Epilepsy & Behavior 36 (2014) 24–32
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Panayiotopoulos syndrome: A case series from Turkey Aydan Değerliyurt a,⁎, Serap Teber a, Ömer Bektaş a, Gözde Şenkon b a b
Department of Pediatric Neurology, Ankara Pediatrics, Hematology-Oncology Training and Research Hospital, Ankara, Turkey Department of Pediatrics, Ankara Pediatrics, Hematology-Oncology Training and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 23 March 2014 Revised 17 April 2014 Accepted 21 April 2014 Available online xxxx Keywords: Panayiotopoulos syndrome Early-onset benign occipital epilepsy Childhood autonomic epilepsy
a b s t r a c t The aim of the study was to evaluate the demographic, clinical, and EEG characteristics of patients with Panayiotopoulos syndrome (PS) and the course of their illness. Thirty-eight patients followed up with a diagnosis of PS between January 2011 and December 2013 were evaluated. We found high rates of personal history of febrile convulsions, breath-holding spells, and family history of febrile convulsions, afebrile convulsion/epilepsy, migraine, and breath-holding spells. Seizures started before the age of eight in 87% of the patients, and the mean age at seizure onset was 4.6 years. Seizures were sleep-related in 81.5%, and autonomic status was seen in a third of the patients. The number of seizures was between 2 and 10 in 66% of the patients. The most common symptoms were ictus emeticus, eye/head deviation, and altered consciousness. Rolandic features were seen in 26% of the patients, and visual symptoms in 5%. Multifocal epileptiform discharges on EEG were identified in 84% of the patients. Two or more antiepileptic drugs were required in only 13% of the patients. Evolution to electrical status epilepticus in sleep and Gastaut-type epilepsy were seen in patients with more than ten seizures. The high rates of febrile convulsions, afebrile convulsions/epilepsy, migraine, and breath-holding spells in the patients and families suggest the importance of genetic factors and, perhaps, a common pathogenesis. However, the high rates of febrile convulsions and breath-holding spells in patients can be related to a misdiagnosis because of the similar symptoms. Despite its disturbing symptoms, PS is a benign epileptic syndrome requiring multiple antiepileptic drug use only in a small proportion of patients. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Panayiotopoulos syndrome (PS), along with rolandic epilepsy (RE), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and idiopathic photosensitive occipital lobe epilepsy, is one of the benign seizure susceptibility syndromes of childhood, which are believed to be genetic and akin to each other [1]. It is a common epileptic syndrome seen in 6% of children with epilepsy the ages of 1 and 15 and in 13% between the ages of 3 and 6 with a history of one or more nonfebrile seizures [2]. Febrile convulsions (FCs) [3] and family history of convulsive disorder [4] are also common in PS [5]. Panayiotopoulos syndrome mainly consists of autonomic symptoms [6,7]. These symptoms are not usually considered as ictal epileptic symptoms when not accompanied by conventional seizure symptoms, and therefore attacks can be
Abbreviations: PS, Panayiotopoulos syndrome; RE, rolandic epilepsy; ICOE-G, idiopathic childhood occipital epilepsy of Gastaut; FCs, febrile convulsions; MRI, magnetic resonance imaging; BHS, breath-holding spells; ESES, electrical status epilepticus in sleep. ⁎ Corresponding author at: Bebek sokak, 9/7 Aydınlıkevler, Ankara, Turkey. Tel.: +90 312 596 97 16; fax: +90 312 347 23 30. E-mail address: [email protected] (A. Değerliyurt).
http://dx.doi.org/10.1016/j.yebeh.2014.04.018 1525-5050/© 2014 Elsevier Inc. All rights reserved.
often confused with other paroxysmal disorders, such as migraine, motion sickness, syncope, sleep terrors, and gastroenteritis, and with serious neurological disorders, such as encephalitis and intoxication [7,8]. Despite its frequency and having one of the best prognoses among the seizure disorders [9], Panayiotopoulos syndrome is stil not known as well as FC and RE [10], and this in turn causes delays in the diagnosis and exposure of the patients to unnecessary and sometimes even hazardous investigations and treatments. We aimed to emphasize the demographic and clinical characteristics and especially the autonomic symptoms as ictal seizure manifestations within this context and investigate the electrographic features and course of illness of patients with PS. 2. Patients and method Ankara Children's Health and Diseases Hematology-Oncology Training and Research Hospital's Department of Child Neurology is a reference center where 120–150 child neurology patients are seen daily. We retrospectively analyzed patients with PS seen at this center between January 2011 and December 2013 after being diagnosed by Drs. AD, ST, and ÖB and followed up for more than one year from their charts and computerized notes. All patients had a detailed history,
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neurological examinations, brain magnetic resonance imaging (MRI) examinations, and at least two EEGs, one while asleep. The PS diagnosis was made according to the following criteria [11,12]: 1. autonomic seizure semiology and/or simple focal motor seizures whether associated with loss of consciousness and secondary generalization or not; 2. occipital or extraoccipital spikes on interictal EEG or a normal EEG; 3. normal neurological examination and mental development; and 4. normal neuroimaging. Patients with genetic or metabolic–structural epilepsy, mental or motor retardation, or disorganized background activity on EEG and patients who did not come to follow-up after the first presentation were not included in the study even if they met the criteria for PS. However, 4 patients with a coincidental lesion on MRI were included in the study [13]. The patients were investigated in terms of kinship, FC, migraine, breath-holding spells (BHS) history; family history of epilepsy, FC, migraine and BHS; age at seizure onset, seizure frequency, circadian distribution, durations, detailed ictal symptoms, EEG findings, imaging findings, treatment, atypical course, and conversion to other epileptic syndromes. 3. Results 3.1. Demographic characteristics The mean follow-up duration was three years. A total of 38 patients with 21 males and 17 females were included in the study. The mean age at seizure onset was 4.6 years, ranging from 1 to 10.5 years. Seizure onset was before the age of eight in 87% of the patients. Thirteen percent of the patients had FCs, 31.5% had a family history of FCs, and 29% had a family history of afebrile convulsion or epilepsy, and all were in firstdegree relatives. Three patients had a family history of both FC and afebrile convulsion/epilepsy. In the patients, the frequency of migraine and BHS was 13% and 15.7%, respectively. A family history of migraine was found in 37% and a family history of BHS in 26% (Table 1). A couple of siblings of patients also had an uncle with seizures that had occurred during sleep and were accompanied by urinary and fecal incontinence. The disappearance of the seizures after the age of seven suggests the presence of PS in the uncle as well. Another female patient who had her first seizure at the age of 5.5 years had an aunt and a cousin with epilepsy. The cousin had also been followed by us. The cousin had experienced two convulsive seizures with fever while awake for the first time at the age of 9 and had been started on phenobarbital at another center and followed for two years. Afterwards, generalized epileptiform discharges sensitive to photic stimulation were found in the first EEG obtained at our center. No abnormality was found in the five control EEGs of the cousin who was not observed to have seizure recurrence in the five-year follow-up after discontinuation of the drug at our center. There was only one patient with a parent with epilepsy (father) among the patients with a family history. 