Scientific Letter
Induced atypical absence seizures during treatment with perampanel
Inducción de crisis de ausencia atípica durante el tratamiento con perampanel
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Se observa una actividad punta-onda lenta de gran amplitud, más o menos rítmica, de expresión difusa con predominio en regiones posteriores, con inicio y fin bruscos. En este momento estaba en tratamiento con PER 2<span class="elsevierStyleHsp" style=""></span>mg/día.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">En la imagen inferior (B) se observa el trazado EEG interictal 2 semanas después, tras retirar el PER. Se observa una actividad en vigilia aceptablemente organizada, de tendencia lenta, sin asimetrías ni anomalías epileptiformes. 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] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Verónica" "apellidos" => "Cantarín Extremera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Marta" "apellidos" => "García Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Juan José" "apellidos" => "García Peñas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "María Luz" "apellidos" => "Ruiz-Falcó Rojas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Niño Jesús, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Neurofisiología, Hospital Universitario Niño Jesús, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inducción de crisis de ausencia atípica durante el tratamiento con perampanel" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3557 "Ancho" => 3175 "Tamanyo" => 1636554 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electroencephalogram of case 3 during treatment with PER (A) and after discontinuation of PER (B).</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The top image (A) shows the ictal tracing during one of the episodes of reduced movement and changes in facial expression, associated with continuous mild blinking occurring every 5–10<span class="elsevierStyleHsp" style=""></span>s. The tracings show a slow, high-amplitude spike-wave activity, more or less rhythmical, diffuse and with predominance of the posterior regions pattern, with abrupt onset and end. At this time, the patient was receiving PER at a dose of 2<span class="elsevierStyleHsp" style=""></span>mg/day.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The lower image (B) shows the interictal EEG 2 weeks later, after discontinuation of PER. The tracings reveal adequately organised wake activity, with a tendency towards slowing, without epileptiform abnormalities or asymmetries. There were no atypical absence seizures.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Perampanel (PER) is an antiepileptic drug approved for patients aged more than 12 years with partial and generalised tonic-clonic seizures. At present, the available data on their effectiveness in the management of absence seizures are scarce, and the number of patients aged less than 4 years included in these studies in negligible.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2</span></a> We present the cases of 3 children that developed atypical absence seizures at the time of initiation of PER.</p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case</span> 1<span class="elsevierStyleItalic">.</span> Girl aged 3 years with no history of interest with onset at age 2 years of progressive myoclonus epilepsy of unknown aetiology, with impairment predominantly of motor skills, ataxia and dysarthria. The patient did not respond to multiple antiepileptic drugs (valproic acid, levetiracetam, ethosuximide, phenytoin, lacosamide, topiramate, zonisamide, clobazam, piracetam and brivaracetam) or a ketogenic diet. Treatment with PER was initiated, reaching a total dose of 2<span class="elsevierStyleHsp" style=""></span>mg/day, in combination with brivaracetam, clobazam and piracetam. After 1 week she started experiencing frequent atypical absence seizures associated with episodes of progressive atony with a slow drooping of the head and trunk that were documented by video encephalography (VEEG). The patient experienced electroencephalographic resolution of the atypical absence seizures 1 week after discontinuation of PER.</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case</span> 2<span class="elsevierStyleItalic">.</span> Girl aged 3 years and 2 months with Angelman syndrome. The patient presented with psychomotor delay and myoclonic seizures with onset at 12 months, and developed an epileptic encephalopathy electroencephalographic pattern with daily episodes of myoclonus refractory to antiepileptic drugs (levetiracetam, valproic acid and clobazam). Treatment with PER in combination with valproic acid and clobazam was initiated, reaching a maximum daily dose of 4<span class="elsevierStyleHsp" style=""></span>mg/day. The patient exhibited progressive general deterioration with continuous episodes of halts in activity accompanied by repetitive blinking, and VEEG monitoring revealed features of nonconvulsive status epilepticus (continuous atypical absence seizures). After discontinuation of PER, there was a decrease in the absence episodes, with evidence of electrographic improvement.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case</span> 3<span class="elsevierStyleItalic">.</span> Boy aged 1 year and 7 months with psychomotor delay from the early months of life of unknown aetiology. He had onset of epilepsy at age 6 months, with focal hypomotor seizures and several forms of status epilepticus in the posterior cortex. The epilepsy was refractory to valproic acid, levetiracetam, clobazam, zonisamide, carbamazepine, lacosamide and the ketogenic diet. Treatment with PER was initiated in association with valproic acid, levetiracetam and clobazam. The patient reached a maximum dose of 2<span class="elsevierStyleHsp" style=""></span>mg/day. Perampanel was discontinued after 3 and a half months following evidence in VEEG of nonconvulsive status epilepticus with atypical absence seizures that disappeared after discontinuation of the drug (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Changes in the concomitant treatments were not made in any of the patients, and none experienced any relevant side effects from these treatments.