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Hyperammonemic Encephalopathy: valproic acid-induced adverse reaction
- E. Gómez, L. Gallardo, R. Fernández, E. Talaya, L. Al Chaal, E. Rybak
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1053-S1054
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Introduction
Hyperammonemic encephalopathy is an unusual but fatal consequence of patients being treated with valproic acid (VPA). The most relevant clinical features in cases of valproic acid-induced hyperammonemia include confusion, lethargy, vomiting, and increased seizure frequency and may progress to stupor, coma, and lead to death in isolated cases. The causes are not fully elucidated, but studies suggest alterations in liver and kidney function with abnormalities in the urea cycle causing increased ammonium levels.
ObjectivesClinical review and treatment approach for VPA-induced hyperammonemia encephalopathy.
MethodsClinical case and literature review.
ResultsA 23 - years - old male, admitted to the psychiatric unit for a psychotic episode in the context of drug use and associated affective symptoms. Treatment with antipsychotic (Risperidone 6mg per day) and mood stabilizer (valproic acid up to 1000/mg per day) was prescribed. After ten days of treatment, the patient started with low level of awareness and abnormal behaviour. Neurological examination showed marked somnolence, dysarthric language, unstable gait and behavioral alterations. In the physical examination the constants are stable with discrete tachycardia. Laboratory tests revealed hyperammonemia (609μg/dL), with normal liver function and serum concentration of total valproic acid was therapeutic (69mg/L). Brain computed tomography (CT) revealed no significant anomalies. Doctors initiated treatment with daily cleansing enema and VPA was suspended immediatly. After forty-eight hours the patient’s mental status gradually improved back to baseline and the ammonium levels were normalized in medical tests.
ConclusionsValproate-induced hyperammonemic encephalopathy is an unusual but serious complication. It is often underdiagnosed, with an unclearly incidence. The consequences of undertreatment can be potentially deadly. Clinical suspicion should be established in all patients with decreased level of consciousness in patients receiving VPA. Hyperammonemia can be asymptomatic in half of the cases and can occur in people with normal therapeutic doses and normal serum valproate levels. The mechanism of VPA-induced hyperammonemic encephalopathy is unclear. At present, it is thought to be primarily due to propionic acid, a metabolite of VPA, which inhibits an enzyme necessary for the elimination of ammonia in the urea cycle. In addition, VPA can raise plasma ammonia levels through interaction with carnitine, leading to increased renal excretion of carnitine. In terms of treatment, the main recommendations agree that discontinuation of valproate is the most effective therapy, followed by administration of lactulose to reduce ammonium levels. Carnitine supplementation may be useful in the following cases: for seizure disorders in children at risk of developing carnitine deficiency, in VPA poisoning and in VPA-induced hepatotoxicity.
Disclosure of InterestNone Declared
A clinical case of anosognosia in a CADASIL disease.
- E. Talaya Navarro, L. Gallardo Borge, E. Gómez Fernández, R. Fernández Díaz, L. Al Chaal Marcos, E. Rybak Koite
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1000-S1001
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- Article
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- You have access Access
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Introduction
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a cerebrovascular disease, tht appears in 1.98/100,000. It´s caused by a mutation of the Notch3 gene and is characterized by accumulation of granular osmiophilic material in the middle layer of the small and median sized cerebral arteries.
Sypmtoms are migraine, recurrent cerebral ischemic episodes, dementia, neuropsychiatric disorders (anosognosia, character disorders, apathy and cognitive impairment). It usually appears between 30-60 years, although there is an important variability. There is no curative treatment, only palliative.
ObjectivesClinical review of anosognosia and its presence in CADASIL disease.
MethodsClinical case and literatura review.
ResultsWe presented the clinical case of a 68-year-old man, who was diagnosed with CADASIL after a stroke 3 years earlier. In his family, his brother was diagnosed also with CADASIL. The patient had previously presented disturbances in impulse control (hyperorality) and important executive failures. He currently presented anosognosia, deficits in verbal memory, spatial perception and executive functions, in addition to behavioral alterations and apathy. Due to these deficits he was prohibited from certain activities (driving, hunting).
The patient was not aware of these deficits and becouse of his “no knowledge of his illness”, he disagreed with these prohibitions, so he showed rage and anger at the impotence of not understanding why certain actions are prohibited.
In the consultation, mnesic errors and in naming objects were also objectified, for which it was recommended to carry out cognitive stimulation on a daily basis. In addition, he presented failures of sphincter incontinence, especially of urine and occasionally also of the anal sphincter. He had previously had episodes of myoclonus or fasciculations.
A genetic study by massive sequencing confirmed the heterozygous presence of the pathogenic variant c.1819C>T p.(Arg607Cys) in the NOTCH3 gene, a CADASIL disease.
ConclusionsThe anosognosia that many patients with CADASIL disease present constitutes a problem because it contributes to the delay in consultation and, therefore, the delay in the adequate diagnostic approach, therapeutic possibilities and family genetic counseling. Due in part to anosognosia, CADASIL is considered an underdiagnosed entity. Due to the lack of awareness and the consequent lack of recognition of the deficit, these people are often seen as stubborn and difficult to deal with by people in their immediate environment.
In addition, there is general difficulty in the rehabilitation process, since patients do not think the neccesity to be treated. This can generate frustration and despair both in their relatives and in the health personnel.
For all these reasons, both in anosognosia and in CADASIL disease, adequate psychological support is needed for both those affected and their families.
Disclosure of InterestNone Declared