3.2. Clinical characteristics The seizures occurred only in sleep or during both sleep and wakefulness in 81.5% of patients. Thirteen patients (34%) had a seizure duration of over 30 min. The number of seizures was only one in 18.4%, 2 to 10 in 66%, and more than 10 in 15.7% (Table 2). Ictal vomiting, retching, and nausea were the most common seizure symptoms seen in 90% of the patients. Deviation of the eyes or head in 58% of the patients; loss or fluctuations of consciousness, usually towards the end of the seizure, in 55%; consciousness alterations with behavioral changes at the beginning of the seizure such as waking up from sleep scared or crying and not recognizing the parents in 26%; vasomotor changes such as pallor in 37% and cyanosis in 18%; urinary/
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Table 1 Clinical and demographic features of the patients. Follow-up/years/mean (range) Patients Girls Boys Age at seizure onset/years/mean (range) Number of patients with: Single seizure 2–10 seizures 2–5 seizures 5–10 seizures ≥10 seizures Number of patients with seizures only during sleep Number of patients with seizures both during sleep and wakefulness Total number of patients with sleep-related seizures Seizures longer than 30 min Seizures without autonomic symptoms Atypical evolution to ESES Evolution to ICOE-Gastaut Consanguinity Number of sibling patients Febrile convulsions Breath-holding spells Migraine Family history of febrile convulsions Family history of afebrile convulsions or epilepsy Family history of febrile and afebrile convulsions or epilepsy (total) Family history of breath-holding spells Family history of migraine
3 (1–8.5) 38 17 (45%) 21 (55%) 4.6 (1–10.5) 7 (18.4%) 25 (65.7%) 17 (44.7%) 8 (21%) 6 (15.7%) 16 (42.1%) 15 (39.4%) 31 (81.5%) 13 (34%) 2 (5.2%) 3 (7.8%) 2 (5.2%) 6 (15.7%) One couple 5 (13.1%) 6 (15.7%) 5 (13.1%) 12 (31.5%) 11 (29%) 20 (52.6%) 10 (26.3%) 14 (36.8%)
fecal incontinence in 26%; and secondarily generalized seizures in 29% of the patients were the other common symptoms. Ictal syncope occurred in 21% of the patients. Changes in mood in the preseizure period such as fears without reason, fatigue, malaise, weakness, and nervousness during the day or half an hour before the seizure occurred in six patients (16%). The less common ictal symptoms were headache (15.7%), stomachache (13%), fever (13%), speech arrest (13%), hemiclonic seizures (10.4%), sweating (10.4%), hypersalivation (7.8%), oral twitching (5.2%), simple visual hallucination or blindness (5.2%), and diarrhea (5.2%). Coughing was seen in only one patient (2.6%). This six-year-
Table 2 Ictal features. Vomiting/retching/nausea Head/eye deviation Impairment of consciousness Pallor Cyanosis Secondarily generalized seizures Alteration of consciousness with behavioral changes like crying/fear/wandering Incontinence Rolandic features Speech arrest Oral twitching Hypersalivation Syncopal seizure Headache Stomachache Fever Hemiclonus Sweating Visual symptoms Diarrhea Cough Tachycardia (subjective)
34 (89.4%) 22 (57.8%) 21 (55.2%) 14 (36.8%) 7 (18.4%) 11 (29%) 10 (26.3%) 10 (26.3%) 10 (26.3%) 5 (13%) 2 (5.2%) 3 (7.8%) 8 (21%) 6 (15.7%) 5 (13%) 5 (13%) 4 (10.5%) 4 (10.5%) 2 (5.2%) 2 (5.2%) 1 (2.6%) 1 (2.6%)
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old patient woke up from sleep twice within an interval of 15 days with severe cough and mumbling and experienced a seizure lasting 10– 15 min characterized by contraction on one side, deviation of the eyes, and urinary incontinence. Tachycardia was the first symptom noticed by the family of another patient. It had been noticed by this patient's parents that her heart beats very fast during sleep, she could not swallow or breathe, and she showed fatigue, eye deviation, and pallor but no contractions or convulsions. She was confused for about an hour and vomited three times. Similar seizures occurred several times, and each time, she was reported to have a “fast heartbeat”. The family mentioned this symptom themselves without any query, and this was found to be significant in terms of tachycardia, despite lack of any ictal
monitoring. Seizures without autonomic symptoms were seen in two patients and only in their first seizures. 3.3. Electroencephalography findings EEG samples of the patients are shown in Fig. 1. Electroencephalography was performed two to nine times with a mean number of 3.6 times per patient during follow-up. Electroencephalographies most commonly revealed epileptiform abnormalities in the occipital region or together with frontal, centrotemporal, or parietal foci in 23 patients (60.5%). Generalized discharges were also seen in three of these patients. Only extraoccipital abnormalities were found in nine patients
Fig. 1. Electroencephalography samples of the patients.
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Fig. 1 (continued).
(23.6%). The EEGs of six patients was normal. Electrical status epilepticus in sleep (ESES) developed in two patients with generalized discharges on the EEG.
3.4. Neuroimaging Brain MRI examinations were performed for all patients. We found an arachnoid cyst in two patients, with one in the right temporobasal region and the other in the left anterior temporal region, and nonspecific hyperintensities lesions in the cerebellum in two patients, with one at the level of the vermis and the other at the level of the vermis junction and adjacent to the fourth ventricle. All other MRIs were normal.
3.5. Treatment and prognosis About three-quarters of the patients (74%) were started on only one antiepileptic drug. Five patients were not started on any antiepileptic drug at all. Double or triple antiepileptic drugs were started merely in three patients showing only evolution to ESES and in two patients with more than ten seizures. An atypical evolution to ESES was seen in half of the patients (3/6) with more than ten seizures. The male of the sibling patients developed seizures with visual symptoms in the form of complex hallucinations (seeing monsters) at the age of 11 after ESES has improved and a seizure-free period of three years. Seizures emerging with macropsy illusions developed in another male patient who had more than ten seizures. Both patients showing evolution to ICOE-G were in the group of patients with more than ten seizures.