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We did not find any reports in the literature of cases of development of atypical absence seizures with PER, but the paradoxical worsening of epilepsy induced by antiepileptic drugs is already a well-known complication.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At present, the literature on the use of PER in the treatment of absence seizures is scarce. French et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> included patients with absence seizures, and although they found no evidence that the drug exacerbated these seizures, they did not analyse the efficacy of PER against them.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Villanueva et al. included 37 patients with absence epilepsy, of who only 7% experienced worsening.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We believe that certain characteristics of our patients may have contributed to their clinical worsening. One was their age, as the study by Biro et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> revealed a greater increase in seizures during treatment with PER in the 2-to-5-year age group. On the other hand, the data on the effectiveness of PER for treatment of atypical absence seizures are scarce. Swiderska et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> analysed the efficacy of PER in 4 patients with atypical absence seizures, and none exhibited a reduction in the seizures. Biro et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> included 4 patients with atypical absence seizures and found 2 patients that did not respond and 1 that experienced an exacerbation of these seizures.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> Last of all, we think a relevant factor was that our patients had epilepsy refractory to drugs in addition to other unfavourable conditions. For instance, when Villanueva et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> compared the outcomes of treatment with PER in patients with myoclonic seizures, they found a higher frequency of improvement compared to other studies that included patients with refractory epilepsy and other unfavourable conditions, such as progressive myoclonic epilepsy.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The limitations of our study are significant due to its retrospective design and a small sample. However, we believe that contributing information from clinical experience is of great interest for the purpose of starting to profile the characteristics of patients at higher risk of experiencing worsening of specific seizures with PER.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Duat Rodríguez A, Cantarín Extremera V, García Fernández M, García Peñas JJ, Ruiz-Falcó Rojas ML. Inducción de crisis de ausencia atípica durante el tratamiento con perampanel. An Pediatr (Barc). 2019;91:346–348.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3557 "Ancho" => 3175 "Tamanyo" => 1636554 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electroencephalogram of case 3 during treatment with PER (A) and after discontinuation of PER (B).</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The top image (A) shows the ictal tracing during one of the episodes of reduced movement and changes in facial expression, associated with continuous mild blinking occurring every 5–10<span class="elsevierStyleHsp" style=""></span>s. The tracings show a slow, high-amplitude spike-wave activity, more or less rhythmical, diffuse and with predominance of the posterior regions pattern, with abrupt onset and end. At this time, the patient was receiving PER at a dose of 2<span class="elsevierStyleHsp" style=""></span>mg/day.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The lower image (B) shows the interictal EEG 2 weeks later, after discontinuation of PER. The tracings reveal adequately organised wake activity, with a tendency towards slowing, without epileptiform abnormalities or asymmetries. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 5 | 13 |
| 2024 October | 58 | 53 | 111 |
| 2024 September | 73 | 45 | 118 |
| 2024 August | 63 | 78 | 141 |
| 2024 July | 41 | 61 | 102 |
| 2024 June | 59 | 50 | 109 |
| 2024 May | 51 | 46 | 97 |
| 2024 April | 50 | 34 | 84 |
| 2024 March | 51 | 31 | 82 |
| 2024 February | 67 | 32 | 99 |
| 2024 January | 72 | 27 | 99 |
| 2023 December | 71 | 41 | 112 |
| 2023 November | 69 | 40 | 109 |
| 2023 October | 74 | 53 | 127 |
| 2023 September | 63 | 37 | 100 |
| 2023 August | 48 | 14 | 62 |
| 2023 July | 59 | 33 | 92 |
| 2023 June | 44 | 26 | 70 |
| 2023 May | 84 | 28 | 112 |
| 2023 April | 36 | 14 | 50 |
| 2023 March | 60 | 24 | 84 |
| 2023 February | 70 | 20 | 90 |
| 2023 January | 40 | 12 | 52 |
| 2022 December | 70 | 33 | 103 |
| 2022 November | 63 | 39 | 102 |
| 2022 October | 85 | 40 | 125 |
| 2022 September | 48 | 25 | 73 |
| 2022 August | 62 | 50 | 112 |
| 2022 July | 70 | 52 | 122 |
| 2022 June | 70 | 35 | 105 |
| 2022 May | 77 | 44 | 121 |
| 2022 April | 66 | 36 | 102 |
| 2022 March | 73 | 49 | 122 |
| 2022 February | 59 | 19 | 78 |
| 2022 January | 53 | 34 | 87 |
| 2021 December | 47 | 33 | 80 |
| 2021 November | 67 | 40 | 107 |
| 2021 October | 66 | 62 | 128 |
| 2021 September | 50 | 32 | 82 |
| 2021 August | 63 | 43 | 106 |
| 2021 July | 46 | 25 | 71 |
| 2021 June | 57 | 31 | 88 |
| 2021 May | 43 | 35 | 78 |
| 2021 April | 133 | 66 | 199 |
| 2021 March | 100 | 26 | 126 |
| 2021 February | 68 | 22 | 90 |
| 2021 January | 75 | 15 | 90 |
| 2020 December | 112 | 10 | 122 |
| 2020 November | 96 | 36 | 132 |
| 2020 October | 60 | 29 | 89 |
| 2020 September | 133 | 18 | 151 |
| 2020 August | 116 | 7 | 123 |
| 2020 July | 127 | 12 | 139 |
| 2020 June | 41 | 4 | 45 |
| 2020 May | 67 | 22 | 89 |
| 2020 April | 62 | 10 | 72 |
| 2020 March | 48 | 12 | 60 |
| 2020 February | 157 | 21 | 178 |
| 2020 January | 53 | 18 | 71 |
| 2019 December | 47 | 15 | 62 |
| 2019 November | 33 | 4 | 37 |
| 2019 October | 18 | 7 | 25 |
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