina di sensor tegangan S4 dari saluran ini. Arginine mutations in S4 segments are

responsible for 90% of HypoPP cases. 3 mutasi Arginine di segmen S4 bertanggung jawab untuk 90% kasus HypoPP. 3 Glucocorticosteroids cause HypoPP by stimulating Na + K + ATPase mediated by insulin and amylin. 4 Glukokortikosteroid menyebabkan HypoPP dengan merangsang Na + K + ATPase dimediasi oleh insulin dan amylin. 4 Potassium channel gene Kalium saluran gen Potassium channel mutations are seen in Andersen-Tawil syndrome. mutasi saluran Kalium terlihat pada sindrom Andersen-Tawil. The triad of dysmorphic features, periodic paralysis, and cardiac arrhythmias characterizes Andersen-Tawil syndrome. Tiga serangkai fitur dismorfik, paralisis periodik, dan aritmia jantung ciri sindrom Andersen-Tawil. This syndrome is associated with mutations in the KCNJ2 gene. 5 The KCNJ2 gene encodes the inward-rectifying potassium channel Kir2.1. Sindrom ini dikaitkan dengan mutasi pada gen KCNJ2. 5 Gen KCNJ2 mengkodekan kalium perbaikan saluran-ke dalam Kir2.1. Potassium channel mutations in KCNE3 are reported to cause hypokalemic PP, but this has not been substantiated. mutasi saluran Kalium dalam KCNE3 dilaporkan menyebabkan PP hipokalemik, tetapi hal ini belum dibuktikan.

Frequency Frekuensi
United States Amerika Serikat The frequencies of hyperkalemic periodic paralysis, paramyotonia congenita (PC), and potassium-aggravated myotonias (PAM) are not known. Frekuensi kelumpuhan periodik hyperkalemic, congenita paramyotonia (PC), dan-kalium myotonias diperburuk (PAM) tidak diketahui. Hypokalemic periodic paralysis has a prevalence of 1 case per 100,000 population. hipokalemik paralisis periodik memiliki prevalensi 1 kasus per 100.000 penduduk. International Internasional Not known Tidak diketahui

Race Ras
Thyrotoxic PP is most common in males (85%) of Asian descent with a frequency of approximately 2%. Thyrotoxic PP adalah paling umum pada laki-laki (85%) dari keturunan Asia dengan frekuensi sekitar 2%.

Clinical Klinis
History Sejarah

All periodic paralyses (PPs) are characterized by episodic weakness. Semua melumpuhkan periodik (PP) yang ditandai dengan kelemahan episodik. Strength is normal between attacks. Kekuatan normal diantara serangan. Fixed weakness may develop later in some forms. kelemahan tetap dapat berkembang kemudian dalam beberapa bentuk. Most patients with primary PP develop symptoms before the third decade. Kebanyakan pasien dengan PP primer mengalami gejala sebelum dasawarsa ketiga.

Hyperkalemic periodic paralyses Hyperkalemic periodik melumpuhkan o Age at onset is younger than 10 years. Umur saat onset lebih muda dari 10 tahun. Patients usually describe a sense of heaviness or stiffness in the muscles. Pasien biasanya menggambarkan rasa berat atau kekakuan pada otot. Weakness starts in the thighs and calves, which then spreads to arms and neck. Kelemahan dimulai pada paha dan betis, yang kemudian menyebar ke lengan dan leher. Proximal weakness predominates; distal muscles may become involved after vigorous exercise. kelemahan proksimal mendominasi; otot distal dapat menjadi terlibat setelah olahraga berat. o In children, a myotonic lid lag (lagging of upper eyelid on downward gaze) may be the earliest symptom. Pada anak-anak, sebuah lag tutup myotonic (tertinggal dari kelopak mata atas pada pandangannya ke bawah) mungkin gejala awal. Complete paralysis is rare and some residual mobility remains. kelumpuhan Lengkap jarang dan beberapa mobilitas sisa tetap. Respiratory muscle involvement is rare. Keterlibatan otot pernapasan jarang. The attacks last less than 4 hours and in the majority of cases, less than 1 hour. Serangan terakhir kurang dari 4 jam dan dalam sebagian besar kasus, kurang dari 1 jam. Sphincters are not involved; any bowel and bladder dysfunction is due to abdominal muscle weakness. Sphincters tidak terlibat, setiap disfungsi usus dan kandung kemih disebabkan kelemahan otot perut. o Weakness occurs during rest after a period of strenuous exercise or during fasting. Kelemahan terjadi selama beristirahat setelah periode latihan berat atau selama puasa. It also may be provoked by potassium, cold, ethanol, or stress. Mungkin juga terprovokasi oleh kalium, dingin, ethanol, atau stres. It may be relieved by mild prolonged exercise or carbohydrate intake. Ini mungkin lega dengan latihan ringan atau berkepanjangan asupan karbohidrat. Patients also may report muscle pains and paresthesias. Pasien juga dapat melaporkan nyeri otot dan parestesia. Between attacks, clinical and electrical myotonia is present in the majority of patients. Antara serangan, myotonia klinis dan listrik hadir pada sebagian besar pasien. Some families have no myotonia. Beberapa keluarga memiliki myotonia tidak. Clinically apparent myotonia is seen less than 20% of patients, but electrical myotonia may be found in 50-75%. Myotonia klinis jelas terlihat kurang dari 20% pasien, tetapi myotonia listrik dapat ditemukan pada 50-75%. Interictal weakness, if present, is not as severe as in hypokalemic PP. Interictal kelemahan, jika ada, tidak begitu parah seperti di PP hipokalemik. Hypokalemic periodic paralyses Hipokalemik periodik melumpuhkan o This can be divided into HypoPP1 (calcium channel mutation) and HypoPP2 (sodium channel mutation). Hal ini dapat dibagi menjadi HypoPP1 (mutasi saluran kalsium) dan HypoPP2 (mutasi natrium channel).

Severe cases present in early childhood and mild cases may present as late as the third decade. kasus berat hadir dalam anak usia dini dan kasus-kasus ringan dapat hadir hingga akhir dekade ketiga. A majority of cases present before age 16 years. Sebagian besar kasus ini sebelum usia 16 tahun. Weakness may range from slight transient weakness of an isolated muscle group to severe generalized weakness. Kelemahan bisa berkisar dari kelemahan transient sedikit kelompok otot terisolasi untuk kelemahan umum yang parah. Severe attacks begin in the morning, often with strenuous exercise or a high carbohydrate meal on the preceding day. serangan berat mulai di pagi hari, seringkali dengan latihan berat atau makan karbohidrat yang tinggi pada hari sebelumnya. Sometimes, the time between premonitory symptoms to full-blown attack is in order of minutes. Kadangkadang, waktu antara gejala pertanda untuk menyerang besar-besaran adalah dalam rangka menit. Attacks may also be provoked by stress, including infections, menstruation, lack of sleep, and certain medications (eg, beta-agonists, insulin, corticosteroids). Serangan juga dapat dipicu oleh stres, termasuk infeksi, menstruasi, kurang tidur, dan obat-obatan tertentu (misalnya, beta-agonis, insulin, kortikosteroid). Patients wake up with severe symmetrical weakness, often with truncal involvement. Pasien bangun dengan kelemahan simetris parah, seringkali dengan keterlibatan truncal. Mild attacks are frequent and involve only a particular group of muscles, and may be unilateral, partial, or monomelic. serangan ringan sering terjadi dan hanya melibatkan kelompok tertentu otot, dan mungkin sepihak, parsial, atau monomelic. This may affect predominantly legs; sometimes, extensor muscles are affected more than flexors. Hal ini dapat mempengaruhi terutama kaki, kadangkadang, otot ekstensor dipengaruhi lebih dari fleksor. Duration varies from a few hours to almost 8 days but seldom exceeds 72 hours. Jangka waktu bervariasi dari beberapa jam sampai hampir 8 hari tapi jarang melebihi 72 jam. The attacks are intermittent and infrequent in the beginning but may increase in frequency until attacks occur almost daily. Serangan yang intermiten dan jarang pada awalnya tetapi mungkin peningkatan frekuensi sampai serangan terjadi hampir setiap hari. The frequency starts diminishing by age 30 years; it rarely occurs after age 50 years. Frekuensi mulai berkurang pada usia 30 tahun, itu jarang terjadi setelah usia 50 tahun. Urinary output is decreased during the attack because water accumulates intracellularly in muscles. keluaran urin menurun selama serangan karena air terakumulasi intrasel pada otot. 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). Pada pasien HypoPP1, usia onset yang lebih awal (10 y), gejala-gejala berlangsung lama (20 jam), dan kelemahan proksimal tetap lebih sering (sekitar 70%), dibandingkan dengan pasien HypoPP2 (16 y, 1 jam, tidak ada ). Permanent muscle weakness may be seen later in the course of the disease and may become severe. Tetap kelemahan otot dapat dilihat kemudian dalam perjalanan penyakit dan bisa menjadi berat. Hypertrophy of the calves has been observed. Hipertrofi dari betis telah diamati. Proximal muscle wasting, rather than hypertrophy, may be seen in patients with permanent weakness. Wasting