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Fig. 1 (continued).
4. Discussion A high rate of FCs was found in our patients (13%) and their families (31.5%). These rates were reported to be 4.4–43.4% in patients and 10.8–16.6% in families in previous publications [4,6,10–14]. Febrile convulsions are an age-specific seizure disorder and frequently accompany PS, RE, and ICOE-G [1]; a common pathophysiological basis such as age-related susceptibility to benign seizures may be the reason for these high accompaniment rates. However, FC rates may also be reported as high in patients and families because the seizures seen in PS that emerge in early childhood that are accompanied by hyperthermia depending on autonomic thermoregulatory dysfunction, with patients recovering without complications, are incorrectly classified as FC. The history of our four-and-a-half-year-old patient who experienced fixed gaze,
floppiness, pallor, and urinary incontinence followed by right hemiclonic seizures that were stopped with intravenous diazepam injections in the emergency department revealed two previous febrile convulsions. Detailed questioning revealed that these seizures had been experienced during sleep and were associated with vomiting. This means that atypical febrile seizures that occur during sleep and are associated with autonomic symptoms [14] such as vomiting may be of epileptic origin especially if not convulsive [15] and can be incorrectly classified as FC. Epilepsy/afebrile convulsion history among relatives was also high in our group. The presence of sibling patients with an uncle with epilepsy, another patient with an aunt with epilepsy, and a cousin with probable photosensitive idiopathic epilepsy and the presence of a patient with a father with epilepsy in our group may support a genetic etiology.
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Fig. 1 (continued).
Similarly, the presence of many sibling cases in the literature [10,11, 16,17] and reports of a high rate of family history of epilepsy/seizure (27.6–54.2%) [4,11–14,18] are important findings in terms of a genetic etiology for PS [19]. Although SCN1A mutations have been shown in cases [20,21], especially in those that started early, had frequent seizures, and progressed with a severe clinical picture together with febrile illness, their absence in other patients suggests that SCN1A mutations only determine the severity of the disease but are not the main reason [17]. Migraine is seen with a frequency of 10–12% in adults [22] and 14% in schoolchildren [23]. Dysautonomia is thought to be among the responsible factors in the pathophysiology of migraine [24]. Disorders showing autonomic dysfunction such as syncopal events [25] and sleep terror [26] are commonly associated with migraine. A family history of migraine was found to be high (36.8%) in our group. Rolandic
epilepsy and migraine have recently been shown to be comorbid disorders [27]. Migraine can also be a comorbid disorder with PS because of the development of PS on a common genetic ground with RE [28]. This may be the reason for the high rate of migraine in families with PS. However, migraine frequency may not be as high in the patients as in families, because the patients with PS are young children, and young children less frequently manifest headaches with migraine as do older children and adults, and hence the symptoms in young children may not be identified with migraine. Breath holding associated with autonomic symptoms such as bradycardia-asystole (pallid syncope) or apnea (cyanotic syncope) is a nonepileptic paroxysmal disorder [29]. A history of BHS was found both in our patients (16%) and in the families (26%) at a rate above the general prevalence (3.6%) [30]. Although the high rates of BHS
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Fig. 1 (continued).
may indicate the presence of a common pathogenesis causing autonomic dysfunction, they may also be due to a misdiagnosis because of the similarity of some symptoms of BHS with PS. An eighteen-month-old female patient presented with a history of several sudden blackouts and cyanosis without any reason repeated every day for the last three days. She was flaccid and unresponsive during the attacks but had no emetic symptoms. The patient completely returned to normal after 3– 4 min. Cardiac examinations and the EEG taken twice were normal. The unprovoked attacks were thought to be ictal syncope-like seizures, and phenobarbital treatment was started. The unprovoked attacks of the patient did not repeat with treatment, and EEG obtained at the age of four after the discontinuation of the drug revealed generalized discharges (Fig. 1k). The seizures in PS can be confused with syncope when they are short and mild [31], and this kind of seizure may be
falsely interpreted as BHS when seen in infants and young children. The most important differentiating feature of this type of seizure from BHS is the lack of a provoking factor such as pain or anger. The seizures started before the age of eight in nearly 90% of our patients, and the mean age at seizure onset was 4.6 years. The seizures were sleep-related in most of the patients, and autonomic status was observed in one-third of the cases (Table 1). These results were consistent with the literature [1,9–13]. Seizure semiology in our series coincided with the typical symptoms of PS. Feeling bad at the onset of the seizure, followed by nausea, retching, or vomiting, was reported in 90% of the patients. Pallor or, less frequently, cyanosis, or urinary or fecal incontinence, often accompanies emetic symptoms. Fever that occurs only during the seizure and disappears after the seizure, found in five of our patients, was identified
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Fig. 1 (continued).
