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Wilson’s disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes
Epilepsy & Behavior 8 (2006) 438–441 www.elsevier.com/locate/yebeh
Case Report
Wilson’s disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes Panagiotis Polychronopoulos a,*, Andreas A. Argyriou a, Spiridon Papapetropoulos a, Philippos Gourzis b, Georgios Rigas b, Elisabeth Chroni a a b
Department of Neurology, University Hospital of Patras, 26504, Rion-Patras, Greece Department of Psychiatry, University Hospital of Patras, 26504, Rion-Patras, Greece Received 19 October 2005; revised 28 November 2005; accepted 9 December 2005
Abstract Cases with a clinical and electroencephalographic phenotype of benign epilepsy of childhood with centrotemporal spikes (BECTS) in association with a proven organic brain lesion have rarely been reported. To our knowledge, we herein describe for the first time a patient with Wilson’s disease who subsequently manifested BECTS. Our case bolsters the argument that in at least some cases, BECTS is associated with organic brain disease. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Clinical pattern; Electroencephalographic pattern; Rolandic epilepsy; Wilson’s disease
1. Introduction Benign epilepsy of childhood with centrotemporal spikes (BECTS), or rolandic epilepsy, is a common idiopathic partial epilepsy, manifesting mainly with hemifacial seizures and ictal oropharyngolaryngeal symptoms. No underlying cause other than a possible hereditary predisposition has been recognized, and the prognosis for remission is excellent [1,2]. Cases with a clinical and electroencephalographic phenotype of BECTS in association with a proven organic brain lesion have rarely been reported [3,4]. The pathogenetic mechanism of the epileptic discharges remains controversial, with some authors suggesting a direct relationship to the structural brain lesion [3], and others supporting the hypothesis of a coincidence [4]. We herein provide the first description of a patient with Wilson’s disease complicated with BECTS. Our case bolsters the argument that in
*
Corresponding author. Fax: +30 261 0993949. E-mail address: [email protected] (P. Polychronopoulos).
1525-5050/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2005.12.008
at least some cases, BECTS is associated with organic brain disease. 2. Case report A 9-year-old schoolgirl attending the outpatient pediatrics department reported a 2-year history of slowly progressive deterioration in school performance and a 1-year history of progressive dysarthria, sialorrhea, tremor, and unsteady gait. Her otherwise personal and familial medical history was negative. Neurological examination revealed emotional lability, bradykinesia, and generalized rigidity with postural and intention tremor involving the upper limbs. Dysgraphia, severe hypokinetic dysarthria, dysphagia accompanied by profuse drooling, and shuffling gait were also evident. Low plasma copper and ceruloplasmin concentrations, Kayser–Fleischer rings in the corneas, and a liver biopsy revealing increased copper content substantiated the diagnosis of Wilson’s disease (WD). Psychiatric evaluation revealed no abnormalities. The brain CT scan was normal, and an awake EEG showed rare and mild, diffuse,
Case Report / Epilepsy & Behavior 8 (2006) 438–441
nonspecific slow activity without focal or epileptiform discharges. The patient was placed on zinc acetate (150 mg/ day) and restriction of dietary copper (<1 mg/day) with satisfactory compliance. Seven months later she manifested clusters of focal seizures both during sleep and while awake. They were short in duration and simple partial in origin and occurred several times per day (20–25). The seizure activity consisted of clonic movements and paresthesias involving the left side of the face, lips, tongue, gums, and cheek. Occasionally, ictal activity was propagated to the left arm or the eyelid. Consciousness was fully retained during episodes, but the child was anarthric, trying to communicate with gestures. A new awake EEG showed epileptiform spikes in rolandic areas bilaterally, and maximum electronegativity (phase reversal) was observed at F3 or F4. The background was mildly slow. During sleep, epileptiform abnormalities were clearly activated and some bursts of spike–wave discharges appeared (Figs. 1A and B). High signal intensities on T2weighted images in the thalami and basal ganglia, more prominent on the right side were depicted, and mild diffuse brain atrophy and mild enlargement of lateral ventricles were also evident. Carbamazepine 400 mg daily was prescribed and resulted in complete remission of seizures shortly after administration. Five years later (still under the same treatment with zinc acetate and dietary copper restriction), she remains seizure-free despite discontinuation of carbamazepine 3 years earlier. Recent EEGs show mild, diffuse, nonspecific disturbances without epileptiform activity. Written informed consent was obtained from both parents of the child. 