Clinical analysis of valproate-induced hyperammonemic encephalopathy in children

Objective To explore the clinical characteristics of valproic acid-induced hyperammone-mic encephalopathy (VHE) in children. Methods The digital administration system of medical record in the First Hospital of Shanxi Medical University was searched. The clinical data of children who with VHE, age <16 years and hospitalized from July 2006 to July 2015 were collected and analyzed retrospectively. The main indicators of analysis included children′ clinical manifestations, treatments, blood concentration of valproate (VPA) and level of blood ammonia before and after treatment, results of electrocardiogram (ECG), video electroencephalogram (EEG), cranial computed tomography and clinical outcome. Results A total of 12 children were enrolled in the analysis comprising 7 boys and 5 girls with age from 10 to 15 years. The number of children with primary diseases of epilepsy, bipolar affective disorder, glioma and viral encephalitis were 5, 4, 2 and 1, respectively. The doses of VPA was 22-28 mg/kg for all cases. Seven cases were treated with VPA first time. Four cases were treated with VPA only. Eight cases received combined medications with other anti-epileptic drugs. There were 4 and 2 cases who were misdiagnosed as cerebral hemorrhage and brain edema, respectively. The 12 patients developed disorder of consciousness, drowsiness, and 7 cases developed to coma. Six cases had digestive symptoms which including nausea and vomiting before the appearance of nervous system symptoms.In addition, the number of cases with asterixis, irritability and agitation, ataxia, and frequent seizures were 4, 3, 2, and 1, respectively. The results of laboratory tests showed the children′ blood ammonia level were increased to 85-219 μmol/L, the average level was (143±47)μmol/L. Seven cases′ VPA blood concentration was 102-125 mg/L, which was the upper limit reference. The results of 12 patients′ vedio-EEG were diffused inactive echoes which mainly δ and θ wave. After the appearance of symptom of VHE, seven cases were stopped VPA, five cases halved the dosage of VPA. All the patients received symptomatic treatments (reducing blood ammonia and intracranial decompression). On day 1 to 5 of treatments, all the patients′ symptoms were relieved, the blood ammonia levels were descended to 22-66 μmol/L. On day 7 of treatment, their VPA blood concentration were 30-63 mg/L, the rhythms of vedio-EEG recovered to α wave. Conclusions Child′s VHE is easy to be misdiagnosed. The main clinical characteristics of child with VEH include mental confusion, drowsiness, coma, ataxia, asterixis, and frequent seizures. Some children appear digestive symptoms before the appearance of nervous symptoms. The serum ammonia level in children with VHE may not increase remarkably. The patient′s outcome is better after drug withdrawal, half the dose, and symptomatic treatments. Key words: Valproic acid; Child; Hyperammonemic encephalopathy