as an autonomic symptom. Headache is most commonly seen at the beginning of the seizure in PS [32]. Headache occurred before the autonomic symptoms and alteration of consciousness in five patients and subsequently other seizure symptoms were observed within minutes or hours. In one of these patients, headache continued for four days before the typical autonomic seizure during sleep. The headache emerged right after the seizure for 1–2 h in only one other patient. Ictal syncope, where the child is completely unresponsive and flaccid, is rare except in PS [6–9]. Ictal syncope can rarely be considered as an epileptic ictal sign if not accompanied by other autonomic signs [11,13,18,19]. Ictal syncope attacks occurring alone and independent of typical autonomic seizures in two patients were described as sudden and prolonged fainting by the families. Syncope usually lasts for a few seconds or 1– 2 min, [33], and the possibility of an ictal epileptic symptom should be considered if it lasts longer. Sweating, abdominal pain, diarrhea, and coughing were the other accompanying autonomic symptoms in our patients. Coughing has been rarely (2.2%) reported as an ictal autonomic symptom [13,34]. Seizures with visual symptoms were seen in two patients. One had a typical autonomic seizure followed by the hallucination of seeing a line, and the other experienced loss of vision followed by ocular deviation, nausea, and vomiting. Rolandic symptoms such as speech arrest, hypersalivation, and oral automatisms were accompanied by other autonomic symptoms in a total of 10 patients. These overlapping symptoms that are mainly seen in RE and ICOE-G support the view that these epileptic syndromes constitute a neurobiological spectrum [1,31,35]. Head/eye deviation was the most common nonautonomic symptom accompanying the seizures in our patients as in previous studies. Head and eye deviation is also seen in paroxysmal torticollis, a migraine precursor, and accompanies autonomic symptoms such as vomiting and pallor. Furthermore, the fact that a typical synchronous ictal EEG correspondence can hardly be shown as in other autonomic symptoms in PS [36] suggests that head deviation probably develops as a result of the activation of the central autonomic network, not due to the activation of any cortical area. Changes in consciousness with night terror-like behavioral symptoms in the form of waking up crying, agitation, fear, wandering in sleep, and consciousness changes progressing from absent-mindedness to complete loss of consciousness if awake usually follow autonomic
symptoms and are seen in more than half of the patients. If not accompanied by other seizure symptoms alterations of consciousness in sleep mimics sleep disorders and causes difficulties in differential diagnosis. When there is long-term altered consciousness together with such as vomiting and head/eye deviation in PS, confusion with serious neurological problems such as encephalitis or toxic encephalopathy is possible [37]. Rapid recovery from such a severe encephalopathic state with a few hours of sleep is typical for PS [1]. A patient in this series with autonomic symptoms who was thought to have a focal seizure because of vomiting, prolonged altered consciousness, and head deviation in the first attack was therefore initially diagnosed with viral encephalitis. Electroencephalography abnormalities in PS are now well known not only to be occipital but also multifocal and can vary greatly even in the same patient at different times [6,19,32]. The EEG abnormalities in our patients were similar to those in previous studies [18,19], and multifocal discharges were observed in the majority of patients (Fig. 1). Ictal EEG studies in PS have shown similar seizure semiology and sequence of ictal symptoms regardless of the initial spike localization [36]. None of the autonomic symptoms was found to be associated with EEG discharges in a specific area [36]. Despite the marked and prolonged focal discharges in the EEG, there are few focal clinical nonautonomic symptoms consistent with these discharges [36]. Recorded ictal discharges mainly consist of rhythmic theta or delta activities, and small spikes among them suggest that the electrical activity reflected in the scalp EEG belongs to the inhibitory activity around the original discharge source [38]. Cortical clinical manifestations consistent with electrographic findings may not be observed in patients with PS as the epileptic discharges in PS may originate from the subcortical central autonomic network, notably the hypothalamus [38] and pons/medulla. More than ten seizures can be seen in 5–23% of the cases in PS [8,11, 18], and these were experienced by 15.7% of our patients. Only 13% of our patients required double or triple antiepileptic drug treatment. Electrical status epilepticus in sleep developed in half of the patients who had more than ten seizures. Evolution to ESES has been reported in about 3% of patients with PS in the literature [11,12], but no relationship between the evolution to ESES and the frequency of seizures was mentioned previously. In addition, two patients who went on to have seizures with visual symptoms were in the group that had more than
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ten seizures. These results suggest that cases with a large number of seizures might have an atypical course with more frequent evolution to ESES and other epilepsies. Evolution to ICOE-G appeared only in two patients of this series. Although rare, the emergence of ICOE-G in patients with PS [10,12] supports the view that these entities are variances of the benign childhood seizure susceptibility syndrome characterized by various age-related EEG and clinical symptoms [1]. The follow-up of two patients is peculiar. In one of them, two seizures with fever occurred on the same day during perforated appendicitis treatment after a three-year seizure-free period following two autonomic seizures. This suggests that fever is a precipitating factor for seizures in PS [14]. The other patient had an autonomic seizure 6 months after discontinuation of medication at the age of 14 and after a 5-year seizure-free period. This patient had more than ten seizures, and his seizures were accompanied by fever. This case suggests that seizure recurrence may occur after a very long seizure-free period and even at an age that may be considered advanced for PS. 5. Conclusion The presence of a history of afebrile convulsions/epilepsy or febrile convulsions in the first-degree relatives in half of the patients with PS shows that genetic factors are important in the etiology. The high rate of febrile seizures may be due to the wrong interpretation of a seizure accompanied by hyperthermia as a febrile convulsion. If a ‘febrile seizure’, especially one that occurs in sleep, is accompanied by autonomic symptoms such as vomiting and is not convulsive, and if the fever recovers immediately after the seizure, it may be of epileptic origin. The high rate of BHS in patients and a family history of migraine and BHS may indicate a common pathophysiological or genetic basis. However, ictal syncope-like seizures not accompanied by other autonomic symptoms except cyanosis or pallor being misdiagnosed as BHS in young children may also be the reason. An isolated ictal syncope can also be confused with nonictal syncope.. The appearance of visual/rolandic symptoms together with PS and evolution into ICOE-G supports the presence of clinical variants emerging according to age on a common benign childhood seizure susceptibility syndrome background. In summary, Panayiotopoulos syndrome is a benign epileptic syndrome, requiring two or more antiepileptic drugs in a small proportion of patients. Transition to ESES or other epilepsies is more common in patients with frequent seizures. Fever is a precipitating factor in PS. Conflict of interest None of the authors has any conflict of interest to disclose. References [1] Panayiotopoulos CP, Michael M, Sanders S, Valeta T, Koutroumanidis M. Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. Brain 2008;131:2264–86. [2] Panayiotopoulos CP. Panayiotopoulos syndrome: a common and benign childhood epileptic syndrome. London: John Libbey & Company; 2002. [3] Oguni H, Hayashi K, Imai K, Hirano Y, Mutoh A, Osawa M. Study on the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early onset benign occipital seizure susceptibility syndrome. Epilepsia 1999;40:1020–30. [4] Ohtsu M, Oguni H, Hayashi K, Funatsuka M, Imai K, Osawa M. EEG in children with early-onset benign occipital seizure susceptibility syndrome: Panayiotopoulos syndrome. Epilepsia 2003;44:435–42. [5] Caraballo R, Cersosimo R, Medina C, Fejerman N. Panayiotopoulos-type benign childhood occipital epilepsy. Neurology 2000;55:1096–100. [6] Michael M, Tsatsou K, Ferrie CD. Panayiotopoulos syndrome: an important childhood autonomic epilepsy to be differentiated from occipital epilepsy and acute non-epileptic disorders. Brain Dev 2010;32:4–9.