proksimal otot, daripada hipertrofi, dapat dilihat pada pasien dengan kelemahan permanen. o HypoPP2 differs from HypoPP1 by (1) late onset, (2) tubular aggregates in muscle biopsy (vacuolar myopathy in HypoPP1), (3) aggravation by acetazolamide in HypoPP2. HypoPP2 berbeda dari HypoPP1 oleh (1) terlambat onset, (2) agregat tubular di biopsi otot (miopati vacuolar di HypoPP1), (3) kejengkelan oleh acetazolamide di HypoPP2. Paramyotonia congenita Paramyotonia congenita o In this autosomal dominant inherited disorder, myotonia worsens with activity (paradoxical myotonia) or cold temperatures. Dalam gangguan ini diwariskan autosomal dominan, myotonia memburuk dengan aktivitas (myotonia paradoks) atau suhu dingin. o Symptoms are most pronounced in the face, tongue, and hand muscles with lesser involvement of lower limb. Gejala yang paling diucapkan dalam lidah, wajah, dan otot tangan dengan keterlibatan yang lebih rendah dari tungkai bawah. o Muscle hypertrophy may be seen in 30% of patients. Hipertrofi otot dapat dilihat pada 30% pasien. o Myotonia lasts for seconds to minutes, but weakness may persist for hours and sometimes days. Myotonia berlangsung selama detik untuk menit, namun kelemahan dapat bertahan selama berjam-jam dan kadang-kadang hari. Frequency of paralytic attacks declines with age. Frekuensi menurun serangan lumpuh dengan usia. o Permanent and severe myopathy is more frequent in patients with periodic paralysis. Permanen dan parah miopati lebih sering pada pasien dengan kelumpuhan periodik. 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. kelemahan Episodic juga dapat berkembang setelah suhu latihan atau dingin dan biasanya berlangsung hanya beberapa menit, namun dapat berlangsung selama hari. o Potassium loading usually worsens the symptoms, but in some cases, lowering the serum potassium level precipitates the attacks. loading Kalium biasanya memperburuk gejala, tetapi dalam beberapa kasus, menurunkan tingkat serum kalium presipitat serangan. Thyrotoxic periodic paralyses Thyrotoxic periodik melumpuhkan o Thyrotoxicosis periodic paralyses (TPP) are the most common secondary hypokalemic PP. melumpuhkan Thyrotoxicosis periodik (TPP) adalah PP yang paling umum hipokalemik sekunder. TPP is most common in adults aged 20-40 years. TPP yang paling umum pada orang dewasa berusia 20-40 tahun. Hyperinsulinemia, a carbohydrate load, and exercise are important in precipitating paralytic attacks. Hyperinsulinemia, beban karbohidrat, dan latihan yang penting dalam mempercepat serangan paralitik. Weakness is proximal and, if severe, may involve respiratory or bulbar muscles. Kelemahan proksimal dan, jika parah, mungkin melibatkan otot pernafasan atau yg berhubungan dgn bengkak. Attacks last hours to days. Serangan terakhir jam untuk hari. o The prevalence of TPP in patients with thyrotoxicosis is estimated to be 0.1-0.2% in Caucasians and 13-14% in Chinese. Prevalensi TPP pada pasien dengan

tirotoksikosis diperkirakan 0,1-0,2% di Kaukasia dan 13-14% di Cina. Ninety-five percent of TPP cases are sporadic. Sembilan puluh lima persen kasus TPP yang sporadis. As TPP is more common in Asians, a genetic predisposition is strongly suspected. Seperti TPP lebih umum di Asia, kecenderungan genetik diduga kuat. Familial clustering of TPP indicates unmasking of an inherited disease (which is sporadic) by thyrotoxicosis. clustering Familial dari TPP menunjukkan unmasking dari penyakit warisan (yang sporadis) dengan tirotoksikosis. A mutation in KCNE3 potassium channel gene was identified in one series. 6 Sebuah mutasi dalam gen saluran kalium KCNE3 diidentifikasi dalam satu seri. 6 Andersen-Tawil syndrome Andersen-Tawil syndrome o Andersen-Tawil syndrome is characterized by variable expression of the triad of dysmorphic features, periodic paralysis, and cardiac arrhythmias. Andersen-Tawil syndrome ditandai oleh variabel ekspresi tiga serangkai fitur dismorfik, paralisis periodik, dan aritmia jantung. Patients may have short stature, hypertelorism, lowset ears, micrognathia, fifth finger clinodactyly, and scoliosis. Pasien mungkin memiliki perawakan pendek, hypertelorism, telinga rendah-set, micrognathia, jari kelima clinodactyly, dan scoliosis. Episodic weakness lasting a few hours to several days may arise spontaneously but usually follows physical activity. kelemahan Episodic berlangsung beberapa jam sampai beberapa hari mungkin timbul secara spontan tetapi biasanya mengikuti aktivitas fisik. The periodic paralysis is not associated with myotonia. Kelumpuhan periodik tidak terkait dengan myotonia. o Prolonged QT interval and ventricular arrhythmias are the most common cardiac manifestations. Berkepanjangan QT interval dan ventrikel aritmia adalah manifestasi jantung yang paling umum. Other ECG abnormalities include PVCs, ventricular bigeminy, supraventricular and ventricular tachycardias, prominent U waves, and torsades de pointes. kelainan EKG lainnya termasuk PVC, bigeminy ventrikel, tachycardias supraventrikuler dan ventrikel, menonjol U gelombang, dan de torsades pointes. Bidirectional ventricular tachycardia, which is characterized by beat-to-beat alternating QRS axis polarity, is unique to a subset of patients. takikardia ventrikel dua arah, yang ditandai dengan memukul-to-beat bolak sumbu QRS polaritas, adalah unik untuk subset dari pasien. Patients may be completely asymptomatic. Pasien mungkin sama sekali tanpa gejala. Patients may experience palpitations, syncopal episodes, and cardiac arrest. Pasien mungkin mengalami palpitasi, episode syncopal, dan serangan jantung. Sudden cardiac death is less frequent in ATS when compared with the other long QT syndromes. kematian mendadak jantung kurang sering di ATS bila dibandingkan dengan sindrom QT panjang lainnya. o Andersen-Tawil syndrome should always be considered in any patient with periodic paralysis as facial dysmorphism may be subtle and cardiac symptoms are not always present in spite of an abnormal ECG. Andersen-Tawil syndrome harus selalu dipertimbangkan dalam setiap pasien dengan kelumpuhan periodik sebagai dysmorphism wajah mungkin gejala halus dan jantung tidak selalu hadir meskipun EKG abnormal.