3. Discussion Occurrence of epilepsy in patients with WD is rarely reported [5,6]. Denning et al. [5] reported that WD carries a mildly elevated risk for epilepsy, estimated in less than 10% of cases. Although uncertain conclusions were drawn concerning the type of epilepsy and its clinical and electroencephalographic features, Denning and colleagues suggested that seizures, mostly of the partial type, may occur at any stage of the disease, and their prognosis does not significantly differ from that in general population surveys [5]. We reported on a child with rolandic seizures who also has a probably unrelated brain disease, i.e., WD. Rolandic seizures are very common, with a prevalence of 15% in children aged 1–15 with afebrile seizures and an incidence of 10–20 per 100,000 [2]. Hence, it should be expected that rolandic seizures can also occur in children with brain damage. With respect to the treatment for WD administered, it should be mentioned that our patient did not receive D-penicillamine, which has been linked to seizure activity [5]. She was treated with zinc acetate, which has an excellent safety profile. The only toxic effect is gastric irritation in 5–10% of patients [7].
439
Clinically, the age at onset and pattern of seizures in our case are characteristic and virtually diagnostic of the BECTS type of epilepsy [1]. Seizures began at the age of 9, were focal in origin, occurred during sleep, and consisted of unilateral facial sensorimotor symptoms, oropharyngolaryngeal manifestations, and speech arrest without impairment of consciousness. The seizures did not become more frequent, were responsive to carbamazepine, and failed to recur 3 years after its discontinuation. The electroencephalographic pattern showing rolandic high-voltage, usually diphasic spikes or sharp waves with prominent aftercoming slow waves is consistent with the BECTS electroencephalographic pattern [2]. These recordings are typical in their morphology, amplitude, duration, frequency, and pattern, but atypical in localization, due to the fact that although spikes were evident in T3, T4, C3, C4, F3, and F4, maximum electronegativity was observed at F3 or F4. Nevertheless, although in most children, spikes usually have a centrotemporal origin, atypical localizations are not uncommon [2,8]. Additionally, patients with purely centrotemporal spikes may have autonomic and not rolandic seizures [9]. The evidence of mildly slow background activity, presumably attributed to WD, is the only differentiation from the typical BECTS pattern. Brain MRI revealed no lesions in the rolandic or perirolandic areas. One could hypothesize that copper may accumulate in rolandic areas not visible on MRI, but the absence of relapse after discontinuation of therapy underlines the benign nature of this epilepsy [10]. The presence of the characteristic rolandic spikes alone is not diagnostic of BECTS. Age-related rolandic spikes may occur in 2–3% of normal nonepileptic children [2,11], and the rate is much higher in children with various brain diseases with or without seizures, such as Rett syndrome, fragile X syndrome, and cortical dysplasia [2]. Because of its prevalence, fortuitous associations may be found between BECTS and nonevolutional brain lesions [2,12]. Shevell et al. [13] reported on five children with cerebral tumors and an electroclinical phenotype suggestive of BECTS, and termed this disorder pseudo-BECTS. Many authors do not accept the occurrence of BECTS in children with brain damage, excluding them from their studies [14]. Loiseau [15] believed that epileptogenic focal cortical lesions can provoke focal motor seizures with an age-related expression of centrotemporal sharp waves. Gelisse et al. [4] found neuroimaging abnormalities in 14.8% of a population of children with BECTS, concluding that neuroimaging may be abnormal in such patients, whereas brain lesions had no influence on the prognosis. Our case supports this view, as recent EEGs did not show rolandic epileptiform activity, the patient is seizure-free despite discontinuation of carbamazepine, and MRI did not show clear evidence of organic lesions in the ‘‘perisylvian area.’’ Two main points of clinical importance are raised by this case report. First, the child experienced a very high seizure frequency (20–25/day), a fact that is relatively uncom-
440
Case Report / Epilepsy & Behavior 8 (2006) 438–441
Fig. 1. Sleep EEG showing frequent epileptiform activity bilaterally in the form of high-amplitude rolandic spikes or sharp waves (1–3 Hz) unilaterally or bilaterally. Maximum electronegativity was observed at F3 or F4. Both bipolar (A) and referential (B) montages are presented.
