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Levetiracetam as alternative treatment in Jeavons syndrome
Journal of the Neurological Sciences 341 (2014) 147–149
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Levetiracetam as alternative treatment in Jeavons syndrome D. Parissis ⁎, P. Ioannidis, D. Karacostas AHEPA Hospital, Stilponos Kyriakidi 1, Thessaloniki, Greece
a r t i c l e
i n f o
Article history: Received 22 January 2014 Received in revised form 23 March 2014 Accepted 26 March 2014 Available online 3 April 2014 Keywords: Eyelid myoclonia Jeavons syndrome Levetiracetam
a b s t r a c t We report on a 25 year old female patient who had a diagnosis of Jeavons syndrome since her childhood. Although valproate led to seizure freedom, she developed persistent reproductive endocrine disorders attributed to this drug. The withdrawal of valproate in parallel with an initiation of levetiracetam monotherapy resulted in a maintenance of clinical remission and a resolution of these abnormalities. This case together with relevant literature data supports the view that the use of levetiracetam might be of benefit for female patients with Jeavons syndrome. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Eyelid myoclonia with absences (EMA), or Jeavons syndrome, is an epileptic disorder characterized by episodic eyelid myoclonia, sometimes followed by absences, and prominent photosensitivity [1]. The syndrome has its onset during childhood and tends to persist throughout life. EEG shows brief generalized polyspikes or polyspike-wave complexes typically triggered by eye closure, whereas intermittent photic stimulation (IPS) induces generalized photoparoxysmal response [1]. Valproate is considered a useful drug in the treatment of EMA. However, several adverse effects make the use of this drug in the young female population problematic [2]. In this report, we describe the case of a female patient with Jeavons syndrome who had successfully switched from valproate to levetiracetam monotherapy due to the emergence of valproate related gynecological abnormalities.
2. Case report The history of our 25 year old patient started at the age of 6, when her mother noticed that she had rare episodes of eyelid fluttering of short duration, sometimes associated with upward turning of the eyeballs. The episodes gradually increased in frequency (3/min), whereas on one occasion at the age of 10 she experienced loss of consciousness during an attempt to face towards the sun. EEG showed generalized
⁎ Corresponding author. Tel.: + 30 2310272102, + 30 2310994682; fax: + 30 2310994689. E-mail address: [email protected] (D. Parissis).
http://dx.doi.org/10.1016/j.jns.2014.03.051 0022-510X/© 2014 Elsevier B.V. All rights reserved.
epileptiform discharges elicited by eye closure and IPS (Fig. 1a, b) and a diagnosis of EMA was given according to the criteria suggested by Striano S et al. [3]. Treatment with valproate at a dose of 600 mg/d was initiated at the age of 10 leading to complete seizure freedom. However, the drug was discontinued after a period of 2 years due to weight gain approximating 8% from baseline and clonazepam 1.5 mg/d was introduced resulting in seizure relapse. The patient experienced her menarche at the age of 12 having regular menstrual cycles and no evidence of endocrine abnormalities. She was switched again to valproate at the age of 13.5 due to frequent seizures and she showed an excellent clinical response. However, she gradually developed persistent menstrual irregularities consisting mainly of oligomenorrhea, whereas polycystic ovaries consisting of 12 follicular cysts measuring 4–6 in diameter were discovered on transvaginal ultrasonography. These findings were compatible with a diagnosis of polycystic ovary syndrome (PCOS) based on the Rotterdam criteria [12]. However, the patient had no clinical or biochemical evidence of androgen excess. Accordingly, she did not fulfill the more strict criteria for PCOS proposed by the PCOS-Society Task Force [4]. Valproate was then gradually withdrawn, but 4 months later the patient suffered a generalized tonic clonic seizure on exposure to bright light. At this point the patient discussed with us alternative drug options and finally levetiracetam 1.5 g/d was prescribed. During follow-up of 18 months, she remains in full clinical remission, whereas serial EEG recordings revealed absence of paroxysmal activity upon eye closure and notable decrease in photosensitivity (Fig. 1c, d). Furthermore, her body weight returned to baseline, her menstrual cycle length decreased from 47 to 33 days and the polycystic ovarian morphology significantly improved in terms of number of cysts during the above period.
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D. Parissis et al. / Journal of the Neurological Sciences 341 (2014) 147–149
Fig. 1. (a) Brief generalized discharges of spikes/polyspike-waves occurring within 1 s of eye closure. (b) Typical photoparoxysmal response induced by 16 Hz IPS. (c) Total suppression of eye closure induced EEG abnormalities during levetiracetam treatment. (d) Clear improvement in the degree of paroxysmal response triggered by IPS during levetiracetam treatment compared to baseline EEG.
