Challenges of Valproate Treatment During Pregnancy: Pros and Cons

Arbune, Anca-Adriana; Craiu, Dana; Cuciureanu, Iulian Dan; Constantin, Iulian; Pavel, Liliana Lacramioara; Berbece, Sorin; Grigore, Camelia Ana; Dulamea, Adriana Octaviana

doi:10.37358/rc.20.2.7949

Cited by 2 publications

(3 citation statements)

References 18 publications

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“…Hyperammonaemia induced by VPA may be an important clinical consideration, especially when associated with liver disease or encephalopathy. The reported frequency of hyperammonaemia induced by VPA ranges from 16.2% to 83.3% [2,9,22,23,25]. Hyperammonaemia has been frequently reported in valproic acid ingestion and was found in 9 of the 10 patients in this series who had ammonia concentrations measured [24].…”

Section: Figure 1 the Variation Of Valproic Acid Serum Levelsmentioning

confidence: 64%

Study Regarding the Determination of Valproic Acid Serum Levels by Emit

Tudosie¹

2020

FARMACIA

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Valproic acid (n-dipropylacetic acid) is a unique anticonvulsant due to its structure, used in treating anxiety, alcoholism and mood disorders. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. It is metabolized at hepatic level into several metabolites of which two in larger quantities, namely 2-en-VPA (2-propyl-2-pentenoic acid) and 3-keto VPA (2-propyl-3-keto-pentanoic acid) which form as a result of a beta hepatic microsomal oxidation. These two metabolites can be identified in urine in proportion of 70%. In case of an overdose or of longterm treatment, high serum levels of hepatic enzymes and hyperammonaemia may appear. A less frequent side effect is acute pancreatitis, with high serum amylase. The plasma concentration of VPA higher than 100 mg/L is concerning and a concentration higher than 450 mg/L is associated with a moderate or severe prognostic, although there is no tight correlation between plasma levels of VPA and the severity of clinical signs. Immunochemical methods use a specific antibody for the tested molecule and a marked form of the same compounds. There are two main ways to quantify the reaction: homogenous phase method and heterogeneous phase method. The homogenous methods, faster and completely automized are: EMIT (Enzyme Multiplied Immunoassay Technique) and FPIA (Fluorescence Polarization Immunoassay Technique). In the EMIT method, the marking is made through an enzyme by binding the antibody to the labelled enzyme molecule and this method can be applied confidently to determine the serum levels of valproic acid. Also, it is useful both in monitoring valproic acid treatment and, especially, in establishing a certain diagnosis in acute mono or multidrug acute intoxications. Rezumat Acidul valproic (acid n-dipropilacetic) este un anticonvulsivant unic datorită structurii sale, utilizat în tratarea anxietății, alcoolismului și tulburărilor de dispoziție. La doze terapeutice, timpul de înjumătățire al acidului valproic variază de la 10 la 20 de ore la adulți, în timp ce la copii este semnificativ mai scurt (6 până la 9 ore). Este metabolizat la nivel hepatic în mai mulți metaboliți dintre care doi în cantități mai mari, și anume 2-en-VPA (acid 2-propil-2-pentenoic) și 3-ceto VPA (acid 2-propil-3ceto-pentanoic) care se formează ca urmare a unei beta-oxidări microzomale hepatice. Acești doi metaboliți pot fi identificați în urină în proporție de 70%. În caz de supradozaj sau de tratament de lungă durată, pot apărea niveluri serice ridicate ale enzimelor hepatice și hiperamoniemie. Un efect secundar mai puțin frecvent este pancreatita acută, cu amilază serică ridicată. Concentrația plasmatică a VPA mai mare de 100 mg/L este potențial toxică, iar o concentrație mai mare de 450 mg/L este asociată cu un prognostic moderat sau sever, deși nu există o corelație strânsă între nivelurile plasmatice ale VPA și severitatea semnelor clinice. Metodele imunochimice folosesc un anticorp specific pentru molecula te...

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Section: Figure 1 the Variation Of Valproic Acid Serum Levelsmentioning

confidence: 64%

Study Regarding the Determination of Valproic Acid Serum Levels by Emit

Tudosie¹

2020

FARMACIA

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“…Periodical neurological consults in the long run were recommended, especially in the event of a pregnancy, considering a higher risk of recurrent bleeding, as well as a possible increase in seizure frequency, secondary to hemodynamic and hormonal changes related to pregnancy (3,6,9,21,22,25). Familial CCMs have been described to be associated with a wide array of skin lesions: hyperkeratotic cutaneous capillary-venous malformations (HCCVM), angiokeratoma, cherry angiomas, cutaneous bluish nodules, multiple small bluish papules, capillary vascular anomalies, nodular venous malformations, and port-wine stains (11,12,26).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report)

et al. 2021

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Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multisystemic involvement usually resulting from mutations in the tuberous sclerosis 1 (TSC1) or TSC2 genes. However, 10 to 25% of patients do not exhibit these mutations. Cerebral cavernous malformations (CCMs) are capillary-venous malformations that can be asymptomatic or cause variable neurological manifestations, including seizures. Familial CCMs are recognized. In both conditions, specific dermatological lesions are associated. We present the case of a 31-year-old female with TSC diagnosed at the age of 18 years who presented with negative genetic testing. She was admitted to our department in 2019 for a sudden increased frequency of focal seizures. Patient examination revealed multiple facial and intraoral angiofibroma, diplopia, right hemihypoesthesia, brisk deep tendon reflexes, and distal leg paresthesia. VideoEEG indicated a frontal paramedian epileptogenic focus. Cerebral magnetic resonance imaging (MRI) and angioMRI identified multiple fronto-parietal cortical tubers, as well as multiple CCMs, with evidence of bleeding in one. Under antiepileptic drug (AED) and mTOR inhibitor treatment, the seizure frequency significantly improved in a short period of time. This is the first reported case of tuberous sclerosis with negative genetic testing associated with multiple cerebral cavernoma. Such complex patients require multidisciplinary management and detailed genetic testing for increasing knowledge on neuro-cutaneous disorders.

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Challenges of Valproate Treatment During Pregnancy: Pros and Cons

Cited by 2 publications

References 18 publications

Study Regarding the Determination of Valproic Acid Serum Levels by Emit

Study Regarding the Determination of Valproic Acid Serum Levels by Emit

Tuberous sclerosis with negative genetic testing and multiple cerebral cavernomas: A new association (Case report)

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