Decoding the enigma: Valproate encephalopathy in a bipolar affective disorder without hyperammonemia

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Bárbara Castro Sousa
 

Cova da Beira Hospital Centre, Covilha, Portugal

: Int J Ment Health Psychiatry

Abstract

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Statement of the problem: While valproic acid (VA) is widely used to treat seizures, bipolar disorder and migraines, its side effects, including rare occurrences of hyperammonaemic parkinsonism, are well documented. These adverse effects are more prevalent in polytherapy regimens, young patients and those with urea cycle defects. Clinicians must be alert to the temporal association between VA initiation and symptom onset, as well as for idiosyncratic reactions such as nonhyperammonaemic encephalopathy, which may present without typical biochemical abnormalities. Management involves prompt discontinuation of VA and consideration of alternative treatments. Individualized approaches, such as adjusting the dosage or switching medications, may be necessary to ensure patient stability and well-being. Methodology & theoretical orientation: The authors report the case of a woman with bipolar affective disorder who developed ataxia and cognitive impairment after switching from mood-stabilizing therapy lithium to VA, highlighting the importance of careful monitoring of adverse effects in VA therapies, especially in polytherapy regimens and vulnerable populations. The analysis was based on a review of the patient's clinical history, including the evaluation of symptoms before and after the medication switch. Clinical data were collected to establish a temporal correlation between the initiation of VA administration and the onset of symptoms. The literature on the adverse effects of VA was reviewed to contextualize the findings of the reported case. This theoretical framework integrates pharmacological principles, neurotransmitter system dynamics, the pathophysiology of drug-induced conditions and clinical management strategies. This comprehensive approach provides a solid foundation for understanding the patient's clinical course and optimizing treatment outcomes in complex cases involving multiple psychotropic medications. Findings/Results: This clinical case highlights the existence of valproate-induced encephalopathy with nontoxic valproate serum, most likely due to drug interactions. Despite the many clinical features of parkinsonism, including hypomimia, bradykinesia and resting tremor, the marked ataxia and rapidly evolving cognitive impairment made the authors suspicious of an alternative diagnosis. Conclusion: Our clinical case demonstrates a rare and intriguing case of valproate encephalopathy in a patient with bipolar affective disorder without the presence of hyperammonemia. This case offers a unique perspective on the clinical manifestations, underlying mechanisms and treatment challenges associated with valproate-induced encephalopathy, particularly when hyperammonemia, a commonly associated feature, is absent. This manuscript presents a comprehensive description of the patient's clinical presentation, neuroimaging findings, laboratory results and diagnostic dilemmas encountered during treatment. We believe that our findings will be of great interest to the medical community because they shed light on a less understood aspect of valproate-induced encephalopathy, potentially helping clinicians make more informed decisions in managing similar cases in the future.

Biography

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Bárbara Castro Sousa, a Portuguese graduate in Medicine, is currently completing her psychiatry internship, with a special focus on Perinatal psychiatry. Passionate about reading and academic research, she constantly seeks new knowledge. Her commitment and dedication shine both in clinical practice and scientific contributions.