mon, as only a few articles have reported high seizure frequency in children with BECTS [16]. Second, the development of seizures in a child known to have WD would probably raise the possibility of a symptomatic and not
self-limiting epileptic syndrome. However, in this case of a girl with WD having daily seizures, rolandic epilepsy was benign and age-limited, irrespective of the associated metabolic disease.
Case Report / Epilepsy & Behavior 8 (2006) 438–441
In summary, in this case report, the age at onset, ictal clinical signs, interictal electroencephalographic pattern, negative neuroimaging findings, and favorable outcome led to the diagnosis of BECTS. To our knowledge, this is the first case of BECTS occurring in a patient known to have WD. References [1] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389– 99. [2] Panayiotopoulos CP. Benign childhood focal seizures and related epileptic syndromes. In: Panayiotopoulos CP, editor. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical; 2005. p. 223–70. [3] Degen R, Holthausen H, Pieper T, et al. Benign epileptic discharges in patients with lesional partial epilepsies. Pediatr Neurol 1999;20:354–9. [4] Gelisse P, Corda D, Raybaud C, et al. Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes. Epilepsia 2003;44:372–8. [5] Denning TR, Berrios GE, Walshe JM. Wilson’s disease and epilepsy. Brain 1988;111:1139–55.
441
[6] Saka E, Elibol B, Saygi S. Circling seizures in a case with Wilson’s disease. Clin Electroencephalogr 1999;30:118–21. [7] Brewer GJ, Askari FK. Wilson’s disease: clinical management and therapy. J Hepatol 2005;42(Suppl. 1):S13–21. [8] Wirrell EC. Benign epilepsy of childhood with centrotemporal spikes. Epilepsia 1998;39(Suppl. 4):S32–44. [9] Covanis A, Lada C, Skiadas K. Children with rolandic spikes and ictus emeticus: rolandic epilepsy or Panayiotopoulos syndrome? Epileptic Disord 2003;5:139–43. [10] Yoshi F, Takanashi W, Shinohara Y. A Wilson’s disease patient with prominent cerebral white matter lesions: five years follow-up by MRI. Eur Neurol 1996;36:392–3. [11] Lerman P, Kivity S. Focal epileptic EEG discharges in children not suffering from clinical epilepsy. Epilepsy Res Suppl 1992;6:99–103. [12] Santanelli P, Bureau M, Magauda A, Gobbi G, Roger J. Benign partial epilepsy with centrotemporal (or rolandic) spikes and brain lesion. Epilepsia 1989;30:182–8. [13] Shevell MI, Rosenblatt B, Watters GV, et al. ‘‘Pseudo-BECTS’’: intracranial focal lesions suggestive of a primary partial epilepsy syndrome. Pediatr Neurol 1996;14:31–5. [14] Loiseau P, Beaussart M. The seizures of benign childhood epilepsy with rolandic paroxysmal discharges. Epilepsia 1973;14:381–9. [15] Loiseau P. Benign focal epilepsies of childhood. In: Wyllie E, editor. The treatment of epilepsy. Philadelphia: Lea & Febiger; 1993. p. 509–12. [16] Ong HT, Willie E. Benign childhood epilepsy with centrotemporal spikes: is it always benign? Neurology 2000;54:1182–5.