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Benign childhood partial epilepsies: benign childhood seizure susceptibility syndromes. J Neurol Neurosurg Psychiatry 1993;56:2–5. [29] Goyal M, Avery JA. Paroxysmal disorders and the autonomic nervous system in pediatrics. Am J END Technol 2005;45:240–7. [30] Çarman KB, Ekici A, Yimenicioğlu S, Arslantaş D, Yakut A. Breath holding spells: point prevalence and associated factors among Turkish children. Pediatr Int 2013;55:328–31. [31] Koutroumanidis M. Panayiotopoulos syndrome: an important electroclinical example of benign childhood system epilepsy. Epilepsia 2007;48:1044–53. [32] Covanis A, Panayiotopoulos CP. Improving the diagnostic yield in Panayiotopoulos syndrome. Eur J Neurol 2008;15:317–9. [33] Moodley M. Clinical approach to syncope in children. Semin Pediatr Neurol 2013;20:12–7. [34] Koutroumanidis M, Rowlinson S, Sanders S. Recurrent autonomic status epilepticus in Panayiotopoulos syndrome: video/EEG studies. Epilepsy Behav 2005;7:543–7. 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Panayiotopoulos syndrome: A case series from Turkey Aydan Değerliyurt a,⁎, Serap Teber a, Ömer Bektaş a, Gözde Şenkon b a b
Department of Pediatric Neurology, Ankara Pediatrics, Hematology-Oncology Training and Research Hospital, Ankara, Turkey Department of Pediatrics, Ankara Pediatrics, Hematology-Oncology Training and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 23 March 2014 Revised 17 April 2014 Accepted 21 April 2014 Available online xxxx Keywords: Panayiotopoulos syndrome Early-onset benign occipital epilepsy Childhood autonomic epilepsy
a b s t r a c t The aim of the study was to evaluate the demographic, clinical, and EEG characteristics of patients with Panayiotopoulos syndrome (PS) and the course of their illness. Thirty-eight patients followed up with a diagnosis of PS between January 2011 and December 2013 were evaluated. We found high rates of personal history of febrile convulsions, breath-holding spells, and family history of febrile convulsions, afebrile convulsion/epilepsy, migraine, and breath-holding spells. Seizures started before the age of eight in 87% of the patients, and the mean age at seizure onset was 4.6 years. Seizures were sleep-related in 81.5%, and autonomic status was seen in a third of the patients. The number of seizures was between 2 and 10 in 66% of the patients. The most common symptoms were ictus emeticus, eye/head deviation, and altered consciousness. Rolandic features were seen in 26% of the patients, and visual symptoms in 5%. Multifocal epileptiform discharges on EEG were identified in 84% of the patients. Two or more antiepileptic drugs were required in only 13% of the patients. Evolution to electrical status epilepticus in sleep and Gastaut-type epilepsy were seen in patients with more than ten seizures. The high rates of febrile convulsions, afebrile convulsions/epilepsy, migraine, and breath-holding spells in the patients and families suggest the importance of genetic factors and, perhaps, a common pathogenesis. However, the high rates of febrile convulsions and breath-holding spells in patients can be related to a misdiagnosis because of the similar symptoms. Despite its disturbing symptoms, PS is a benign epileptic syndrome requiring multiple antiepileptic drug use only in a small proportion of patients. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Panayiotopoulos syndrome (PS), along with rolandic epilepsy (RE), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and idiopathic photosensitive occipital lobe epilepsy, is one of the benign seizure susceptibility syndromes of childhood, which are believed to be genetic and akin to each other [1]. It is a common epileptic syndrome seen in 6% of children with epilepsy the ages of 1 and 15 and in 13% between the ages of 3 and 6 with a history of one or more nonfebrile seizures [2]. Febrile convulsions (FCs) [3] and family history of convulsive disorder [4] are also common in PS [5]. Panayiotopoulos syndrome mainly consists of autonomic symptoms [6,7]. These symptoms are not usually considered as ictal epileptic symptoms when not accompanied by conventional seizure symptoms, and therefore attacks can be
Abbreviations: PS, Panayiotopoulos syndrome; RE, rolandic epilepsy; ICOE-G, idiopathic childhood occipital epilepsy of Gastaut; FCs, febrile convulsions; MRI, magnetic resonance imaging; BHS, breath-holding spells; ESES, electrical status epilepticus in sleep. ⁎ Corresponding author at: Bebek sokak, 9/7 Aydınlıkevler, Ankara, Turkey. Tel.: +90 312 596 97 16; fax: +90 312 347 23 30. E-mail address: [email protected] (A. Değerliyurt).
http://dx.doi.org/10.1016/j.yebeh.2014.04.018 1525-5050/© 2014 Elsevier Inc. All rights reserved.
often confused with other paroxysmal disorders, such as migraine, motion sickness, syncope, sleep terrors, and gastroenteritis, and with serious neurological disorders, such as encephalitis and intoxication [7,8]. Despite its frequency and having one of the best prognoses among the seizure disorders [9], Panayiotopoulos syndrome is stil not known as well as FC and RE [10], and this in turn causes delays in the diagnosis and exposure of the patients to unnecessary and sometimes even hazardous investigations and treatments. We aimed to emphasize the demographic and clinical characteristics and especially the autonomic symptoms as ictal seizure manifestations within this context and investigate the electrographic features and course of illness of patients with PS. 2. Patients and method Ankara Children's Health and Diseases Hematology-Oncology Training and Research Hospital's Department of Child Neurology is a reference center where 120–150 child neurology patients are seen daily. We retrospectively analyzed patients with PS seen at this center between January 2011 and December 2013 after being diagnosed by Drs. AD, ST, and ÖB and followed up for more than one year from their charts and computerized notes. All patients had a detailed history,
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neurological examinations, brain magnetic resonance imaging (MRI) examinations, and at least two EEGs, one while asleep. The PS diagnosis was made according to the following criteria [11,12]: 1. autonomic seizure semiology and/or simple focal motor seizures whether associated with loss of consciousness and secondary generalization or not; 2. occipital or extraoccipital spikes on interictal EEG or a normal EEG; 3. normal neurological examination and mental development; and 4. normal neuroimaging. Patients with genetic or metabolic–structural epilepsy, mental or motor retardation, or disorganized background activity on EEG and patients who did not come to follow-up after the first presentation were not included in the study even if they met the criteria for PS. However, 4 patients with a coincidental lesion on MRI were included in the study [13]. The patients were investigated in terms of kinship, FC, migraine, breath-holding spells (BHS) history; family history of epilepsy, FC, migraine and BHS; age at seizure onset, seizure frequency, circadian distribution, durations, detailed ictal symptoms, EEG findings, imaging findings, treatment, atypical course, and conversion to other epileptic syndromes. 