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Hyperkalemic Periodic Paralysis

HYPP

Hyperkalemic periodic paralysis is a rare genetic disorder in which mutations of proteins encoding sodium channels cause sudden attacks of muscle weakness and a variable degree of paralysis that start in the first decade of life. The diagnosis can be difficult to make in the absence of a meticulous clinical and laboratory workup, including provocative tests, electromyography, muscle magnetic resonance imaging and genetic studies.


Presentation

Hyperkalemic periodic paralysis is an autosomal dominant genetic disease that stems from mutations in the skeletal muscle sodium voltage-gated channel (specifically the alpha subunit 4, or the SCN4A gene) that leads to disruption of normal ion exchange [1] [2] [3]. Although the condition is considered to be quite rare (affecting approximately 1 in 200,000 individuals), its early recognition is vital in reducing the grave disability that is imposed on the individuals [1]. Signs and symptoms arise during the first decade of life in virtually all patients, and the sudden onset of reversible flaccid muscle weakness (or even paralysis) that last from minutes up to several hours is the hallmark of this condition, although certain studies report that attacks may last for even days [1] [2] [3] [4]. Attacks develop as a result of increased serum potassium levels. Consequently, events that cause an increase in serum potassium - hypothermia, fasting, emotional stress, potassium-rich foods, as well as strenuous exercise, are recognized triggers [1] [3]. Additional signs include focal weakness, areflexia of the affected muscles during the attacks (predominantly the calf and the thighs), and preservation of the sensorium and sphincter control, while myotonia may be seen as well [1]. Moreover, many patients report injuries from falls during the attacks, a finding that can be quite debilitating on a long-term basis [5]. Attacks seem to be most frequently reported during the morning, before breakfast, and their appearance peaks during adolescence, after which they gradually subside in adulthood, but persist throughout life [3] [4] [5]. Patients are asymptomatic between the attacks, whereas a minority of individuals suffers from progressive weakness [4].

Masseter Spasm
  • During surgery, avoid use of depolarizing anesthetic agents including suxamethonium and anticholinesterases that increase myotonia, which can result in masseter spasm and stiffness of respiratory and other skeletal muscles, and interfere with intubation[hkpp.org]
  • Prevention of secondary complications: During surgery, avoid use of depolarizing anesthetic agents (including potassium, suxamethonium, and anticholinesterases) that aggravate myotonia and can result in masseter spasm and stiffness of respiratory and[ncbi.nlm.nih.gov]
Tachycardia
  • Increased Q-T interval (Early) Premature ventricular contractions Polymorphic ventricular tachycardia Heart block Long QT syndrome 7 Other EKG U waves: Prominent Semilunar valve abnormalities Treatment Amiodarone Poor response to classical therapy Cardiac[neuromuscular.wustl.edu]
  • Hyperkalemia can cause cardiac arrhythmia, usually tachycardia, and typical ECG abnormalities (i.e., T-wave elevation, disappearance of P waves). Rest after exercise provokes weakness as in hyperPP.[ncbi.nlm.nih.gov]
  • Patients with hyperkalemia may experience a variety of dysrthymias including complete heart block, Mobitz type II second-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation and asystole, muscle cramps, weakness, paralysis,[jpharmacol.com]
Muscle Weakness
  • But repeated attacks may lead to permanent muscle weakness. HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness.[nlm.nih.gov]
  • All three had prominent fixed muscle weakness, while the remaining four did not.[ncbi.nlm.nih.gov]
  • Hyperkalemic periodic paralysis causes episodes of extreme muscle weakness, with attacks often beginning in childhood.[en.wikipedia.org]
  • Paroxysmal muscle weakness: the familial periodic paralyses. J Neurol. 2006 Nov;253(11):1391-8. Epub 2006 Nov 30. Review.[ghr.nlm.nih.gov]
Myopathy
  • We studied four families with the latter disease in which some members developed a progressive myopathy.[ncbi.nlm.nih.gov]
  • Although the concurrence of these findings may be coincidental, these features may evade recognition in other patients by being misattributed to chronic myopathy or depression.[ncbi.nlm.nih.gov]
  • Approximately one-third of individuals experienced progressive myopathy. Permanent muscle weakness was evident and worsened during childhood and after age 40.[ncbi.nlm.nih.gov]
  • The myopathy mainly affects the pelvic girdle and proximal and distal lower-limb muscles.[ncbi.nlm.nih.gov]
Onset at Age <20
Flaccid Paralysis
  • These procedures produced attacks of flaccid paralysis that occurred concomitantly with rapid rises in serum potassium concentrations and decreases in blood glucose and inorganic phosphate levels.[ncbi.nlm.nih.gov]
  • HyperPP is a rare genetic disorder that causes episodes of flaccid paralysis. Disease descriptions in the literature are based upon isolated clinical encounters and case reports.[ncbi.nlm.nih.gov]
  • paralysis or myotonia; these conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle; frequently associated with fluctuations in serum potassium levels; periodic paralysis may also occur as[icd9data.com]
  • Clinical Signs Hyperkalemic Periodic Paralysis is a genetically determined disorder which causes attacks of weakness and flaccid paralysis. Attacks last from 10 min to 1 hour, very rarely up to 1-2 days.[hkpp.org]
  • These disorders are characterized by episodic loss of muscle tone ranging from mild weakness to profound global flaccid paralysis, progressive permanent muscle deterioration, severe muscle stiffness and various degrees of myotonia, twitching or other[rarediseases.org]
Paresthesia
  • In some individuals, paresthesias, probably induced by the hyperkalemia, herald the weakness. During an attack of weakness, the muscle stretch reflexes are abnormally diminished or absent.[ncbi.nlm.nih.gov]
  • Patients with hyperkalemia may experience a variety of dysrthymias including complete heart block, Mobitz type II second-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation and asystole, muscle cramps, weakness, paralysis, paresthesias[jpharmacol.com]
Clumsiness
  • After an attack, affected individuals report clumsiness, weakness, and irritability, and in 62% muscle pain secondary to the attack. Between attacks, the majority report no or mild symptoms.[ncbi.nlm.nih.gov]

