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Atypical evolution of Panayiotopoulos syndrome: a case report [published with videosequences]. Volume 4, numéro 1, March 2002

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  • Atypical evolution of Panayiotopoulos syndrome: a case report

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Panayiotopoulos syndrome [1] has been thoroughly documented in over 600 cases around the world [2-6]. It has been included in the proposal for revision of the current classification scheme by the ILAE Task Force for Classification and Terminology [7], and recently attracted considerable interest in the medical community beyond epileptologists [1, 8-10]. It manifests mainly with autonomic seizures (80%), half of which constitute autonomic status epilepticus [1-6]. It affects around 13% of children, 3-6 years old with one or more non-febrile seizures and 6% of the age group 1-15 [6, 11]. The EEG is characterised by multifocal spikes that predominate in the posterior regions. The EEG may have extra-occipital spikes only, or be consistently normal [6]. Though erroneously recognised as occipital epilepsy [7], the clinical and EEG features of Panayiotopoulos syndrome support a diffuse brain epileptogenesis that generates similar seizures from various locations [6, 12]. Ictal EEG documents that the seizure may start either from the posterior [13, 14] or frontal regions [3]. Panayiotopoulos syndrome is a remarkably benign condition despite the high incidence of autonomic status epilepticus [1-6, 11]. Even after the most severe seizures and status, the patient recovers within a few hours. Lengthy seizures and status are not followed by residual deficits, do not have any adverse prognostic significance and the risk of developing epilepsy in adult life is probably no more than for the general population [6]. In contrast, even febrile seizures, if lengthy, are associated with a higher risk of developing "epilepsy" [15]. There is no evidence of neuro-psychological impairment. Many children with Panayiotopoulos syndrome perform with distinction at school; of those with long follow-up, many have excellent professional records [6]. Remission usually occurs within 1 to 2 years from onset [1].

It is considered likely that Panayiotopoulos syndrome represents the early while Rolandic epilepsy is the late phenotype of the same syndrome (benign childhood seizure susceptibility syndrome) [16, 17]. Children with Rolandic seizures may develop reversible language problems during the active phase of their disease [17], and a few (less than 1%) [17] have atypical evolutions with severe linguistic, behavioural and neuropsychological deficits [18-20], as in the Landau-Kleffner syndrome, atypical partial epilepsy of childhood and epilepsy with continuous spikes and waves during slow sleep [17, 21]. Therefore, it was expected that a small percentage of children with Panayiotopoulos syndrome would have similar atypical evolutions as documented by Caraballo and associates in 2 out of 120 (1.7%) patients [22].

We present a further case of an atypical evolution of Panayiotopoulos syndrome with video-EEG documentation.

Methods and patients

We are currently conducting a prospective study of Panayiotopoulos syndrome. In the last 3 years, 424 EEG have been performed in 308 children, aged 1-13 years, at St. Thomas' Hospital [6, 23]. Of the 308 patients, 228 (74%) had one or more epileptic seizures. The other 80 children (26%) had been referred for possible seizures or other medical conditions. Fourteen patients had Panayiotopoulos syndrome (6.1% of those with seizures) diagnosed mainly on clinical grounds. Six additional patients were classified as having possible Panayiotopoulos syndrome either because clinical features were atypical at onset or inadequate information was available. Eighteen patients (7.9%) had Rolandic epilepsy. One of the 14 patients with Panayiotopoulos syndrome had an atypical evolution.

Case study

This girl of English parentage was born slightly premature and rather rapidly, in 1994. She had minor problems in the neonatal period requiring treatment in the special baby care unit for 5 days. Her subsequent development was normal.

Her first seizure occurred at age 5 years and 7 months. Prior to going to school, she complained of headache, abdominal pain and of feeling sick. She was pale and quiet, but said, "If I feel sick I will tell my teacher." Two hours later the mother was called to school. Her daughter was gagging and retching but did not vomit. She was fully responsive but still pale. At home she went to sleep but within half an hour awoke coughing and complaining that she felt sick and wanted a glass of water. Soon after she saw a red colour and became quiet and appeared disoriented, she looked blank and then became floppy, unresponsive and incontinent of urine. Other symptoms noted were hypersalivation, gagging, teeth grinding, shaking, eyes widely opened and rolling upwards. The seizure progressed to generalised tonic clonic convulsions, which were terminated in hospital with intravenous diazepam. She gradually recovered consciousness and started speaking half an hour later. Temperature on arrival at hospital was 37 °C. It was recorded as 38 °C, 2 hours later but then normalised. By the next day she was afebrile, quiet and sleepy but otherwise normal.