3. Discussion The nosological position of Jeavons syndrome has not been clearly delineated. Several authors consider EMA as a distinct syndrome belonging to idiopathic generalized epilepsy [1]. Nevertheless, EMA is not recognized as a separate epileptic syndrome by the recent report of ILAE on Classification and Terminology, and currently eyelid myoclonia has been adopted in the classification only as a seizure type [5].
The pharmacological treatment of EMA is based on anecdotal evidence and experts' opinion [2]. Valproate, ethosuximide, benzodiazepines and phenobarbital are usually used with variable efficacy, whereas combination of drugs is necessary in resistant cases [2,6]. To our knowledge, only one prospective clinical trial has examined the role of an antiepileptic drug, specifically levetiracetam, in the treatment of EMA. In this pilot study, Striano P et al. demonstrated that the drug is effective in the majority of patients given in mono or adjunctive therapy, showing also an acceptable tolerability profile [6].
D. Parissis et al. / Journal of the Neurological Sciences 341 (2014) 147–149
Theoretically, levetiracetam appears to be suitable for EMA patients, principally because of its well established anti-myoclonic activity in various types of epileptic disorders [7,8]. Additionally, there are data suggesting that levetiracetam may reduce or eliminate the abnormal EEG response to IPS in photosensitive epilepsies [9]. Furthermore, in contrast to valproate, no reproductive endocrine effects of levetiracetam in women with epilepsy have been described [10]. This reassuring information of no-drug specific endocrine effects of levetiracetam combined with its low teratogenic potential demonstrated in recent pregnancy registers [11], is especially important for female patients with EMA. On the other hand, numerous studies have shown that valproate is associated with reproductive endocrine disorders, such as polycystic changes in the ovaries, high serum concentrations of testosterone and androstendione, increase in levels of LH/FSH ratio as well as menstrual cycle abnormalities [12]. These findings are common among women who have gained weight during valproate therapy, whereas young women at an age b 20 years seem to be especially vulnerable to these effects [13]. The above endocrine disorders may occur either in isolation or in the form of PCOS and indeed a large body of literature has suggested that treatment with valproate increases the incidence of PCOS [12,14]. Furthermore, another important concern in women of childbearing potential treated with valproate is the well established risk of major malformations in their offsprings [15]. We conclude that levetiracetam is a reasonable treatment option for female patients with Jeavons syndrome. Conflict of interest There is no conflict of interest. References [1] Striano S, Capovilla G, Vito S, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;50(Suppl. 5):15–9.
149
[2] Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. 1st ed. Oxfordshire: Bladon Medical Publishing; 2005. [3] Striano S, Striano P, Nocerino C, Boccella P, Bilo L, Meo R, et al. Eyelid myoclonia with absences: an overlooked epileptic syndrome? Neurophysiol Clin 2002;32(5): 287–96. [4] Azziz R, Carmina R, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91(2):456–88. [5] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51(4):676–85. [6] Striano P, Vito S, Capovilla G, Rubboli G, Di Bonaventura C, Coppola A, et al. A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome). Epilepsia 2008;49(3):425–30. [7] Mantoan L, Walker M. Treatment options in juvenile myoclonic epilepsy. Curr Treat Options Neurol 2011;13(4):355–70. [8] Magaudda A, Gelisse P, Genton P. Antimyoclonic effect of levetiracetam in 13 patients with Unverricht–Lundborg disease: clinical observations. Epilepsia 2004;45: 678–81. [9] Covanis A. Photosensitivity in idiopathic generalized epilepsies. Epilepsia 2005;46(Suppl. 9):67–72. [10] Svalheim S, Tauboll E, Luef G, Lossius A, Rauchenzauner M, Sandwand F, et al. Differential effects of levetiracetam, carbamazepine and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav 2009;16:281–7. [11] Mawhinney E, Craig J, Morrow J, Russell A, Smithson JH, Parsons L, et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013;80(4):400–5. [12] Verrotti A, D' Egidio C, Mohn A, Coppola G, Parisi P, Chiarelli F. Antiepileptic drugs, sex hormones, and PCOS. Epilepsia 2011;52(2):199–211. [13] Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013;107(1–2):1–8. [14] Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, et al. Hyperandrogenism, ovulatory dysfunction and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol 2008;64:200–11. [15] Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010;362(23): 2185–93.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Levetiracetam as alternative treatment in Jeavons syndrome D. Parissis ⁎, P. Ioannidis, D. Karacostas AHEPA Hospital, Stilponos Kyriakidi 1, Thessaloniki, Greece