Workup

The diagnosis of hyperkalemic periodic paralysis may not be easy to make, but its life-long disability and marked impairment of the quality of life mandate early recognition of the disorder. Furthermore, studies have confirmed that the diagnosis is made approximately 26 years after symptoms have appeared, emphasizing the pivotal role of clinical suspicion toward hyperkalemic periodic paralysis [5]. For this reason, the importance of a detailed patient history and a proper physical examination is perhaps of paramount importance [1]. The age of onset, appearance, and course of symptoms should be noted, while information regarding recent complaints within the close family (parents, grandparents, siblings) must be evaluated as well during the interview [1]. On the other hand, a meticulous neurological and muscle examination, especially during the attacks, can provide key findings in order to pursue the diagnosis of hyperkalemic periodic paralysis. Several diagnostic tests are used to solidify the diagnosis, including electromyography (EMG) that will show signs of myotonia in 50% of cases, provocative testing in the form of potassium challenge test, muscle biopsy and muscle magnetic resonance imaging (MRI) [1] [2] [3]. Genetic testing for SCN4A mutations, although positive in only 60% of cases with evident clinical criteria, is a definite tool to confirm hyperkalemic periodic paralysis [1] [3].

Electromyogram Abnormal
  • Electrocardiogram and electromyogram abnormalities are also visible. In some cases, the anomalies result in cardiac arrhythmias. For the moment there is no effective treatment in 100% of cases.[testprenataleaurora.it]
Peaking T Wave
  • EKG change sequence: tall peaked T waves, diminished R waves amplitude, increased QRS or PR intervals and P wave disappearance. Slow infusion (over 5 min) of 10% calcium gluconate (reduces cardiac sensitivity to hyperkalemia).[hkpp.org]

Treatment

  • He rapidly recovered from weakness after acetazolamide treatment. Magnetic resonance imaging of thighs comparing pre- and post-treatment revealed a significant increase in muscle bulk.[ncbi.nlm.nih.gov]
  • None of the available treatments is fully effective.[ncbi.nlm.nih.gov]
  • HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness.[nlm.nih.gov]
  • Five patients underwent follow-up MR after diuretic treatment.[ncbi.nlm.nih.gov]

Prognosis

  • Outlook (Prognosis) Sometimes, attacks disappear later in life on their own. But repeated attacks may lead to permanent muscle weakness. HyperPP responds well to treatment. Treatment may prevent, and may even reverse, progressive muscle weakness.[leehealth.org]
  • Outlook (Prognosis) Sometimes, attacks disappear later in life on their own. But repeated attacks may lead to permanent muscle weakness. Hyperkalemic periodic paralysis responds well to treatment.[coordinatedhealth.com]
  • Family history Timing Intensity History of administration of certain drugs Clinical examination Differential Diagnosis Laboratory investigations Serum K CPK and serum myoglobin ECG EMG Nerve conduction studies Provocative Testing Muscle biopsy Treatment Prognosis[slideshare.net]
  • Severe prognosis in a large family with hypokalemic periodic paralysis. Muscle Nerve. 2003;27:165–9. 13. Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia. Muscle Nerve. 2004;30:114–7.[revistas.fucsalud.edu.co]
  • With treatment now available to help patients manage their attacks, getting a diagnosis can greatly improve a their long term prognosis and quality of life.[raredr.com]