Physical Fisik

Most of the patients with a periodic paralysis (PP) have similar clinical features, which are as follows: Sebagian besar pasien dengan kelumpuhan periodik (PP) memiliki fitur klinis yang serupa, yang adalah sebagai berikut:

Interictal lid lag and eyelid myotonia - May be the only clinical signs in hyperkalemic PP Interictal tutup lag dan myotonia kelopak mata - Mei menjadi satu-satunya tanda-tanda klinis pada PP hyperkalemic Normal sensation Normal sensasi Fixed proximal weakness - May develop in patients with either hyperkalemic or hypokalemic PP kelemahan proksimal Tetap - Mei mengembangkan pada pasien dengan baik hyperkalemic atau hipokalemik PP Diminished stretch reflexes during attacks Berkurang refleks peregangan selama serangan

Table 2. Tabel 2. Distinguishing Features Among the Common Forms of Periodic Paralyses Fitur Membedakan antara Bentuk umum dari Paralyses Berkala Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Age of Duration of Precipitating Severity of Associated Onset Age Attack Durasi Pengendapan Attacks Asosiasi of Onset Attack Factors Faktor- Keparahan Features Fitur faktor Serangan Hyper-kalemic First Few minutes to Low Rarely severe Perioral and limb periodic decade of less than 2 h carbohydrate Jarang parah paresthesias paralyses life (mostly less intake (fasting) Perioral dan Hyper-kalemic Pertama than 1 h) Rendah asupan parestesia anggota periodik dekade Beberapa karbohidrat tubuh melumpuhkan kehidupan menit sampai (puasa) kurang dari 2 Myotonia frequent jam Cold Dingin Myotonia sering (kebanyakan kurang dari 1 Rest following Occasional jam) exercise Istirahat pseudoLatihan berikut hypertrophy of muscles Sesekali pseudo-hipertrofi Alcohol Alkohol otot Infection Infeksi Emotional stress

Syndrome Sindroma

Stres emosional Trauma Trauma Menstrual period Periode menstruasi Few hours to Early morning almost a week attacks after Beberapa jam previous day untuk hampir physical activity seminggu Dini hari serangan setelah Typically no melakukan longer than 72 aktivitas fisik hari sebelumnya h Biasanya tidak lebih dari 72 jam Highcarbohydrate meal, Chinese food, alcohol Tinggikarbohidrat makan, makanan Cina, alkohol Cold, change in barometric pressure or humidity Dingin, perubahan tekanan udara atau kelembaban Fever, upper respiratory tract infections Demam, infeksi saluran pernapasan atas Lack of sleep, Kurang tidur, fatigue kelelahan Menstrual cycle

Hypo-kalemic periodic paralyses Hypo-kalemic periodik melumpuhkan

Variable Childhood to third decade VariabelAnak untuk dekade ketiga Majority of cases before 16 years Mayoritas kasus sebelum 16 tahun

Severe Parah Occasional myotonic lid lag Sesekali lag Complete myotonic tutup paralysis Lengkap kelumpuhan Myotonia between attacks rare Myotonia antara serangan langka Unilateral, partial, monomelic Sepihak, parsial, monomelic Fixed muscle weakness late in disease kelemahan otot tetap terlambat dalam penyakit

Potassiumassociated myotonia Kalium terkait myotonia

First decade Pertama dekade

No weakness Tidak ada kelemahan

Siklus menstruasi Cold Dingin

Para-myotonia congenita Paramyotonia congenita

First decade Pertama dekade

2-24 h 2-24 h

Attacks of stiffness can be mild to Rest after exercise Istirahat severe setelah latihan Serangan kekakuan dapat ringan sampai berat Cold Dingin Rarely severe Jarang parah

Muscle hypertrophy Otot hipertrofi

Pseudohypertrophy of muscles Pseudohipertrofi otot Paradoxical myotonia Paradoks myotonia Fixed weakness rare Tetap kelemahan langka Fixed muscle weakness may develop kelemahan otot tetap dapat mengembangkan

Thyrotoxic periodic paralyses Thyrotoxic periodik melumpuhkan

Third and Few hours to 7 fourth d Beberapa decades jam untuk 7 d Ketiga dan dekade keempat

Same as hypokalemic PP Sama seperti PP hipokalemik Hyperinsulinemia Hyperinsulinemia

Same as hypokalemic PP Sama seperti PP hipokalemik

Hypokalemia during attacks Hipokalemia saat serangan Syndrome Age of Duration of Precipitating Severity of Associated Sindroma Onset Age Attack Durasi Pengendapan Attacks Asosiasi of Onset Attack Factors Faktor- Keparahan Features Fitur faktor Serangan Hyper-kalemic First Few minutes to Low Rarely severe Perioral and limb periodic decade of less than 2 h carbohydrate Jarang parah paresthesias paralyses life (mostly less intake (fasting) Perioral dan Hyper-kalemic Pertama than 1 h) Rendah asupan parestesia anggota periodik dekade Beberapa karbohidrat tubuh melumpuhkan kehidupan menit sampai (puasa) kurang dari 2 Myotonia frequent

jam (kebanyakan kurang dari 1 jam)

Cold Dingin Rest following exercise Istirahat Latihan berikut Alcohol Alkohol Infection Infeksi Emotional stress Stres emosional Trauma Trauma

Myotonia sering Occasional pseudohypertrophy of muscles Sesekali pseudo-hipertrofi otot

Hypo-kalemic periodic paralyses Hypo-kalemic periodik melumpuhkan

Variable Childhood to third decade VariabelAnak untuk dekade ketiga Majority of cases before 16 years Mayoritas kasus sebelum 16 tahun

Menstrual period Periode menstruasi Few hours to Early morning almost a week attacks after Beberapa jam previous day untuk hampir physical activity seminggu Dini hari serangan setelah Typically no melakukan longer than 72 aktivitas fisik hari sebelumnya h Biasanya tidak lebih dari 72 jam Highcarbohydrate meal, Chinese food, alcohol Tinggikarbohidrat makan, makanan Cina, alkohol Cold, change in barometric pressure or humidity Dingin, perubahan tekanan udara atau kelembaban Fever, upper

Severe Parah Occasional myotonic lid lag Sesekali lag Complete myotonic tutup paralysis Lengkap kelumpuhan Myotonia between attacks rare Myotonia antara serangan langka Unilateral, partial, monomelic Sepihak, parsial, monomelic Fixed muscle weakness late in disease kelemahan otot tetap terlambat dalam penyakit

respiratory tract infections Demam, infeksi saluran pernapasan atas Lack of sleep, Kurang tidur, fatigue kelelahan Menstrual cycle Siklus menstruasi Cold Dingin Attacks of stiffness can be mild to Rest after exercise Istirahat severe setelah latihan Serangan kekakuan dapat ringan sampai berat Cold Dingin Rarely severe Jarang parah

Potassiumassociated myotonia Kalium terkait myotonia

First decade Pertama dekade

No weakness Tidak ada kelemahan

Muscle hypertrophy Otot hipertrofi

Para-myotonia congenita Paramyotonia congenita

First decade Pertama dekade

2-24 h 2-24 h

Pseudohypertrophy of muscles Pseudohipertrofi otot Paradoxical myotonia Paradoks myotonia Fixed weakness rare Tetap kelemahan langka Fixed muscle weakness may develop kelemahan otot tetap dapat mengembangkan Hypokalemia during attacks Hipokalemia saat serangan

Thyrotoxic periodic paralyses Thyrotoxic periodik melumpuhkan

Third and Few hours to 7 fourth d Beberapa decades jam untuk 7 d Ketiga dan dekade keempat

Same as hypokalemic PP Sama seperti PP hipokalemik Hyperinsulinemia Hyperinsulinemia

Same as hypokalemic PP Sama seperti PP hipokalemik

Causes Penyebab
Refer to Pathophysiology and Table 2 and Table 3 . Lihat Patofisiologi dan Tabel 2 dan Tabel 3 .

