Abstracts

Rationale: Up to 88% of patients treated with anti-epileptic drugs (AED) experience at least one adverse event (AE) (Baker et al., 1997). A recent study indicated that 42% of AED side effects are cosmetic. These side effects can increase the economic burden of treatment by necessitating the addition of more expensive medications and more clinic visits, not to mention the emotional implications of modifications to physical appearance (De Kinderen et al., 2014). The most frequent cosmetic side effects are weight gain, associated with valproic acid and pregabalin, hair loss with valproic acid, and gingival hyperplasia with phenytoin (Chen et al., 2015). We present the case of a 13-year-old girl who developed curling hair without hair loss after the introduction of perampanel. Methods: The patient has medically refractory epilepsy, developmental delay, and stereotypes due to genetically confirmed Pitt-Hopkins Syndrome. Since 2016, she has had 3-4 seizures per year on valproate and levetiracetam (Figure 1). Her seizures were controlled with the addition of 2 mg daily of perampanel. The patient’s mother noticed hair curling in the occipital area a few weeks after the introduction of perampanel; the curling extended to the whole head in the following weeks (Figure 2). No change in hair texture was noticed while the patient was on stable doses of valproic acid and levetiracetam for 16 months. The family declined weaning off perampanel because of its efficacy in seizure control. The new hair texture remains after several months of treatment. Naranjo Assessment for drug-related side effects was 6. Results: Hair changes in volume, texture, and color have been reported with several medications, including the older AEDs (especially valproic acid, phenytoin and phenobarbital) (Chen et al., 2015) (Ricci et al., 2016) and some of the newer like levetiracetam (Zou, Hong and Zhou, 2014). A decreased concentration of zinc has been proposed as the cause for hair loss (Yilmaz, Tasdemir and Paksu, 2009). There are no clear possible explanations for changes in color and texture. Hair curling is an infrequent AE for AEDs. It was first described in 1977 in five patients taking valproic acid (Jeavons, Clark and Harding, 1977). Since then, several cases have described the presence of curly hair weeks after the first administration of this AED (Caneppele, Mazereeuw-Hautier and Bonafé, 2001), some of them showing improvement of the condition after downtitration of the dosage (Wilting et al., 2007). Our patient was treated with valproic acid for 16 months but experienced no changes in hair texture until perampanel was added. This new AED is a partially selective, non competitive antagonist of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor that reduces neuronal excitability. The most frequently reported side effects are dizziness and fatigue. The only reported cosmetic side effects were weight gain in 7.4 to 19.2% of the analyzed population (French et al., 2015) (French et al., 2012); and skin rash in 10.6% of Asian patients (Lin et al., 2018). A comprehensive search in PUBMED, EMBASE, and Scielo using the MESH terms “hair,” “antiepileptic drug side effects,” and “perampanel,” did not bring up any articles about hair changes associated with perampanel. The mechanism of action of perampanel shows no known impact of AMPA receptor deactivation on hair growth and texture. When the Naranjo Assessment for drug-related side effects was applied, however, the patient got a score of 6, which means perampanel is a probable cause for the hair curling (Naranjo et al., 1981). Given the scarce evidence of hair texture changes associated with the first AED, it is impossible to rule out an additive effect between valproate and perampanel.Our patient is also afflicted with Pitt-Hopkins Syndrome, a genetic disorder caused by mutations in the transcription factor TCF4 that cause several problems, including central nervous system symptoms such as developmental delay and epilepsy. We found no case reports of changes in hair texture related to this disease, which provides more support for the causative effect of perampanel in this patient’s hair curling (Zollino et al., 2019). 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Zollino M, Zweier C, Van Balkom I. et al. ‘Diagnosis and management in Pitt-Hopkins Syndrome: First international consensus statement’, Clin Genet 2019. Epub Ahead of Imprint.Zou, X., Hong, Z. and Zhou, D. ‘Hair loss with levetiracetam in five patients with epilepsy’, Seizure 2014, 23, 158–160. Conclusions: Hair curling is a rare cosmetic side effect of AED, reported mainly in patients undergoing valproic acid treatment. Perampanel is a recently-introduced pharmaceutical agent with no prior reports of hair change. We report on a change in hair texture from straight to curly after the introduction of parampanel. There is no clear explanation for this side effect, but it should be discussed with patients taking valproate whenever parampanel is added to the treatment. Funding: No funding