3. Results 3.1. Demographic characteristics The mean follow-up duration was three years. A total of 38 patients with 21 males and 17 females were included in the study. The mean age at seizure onset was 4.6 years, ranging from 1 to 10.5 years. Seizure onset was before the age of eight in 87% of the patients. Thirteen percent of the patients had FCs, 31.5% had a family history of FCs, and 29% had a family history of afebrile convulsion or epilepsy, and all were in firstdegree relatives. Three patients had a family history of both FC and afebrile convulsion/epilepsy. In the patients, the frequency of migraine and BHS was 13% and 15.7%, respectively. A family history of migraine was found in 37% and a family history of BHS in 26% (Table 1). A couple of siblings of patients also had an uncle with seizures that had occurred during sleep and were accompanied by urinary and fecal incontinence. The disappearance of the seizures after the age of seven suggests the presence of PS in the uncle as well. Another female patient who had her first seizure at the age of 5.5 years had an aunt and a cousin with epilepsy. The cousin had also been followed by us. The cousin had experienced two convulsive seizures with fever while awake for the first time at the age of 9 and had been started on phenobarbital at another center and followed for two years. Afterwards, generalized epileptiform discharges sensitive to photic stimulation were found in the first EEG obtained at our center. No abnormality was found in the five control EEGs of the cousin who was not observed to have seizure recurrence in the five-year follow-up after discontinuation of the drug at our center. There was only one patient with a parent with epilepsy (father) among the patients with a family history. 3.2. Clinical characteristics The seizures occurred only in sleep or during both sleep and wakefulness in 81.5% of patients. Thirteen patients (34%) had a seizure duration of over 30 min. The number of seizures was only one in 18.4%, 2 to 10 in 66%, and more than 10 in 15.7% (Table 2). Ictal vomiting, retching, and nausea were the most common seizure symptoms seen in 90% of the patients. Deviation of the eyes or head in 58% of the patients; loss or fluctuations of consciousness, usually towards the end of the seizure, in 55%; consciousness alterations with behavioral changes at the beginning of the seizure such as waking up from sleep scared or crying and not recognizing the parents in 26%; vasomotor changes such as pallor in 37% and cyanosis in 18%; urinary/
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Table 1 Clinical and demographic features of the patients. Follow-up/years/mean (range) Patients Girls Boys Age at seizure onset/years/mean (range) Number of patients with: Single seizure 2–10 seizures 2–5 seizures 5–10 seizures ≥10 seizures Number of patients with seizures only during sleep Number of patients with seizures both during sleep and wakefulness Total number of patients with sleep-related seizures Seizures longer than 30 min Seizures without autonomic symptoms Atypical evolution to ESES Evolution to ICOE-Gastaut Consanguinity Number of sibling patients Febrile convulsions Breath-holding spells Migraine Family history of febrile convulsions Family history of afebrile convulsions or epilepsy Family history of febrile and afebrile convulsions or epilepsy (total) Family history of breath-holding spells Family history of migraine
3 (1–8.5) 38 17 (45%) 21 (55%) 4.6 (1–10.5) 7 (18.4%) 25 (65.7%) 17 (44.7%) 8 (21%) 6 (15.7%) 16 (42.1%) 15 (39.4%) 31 (81.5%) 13 (34%) 2 (5.2%) 3 (7.8%) 2 (5.2%) 6 (15.7%) One couple 5 (13.1%) 6 (15.7%) 5 (13.1%) 12 (31.5%) 11 (29%) 20 (52.6%) 10 (26.3%) 14 (36.8%)
fecal incontinence in 26%; and secondarily generalized seizures in 29% of the patients were the other common symptoms. Ictal syncope occurred in 21% of the patients. Changes in mood in the preseizure period such as fears without reason, fatigue, malaise, weakness, and nervousness during the day or half an hour before the seizure occurred in six patients (16%). The less common ictal symptoms were headache (15.7%), stomachache (13%), fever (13%), speech arrest (13%), hemiclonic seizures (10.4%), sweating (10.4%), hypersalivation (7.8%), oral twitching (5.2%), simple visual hallucination or blindness (5.2%), and diarrhea (5.2%). Coughing was seen in only one patient (2.6%). This six-year-
Table 2 Ictal features. Vomiting/retching/nausea Head/eye deviation Impairment of consciousness Pallor Cyanosis Secondarily generalized seizures Alteration of consciousness with behavioral changes like crying/fear/wandering Incontinence Rolandic features Speech arrest Oral twitching Hypersalivation Syncopal seizure Headache Stomachache Fever Hemiclonus Sweating Visual symptoms Diarrhea Cough Tachycardia (subjective)
34 (89.4%) 22 (57.8%) 21 (55.2%) 14 (36.8%) 7 (18.4%) 11 (29%) 10 (26.3%) 10 (26.3%) 10 (26.3%) 5 (13%) 2 (5.2%) 3 (7.8%) 8 (21%) 6 (15.7%) 5 (13%) 5 (13%) 4 (10.5%) 4 (10.5%) 2 (5.2%) 2 (5.2%) 1 (2.6%) 1 (2.6%)
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old patient woke up from sleep twice within an interval of 15 days with severe cough and mumbling and experienced a seizure lasting 10– 15 min characterized by contraction on one side, deviation of the eyes, and urinary incontinence. Tachycardia was the first symptom noticed by the family of another patient. It had been noticed by this patient's parents that her heart beats very fast during sleep, she could not swallow or breathe, and she showed fatigue, eye deviation, and pallor but no contractions or convulsions. She was confused for about an hour and vomited three times. Similar seizures occurred several times, and each time, she was reported to have a “fast heartbeat”. The family mentioned this symptom themselves without any query, and this was found to be significant in terms of tachycardia, despite lack of any ictal
monitoring. Seizures without autonomic symptoms were seen in two patients and only in their first seizures. 3.3. Electroencephalography findings EEG samples of the patients are shown in Fig. 1. Electroencephalography was performed two to nine times with a mean number of 3.6 times per patient during follow-up. Electroencephalographies most commonly revealed epileptiform abnormalities in the occipital region or together with frontal, centrotemporal, or parietal foci in 23 patients (60.5%). Generalized discharges were also seen in three of these patients. Only extraoccipital abnormalities were found in nine patients
Fig. 1. Electroencephalography samples of the patients.
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Fig. 1 (continued).
(23.6%). The EEGs of six patients was normal. Electrical status epilepticus in sleep (ESES) developed in two patients with generalized discharges on the EEG.
3.4. Neuroimaging Brain MRI examinations were performed for all patients. We found an arachnoid cyst in two patients, with one in the right temporobasal region and the other in the left anterior temporal region, and nonspecific hyperintensities lesions in the cerebellum in two patients, with one at the level of the vermis and the other at the level of the vermis junction and adjacent to the fourth ventricle. All other MRIs were normal.