Diferensial Diagnosa
Acute Inflammatory Demyelinating Spinal Cord Hemorrhage Spinal Cord Polyradiculoneuropathy Polyradiculoneuropathy Perdarahan inflamasi akut demielinasi Cauda Equina and Conus Medullaris Syndromes Spinal Cord Infarction Spinal Cord Cauda equina dan Conus medullaris Syndromes Infarction Chronic Inflammatory Demyelinating Spinal Cord, Topographical and Polyradiculoneuropathy Polyradiculoneuropathy Functional Anatomy Spinal Cord, dan kronis inflamasi demielinasi Fungsional Anatomi Topografi Guillain-Barre Syndrome in Childhood GuillainSpinal Epidural Abscess Spinal Epidural Barre Syndrome in Childhood Abses Lambert-Eaton Myasthenic Syndrome Lambert-Eaton Sindrom miasthenik Multiple Sclerosis Multiple Sclerosis Myasthenia Gravis Gravis gravis

Other Problems to Be Considered Masalah lain untuk Be Dianggap

Table 3. Tabel 3. Differential Diagnosis of Secondary Periodic Paralyses Diferensial Diagnosis Paralyses Berkala Sekunder Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Hypokalemic Hipokalemik Urinary potassium-wasting syndromes Kencing kalium-buang sindrom

Hyperkalemic Hyperkalemic

Hyperaldosteronism Hyperaldosteronism Conn syndrome Conn sindrom Bartter syndrome Bartter sindrom Licorice intoxication Licorice keracunan Addison disease Penyakit Addison Chronic renal failure Gagal ginjal kronis

Alcohol Alkohol

Drugs - Amphotericin B, barium Obat - Amfoterisin B, barium Renal tubular acidosis Renal tubular asidosis GI potassium-wasting syndromes GI kalium-buang sindrom

Hyporeninemic Hyporeninemic Hypoaldosteronism Hypoaldosteronism Ileostomy with tight stoma Ileostomy dengan stoma ketat Potassium load Kalium beban Potassium-sparing diuretics Potassiumsparing diuretic

Laxative abuse Penyalahgunaan pencahar Severe diarrhea Diare berat Hyperkalemic Hyperkalemic

Hypokalemic Hipokalemik Urinary potassium-wasting syndromes Kencing kalium-buang sindrom

Hyperaldosteronism Hyperaldosteronism Conn syndrome Conn sindrom Bartter syndrome Bartter sindrom Licorice intoxication Licorice keracunan Addison disease Penyakit Addison Chronic renal failure Gagal ginjal kronis Hyporeninemic Hyporeninemic Hypoaldosteronism Hypoaldosteronism Ileostomy with tight stoma Ileostomy dengan stoma ketat Potassium load Kalium beban Potassium-sparing diuretics Potassiumsparing diuretic

Alcohol Alkohol

Drugs - Amphotericin B, barium Obat - Amfoterisin B, barium Renal tubular acidosis Renal tubular asidosis GI potassium-wasting syndromes GI kalium-buang sindrom

Laxative abuse Penyalahgunaan pencahar Severe diarrhea Diare berat

Table 4. Tabel 4. Differential Diagnosis of Other Entities Causing Acute Generalized Weakness Diferensial Diagnosis Entitas Lain Menyebabkan Kelemahan Generalized Akut Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Disorder Kekacauan

Pattern and Pola dan

Transient ischemic attacks Serangan iskemik transien

Sleep attacks Tidur serangan

Myelopathy Myelopathy

Traumatic Trauma Transverse myelitis Melintang myelitis Ischemic Iskemik

Distribution of Distribusi Weakness Kelemahan Follow CNS distribution (ie, hemiparetic) Ikuti distribusi SSP (yaitu, hemiparetic) May have sensory symptoms and signs Mungkin memiliki gejala sensorik dan tandatanda Occur at onset or termination of sleep Terjadi pada awal atau pemutusan tidur Last only minutes Terakhir hanya beberapa menit Sensory symptoms Sensory gejala Presence of a sensory level Hadirnya tingkat sensorik Sphincter involvement Sphincter keterlibatan

Myasthenia gravis Myasthenia gravis Lambert-Eaton myasthenic syndrome Sindrom Lambert-Eaton miasthenik

Peripheral neuropathy of acute onset Neuropati perifer onset akut

Subacute in onset Subakut di awal Associated autonomic symptoms in LEMS Asosiasi gejala otonom memiliki kualifikasi Hyporeflexia in LEMS Hyporeflexia di ditempat anda Abnormal repetitive nerve stimulation Abnormal stimulasi saraf berulang Presence of distinct antibodies Kehadiran antibodi yang berbeda Pattern of weakness Pola kelemahan Absent stretch reflexes Tidak ada stretch refleks

Acute inflammatory Inflamasi akut demyelinating poly-radiculoneuropathy demielinasi poli-radiculoneuropathy Porphyria Porfiria Clinical presentation Presentasi klinis

Toxins Racun

Ciguatera Ciguatera Tetrodotoxin Tetrodotoxin Disorder Kekacauan Pattern and Pola dan Distribution of Distribusi Weakness Kelemahan Follow CNS distribution (ie, hemiparetic) Ikuti distribusi SSP (yaitu, hemiparetic)

Transient ischemic attacks Serangan iskemik transien

Sleep attacks Tidur serangan

Myelopathy Myelopathy

Traumatic Trauma Transverse myelitis Melintang myelitis Ischemic Iskemik

May have sensory symptoms and signs Mungkin memiliki gejala sensorik dan tandatanda Occur at onset or termination of sleep Terjadi pada awal atau pemutusan tidur Last only minutes Terakhir hanya beberapa menit Sensory symptoms Sensory gejala Presence of a sensory level Hadirnya tingkat sensorik Sphincter involvement Sphincter keterlibatan

Myasthenia gravis Myasthenia gravis Lambert-Eaton myasthenic syndrome Sindrom Lambert-Eaton miasthenik

Peripheral neuropathy of acute onset Neuropati perifer onset akut

Subacute in onset Subakut di awal Associated autonomic symptoms in LEMS Asosiasi gejala otonom memiliki kualifikasi Hyporeflexia in LEMS Hyporeflexia di ditempat anda Abnormal repetitive nerve stimulation Abnormal stimulasi saraf berulang Presence of distinct antibodies Kehadiran antibodi yang berbeda Pattern of weakness Pola kelemahan Absent stretch reflexes Tidak ada stretch refleks

Acute inflammatory Inflamasi akut demyelinating poly-radiculoneuropathy demielinasi poli-radiculoneuropathy Porphyria Porfiria Clinical presentation Presentasi klinis

Toxins Racun

Ciguatera Ciguatera Tetrodotoxin Tetrodotoxin

Workup Hasil pemeriksaan

Laboratory Studies Laboratorium Studi
Hypokalemic periodic paralyses Hipokalemik periodik melumpuhkan

Serum potassium level decreases during attacks but not necessarily below normal. Tingkat kalium serum menurun selama serangan tetapi belum tentu di bawah normal. Creatine phosphokinase (CPK) level rises during attacks. Creatine phosphokinase (CPK) tingkat meningkat selama serangan. In a recent study, transtubular potassium concentration gradient (TTKG) and potassium-creatinine ratio (K/C) distinguished primary hypokalemic PP from secondary PP resulting from a large deficit of potassium. Dalam penelitian terbaru, kalium gradien konsentrasi transtubular (TTKG) dan rasio kalium-kreatinin (K / C) dibedakan PP hipokalemik primer dari PP sekunder yang dihasilkan dari defisit besar kalium. Values of more than 3.0 mmol/mmol (TTKG) and 2.5 mmol/mmol (PCR) indicated secondary hypokalemic PP. Nilai lebih dari 3,0 mmol / mmol (TTKG) dan 2,5 mmol / mmol (PCR) menunjukkan PP hipokalemik sekunder. A random urine potassium-creatinine ratio (K/C) of less than 1.5 is indicative of poor intake, gastrointestinal loss, and potassium shift into the cells. Sebuah rasio urin acak-kreatinin kalium (K / C) kurang dari 1,5 adalah indikasi dari asupan miskin, kehilangan gastrointestinal, dan pergeseran kalium ke dalam sel. If hypokalemia is associated with paralysis, one should consider hyperthyroidism or familial or sporadic periodic paralysis. Jika hipokalemia dikaitkan dengan kelumpuhan, kita harus mempertimbangkan hipertiroidisme atau kelumpuhan periodik keluarga atau sporadis. Some of the medical conditions associated with hypokalemia are included in the table below (modified from Assadi 2008 7 ). Beberapa kondisi medis yang terkait dengan hipokalemia termasuk dalam tabel di bawah ini (dimodifikasi dari Assadi 2008 7 ). Table 5. Tabel 5. Medical Conditions Associated With Hypokalemia Kondisi medis Asosiasi Dengan hipokalemia Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Urine Acid Base K/C Status Asam Ratio Base Status Urine K / Rasio C <1.5 <1,5 Metabolic acidosis Asidosis metabolik <1.5 <1,5 Metabolic alkalosis Metabolic alkalosis