Etiology

  • To investigate the role of this gene in the etiology of PC, a linkage analysis in 17 well-defined families was carried out.[ncbi.nlm.nih.gov]
  • Hyperkalemic Periodic Paralysis Etiology : mutations in sodium channel NaV1.4 Precipitated By : hyperkalemia, potassium-rich meal, rest after exercise, stressful situations, possibly hypoglycemia Anesthesia Management : avoid cholinesterase inhibitors[openanesthesia.org]
  • Familial periodic paralysis is a disease of unknown etiology characterized by recurrent acute attacks of weakness associated with a fall in serum potassium levels.[jamanetwork.com]
  • […] taking ibuprofen. [15] Periodic paralysis is a condition which is manifested by episodes of short lived, hyporeflexic skeletal muscle weakness with or without myotonia and without any sensory deficit or loss of consciousness. [16] There are number of etiological[jpharmacol.com]

Epidemiology

  • (including hypokalemic periodic paralysis and thyrotoxic periodic paralysis, and other “Channelopathies” or “Membranopathies) Pathophysiology Epidemiology Primary or familial periodic paralysis Secondary periodic paralysis Conventional classification[slideshare.net]
  • Home, Search, Index, Links, Pathology, Molecules, Syndromes, Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info EPISODIC MUSCLE WEAKNESS Hypokalemic Periodic Paralysis Hypokalemic periodic paralysis, Hereditary: General features Epidemiology[neuromuscular.wustl.edu]
Sex distribution
Age distribution

Pathophysiology

  • The pathophysiological mechanism is still unknown. Pathophysiological studies suggest that in this disorder the kidney lacks sensitivity to atrial natriuretic peptide.[ncbi.nlm.nih.gov]
  • Acta Paediatr Stockholm (Suppl) 108:1–126 Google Scholar Lehmann-Horn F, Iaizzo PA (1990) Resealed fiber segments for the study of the pathophysiology of human skeletal muscle.[link.springer.com]
  • Br J Anaesth 1980; 52: 153–64Ellis, FR Miller J, Katz RL: Muscle diseases, Anesthesia and Uncommon Disease: Pathophysiologic and Clinical Correlations, 2nd edition. Edited by Katz J, Benumof J, Kadis LB.[anesthesiology.pubs.asahq.org]
  • (including hypokalemic periodic paralysis and thyrotoxic periodic paralysis, and other “Channelopathies” or “Membranopathies) Pathophysiology Epidemiology Primary or familial periodic paralysis Secondary periodic paralysis Conventional classification[slideshare.net]
  • Adrien Moreau, Pascal Gosselin-Badaroudine and Mohamed Chahine, Biophysics, pathophysiology, and pharmacology of ion channel gating pores, Frontiers in Pharmacology, 5, (2014).[doi.org]

Prevention

  • Treatment may prevent, and may even reverse, progressive muscle weakness.[nlm.nih.gov]
  • To prevent the muscle from being perpetually contracted, the channel contains a fast inactivation gate that plugs the sodium pore very quickly after it opens. This prevents further entry of sodium.[en.wikipedia.org]
  • In a patient with hyperkalemic periodic paralysis, metaproterenol prevented muscular weakness and hyperkalemia in periods of rest after exercise.[ncbi.nlm.nih.gov]
  • Prevention The medicines acetazolamide and thiazides prevent attacks in many cases. A low potassium, high carbohydrate diet, and light exercise may help prevent attacks. Avoiding fasting, strenuous activity, or cold temperatures also may help.[leehealth.org]

References

Article

  1. Charles G, Zheng C, Lehmann-Horn F, Jurkat-Rott K, Levitt J. Characterization of hyperkalemic periodic paralysis: a survey of genetically diagnosed individuals. J Neurol. 2013;260(10):2606-2613.
  2. Han J-Y, Kim J-B. Familial hyperkalemic periodic paralysis caused by a de novo mutation in the sodium channel gene SCN4A. Korean J Pediatr. 2011;54(11):470-472.
  3. Patangi SO, Garner M, Powell H. Management of a patient with hyperkalemic periodic paralysis requiring coronary artery bypass grafts. Ann Card Anaesth. 2012;15(4):302-304.
  4. Lee YH, Lee H-S, Lee HE, et al. Whole-Body Muscle MRI in Patients with Hyperkalemic Periodic Paralysis Carrying the SCN4A Mutation T704M: Evidence for Chronic Progressive Myopathy with Selective Muscle Involvement. J Clin Neurol. 2015;11(4):331-338.
  5. Cavel-Greant D, Lehmann-Horn F, Jurkat-Rott K. The impact of permanent muscle weakness on quality of life in periodic paralysis: a survey of 66 patients. Acta Myol. 2012;31(2):126-133.

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Last updated: 2019-07-11 20:07