a r t i c l e
i n f o
Article history: Received 22 January 2014 Received in revised form 23 March 2014 Accepted 26 March 2014 Available online 3 April 2014 Keywords: Eyelid myoclonia Jeavons syndrome Levetiracetam
a b s t r a c t We report on a 25 year old female patient who had a diagnosis of Jeavons syndrome since her childhood. Although valproate led to seizure freedom, she developed persistent reproductive endocrine disorders attributed to this drug. The withdrawal of valproate in parallel with an initiation of levetiracetam monotherapy resulted in a maintenance of clinical remission and a resolution of these abnormalities. This case together with relevant literature data supports the view that the use of levetiracetam might be of benefit for female patients with Jeavons syndrome. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Eyelid myoclonia with absences (EMA), or Jeavons syndrome, is an epileptic disorder characterized by episodic eyelid myoclonia, sometimes followed by absences, and prominent photosensitivity [1]. The syndrome has its onset during childhood and tends to persist throughout life. EEG shows brief generalized polyspikes or polyspike-wave complexes typically triggered by eye closure, whereas intermittent photic stimulation (IPS) induces generalized photoparoxysmal response [1]. Valproate is considered a useful drug in the treatment of EMA. However, several adverse effects make the use of this drug in the young female population problematic [2]. In this report, we describe the case of a female patient with Jeavons syndrome who had successfully switched from valproate to levetiracetam monotherapy due to the emergence of valproate related gynecological abnormalities.
2. Case report The history of our 25 year old patient started at the age of 6, when her mother noticed that she had rare episodes of eyelid fluttering of short duration, sometimes associated with upward turning of the eyeballs. The episodes gradually increased in frequency (3/min), whereas on one occasion at the age of 10 she experienced loss of consciousness during an attempt to face towards the sun. EEG showed generalized
⁎ Corresponding author. Tel.: + 30 2310272102, + 30 2310994682; fax: + 30 2310994689. E-mail address: [email protected] (D. Parissis).
http://dx.doi.org/10.1016/j.jns.2014.03.051 0022-510X/© 2014 Elsevier B.V. All rights reserved.
epileptiform discharges elicited by eye closure and IPS (Fig. 1a, b) and a diagnosis of EMA was given according to the criteria suggested by Striano S et al. [3]. Treatment with valproate at a dose of 600 mg/d was initiated at the age of 10 leading to complete seizure freedom. However, the drug was discontinued after a period of 2 years due to weight gain approximating 8% from baseline and clonazepam 1.5 mg/d was introduced resulting in seizure relapse. The patient experienced her menarche at the age of 12 having regular menstrual cycles and no evidence of endocrine abnormalities. She was switched again to valproate at the age of 13.5 due to frequent seizures and she showed an excellent clinical response. However, she gradually developed persistent menstrual irregularities consisting mainly of oligomenorrhea, whereas polycystic ovaries consisting of 12 follicular cysts measuring 4–6 in diameter were discovered on transvaginal ultrasonography. These findings were compatible with a diagnosis of polycystic ovary syndrome (PCOS) based on the Rotterdam criteria [12]. However, the patient had no clinical or biochemical evidence of androgen excess. Accordingly, she did not fulfill the more strict criteria for PCOS proposed by the PCOS-Society Task Force [4]. Valproate was then gradually withdrawn, but 4 months later the patient suffered a generalized tonic clonic seizure on exposure to bright light. At this point the patient discussed with us alternative drug options and finally levetiracetam 1.5 g/d was prescribed. During follow-up of 18 months, she remains in full clinical remission, whereas serial EEG recordings revealed absence of paroxysmal activity upon eye closure and notable decrease in photosensitivity (Fig. 1c, d). Furthermore, her body weight returned to baseline, her menstrual cycle length decreased from 47 to 33 days and the polycystic ovarian morphology significantly improved in terms of number of cysts during the above period.
148
D. Parissis et al. / Journal of the Neurological Sciences 341 (2014) 147–149
Fig. 1. (a) Brief generalized discharges of spikes/polyspike-waves occurring within 1 s of eye closure. (b) Typical photoparoxysmal response induced by 16 Hz IPS. (c) Total suppression of eye closure induced EEG abnormalities during levetiracetam treatment. (d) Clear improvement in the degree of paroxysmal response triggered by IPS during levetiracetam treatment compared to baseline EEG.