Case Report
Wilson’s disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes Panagiotis Polychronopoulos a,*, Andreas A. Argyriou a, Spiridon Papapetropoulos a, Philippos Gourzis b, Georgios Rigas b, Elisabeth Chroni a a b
Department of Neurology, University Hospital of Patras, 26504, Rion-Patras, Greece Department of Psychiatry, University Hospital of Patras, 26504, Rion-Patras, Greece Received 19 October 2005; revised 28 November 2005; accepted 9 December 2005
Abstract Cases with a clinical and electroencephalographic phenotype of benign epilepsy of childhood with centrotemporal spikes (BECTS) in association with a proven organic brain lesion have rarely been reported. To our knowledge, we herein describe for the first time a patient with Wilson’s disease who subsequently manifested BECTS. Our case bolsters the argument that in at least some cases, BECTS is associated with organic brain disease. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Clinical pattern; Electroencephalographic pattern; Rolandic epilepsy; Wilson’s disease
1. Introduction Benign epilepsy of childhood with centrotemporal spikes (BECTS), or rolandic epilepsy, is a common idiopathic partial epilepsy, manifesting mainly with hemifacial seizures and ictal oropharyngolaryngeal symptoms. No underlying cause other than a possible hereditary predisposition has been recognized, and the prognosis for remission is excellent [1,2]. Cases with a clinical and electroencephalographic phenotype of BECTS in association with a proven organic brain lesion have rarely been reported [3,4]. The pathogenetic mechanism of the epileptic discharges remains controversial, with some authors suggesting a direct relationship to the structural brain lesion [3], and others supporting the hypothesis of a coincidence [4]. We herein provide the first description of a patient with Wilson’s disease complicated with BECTS. Our case bolsters the argument that in
*
Corresponding author. Fax: +30 261 0993949. E-mail address: [email protected] (P. Polychronopoulos).
1525-5050/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2005.12.008
at least some cases, BECTS is associated with organic brain disease. 2. Case report A 9-year-old schoolgirl attending the outpatient pediatrics department reported a 2-year history of slowly progressive deterioration in school performance and a 1-year history of progressive dysarthria, sialorrhea, tremor, and unsteady gait. Her otherwise personal and familial medical history was negative. Neurological examination revealed emotional lability, bradykinesia, and generalized rigidity with postural and intention tremor involving the upper limbs. Dysgraphia, severe hypokinetic dysarthria, dysphagia accompanied by profuse drooling, and shuffling gait were also evident. Low plasma copper and ceruloplasmin concentrations, Kayser–Fleischer rings in the corneas, and a liver biopsy revealing increased copper content substantiated the diagnosis of Wilson’s disease (WD). Psychiatric evaluation revealed no abnormalities. The brain CT scan was normal, and an awake EEG showed rare and mild, diffuse,
Case Report / Epilepsy & Behavior 8 (2006) 438–441
nonspecific slow activity without focal or epileptiform discharges. The patient was placed on zinc acetate (150 mg/ day) and restriction of dietary copper (<1 mg/day) with satisfactory compliance. Seven months later she manifested clusters of focal seizures both during sleep and while awake. They were short in duration and simple partial in origin and occurred several times per day (20–25). The seizure activity consisted of clonic movements and paresthesias involving the left side of the face, lips, tongue, gums, and cheek. Occasionally, ictal activity was propagated to the left arm or the eyelid. Consciousness was fully retained during episodes, but the child was anarthric, trying to communicate with gestures. A new awake EEG showed epileptiform spikes in rolandic areas bilaterally, and maximum electronegativity (phase reversal) was observed at F3 or F4. The background was mildly slow. During sleep, epileptiform abnormalities were clearly activated and some bursts of spike–wave discharges appeared (Figs. 1A and B). High signal intensities on T2weighted images in the thalami and basal ganglia, more prominent on the right side were depicted, and mild diffuse brain atrophy and mild enlargement of lateral ventricles were also evident. Carbamazepine 400 mg daily was prescribed and resulted in complete remission of seizures shortly after administration. Five years later (still under the same treatment with zinc acetate and dietary copper restriction), she remains seizure-free despite discontinuation of carbamazepine 3 years earlier. Recent EEGs show mild, diffuse, nonspecific disturbances without epileptiform activity. Written informed consent was obtained from both parents of the child. 