Other Associated Features Fitur lainnya Asosiasi

Medical Medis Conditions Kondisi

Lower GI loss Laxative abuse, diarrhea Lower GI rugi - penyalahgunaan Laksatif, diare

Normal BP Normal BP

Surreptitious vomiting Diam-diam muntah

>1.5 > 1,5

>1.5 > 1,5

1.5 1,5

Metabolic acidosis Asidosis metabolik Metabolic alkalosis Metabolic alkalosis Metabolic alkalosis Metabolic alkalosis

DKA, type 1 or type 2 distal RTA DKA, tipe 1 atau tipe 2 RTA distal

Normal BP Normal BP

Diuretic use, Bartter syndrome, Gitelman syndrome Diuretik digunakan, Bartter sindrom, sindrom Gitelman

Urine K/C Ratio Urine K / Rasio C <1.5 <1,5 Metabolic acidosis Asidosis metabolik <1.5 <1,5 Metabolic alkalosis Metabolic alkalosis >1.5 > Metabolic 1,5 acidosis Asidosis metabolik >1.5 > Metabolic 1,5 alkalosis Metabolic alkalosis 1.5 Metabolic 1,5 alkalosis Metabolic alkalosis

Primary aldosteronism, Cushing syndrome, renal artery stenosis, congenital adrenal hyperplasia, apparent mineralocorticoid excess, Liddle syndrome Primer aldosteronisme, sindrom Cushing, stenosis arteri ginjal, hiperplasia adrenal bawaan, kelebihan mineralokortikoid jelas, Liddle sindrom Acid Base Other Associated Medical Medis Status Asam Features Fitur Conditions Kondisi Base Status lainnya Asosiasi

Hypertension Hipertensi

Lower GI loss Laxative abuse, diarrhea Lower GI rugi - penyalahgunaan Laksatif, diare

Normal BP Normal BP

Surreptitious vomiting Diam-diam muntah

DKA, type 1 or type 2 distal RTA DKA, tipe 1 atau tipe 2 RTA distal

Normal BP Normal BP

Diuretic use, Bartter syndrome, Gitelman syndrome Diuretik digunakan, Bartter sindrom, sindrom Gitelman Primary aldosteronism, Cushing syndrome, renal artery stenosis, congenital adrenal hyperplasia, apparent mineralocorticoid excess, Liddle syndrome Primer aldosteronisme, sindrom Cushing, stenosis arteri ginjal, hiperplasia adrenal bawaan, kelebihan mineralokortikoid jelas, Liddle sindrom

Hypertension Hipertensi

ECG may show sinus bradycardia and evidence of hypokalemia (flattening of T waves, U waves

in leads II, V 2 , V 3 , and V 4 , and ST-segment depression). EKG dapat menunjukkan bradikardia sinus dan bukti hipokalemia (mendatarkan gelombang T, gelombang U dalam lead II, V 2, V 3, dan V 4, dan segmen ST depresi). Hyperkalemic periodic paralyses Hyperkalemic periodik melumpuhkan Serum potassium level may increase to as high as 5-6 mEq/L. Tingkat kalium serum bisa meningkat sampai setinggi 5-6 mEq / L. Sometimes, it may be at the upper limit of normal, and it seldom reaches cardiotoxic levels. Kadang-kadang, mungkin berada di batas atas normal, dan jarang mencapai tingkat kardiotoksik. Serum sodium level may fall as potassium level rises. kadar natrium serum bisa jatuh dan naik tingkat kalium. This results from sodium entry into the muscle. Ini hasil dari entri natrium ke otot. Water also moves in this direction, causing hemoconcentration and further hyperkalemia. Air juga bergerak ke arah ini, menyebabkan hemokonsentrasi dan hiperkalemia lebih lanjut. Hyperregulation may occur at the end of an attack, causing hypokalemia. Hyperregulation dapat terjadi pada akhir serangan, menyebabkan hipokalemia. Water diuresis, creatinuria, and an increase in CPK level also may occur at the end of an attack. diuresis Air, creatinuria, dan peningkatan tingkat CPK dapat juga terjadi pada akhir serangan. ECG may show tall T waves. EKG dapat menunjukkan tinggi gelombang T. Table 6. Tabel 6. Diagnostic Studies of Hypokalemic and Hyperkalemic Periodic Paralyses Studi Diagnostik Paralyses Berkala hipokalemik dan Hyperkalemic Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Hypokalemic PP Hipokalemik Hyperkalemic PP Hyperkalemic PP PP Serum Mildly depressed; may reach 1-5 Increases from baseline but may not increase potassium mEq/L Sedikit depresi; dapat beyond normal range Meningkat dari baseline Serum kalium mencapai 1-5 mEq / L namun mungkin tidak meningkat melebihi batas normal Serum CPK Moderately elevated during Mildly elevated during attacks Sedikit Serum CPK attacks Cukup meningkat selama meningkat selama serangan serangan ECG EKG Bradycardia Bradikardi Tall T waves Tinggi Gelombang T Flat T waves, U waves, STsegment depression T Flat ombak, gelombang U, STsegmen depresi Hypokalemic PP Hipokalemik Hyperkalemic PP Hyperkalemic PP

PP Serum Mildly depressed; may reach 1-5 Increases from baseline but may not increase potassium mEq/L Sedikit depresi; dapat beyond normal range Meningkat dari baseline Serum kalium mencapai 1-5 mEq / L namun mungkin tidak meningkat melebihi batas normal Serum CPK Moderately elevated during Mildly elevated during attacks Sedikit Serum CPK attacks Cukup meningkat selama meningkat selama serangan serangan ECG EKG Bradycardia Bradikardi Tall T waves Tinggi Gelombang T Flat T waves, U waves, STsegment depression T Flat ombak, gelombang U, STsegmen depresi

Other Tests Tes Lainnya

Electrodiagnosis and provocative testing can be performed for periodic paralysis. Electrodiagnosis dan pengujian provokatif dapat dilakukan karena kelumpuhan periodik.

Electrodiagnosis Electrodiagnosis
Nerve conduction studies Studi konduksi saraf

The compound muscle action potential (CMAP) amplitude declines during the paralytic attack, more so in hypokalemic periodic paralysis. Tindakan senyawa otot potensial (CMAP) amplitudo menurun selama serangan lumpuh, lagi di paralisis periodik hipokalemik. Sensory nerve conduction study findings are normal in most patients with periodic paralyses. Sensory temuan studi konduksi saraf normal pada kebanyakan pasien dengan melumpuhkan berkala. Nerve conduction findings may be abnormal when the patient has peripheral neuropathy associated with thyrotoxicosis. Temuan konduksi saraf mungkin abnormal bila pasien memiliki neuropati perifer berhubungan dengan tirotoksikosis. Repetitive nerve stimulation in hyperkalemic periodic paralysis may show a decrement in CMAP (accentuated by cooling) that is steadily progressive without tendency to recover as in myasthenia gravis. stimulasi saraf berulang kelumpuhan periodik hyperkalemic mungkin menunjukkan penurunan dalam CMAP (ditekankan oleh pendingin) yang terus progresif tanpa kecenderungan untuk pulih seperti pada myasthenia gravis. The amount of decrement is variable and increases with increased frequency of stimulation. Jumlah pengurangan tersebut adalah variabel dan meningkat seiring dengan peningkatan frekuensi stimulasi. In some patients, it is seen only with stimulation greater than 25 Hz. 8 Pada beberapa pasien, terlihat hanya dengan rangsangan yang lebih besar dari 25 Hz. 8

