Nocturnal enuresis is one of the side effects of valproic acid treatment, and generally underdiagnosed by clinicians. Studies reported that a variable incidence of valproic acid–induced nocturnal enuresis is 2.2% to 24% with unclear explanations of the reasons behind valproic acid–induced nocturnal enuresis. A retrospective study was carried out on 260 children (aged 5-12 years) diagnosed with idiopathic epilepsy, treated with valproic acid to evaluate the nocturnal enuresis secondary to valproic acid, and to discuss the characteristics of their sleep architecture. Nocturnal enuresis was reported in 28 (10.7%) patients after a mean exposure time to valproate of 18.78±8.4 days. Nocturnal enuresis was significantly associated with younger age and serum level of valproate (P = .05). The polysomnographic study suggested that the underlying mechanism may be related to impaired sleep efficiency, frequent arousals, prolonged sleep latency, snoring, or increased sleep depth which may impair a child’s ability to awaken to the sense of bladder fullness or contractions.
Clayton-SmithBromley RDeanJ, et al.Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability. Orphanet J Rare Dis. 2019;14(1):180.
2.
TomsonTBattinoDPeruccaE. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honored drug. Lancet Neurol. 2016;15(2):210–218.
3.
GlauserTShinnarSGlossD, et al.Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61.
4.
RomoliMMazzocchettiPD’AlonzoR, et al.Valproic acid and epilepsy: from molecular mechanisms to clinical evidences. Curr Neuropharmacol. 2019;17:926.
5.
AndersonMEgunsolaOCherrillJ, et al.A prospective study of adverse drug reactions to antiepileptic drugs in children. BMJ Open. 2015;5:e008298.
6.
CattaneoCIRessicoFValsesiaR, et al.Sudden valproate-induced hyperammonemia managed with l-carnitine in a medically healthy bipolar patient: essential review of the literature and case report. Medicine (Baltimore). 2017;96(39):e8117.
7.
ArdaECakirogluBThomasDT. Primary nocturnal enuresis: a review. Nephrourol Mon. 2016;8(4):e35809.
8.
AlshahraniASelimMAbbasM. Prevalence of nocturnal enuresis among children in Primary Health Care Centers of Family and Community Medicine, PSMMC, Riyadh City, KSA. J Family Med Prim Care. 2018;7(5):937–941.
9.
HamedAYoussefFHusseinMM. Prevalence of nocturnal enuresis and related risk factors in school-age children in Egypt: an epidemiological study. World J Urol. 2017;35:459–465.
10.
NanauRMNeumanMG. Adverse drug reactions induced by valproic acid. Clin Biochem. 2013;46:1323–1338.
11.
KanemuraHSanoFOhyamaT, et al.The relationship between nocturnal enuresis and sequential changes of NAG/morning urine gravity in epileptic children treated with valproate sodium. J Pediatr Epilepsy. 2015;4:61–66.
12.
YamakWRHmaimessGMakkeY, et al.Valproate-induced enuresis: a prospective study. Dev Med Child Neurol. 2015;57:737–741.
13.
FreitagCMRoblingDSeifenS, et al.Neurophysiology of nocturnal enuresis: evoked potential and prepulse inhibition of the startle reflex. Dev Med Child Neurol. 2006;48:278–284.
14.
TsujiSTakewaROhnumaC, et al.Nocturnal enuresis and poor sleep quality. Pediatr Int. 2018;60(11):1020–1023.
15.
PedersenMJRittigSJennumPJKamperisK. The role of sleep in the pathophysiology of nocturnal enuresis. Sleep Med Rev. 2020;49:101228.
16.
DhondtKVan HerzeeleCRoelsSP, et al.Sleep fragmentation and periodic limb movements in children with monosymptomatic nocturnal enuresis and polyuria. Pediatr Nephrol. 2015;30(7):1157e62.
17.
MaJLiSJiangF, et al.Relationship between sleep patterns, sleep problems, and childhood enuresis. Sleep Med. 2018;50:14–20.
18.
HamedHMAbd Al-AzizAMMotawieAA, et al.Polysomnography and antidiuretic hormone secretion pattern in children with primary nocturnal enuresis. Egypt J Neurol Psychiatry Neurosurg. 2015;52:258–263.
19.
YeungCKDiaoMSreedharB. Cortical arousal in children with severe enuresis. N Engl J Med. 2008;358:2414–2415.
