Sleep Architecture in Valproate-induced Nocturnal Enuresis in Primary School and Preschool Children.

More than 50 years ago, valproic acid has become established as an effective broad-spectrum antiepileptic drug. It is a drug of choice in children and adult with generalized or focal types of epilepsy, and in generalized convulsive status epilepticus. It is used in migraine prophylaxis, and as a modulator of chemotherapy in cancer treatment. Moreover, valproic acid may have a potential role in neuroprotection in stroke patients and head trauma.

NE is one of the side effects of VPA treatment, and it is generally underdiagnosed or overlooked by clinicians. A comprehensive review study, about the effects of valproic acid, did not mention that nocturnal enuresis as an adverse event of the valproate however; more recent study reported variable incidence of VPA-induced NE is 2.2-24%.

The investigator's study, retrospectively evaluate the characteristics of and the risk factors for the occurrence of nocturnal enuresis in epileptic children kept on valproate monotherapy.

Method Participants The study was conducted on 260 children with epilepsy receiving valproate monotherapy aged 5-15 years who attended the outpatient clinic of neurology departments, Mansoura University Hospital, Egypt during the period Sep 2019 to Aug 2019.

Clinical, EEG and laboratory assessment at presentation

• The patients' history, clinical, demographic, and laboratory data were acquired.
• The following tests and imaging studies are routinely done for epilepsy patients receiving valproate treatment and developed nocturnal enuresis, blood urea nitrogen (BUN), serum creatinine (Cr), urinary pH (before and after valproate therapy beginning and at enuresis onset), serum levels and therapeutic doses of valproate.
• Urinary tract ultrasonography (with full and void bladder).
• CT brain and EEG.
• Patients were therefore assessed month to month for a follow up over a time of 6 sequential months, with extra visits as required dependent on seizure recurrence or side effects.

Follow-up at least monthly interval for 6 month for the children kept on valproate monotherapy. Evaluation of seizure control and the reported side effects associated with valproate by the parents were determined. In this way special consideration and directly asking parents about the incidence of NE and its recurrence (daily and monthly) is mandatory.

The time from the initiation of valproate monotherapy to the beginning of NE, the daily dose and the duration of treatment of valproic acid (mg/kg) at the onset of enuresis and the serum level of valproate were reported. Also, the time of cessation of NE either spontaneous or following discontinuation of valproate was determined.

Statistical analysis

A multivariate logistic regression analysis was carried out for the following independent variables: age, weight, body weight, duration of treatment and daily dose of valproate, and serum level valproate. P-value <0.05 were considered of statistically significant results.

Inclusion criteria

• Epileptic children kept up on valproate monotherapy and developed nocturnal enuresis.
• Age ranged 5 up to 15 years.

Exclusion criteria

• Combined therapy with other antiepileptic drugs,
• Abnormal cerebral imaging,
• Poor seizure control,
• Primary nocturnal enuresis (a child didn't accomplish any times of evening dryness -over a time of 6 successive months).
• Congenital or acquired defects of the nervous system.
• Urinary system anomalies, or
• Intellectual disability.