Muscle cooling Otot pendinginan

Cooling of muscle to 20C leads to force reduction and prolonged twitch-relaxation in PC and hyperkalemic periodic paralyses. Pendinginan otot sampai 20 C mengarah untuk memaksa pengurangan dan berkepanjangan berkedut-relaksasi di PC dan melumpuhkan hyperkalemic berkala. Muscle paralysis is prolonged and persistent even after rewarming. kelumpuhan otot yang berkepanjangan dan terus-menerus bahkan setelah rewarming. As the muscle depolarizes at different temperatures in different patients, a muscle temperature of 20-25C is preferable. Sebagai otot depolarizes pada temperatur yang berbeda pada pasien yang berbeda, suhu otot 20-25 C adalah lebih baik. This is best achieved by immersing the whole arm in ice water. Hal ini paling baik dicapai dengan merendam seluruh lengan dalam air es. This alone causes weakness in many patients. Ini saja menyebabkan kelemahan pada banyak pasien. Short periods of exercise (2-3 1-second short exercises) enhance the weakness and result in a very small CMAP. 8 periode singkat dari latihan (2-3 kedua pendek latihan-1) meningkatkan kelemahan dan menghasilkan kecil CMAP sangat. 8

Exercise test in periodic paralyses Latihan tes dalam melumpuhkan periodik

This is one of the most informative diagnostic tests for periodic paralyses. Ini adalah salah satu tes diagnostik yang paling informatif untuk melumpuhkan berkala. The test is based on 2 previously described observations: that CMAP amplitude is low in the muscle weakened by periodic paralyses and the weakness can be induced by exercise. Pengujian ini didasarkan pada pengamatan 2 telah dijelaskan sebelumnya: CMAP amplitudo yang rendah pada otot melemah oleh melumpuhkan berkala dan kelemahan dapat ditimbulkan dengan olahraga. Recording electrodes are placed over the hypothenar muscle and a CMAP is obtained by giving supramaximal stimuli. Merekam elektroda ditempatkan di atas otot hipotenar dan CMAP diperoleh dengan memberikan rangsangan supramaksimal. The stimuli are repeated every 30-60 seconds for a period of 2-3 minutes, until a stable baseline amplitude is obtained. Stimuli yang diulang setiap 30-60 detik untuk jangka waktu 2-3 menit, sampai amplitudo dasar yang stabil diperoleh. Two kinds of exercise tests can be performed. Dua jenis tes latihan dapat dilakukan. A short exercise test is one in which the muscle is contracted strongly in isometric conditions for 10-12 seconds. Sebuah test olahraga pendek adalah satu di mana otot dikontrak kuat dalam kondisi isometrik selama 10-12 detik. CMAPs are obtained 2 seconds immediately after exercise an then every 10 seconds for 50 seconds. CMAPs diperoleh 2 detik segera setelah latihan maka setiap 10 detik selama 50 detik. In hyperkalemic periodic paralyses patients carrying T704M mutations, increase in CMAP amplitude (approximately 23%) occurs. Dalam hyperkalemic pasien melumpuhkan berkala tercatat T704M mutasi, peningkatan amplitudo CMAP (sekitar 23%) terjadi. In HypoPP1 and HypoPP2 patients, the increase is not significantly different from the control subjects (about 5%). Pada pasien HypoPP1 dan HypoPP2, kenaikan tersebut tidak berbeda secara signifikan dari subyek kontrol (sekitar 5%). In the long exercise test, the muscle is contracted for 5 minutes, with brief (3- to 4second) rests every 15 seconds to prevent muscle ischemia. Pada uji latihan lama, otot dikontrak selama 5 menit, dengan singkat (3 - to 4-detik) istirahat setiap 15 detik untuk mencegah iskemia otot. The CMAP is recorded every minute during exercise and every 1-2 minutes after exercise for a period of 30 minutes or until no further decrement is

observed in the amplitude of CMAP. The CMAP dicatat setiap menit selama latihan dan setiap 1-2 menit setelah latihan selama 30 menit atau sampai tidak ada pengurangan lebih lanjut diamati dalam amplitudo CMAP. Percentage of decrement is calculated by subtracting the smallest amplitude after exercise from the greatest amplitude after exercise and dividing it by the greatest amplitude after exercise. Persentase pengurangan dihitung dengan mengurangkan amplitudo terkecil setelah latihan dari amplitudo terbesar setelah latihan dan membaginya dengan amplitudo terbesar setelah latihan. After a brief increase in CMAP amplitude, a decrease of more than 40% in the CMAP amplitude after 20 minutes is considered abnormal. Setelah peningkatan singkat di amplitudo CMAP, turun lebih dari 40% pada amplitudo CMAP setelah 20 menit dianggap abnormal. An abnormal result is highly suggestive of periodic paralyses (98% specificity) but does not distinguish between hyperkalemic, hypokalemic, and thyrotoxic periodic paralyses. Hasil abnormal sangat sugestif dari melumpuhkan periodik (spesifisitas 98%) tetapi tidak membedakan antara melumpuhkan periodik hyperkalemic, hipokalemik, dan thyrotoxic. Different electrophysiologic patterns are identified in different group of patients with distinct mutations by using both these tests. elektropsikologi pola yang berbeda diidentifikasi dalam kelompok yang berbeda dari pasien dengan mutasi berbeda dengan menggunakan kedua tes ini. Table 7. Tabel 7. Electrophysiological Patterns to Exercise Testing Pola elektrofisiologi untuk Latihan Pengujian Open table in new window Buka tabel di jendela baru [ CLOSE WINDOW ] [ CLOSE WINDOW ]
Table Tabel

Electrophysiological Elektrofisiologi pattern pola Channel mutations Channel mutasi Short Exercise Test: Pendek Latihan Tes: Post exercise myotonic potentials Post latihan potensi myotonic CMAP amplitude CMAP

Para- ParaHyper- HyperHypo- Hypomyotonia myotonia kalemic kalemic kalemic kalemic Congenita Congenita Periodic Paralysis Periodic Paralysis Kelumpuhan Kelumpuhan Berkala Berkala I Aku IV IV VV

Sodium T1313M, R1448C Sodium T1313M, R1448C

Sodium T704M Sodium T704M

Calcium R528H Kalsium R528H

Yes Ya

No Tidak ada

No Tidak ada

Increase or

Increase

No Tidak ada

amplitudo Meningkatkan atau Meningkatkan change after First trial berubah decrease penurunan setelah sidang Pertama CMAP amplitude CMAP Gradual Bertahap Gradual Bertahap amplitudo increase meningkatkan increase change after second berubah meningkatkan setelah kedua and third trial dan ketiga uji coba Long Exercise Test: Long Latihan Tes: Immediate change of Segera Decrease Penurunan Increase perubahan Meningkatkan CMAP amplitude CMAP amplitudo Late change of CMAP Decrease Penurunan Decrease Penurunan amplitude Akhir perubahan amplitudo CMAP Modified from Fournier et al, 2004. 9 Modifikasi dari Fournier et al, 2004. 9 Para- ParaHyper- Hypermyotonia myotonia kalemic kalemic Congenita Congenita Periodic Paralysis Kelumpuhan Berkala Electrophysiological I Aku IV IV Elektrofisiologi pattern pola Channel mutations Channel Sodium T1313M, Sodium T704M mutasi R1448C Sodium Sodium T704M T1313M, R1448C Short Exercise Test: Pendek Latihan Tes: Post exercise myotonic Yes Ya No Tidak ada potentials Post latihan potensi myotonic CMAP amplitude CMAP Increase or Increase amplitudo Meningkatkan atau Meningkatkan change after First trial berubah decrease penurunan setelah sidang Pertama CMAP amplitude CMAP Gradual Bertahap Gradual Bertahap amplitudo increase meningkatkan increase change after second berubah meningkatkan setelah kedua and third trial dan ketiga uji

No Tidak ada

No Tidak ada

Decrease Penurunan

Hypo- Hypokalemic kalemic Periodic Paralysis Kelumpuhan Berkala VV

Calcium R528H Kalsium R528H

No Tidak ada

No Tidak ada

No Tidak ada

coba Long Exercise Test: Long Latihan Tes: Immediate change of Segera Decrease Penurunan Increase perubahan Meningkatkan CMAP amplitude CMAP amplitudo Late change of CMAP Decrease Penurunan Decrease Penurunan amplitude Akhir perubahan amplitudo CMAP Modified from Fournier et al, 2004. 9 Modifikasi dari Fournier et al, 2004. 9 Needle electrode examination Elektroda jarum pemeriksaan