3.5. Treatment and prognosis About three-quarters of the patients (74%) were started on only one antiepileptic drug. Five patients were not started on any antiepileptic drug at all. Double or triple antiepileptic drugs were started merely in three patients showing only evolution to ESES and in two patients with more than ten seizures. An atypical evolution to ESES was seen in half of the patients (3/6) with more than ten seizures. The male of the sibling patients developed seizures with visual symptoms in the form of complex hallucinations (seeing monsters) at the age of 11 after ESES has improved and a seizure-free period of three years. Seizures emerging with macropsy illusions developed in another male patient who had more than ten seizures. Both patients showing evolution to ICOE-G were in the group of patients with more than ten seizures.
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Fig. 1 (continued).
4. Discussion A high rate of FCs was found in our patients (13%) and their families (31.5%). These rates were reported to be 4.4–43.4% in patients and 10.8–16.6% in families in previous publications [4,6,10–14]. Febrile convulsions are an age-specific seizure disorder and frequently accompany PS, RE, and ICOE-G [1]; a common pathophysiological basis such as age-related susceptibility to benign seizures may be the reason for these high accompaniment rates. However, FC rates may also be reported as high in patients and families because the seizures seen in PS that emerge in early childhood that are accompanied by hyperthermia depending on autonomic thermoregulatory dysfunction, with patients recovering without complications, are incorrectly classified as FC. The history of our four-and-a-half-year-old patient who experienced fixed gaze,
floppiness, pallor, and urinary incontinence followed by right hemiclonic seizures that were stopped with intravenous diazepam injections in the emergency department revealed two previous febrile convulsions. Detailed questioning revealed that these seizures had been experienced during sleep and were associated with vomiting. This means that atypical febrile seizures that occur during sleep and are associated with autonomic symptoms [14] such as vomiting may be of epileptic origin especially if not convulsive [15] and can be incorrectly classified as FC. Epilepsy/afebrile convulsion history among relatives was also high in our group. The presence of sibling patients with an uncle with epilepsy, another patient with an aunt with epilepsy, and a cousin with probable photosensitive idiopathic epilepsy and the presence of a patient with a father with epilepsy in our group may support a genetic etiology.
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29
Fig. 1 (continued).
Similarly, the presence of many sibling cases in the literature [10,11, 16,17] and reports of a high rate of family history of epilepsy/seizure (27.6–54.2%) [4,11–14,18] are important findings in terms of a genetic etiology for PS [19]. Although SCN1A mutations have been shown in cases [20,21], especially in those that started early, had frequent seizures, and progressed with a severe clinical picture together with febrile illness, their absence in other patients suggests that SCN1A mutations only determine the severity of the disease but are not the main reason [17]. Migraine is seen with a frequency of 10–12% in adults [22] and 14% in schoolchildren [23]. Dysautonomia is thought to be among the responsible factors in the pathophysiology of migraine [24]. Disorders showing autonomic dysfunction such as syncopal events [25] and sleep terror [26] are commonly associated with migraine. A family history of migraine was found to be high (36.8%) in our group. Rolandic
epilepsy and migraine have recently been shown to be comorbid disorders [27]. Migraine can also be a comorbid disorder with PS because of the development of PS on a common genetic ground with RE [28]. This may be the reason for the high rate of migraine in families with PS. However, migraine frequency may not be as high in the patients as in families, because the patients with PS are young children, and young children less frequently manifest headaches with migraine as do older children and adults, and hence the symptoms in young children may not be identified with migraine. Breath holding associated with autonomic symptoms such as bradycardia-asystole (pallid syncope) or apnea (cyanotic syncope) is a nonepileptic paroxysmal disorder [29]. A history of BHS was found both in our patients (16%) and in the families (26%) at a rate above the general prevalence (3.6%) [30]. Although the high rates of BHS
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Fig. 1 (continued).
may indicate the presence of a common pathogenesis causing autonomic dysfunction, they may also be due to a misdiagnosis because of the similarity of some symptoms of BHS with PS. An eighteen-month-old female patient presented with a history of several sudden blackouts and cyanosis without any reason repeated every day for the last three days. She was flaccid and unresponsive during the attacks but had no emetic symptoms. The patient completely returned to normal after 3– 4 min. Cardiac examinations and the EEG taken twice were normal. The unprovoked attacks were thought to be ictal syncope-like seizures, and phenobarbital treatment was started. The unprovoked attacks of the patient did not repeat with treatment, and EEG obtained at the age of four after the discontinuation of the drug revealed generalized discharges (Fig. 1k). The seizures in PS can be confused with syncope when they are short and mild [31], and this kind of seizure may be
falsely interpreted as BHS when seen in infants and young children. The most important differentiating feature of this type of seizure from BHS is the lack of a provoking factor such as pain or anger. The seizures started before the age of eight in nearly 90% of our patients, and the mean age at seizure onset was 4.6 years. The seizures were sleep-related in most of the patients, and autonomic status was observed in one-third of the cases (Table 1). These results were consistent with the literature [1,9–13]. Seizure semiology in our series coincided with the typical symptoms of PS. Feeling bad at the onset of the seizure, followed by nausea, retching, or vomiting, was reported in 90% of the patients. Pallor or, less frequently, cyanosis, or urinary or fecal incontinence, often accompanies emetic symptoms. Fever that occurs only during the seizure and disappears after the seizure, found in five of our patients, was identified
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31
Fig. 1 (continued).