20.
FritzGRockneyRBernetW, et al.Practice parameter for the assessment and treatment of children and adolescents with enuresis. J Am Acad Child Adolesc Psychiatry. 2004;43:1540–550.
21.
American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med. 1996;153:866–878.
22.
BeckSMarcusC. Pediatric polysomnography. Sleep Med Clin. 2009;4:393–406.
23.
WingYKHuiSHPakWM, et al.A controlled study of sleep-related disordered breathing in obese children. Arch Dis Child. 2003;88:1043–1047.
24.
NanauRMNeumanMG. Adverse drug reactions induced by valproic acid. Clin Biochem. 2013;46:1323–1338.
25.
ReddyVNAhmedMKothapalliP. Nocturnal enuresis in an epileptic child due to sodium valproate. Eur J Biomed Pharm Sci. 2018;5(4):750–751.
26.
GosaviDDSumanAJainM. Sodium valproate induced increased frequency of micturition and enuresis. Ind J Pharmacol. 2013;45:7–88.
27.
ChengWLinXLuD. Sodium valproate induced enuresis in a pediatric bipolar patient. Neuropsychiatr Dis Treat. 2013;9:1671–1672.
28.
ElyasiFDarziH. Quetiapine-induced enuresis: two case reports. Iran J Psychiatry Behav Sci. 2017;11(3):e5154.
29.
ChengWLinXLuD. Sodium valproate-induced enuresis in a pediatric bipolar patient. Neuropsychiatr Dis Treat. 2013;9:1671–1672.
GosaviDDSumanAJainM. Sodium valproate induced increased frequency of micturition and enuresis. Ind J Pharmacol. 2013;45:87–88.
32.
BadvRSAbbasiAAshrafiMR, et al.The effect of sodium valproate on urinary frequency and enuresis compared to carbamazepine in children with epilepsy. Iran J Pediatr. 2018;28(6):e66083.
33.
DiBiancoJMMorleyCAl-OmarO. Nocturnal enuresis: a topic review and institution experience. Avicenna J Med. 2014;4(4):77–86.
34.
NettoBastos JMRondonAVde LimaGRM, et al.Brazilian consensus in enuresis—recommendations for clinical practice. Int Braz J Urol. 2019;45(5):889–900.
35.
JoinsonCSullivanSvon GontardAHeronJ. Early childhood psychological factors and risk for bedwetting at school age in a UK cohort. Eur Child Adolesc Psychiatry. 2016;25(5):519–528.
36.
SosterLAAlvesRCFagundesSN, et al.Non-REM sleep instability in children with primary monosymptomatic sleep enuresis. J Clin Sleep Med. 2017;13(10):1163–1170.
37.
BakhtiarKPourniaYEbrahimzadehF, et al.Prevalence of nocturnal enuresis and its associated factors in primary school and preschool children of Khorramabad in 2013. Int J Pediatr. 2014;2014:120686.
38.
BaderGNevéusTKruseSSillénU. Sleep of primary enuretic children and controls. Sleep. 2002;25(5):579–583.
39.
AverousMRobertMBilliardMGuiterJGrassetD. The voiding control during sleep. Practitioner’s Rev. 1991;41:2282–2287.
40.
BahnasyWSEl-HeneedyYAEl-SeidyEA, et al.Primary monosymptomatic nocturnal enuresis: an etiological study. Egypt J Neurol Psychiatry Neurosurg. 2018;54:19.
41.
GuYKwonJELeeG, et al.Sleep problems and daytime sleepiness in children with nocturnal enuresis. Child Kidney Dis. 2016;20(2):50–56.
42.
FinelyWW. An EEG study of the sleep of enuretics at three age levels. Clin Electroencephalogr. 1971;2:35–39.
43.
NorgaardJPHansenJHNielsenJBRittingSDjurhuusJC. Nocturnal studies in enuretics: a polygraphic study of sleep—REG and bladder activity. Scand J Urol Nephrol. 1989;125:73–78.
44.
AlexopoulosEIMalakasiotiGVarlamiV, et al.Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring. Pediatr Res. 2014;76:555–559.
45.
El-MitwalliABediwyASZaherAA, et al.Sleep apnea in children with refractory monosymptomatic nocturnal enuresis. Nat Sci Sleep. 2014;13:37–42.