No Tidak ada

Decrease Penurunan

Insertional activity: The presence of myotonia usually excludes the diagnosis of hypokalemic periodic paralyses. Kegiatan insersional: Kehadiran myotonia biasanya tidak termasuk diagnosis melumpuhkan hipokalemik periodik. In hyperkalemic periodic paralyses, no abnormality is detectable between attacks. Dalam melumpuhkan periodik hyperkalemic, tidak ada kelainan terdeteksi antara serangan. In those patients with both clinical and electrical myotonia, mild to moderate spontaneous activity is seen, consisting of fibrillation potentials, positive sharp waves, and myotonic discharges. Pada pasien dengan baik myotonia klinis dan listrik, ringan sampai kegiatan spontan moderat dilihat, terdiri dari potensi fibrilasi, gelombang positif tajam, dan debit myotonic. Myotonia: Electrical myotonia consists of repetitive discharges at rates of 20-80 Hz. Myotonia: myotonia Listrik terdiri dari discharge berulang dengan tarif 20-80 Hz. The shape of the potentials can be either positive sharp waves or small biphasic waves; the former is seen while moving the needle electrode and the latter following muscle contraction. Bentuk potensi dapat berupa gelombang tajam positif atau gelombang biphasic kecil, yang pertama terlihat saat bergerak elektroda jarum dan kontraksi otot terakhir berikut. Another criterion distinct for myotonia is waxing and waning of the amplitude and frequency of the discharges (ie, dive-bomber discharges). Lain kriteria berbeda untuk myotonia adalah waxing dan waning amplitudo dan frekuensi pembuangan (yaitu, menyelam-bomber discharge). These discharges should last a minimum of 500 milliseconds. Pembuangan ini harus berlangsung minimal 500 milidetik. They should be elicited in at least 3 areas outside the endplate region in order to distinguish minimal electromyographic myotonia from insertional activity. Mereka harus ditimbulkan dalam setidaknya 3 daerah di luar wilayah endplate untuk membedakan myotonia elektromiografi minimal dari kegiatan insersional. Demonstration of myotonia may be facilitated by potassium administration and cold temperature. Demonstrasi myotonia dapat difasilitasi oleh administrasi kalium dan suhu dingin. Motor unit action potential (MUAP): During the paralytic attack, recruitment is reduced, with few voluntary MUAPs. Unit Motor potensial aksi (MUAP): Selama serangan lumpuh, rekrutmen berkurang, dengan sukarela MUAPs sedikit. The amplitude and duration of MUAPs may be reduced. Amplitudo dan durasi MUAPs dapat dikurangi. In patients who develop myopathy, the MUAPs tend to show decreased amplitude, reduced

duration, and increased proportion of polyphasic potentials. Pada pasien yang mengalami miopati, yang MUAPs cenderung menunjukkan amplitudo menurun, mengurangi durasi, dan meningkatkan proporsi potensi polyphasic.

Provocative Testing Provokatif Pengujian

General precautions for such testing include (1) physician presence during testing, (2) performance of testing in an intensive care setting, (3) avoidance of testing patients with serum potassium disturbances, diabetes mellitus, or renal or cardiac dysfunction, (4) close monitoring of ECG, and (5) capability for rapid electrolyte and glucose testing and correction. Pencegahan umum untuk pengujian tersebut meliputi (1) kehadiran dokter selama pengujian, (2) kinerja pengujian dalam pengaturan perawatan intensif, (3) menghindari pengujian pasien dengan gangguan kalium serum, diabetes mellitus, atau disfungsi ginjal atau jantung, (4) dekat pemantauan EKG, dan (5) kemampuan untuk elektrolit yang cepat dan pengujian glukosa dan koreksi.

Hypokalemic periodic paralyses: Provocative testing is dangerous and is not the first line of diagnostic testing. Hipokalemik periodik melumpuhkan: pengujian provokatif yang berbahaya dan tidak baris pertama pengujian diagnostik. o Oral glucose loading test: Glucose is given orally at a dose of 1.5 g/kg to a maximum of 100 g over a period of 3 minutes with or without 10-20 units of subcutaneous insulin. Glukosa oral uji beban: Glukosa diberikan secara oral pada dosis 1,5 g / kg sampai maksimal 100 g selama 3 menit dengan atau tanpa 10-20 unit insulin subkutan. Muscle strength is tested every 30 minutes. Kekuatan Otot diuji setiap 30 menit. Full electrolyte profile is tested every 30 minutes for 3 hours and hourly for the next 2 hours. profil elektrolit Full diuji setiap 30 menit selama 3 jam dan per jam untuk 2 jam berikutnya. Weakness usually is detected within 23 hours, and if not patients should be considered for intravenous (IV) glucose challenge. Kelemahan biasanya terdeteksi dalam waktu 2-3 jam, dan jika tidak pasien harus dipertimbangkan untuk intravena (IV) Tantangan glukosa. o Intravenous glucose challenge: Good IV access is essential and availability of more than one IV line is preferred. Glukosa Intravena Tantangan: Bagus IV akses yang penting dan ketersediaan lebih dari satu baris IV lebih disukai. Glucose is infused IV over a period of 1 hour at a dose of 3 g/kg to a maximum of 200 g (in water at 2 g/5 mL). Glukosa diinfuskan IV selama 1 jam pada dosis 3 g / kg maksimal 200 g (di dalam air pada 2 g / 5 mL). If no weakness is detectable at 30 minutes, 0.1 U/kg of IV insulin is given. Jika tidak ada kelemahan terdeteksi pada 30 menit, 0,1 U / kg IV insulin diberikan. Insulin can be repeated in 60 minutes if weakness is not detected. Insulin dapat diulang dalam 60 menit jika kelemahan tidak terdeteksi. Strength is evaluated every 15 minutes for 2 hours. Kekuatan dievaluasi setiap 15 menit selama 2 jam. Electrolytes, glucose, and carbon dioxide are measured every 30 minutes and once more after the patient becomes weak. Elektrolit, glukosa, dan karbon dioksida diukur setiap 30 menit dan sekali lagi setelah pasien menjadi lemah. ECG is repeated every 30 minutes. EKG diulang setiap 30 menit. The most dangerous period of the testing is between 75-150 minutes when severe hypoglycemia occurs. Periode paling berbahaya pengujian

adalah antara 75-150 menit saat terjadi hipoglikemia berat. This should be reversed immediately. Ini harus dibalik segera. o Intra-arterial epinephrine test: Two mcg/min of epinephrine is infused into the brachial artery for 5 minutes and the amplitude of the CMAP is recorded from a hand muscle. Intra-arteri epinefrin test: Dua mcg / menit dari epinefrin adalah dimasukkan ke dalam arteri brakialis selama 5 menit dan amplitudo dari CMAP dicatat dari otot tangan. CMAPs are recorded before, during, and 30 minutes after infusion. CMAPs dicatat sebelum, selama, dan 30 menit setelah infus. The result is considered positive if a decrement of more than 30% occurs within 10 minutes of infusion. Hasilnya dianggap positif jika penurunan lebih dari 30% terjadi dalam 10 menit infus. Hyperkalemic periodic paralyses: Potassium chloride 0.05 g/kg in a sugar-free liquid is given orally over 3 minutes in a fasting state, just after exercise. melumpuhkan Hyperkalemic periodik: Kalium klorida 0,05 g / kg dalam cairan gula-bebas adalah diberikan secara oral selama 3 menit dalam keadaan puasa, hanya setelah latihan. If no weakness occurs, an additional amount of potassium chloride (0.10-0.15 g/kg) is given. Jika kelemahan tidak terjadi, jumlah tambahan kalium klorida (0,10-0,15 g / kg) diberikan. Electrolyte profile, ECG, and strength are tested every 15 minutes for 2 hours and then every 30 minutes for the next 2 hours. profil elektrolit, EKG, dan kekuatan yang diuji setiap 15 menit selama 2 jam dan kemudian setiap 30 menit selama 2 jam berikutnya. Weakness usually is detected between 90-180 minutes after initiation of testing. Kelemahan biasanya terdeteksi antara 90-180 menit setelah dimulainya pengujian.

