|Year : 2020 | Volume
| Issue : 2 | Page : 132-134
Primary hypokalemic periodic paralysis: Long-term management and complications in a child
Indar K Sharawat1, Renu Suthar2, Naveen Sankhyan2, Pratibha Singhi3
1 Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India
2 Pediatric Neurology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Pediatric Neurology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India; Pediatric Neurology and Neurodevelopment, Department of Pediatrics, Medanta, The medicity, Gurugram, Haryana, India
|Date of Submission||17-Aug-2019|
|Date of Decision||04-Sep-2019|
|Date of Acceptance||27-Mar-2020|
|Date of Web Publication||30-Jun-2020|
Dr. Renu Suthar
Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Hypokalemic periodic paralysis (HPP) is a rare genetically determined neuromuscular disorder caused by mutation in skeletal muscles calcium and sodium channels. It presents with recurrent episodes of flaccid paralysis. A 9-year-old girl presented with recurrent episodic flaccid quadriparesis with complete recovery in-between the episodes. Investigations during the acute episode revealed marked hypokalemia with electrocardiogram changes. Next-generation sequencing showed pathogenic missense mutation in CACNA1S gene. She responded well to oral potassium supplementation, acetazolamide, and spironolactone therapy. Muscle weakness in HPP is reversible, and long-term management reduces frequency of paralysis and prevents permanent weakness.
Keywords: CACNA1S, muscle channelopathy, neuromuscular, periodic paralysis, recurrent weakness
|How to cite this article:|
Sharawat IK, Suthar R, Sankhyan N, Singhi P. Primary hypokalemic periodic paralysis: Long-term management and complications in a child. J Pediatr Neurosci 2020;15:132-4
| Introduction|| |
Hypokalemic periodic paralysis (HPP) is a rare neuromuscular disorder characterized by episodic muscle weakness and occasionally life-threatening arrhythmia. The recurrent paralytic episodes are characterized by concomitant hypokalemia (serum potassium <3.5 mmol/L) leading to depolarization-induced loss of excitability. Heavy exercise, carbohydrate-rich evening meals, pregnancy, and menstruation are important triggers. Disease progression and recurrent episodes may result in permanent disability. Here, we report a case of HPP with recurrent episodes of flaccid weakness and long-term management issues.
| Case Report|| |
A 9-year-old girl presented with acute onset neck pain followed by weakness of all limbs for 24h duration. She had a cheese burger with mayonnaise sauce at dinner and slept well. In the morning she reported inability to move limbs, sit, and turn in the bed with neck pain. She had history of three similar episodes in the past from 7.5 years of age. Each episode usually lasted for 24–36 h, and resolve spontaneously without any residual weakness. Most of these episodes were noted early in the morning and relation to food was not noticed by the parents. There was no history of limb pain, stiffness, or cramps in-between the episodes. There was no history of respiratory difficulty, bowel and bladder involvement, recurrent diarrhea, excessive urination, poor weight gain, or any prolonged drug intake. She was born to non-consanguineous parents, and her family history was unremarkable.
On examination, she had normal higher mental functions, was hypotonic, and quadriparetic with hyporeflexia. Respiratory and diaphragmatic functions were normal. During the acute event, she had hypokalemia (1.6 mEq/L, normal: 3.5–5.5 mEq/L) with electrocardiogram (ECG) changes. Other electrolytes, hemogram, liver function, renal function tests, and pH were normal. Her creatine kinase level was elevated (11298U/L, normal: 34–171 U/L). She was treated with intravenous potassium chloride infusion with ECG monitoring and her weakness improved.
Secondary causes of HPP were ruled out. Sanger sequencing of CACN1AS and SCN4A revealed a pathogenic heterozygous missense mutation (R1239H) in exon 30 of CACNA1S gene, confirming the diagnosis of HPP.
For recurrent similar episodes, she was advised to avoid the triggers, and adherence to low-sodium, carbohydrate, and potassium-rich diet. She continued to have similar episodes of weakness, and hence maintenance therapy with oral potassium citrate (4 mEq/kg/day) given. Compliance remained an issue with oral potassium powder; she was initiated on oral acetazolamide (8 mg/kg/day). Tolerance to acetazolamide remained poor, with frequent gastritis and gastroenteritis. Spironolactone (75 mg/day) was initiated. She remained compliant to therapy with good response and frequencies of episodes were reduced markedly. She had occasional recurrence during adolescence, with heavy meals. However, she developed androgenic adverse effects leading to reduced compliance to spironolactone. She is maintained on oral acetazolamide now with oral potassium. Currently she is 18 year old, with relatively stable course and no permanent weakness.
| Discussion|| |
The primary or familial HPP is autosomal dominant skeletal muscle channelopathies with decreased penetrance in females and it is caused by mutation in α subunit of skeletal muscle L-type calcium channel gene CACNA1S or the voltage-gated sodium channel gene SCN4A. Episodic weakness occurs based on the concentration of extracellular potassium ions, which are responsible for membrane excitability. The final pathway is aberrant depolarization that inactivates ion channels leading to muscle fiber inexcitability.