as an autonomic symptom. Headache is most commonly seen at the beginning of the seizure in PS [32]. Headache occurred before the autonomic symptoms and alteration of consciousness in five patients and subsequently other seizure symptoms were observed within minutes or hours. In one of these patients, headache continued for four days before the typical autonomic seizure during sleep. The headache emerged right after the seizure for 1–2 h in only one other patient. Ictal syncope, where the child is completely unresponsive and flaccid, is rare except in PS [6–9]. Ictal syncope can rarely be considered as an epileptic ictal sign if not accompanied by other autonomic signs [11,13,18,19]. Ictal syncope attacks occurring alone and independent of typical autonomic seizures in two patients were described as sudden and prolonged fainting by the families. Syncope usually lasts for a few seconds or 1– 2 min, [33], and the possibility of an ictal epileptic symptom should be considered if it lasts longer. Sweating, abdominal pain, diarrhea, and coughing were the other accompanying autonomic symptoms in our patients. Coughing has been rarely (2.2%) reported as an ictal autonomic symptom [13,34]. Seizures with visual symptoms were seen in two patients. One had a typical autonomic seizure followed by the hallucination of seeing a line, and the other experienced loss of vision followed by ocular deviation, nausea, and vomiting. Rolandic symptoms such as speech arrest, hypersalivation, and oral automatisms were accompanied by other autonomic symptoms in a total of 10 patients. These overlapping symptoms that are mainly seen in RE and ICOE-G support the view that these epileptic syndromes constitute a neurobiological spectrum [1,31,35]. Head/eye deviation was the most common nonautonomic symptom accompanying the seizures in our patients as in previous studies. Head and eye deviation is also seen in paroxysmal torticollis, a migraine precursor, and accompanies autonomic symptoms such as vomiting and pallor. Furthermore, the fact that a typical synchronous ictal EEG correspondence can hardly be shown as in other autonomic symptoms in PS [36] suggests that head deviation probably develops as a result of the activation of the central autonomic network, not due to the activation of any cortical area. Changes in consciousness with night terror-like behavioral symptoms in the form of waking up crying, agitation, fear, wandering in sleep, and consciousness changes progressing from absent-mindedness to complete loss of consciousness if awake usually follow autonomic
symptoms and are seen in more than half of the patients. If not accompanied by other seizure symptoms alterations of consciousness in sleep mimics sleep disorders and causes difficulties in differential diagnosis. When there is long-term altered consciousness together with such as vomiting and head/eye deviation in PS, confusion with serious neurological problems such as encephalitis or toxic encephalopathy is possible [37]. Rapid recovery from such a severe encephalopathic state with a few hours of sleep is typical for PS [1]. A patient in this series with autonomic symptoms who was thought to have a focal seizure because of vomiting, prolonged altered consciousness, and head deviation in the first attack was therefore initially diagnosed with viral encephalitis. Electroencephalography abnormalities in PS are now well known not only to be occipital but also multifocal and can vary greatly even in the same patient at different times [6,19,32]. The EEG abnormalities in our patients were similar to those in previous studies [18,19], and multifocal discharges were observed in the majority of patients (Fig. 1). Ictal EEG studies in PS have shown similar seizure semiology and sequence of ictal symptoms regardless of the initial spike localization [36]. None of the autonomic symptoms was found to be associated with EEG discharges in a specific area [36]. Despite the marked and prolonged focal discharges in the EEG, there are few focal clinical nonautonomic symptoms consistent with these discharges [36]. Recorded ictal discharges mainly consist of rhythmic theta or delta activities, and small spikes among them suggest that the electrical activity reflected in the scalp EEG belongs to the inhibitory activity around the original discharge source [38]. Cortical clinical manifestations consistent with electrographic findings may not be observed in patients with PS as the epileptic discharges in PS may originate from the subcortical central autonomic network, notably the hypothalamus [38] and pons/medulla. More than ten seizures can be seen in 5–23% of the cases in PS [8,11, 18], and these were experienced by 15.7% of our patients. Only 13% of our patients required double or triple antiepileptic drug treatment. Electrical status epilepticus in sleep developed in half of the patients who had more than ten seizures. Evolution to ESES has been reported in about 3% of patients with PS in the literature [11,12], but no relationship between the evolution to ESES and the frequency of seizures was mentioned previously. In addition, two patients who went on to have seizures with visual symptoms were in the group that had more than
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ten seizures. These results suggest that cases with a large number of seizures might have an atypical course with more frequent evolution to ESES and other epilepsies. Evolution to ICOE-G appeared only in two patients of this series. Although rare, the emergence of ICOE-G in patients with PS [10,12] supports the view that these entities are variances of the benign childhood seizure susceptibility syndrome characterized by various age-related EEG and clinical symptoms [1]. The follow-up of two patients is peculiar. In one of them, two seizures with fever occurred on the same day during perforated appendicitis treatment after a three-year seizure-free period following two autonomic seizures. This suggests that fever is a precipitating factor for seizures in PS [14]. The other patient had an autonomic seizure 6 months after discontinuation of medication at the age of 14 and after a 5-year seizure-free period. This patient had more than ten seizures, and his seizures were accompanied by fever. This case suggests that seizure recurrence may occur after a very long seizure-free period and even at an age that may be considered advanced for PS. 5. Conclusion The presence of a history of afebrile convulsions/epilepsy or febrile convulsions in the first-degree relatives in half of the patients with PS shows that genetic factors are important in the etiology. The high rate of febrile seizures may be due to the wrong interpretation of a seizure accompanied by hyperthermia as a febrile convulsion. If a ‘febrile seizure’, especially one that occurs in sleep, is accompanied by autonomic symptoms such as vomiting and is not convulsive, and if the fever recovers immediately after the seizure, it may be of epileptic origin. The high rate of BHS in patients and a family history of migraine and BHS may indicate a common pathophysiological or genetic basis. However, ictal syncope-like seizures not accompanied by other autonomic symptoms except cyanosis or pallor being misdiagnosed as BHS in young children may also be the reason. An isolated ictal syncope can also be confused with nonictal syncope.. The appearance of visual/rolandic symptoms together with PS and evolution into ICOE-G supports the presence of clinical variants emerging according to age on a common benign childhood seizure susceptibility syndrome background. In summary, Panayiotopoulos syndrome is a benign epileptic syndrome, requiring two or more antiepileptic drugs in a small proportion of patients. Transition to ESES or other epilepsies is more common in patients with frequent seizures. Fever is a precipitating factor in PS. Conflict of interest None of the authors has any conflict of interest to disclose. References [1] Panayiotopoulos CP, Michael M, Sanders S, Valeta T, Koutroumanidis M. Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. Brain 2008;131:2264–86. [2] Panayiotopoulos CP. Panayiotopoulos syndrome: a common and benign childhood epileptic syndrome. London: John Libbey & Company; 2002. [3] Oguni H, Hayashi K, Imai K, Hirano Y, Mutoh A, Osawa M. Study on the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early onset benign occipital seizure susceptibility syndrome. Epilepsia 1999;40:1020–30. [4] Ohtsu M, Oguni H, Hayashi K, Funatsuka M, Imai K, Osawa M. EEG in children with early-onset benign occipital seizure susceptibility syndrome: Panayiotopoulos syndrome. Epilepsia 2003;44:435–42. [5] Caraballo R, Cersosimo R, Medina C, Fejerman N. Panayiotopoulos-type benign childhood occipital epilepsy. Neurology 2000;55:1096–100. [6] Michael M, Tsatsou K, Ferrie CD. Panayiotopoulos syndrome: an important childhood autonomic epilepsy to be differentiated from occipital epilepsy and acute non-epileptic disorders. Brain Dev 2010;32:4–9.
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