3. Discussion The nosological position of Jeavons syndrome has not been clearly delineated. Several authors consider EMA as a distinct syndrome belonging to idiopathic generalized epilepsy [1]. Nevertheless, EMA is not recognized as a separate epileptic syndrome by the recent report of ILAE on Classification and Terminology, and currently eyelid myoclonia has been adopted in the classification only as a seizure type [5].
The pharmacological treatment of EMA is based on anecdotal evidence and experts' opinion [2]. Valproate, ethosuximide, benzodiazepines and phenobarbital are usually used with variable efficacy, whereas combination of drugs is necessary in resistant cases [2,6]. To our knowledge, only one prospective clinical trial has examined the role of an antiepileptic drug, specifically levetiracetam, in the treatment of EMA. In this pilot study, Striano P et al. demonstrated that the drug is effective in the majority of patients given in mono or adjunctive therapy, showing also an acceptable tolerability profile [6].
D. Parissis et al. / Journal of the Neurological Sciences 341 (2014) 147–149
Theoretically, levetiracetam appears to be suitable for EMA patients, principally because of its well established anti-myoclonic activity in various types of epileptic disorders [7,8]. Additionally, there are data suggesting that levetiracetam may reduce or eliminate the abnormal EEG response to IPS in photosensitive epilepsies [9]. Furthermore, in contrast to valproate, no reproductive endocrine effects of levetiracetam in women with epilepsy have been described [10]. This reassuring information of no-drug specific endocrine effects of levetiracetam combined with its low teratogenic potential demonstrated in recent pregnancy registers [11], is especially important for female patients with EMA. On the other hand, numerous studies have shown that valproate is associated with reproductive endocrine disorders, such as polycystic changes in the ovaries, high serum concentrations of testosterone and androstendione, increase in levels of LH/FSH ratio as well as menstrual cycle abnormalities [12]. These findings are common among women who have gained weight during valproate therapy, whereas young women at an age b 20 years seem to be especially vulnerable to these effects [13]. The above endocrine disorders may occur either in isolation or in the form of PCOS and indeed a large body of literature has suggested that treatment with valproate increases the incidence of PCOS [12,14]. Furthermore, another important concern in women of childbearing potential treated with valproate is the well established risk of major malformations in their offsprings [15]. We conclude that levetiracetam is a reasonable treatment option for female patients with Jeavons syndrome. Conflict of interest There is no conflict of interest. References [1] Striano S, Capovilla G, Vito S, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;50(Suppl. 5):15–9.
149
[2] Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. 1st ed. Oxfordshire: Bladon Medical Publishing; 2005. [3] Striano S, Striano P, Nocerino C, Boccella P, Bilo L, Meo R, et al. Eyelid myoclonia with absences: an overlooked epileptic syndrome? Neurophysiol Clin 2002;32(5): 287–96. [4] Azziz R, Carmina R, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91(2):456–88. [5] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51(4):676–85. [6] Striano P, Vito S, Capovilla G, Rubboli G, Di Bonaventura C, Coppola A, et al. A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome). Epilepsia 2008;49(3):425–30. [7] Mantoan L, Walker M. Treatment options in juvenile myoclonic epilepsy. Curr Treat Options Neurol 2011;13(4):355–70. [8] Magaudda A, Gelisse P, Genton P. Antimyoclonic effect of levetiracetam in 13 patients with Unverricht–Lundborg disease: clinical observations. Epilepsia 2004;45: 678–81. [9] Covanis A. Photosensitivity in idiopathic generalized epilepsies. Epilepsia 2005;46(Suppl. 9):67–72. [10] Svalheim S, Tauboll E, Luef G, Lossius A, Rauchenzauner M, Sandwand F, et al. Differential effects of levetiracetam, carbamazepine and lamotrigine on reproductive endocrine function in adults. Epilepsy Behav 2009;16:281–7. [11] Mawhinney E, Craig J, Morrow J, Russell A, Smithson JH, Parsons L, et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013;80(4):400–5. [12] Verrotti A, D' Egidio C, Mohn A, Coppola G, Parisi P, Chiarelli F. Antiepileptic drugs, sex hormones, and PCOS. Epilepsia 2011;52(2):199–211. [13] Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013;107(1–2):1–8. [14] Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, et al. Hyperandrogenism, ovulatory dysfunction and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol 2008;64:200–11. [15] Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010;362(23): 2185–93.