The diagnosis of HPP can be made by diagnostics criteria proposed by Sansone et al. [Table 1]. Thyrotoxic periodic paralysis is indistinguishable from HPP and assessment of thyroid profile is mandatory. During an acute attack, patients have hypokalemia (<3.5 mEq/L) with or without ECG changes, elevated creatine kinase, reduced, or rarely absent compound motor action potential on nerve conduction studies. Needle electromyography usually shows reduced insertional activity, polyphasic motor unit potentials, positive sharp waves, and fibrillation potentials. Serum potassium concentration is normal in-between the attacks. During an acute episode, T2-weighted fat saturation magnetic resonance sequences show muscle edema, which is more common in calf muscles as compared to upper limb muscles.
|Table 1: Consensus diagnostic criteria of hypokalemic periodic paralysis|
Click here to view
Treatment strategy starts from patient education and lifestyle changes to decrease the triggers and minimizing attack frequency and severity. Small frequent meals (to avoid high carbohydrate load), low-sodium diet, and avoidance of hyperosmolar (dehydration, hyperglycemia) states decrease the number of attacks. If the potassium level during an acute episode is unknown, mild exercise at the onset can shorten the severity and duration of an acute episode.
Pharmacological therapy is used to abort an acute attack and for preventive measure. For an acute attack, oral potassium (20–30 mEq/L, every 15–20min) is sufficient. Carbonic anhydrase inhibitors (CAIs) particularly acetazolamide (5–10 mg/kg/day) and dichlorphenamide (50–200 mg/day) are used for preventive therapy. CAI stimulates urinary bicarbonate excretion, promotes systemic acidosis, enhances opening of calcium sensitive potassium channels, and reduces intracellular sodium concentration. This decreases the muscle fibers damage and reduces the frequency and duration of further attacks., Acetazolamide and other CAI are more effective in patients with CACNA1S as compared with SCN4A mutation., Dichlorphenamide may be used in those patients who do not respond to acetazolamide. Common adverse reactions associated with CAI are dysguesia, paresthesia, easy fatigability, muscle cramps, renal stones, and reversible mild cognitive disturbance.
Chronic potassium supplementation and potassium sparing diuretics (spironolactone [25–100 mg/day], triamterene [50–150 mg/day], and eplerenone [50–100 mg/day]) are other treatment options in HPP. Spironolactone and other potassium sparing diuretics are alternative to CAI in patients who have partial response or develop intolerable side effects. Our patient responded well with spironolactone and was symptom free for 3 years; however, she developed androgenic side effects during adolescence that leads to discontinuation of drug. The common side effects of spironolactone are hyperkalemia, gynecomastia, hirsutism, acne, hyponatremia, and renal failure.
Long-term outcome of the patients with HPP is good; however, these patients are sensitive to general anesthesia and may develop muscle paralysis and respiratory weakness. Proximal myopathy, malignant hyperthermia, and life-threatening cardiac arrhythmias are other potential complications.
| Conclusion|| |
There are no consensus statements for the treatment and acetazolamide has been the therapy of choice since five decades. Spironolactone is an important alternative of CAIs; however, androgenic side effects limit its use.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Stunnenberg BC, Raaphorst J, Deenen JCW, Links TP, Wilde AA, Verbove DJ, et al
. Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands. Neuromuscul Disord 2018;28:402-7.
Maurya PK, Kalita J, Misra UK. Spectrum of hypokalaemic periodic paralysis in a tertiary care centre in India. Postgrad Med J 2010;86:692-5.
Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ, et al
; CINCH investigators. The primary periodic paralyses: diagnosis, pathogenesis and treatment. Brain 2006;129:8-17.
Jurkat-Rott K, Lehmann-Horn F. Paroxysmal muscle weakness: the familial periodic paralyses. J Neurol 2006;253:1391-8.
Sansone V, Meola G, Links TP, Panzeri M, Rose MR. Treatment for periodic paralysis. Cochrane Database Syst Rev 2008; 23:CD005045.
Jia BX, Yang Q, Li SY, Wan M, Wang H, Huo LY, et al
. Muscle edema of the lower limb determined by MRI in Asian hypokalaemic periodic paralysis patients. Neurol Res 2015;37:246-52.
Lehmann-Horn F, Jurkat-Rott K, Rüdel R; Ulm Muscle Centre. Diagnostics and therapy of muscle channelopathies––guidelines of the Ulm Muscle Centre. Acta Myol 2008;27:98-113.
Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, et al
. Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve 2018;57:522-30.
Matthews E, Portaro S, Ke Q, Sud R, Haworth A, Davis MB, et al
. Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype. Neurology 2011;77:1960-4.
Goland S, Naugolny V, Korbut Z, Rozen I, Caspi A, Malnick S. Appropriateness and complications of the use of spironolactone in patients treated in a heart failure clinic. Eur J Intern Med 2011;22:424-7.
|This article has been cited by|
||The Neurological Spectrum for Acetazolamide Pharmacotherapy: from Basic Science to Clinical Applications
| ||Nevio Cimolai |
| ||SN Comprehensive Clinical Medicine. 2021; |
|[Pubmed] | [DOI]|