3. Discussion Occurrence of epilepsy in patients with WD is rarely reported [5,6]. Denning et al. [5] reported that WD carries a mildly elevated risk for epilepsy, estimated in less than 10% of cases. Although uncertain conclusions were drawn concerning the type of epilepsy and its clinical and electroencephalographic features, Denning and colleagues suggested that seizures, mostly of the partial type, may occur at any stage of the disease, and their prognosis does not significantly differ from that in general population surveys [5]. We reported on a child with rolandic seizures who also has a probably unrelated brain disease, i.e., WD. Rolandic seizures are very common, with a prevalence of 15% in children aged 1–15 with afebrile seizures and an incidence of 10–20 per 100,000 [2]. Hence, it should be expected that rolandic seizures can also occur in children with brain damage. With respect to the treatment for WD administered, it should be mentioned that our patient did not receive D-penicillamine, which has been linked to seizure activity [5]. She was treated with zinc acetate, which has an excellent safety profile. The only toxic effect is gastric irritation in 5–10% of patients [7].
439
Clinically, the age at onset and pattern of seizures in our case are characteristic and virtually diagnostic of the BECTS type of epilepsy [1]. Seizures began at the age of 9, were focal in origin, occurred during sleep, and consisted of unilateral facial sensorimotor symptoms, oropharyngolaryngeal manifestations, and speech arrest without impairment of consciousness. The seizures did not become more frequent, were responsive to carbamazepine, and failed to recur 3 years after its discontinuation. The electroencephalographic pattern showing rolandic high-voltage, usually diphasic spikes or sharp waves with prominent aftercoming slow waves is consistent with the BECTS electroencephalographic pattern [2]. These recordings are typical in their morphology, amplitude, duration, frequency, and pattern, but atypical in localization, due to the fact that although spikes were evident in T3, T4, C3, C4, F3, and F4, maximum electronegativity was observed at F3 or F4. Nevertheless, although in most children, spikes usually have a centrotemporal origin, atypical localizations are not uncommon [2,8]. Additionally, patients with purely centrotemporal spikes may have autonomic and not rolandic seizures [9]. The evidence of mildly slow background activity, presumably attributed to WD, is the only differentiation from the typical BECTS pattern. Brain MRI revealed no lesions in the rolandic or perirolandic areas. One could hypothesize that copper may accumulate in rolandic areas not visible on MRI, but the absence of relapse after discontinuation of therapy underlines the benign nature of this epilepsy [10]. The presence of the characteristic rolandic spikes alone is not diagnostic of BECTS. Age-related rolandic spikes may occur in 2–3% of normal nonepileptic children [2,11], and the rate is much higher in children with various brain diseases with or without seizures, such as Rett syndrome, fragile X syndrome, and cortical dysplasia [2]. Because of its prevalence, fortuitous associations may be found between BECTS and nonevolutional brain lesions [2,12]. Shevell et al. [13] reported on five children with cerebral tumors and an electroclinical phenotype suggestive of BECTS, and termed this disorder pseudo-BECTS. Many authors do not accept the occurrence of BECTS in children with brain damage, excluding them from their studies [14]. Loiseau [15] believed that epileptogenic focal cortical lesions can provoke focal motor seizures with an age-related expression of centrotemporal sharp waves. Gelisse et al. [4] found neuroimaging abnormalities in 14.8% of a population of children with BECTS, concluding that neuroimaging may be abnormal in such patients, whereas brain lesions had no influence on the prognosis. Our case supports this view, as recent EEGs did not show rolandic epileptiform activity, the patient is seizure-free despite discontinuation of carbamazepine, and MRI did not show clear evidence of organic lesions in the ‘‘perisylvian area.’’ Two main points of clinical importance are raised by this case report. First, the child experienced a very high seizure frequency (20–25/day), a fact that is relatively uncom-
440
Case Report / Epilepsy & Behavior 8 (2006) 438–441
Fig. 1. Sleep EEG showing frequent epileptiform activity bilaterally in the form of high-amplitude rolandic spikes or sharp waves (1–3 Hz) unilaterally or bilaterally. Maximum electronegativity was observed at F3 or F4. Both bipolar (A) and referential (B) montages are presented.
