Valproate-Associated Hyperammonemic Encephalopathy: Clinical Correlates and Management Strategies in a Tertiary Care Center.

BACKGROUND: Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center. METHODS: In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done. RESULTS: The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated. CONCLUSIONS: This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management.

Valproate-associated hair abnormalities: Pathophysiology and management strategies.

OBJECTIVE: To review the literature on valproate-associated hair abnormalities and the available treatment options. METHODS: We searched PubMed and Google Scholar with keywords including "valproate", "valproic acid", "hair", "alopecia", and "effluvium," supplemented with hand search from cross-references. We included all types of studies including case reports in this review. RESULTS: The pathophysiology of hair loss includes telogen effluvium, biotin, mineral deficiency, and possibly hyperandrogenism. Diagnosis is based on history of hair loss or abnormalities following valproate treatment, and is confirmed by use of simple clinical tests such as pull test and modified wash test. Treatment involves reassurance and advice on hair care, and if possible drug discontinuation or dose reduction. Medications such as biotin and other vitamins with minerals supplementation is effective for most individuals with hair loss. Other treatment options are agomelatine, topical valproate or minoxidil, though these lack evidence. CONCLUSION: Hair abnormalities with valproate are common, benign adverse effects, and management includes general measures and specific treatment options.

High-dose thiamine strategy in Wernicke-Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder.

Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke-Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava-Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.