Histologic Findings Temuan histologis

Muscle biopsy is abnormal, more typically in patients with hypokalemic periodic paralysis (PP) than in patients with hyperkalemic periodic paralysis (PP). Biopsi otot tidak normal, lebih biasanya pada pasien dengan kelumpuhan periodik hipokalemik (PP) dibandingkan pada pasien dengan kelumpuhan periodik hyperkalemic (PP). Histologic findings in hypokalemic PP include the following: Temuan histologis dalam PP hipokalemik meliputi:

The most characteristic abnormality is the presence of vacuoles in the muscle fibers. Kelainan paling khas adalah adanya vakuola dalam serat otot. Sometimes, they fill the muscle fibers, and in some patients, groups of vacuoles may be noted. Kadang-kadang, mereka mengisi serat otot, dan pada beberapa pasien, kelompok vakuola dapat dicatat. These changes are more marked in hypokalemic PP than in hyperkalemic PP. Perubahan ini lebih ditandai dalam PP hipokalemik daripada di PP hyperkalemic. In the latter, the vacuoles are small and peripherally located. Pada yang terakhir, vakuola kecil dan perifer berada. Reports of muscle biopsy findings in PC are few and the vacuolar changes are less frequent. Laporan temuan biopsi otot pada PC sedikit dan perubahan vacuolar kurang sering. Signs of myopathy include muscle fiber size variability, split fibers, and internal nuclei. Tanda-tanda miopati termasuk variabilitas ukuran serat otot, serat split, dan inti internal. Muscle fiber atrophy may be present in clinically affected muscles. serat otot atrofi mungkin berada di dalam otot yang terkena dampak secara klinis.

Tubular aggregates may be seen in some patients. Tubular agregat dapat dilihat pada beberapa pasien. Tubular aggregates are seen in type II fibers. Tubular agregat terlihat dalam serat tipe II. They are subsarcolemmal in location. Mereka subsarcolemmal di lokasi. This abnormality is seen only in hypokalemic PP. Kelainan ini terlihat hanya dalam PP hipokalemik. Muscle fiber necrosis is rare. Otot serat nekrosis jarang.

Treatment
Medical Care
Treatment is often necessary for acute attacks of hypokalemic periodic paralysis but seldom for hyperkalemic periodic paralysis. Prophylactic treatment is necessary when the attacks are frequent.

Hypokalemic periodic paralyses o During attacks, oral potassium supplementation is preferable to IV supplementation. The latter is reserved for patients who are nauseated or unable to swallow. Potassium chloride is the preferred agent for an acute attack (assuming a normal renal function).10 A reasonable initial dose for a 60-120 kg man (ie, 0.5-1 mEq/kg) is 60 mEq. Typically, 40-60 mEq of K+ raises the potassium concentration by 1.0-1.5 mEq/L, and 135-160 mEq of K+ raises plasma potassium by 2.5-3.5 mEq/L. Aqueous potassium is favored for quicker results. If there is no response in 30 minutes, an additional 0.3 mEq/kg may be given. This should be repeated up to 100 mEq of potassium. Beyond this, monitoring of serum potassium is warranted prior to further supplementation. Typically, one should not exceed a total dose of 200 mEq in a day. o Intravenous potassium is reserved for cardiac arrhythmia or airway compromise due to ictal dysphagia or accessory respiratory muscle paralysis. IV potassium chloride 0.05-0.1 mEq/kg body weight in 5% mannitol as a bolus is preferable to continuous infusion. Mannitol should be used as solvent, as both sodium and dextrose worsen the attack. Only 10 mEq at a time should be infused with intervals of 20-60 minutes, unless in situations of cardiac arrhythmia or respiratory compromise. This is to avoid hyperkalemia at the end of an attack with shift of potassium from intracellular compartment into the blood. Continuous ECG monitoring and sequential serum potassium measurements are mandatory. o For prophylaxis, acetazolamide is administered at a dose of 125-1500 mg/d in divided doses. Dichlorphenamide 50-150 mg/d has been shown recently to be equally effective. This can be used as a first line of therapy or in patients who became refractory after initial improvement with acetazolamide. Potassiumsparing diuretics like triamterene (25-100 mg/d) and spironolactone (25-100 mg/d) are second-line drugs to be used in patients in whom the weakness worsens, or in those who do not respond to carbonic anhydrase inhibitors. Spironolactone may cause gynecomastia, but this is less with eplerenone. Blood pressure monitoring is advised. Because these diuretics are potassium sparing, potassium supplements may not be necessary.

Thyrotoxic periodic paralysis: Treatment consists of controlling thyrotoxicosis and betablocking agents. Potassium supplementation, propranolol, and spironolactone may be helpful during the attacks as well as for prophylaxis. Propranolol in doses of 20-40 mg twice a day may be sufficient to control recurrent attacks of periodic paralysis. Hyperkalemic periodic paralyses o Fortunately, attacks are usually mild and rarely require treatment. Weakness promptly responds to high-carbohydrate foods. Beta-adrenergic stimulants, such as inhaled salbutamol, also improve the weakness (but are contraindicated in patients with cardiac arrhythmias). o In severe attacks, therapeutic measures that reduce hyperkalemia are utilized. Continuous ECG monitoring is always needed during the treatment. Thiazide diuretics and carbonic anhydrase inhibitors are used as prophylaxis. Thiazide diuretics have few short-term side effects; they are tried as first-line treatment. Occasionally, thiazide diuretics may result in paradoxical hypokalemic weakness, which responds to potassium supplementation. Paramyotonia congenita: Because weakness is uncommon, treatment is aimed at reducing myotonia. While the above-mentioned diuretics can be tried, they are often not effective. Mexiletine has been shown to be helpful but is contraindicated in patients with heart block. Potassium-associated myotonia: Treatment with mexiletine or a thiazide diuretic may reduce the severity of the myotonia. Andersen-Tawil syndrome o A combination of amiodarone and acetazolamide resulted in a long-lasting improvement in one study.11 o Implantation of a cardiac defibrillator has rarely been performed. o Carbonic anhydrase inhibitors are used for preventing periodic paralysis. o Potassium supplementation prevents periodic paralysis and also reduces cardiac arrhythmia, shortening the QT interval. o For the control of cardiac symptoms, -blockers or calcium channel blockers may be used. o Flecainide has been shown to be successful in treating bidirectional ventricular tachycardia, ventricular ectopy, and tachycardia-induced cardiomyopathy.12

Surgical Care
Malignant hyperthermia susceptibility has been noted in HypoPP with calcium channel mutations. It is prudent to monitor all patients with periodic paralysis for this complication.

Diet

Hypokalemic periodic paralyses: Low-carbohydrate and low-sodium diet may decrease the frequency of attacks. Hyperkalemic periodic paralyses: Glucose-containing candy or carbohydrate diet with low potassium may improve the weakness.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Carbonic anhydrase inhibitors

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body, including the eye. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid dehydrated.

Acetazolamide (Diamox) Exact mechanism of action unknown. In hypokalemic PP, may decrease potassium inflow to muscle because of metabolic acidosis. In hyperkalemic PP, kaliopenic effect of CA inhibitors may be beneficial. Recent data suggest carbonic anhydrase inhibitors activate skeletal muscle BK channel (Ca2+ -activated potassium channel).
Adult

Dosing Interactions Contraindications Precautions

125-1000 mg/d PO
Pediatric

Not established

Dosing Interactions Contraindications Precautions

Can decrease therapeutic levels of lithium and alter excretion of drugs (eg, amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine

Dosing Interactions Contraindications Precautions

Documented hypersensitivity; hypersensitivity to sulfonamides or thiazide diuretics; hyponatremia; hypokalemia; hepatic or renal insufficiency; hyperchloremic failure; adrenal gland failure; chronic noncongestive glaucoma

Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

Patients with impaired hepatic function may go into coma; may cause substantial increase in blood glucose in some diabetic patients; caution in pulmonary obstruction and emphysema; may cause drowsiness, paresthesias with increasing doses, aplastic anemia, thrombocytopenia

Dichlorphenamide (Daranide) May improve clinical condition of patients with hypokalemic PP or hyperkalemic PP. Kaliopenic effect of CA inhibitors may be beneficial.
Adult

Dosing Interactions Contraindications Precautions

50-150 mg PO qd
Pediatric

Not established