mon, as only a few articles have reported high seizure frequency in children with BECTS [16]. Second, the development of seizures in a child known to have WD would probably raise the possibility of a symptomatic and not
self-limiting epileptic syndrome. However, in this case of a girl with WD having daily seizures, rolandic epilepsy was benign and age-limited, irrespective of the associated metabolic disease.
Case Report / Epilepsy & Behavior 8 (2006) 438–441
In summary, in this case report, the age at onset, ictal clinical signs, interictal electroencephalographic pattern, negative neuroimaging findings, and favorable outcome led to the diagnosis of BECTS. To our knowledge, this is the first case of BECTS occurring in a patient known to have WD. References [1] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389– 99. [2] Panayiotopoulos CP. Benign childhood focal seizures and related epileptic syndromes. In: Panayiotopoulos CP, editor. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical; 2005. p. 223–70. [3] Degen R, Holthausen H, Pieper T, et al. Benign epileptic discharges in patients with lesional partial epilepsies. Pediatr Neurol 1999;20:354–9. [4] Gelisse P, Corda D, Raybaud C, et al. Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes. Epilepsia 2003;44:372–8. [5] Denning TR, Berrios GE, Walshe JM. Wilson’s disease and epilepsy. Brain 1988;111:1139–55.
441
[6] Saka E, Elibol B, Saygi S. Circling seizures in a case with Wilson’s disease. Clin Electroencephalogr 1999;30:118–21. [7] Brewer GJ, Askari FK. Wilson’s disease: clinical management and therapy. J Hepatol 2005;42(Suppl. 1):S13–21. [8] Wirrell EC. Benign epilepsy of childhood with centrotemporal spikes. Epilepsia 1998;39(Suppl. 4):S32–44. [9] Covanis A, Lada C, Skiadas K. Children with rolandic spikes and ictus emeticus: rolandic epilepsy or Panayiotopoulos syndrome? Epileptic Disord 2003;5:139–43. [10] Yoshi F, Takanashi W, Shinohara Y. A Wilson’s disease patient with prominent cerebral white matter lesions: five years follow-up by MRI. Eur Neurol 1996;36:392–3. [11] Lerman P, Kivity S. Focal epileptic EEG discharges in children not suffering from clinical epilepsy. Epilepsy Res Suppl 1992;6:99–103. [12] Santanelli P, Bureau M, Magauda A, Gobbi G, Roger J. Benign partial epilepsy with centrotemporal (or rolandic) spikes and brain lesion. Epilepsia 1989;30:182–8. [13] Shevell MI, Rosenblatt B, Watters GV, et al. ‘‘Pseudo-BECTS’’: intracranial focal lesions suggestive of a primary partial epilepsy syndrome. Pediatr Neurol 1996;14:31–5. [14] Loiseau P, Beaussart M. The seizures of benign childhood epilepsy with rolandic paroxysmal discharges. Epilepsia 1973;14:381–9. [15] Loiseau P. Benign focal epilepsies of childhood. In: Wyllie E, editor. The treatment of epilepsy. Philadelphia: Lea & Febiger; 1993. p. 509–12. [16] Ong HT, Willie E. Benign childhood epilepsy with centrotemporal spikes: is it always benign? Neurology 2000;54:1182–5.