Encephalitis was suspected. An EEG 2 days after the seizure showed scattered occipital and right central spikes (figure 1). The diagnosis of Panayiotopoulos syndrome was made after the EEG technician obtained the aforementioned historical account from the parents.

A different type of seizure with mainly Rolandic features occurred 2 months later. "She went floppy, tried unsuccessfully to talk and convulsed for 1-3 minutes."

A video-EEG at 6 years of age showed frequent left-sided and occasional right-sided occipital spikes. Centro-temporal spikes were not recorded. In addition, there was a brief (2 s) asymptomatic generalised discharge of larval spikes and slow waves.

No further seizures occurred in the next 8 months, although she often complained of headaches accompanied by vomiting and abdominal pain.

The situation then deteriorated, and over a 2-month period she had 10 seizures (both diurnal and nocturnal), lasting for 1-5 minutes. These manifested variously with symptoms of Panayiotopoulos syndrome and Rolandic epilepsy including nausea, retching, gagging, hypersalivation, speech arrest, "vacant look", clonic or tonic-clonic convulsions. In some of them, her eyes were noticed to "go from side to side" (oculo-clonic nystagmus?). At this stage, carbamazepine was introduced but within a week she started having 10-20 atonic seizures (drop attacks) daily, brief absences and slightly decreased attention span.

A new video-EEG was performed while she was awake and during 20 minutes, stage I-III of natural sleep (video and figures 1, 2). This documented frequent atypical absence seizures with impairment of consciousness and atonic features (video and figure 1). The ictal discharges were markedly different from those characterising the absences of idiopathic generalised epilepsies (figure 1). Onset was with a spike or double spike-slow wave at 4 Hz, which was immediately followed by rhythmic high amplitude slow activity at around 2.5 Hz. Small and sometimes inconspicuous functional spikes, mainly in the Fp2, F3, F4, P4 and T4 electrodes were recorded both while the patient was awake and asleep (figure 2). The sleep patterns were well formed and symmetrical with a few scattered spikes and 3 brief, generalised discharges; minor clinical manifestations of opening of the eyes and irregular breathing was observed in only one of them (video). Despite withdrawal of carbamazepine, which was initially suspected as the aggravating factor and introduction of sodium valproate, the absences and atonic seizures continued. Alarmingly, she also had episodes of absence status ending with GTCS. Adding clonazepam was ineffective.

On a further awake video EEG, frequent atypical absences were recorded (video and figure 3). The discharges were generalis-ed and consisted of spikes, double spikes and slow waves at an irregular mixture of frequencies at around 2-3 Hz (figure 3).

The seizures were often subtle and sometimes difficult to detect without simultaneous EEG (video). The ictal discharges were not stereotyped (figures 1 and 3).

Brain MRI was normal.

She remained well between seizures. Her behaviour was normal but her scholastic performance showed a moderate decline.

A significant improvement followed when small doses of lamotrigine (10 mg) were added to sodium valproate and clonazepam. She continued to have a few absences but no atonic seizures. Her school performance improved. A further video-EEG was almost normal except for a few scattered sharp waves at O2, C3, F4, P3 and T5 electrodes.

Discussion

In discussing this case it is important to summarise the main clinical and EEG features of Panayiotopoulos syndrome [6].

Clinical aspects

Seizures comprise an unusual constellation of autonomic, mainly emetic, symptoms often with unilateral deviation of the eyes and other more conventional ictal manifestations. In a typical presentation, the child fully conscious, able to speak and understand complains, "I feel sick", looks pale and vomits. Two thirds of the seizures start in sleep; the child may wake up with similar complaints while still conscious or else may be found vomiting, conscious, confused or unresponsive. The full emetic triad (nausea, retching, vomiting) culminates in vomiting in 74% of the seizures; in others only nausea or retching occur and in a few, emesis may not be apparent. Other autonomic manifestations may occur concurrently or appear later in the course of the ictus. These include pallor and less often flushing or cyanosis, mydriasis and less often miosis, cardio-respiratory and thermo-regulatory alterations, incontinence of urine and/or faeces and modifications of intestinal motility. Hypersalivation (probably a concurrent Rolandic symptom) may occur. Headache or more often cephalic auras and behavioural disturbances may occur, particularly at onset. Brief apnoea and cardiac asystole may be common but only exceptionally severe. More conventional seizure symptoms often ensue. The child gradually or suddenly becomes confused and unresponsive; exceptionally, consciousness may be preserved (6%). Eyes and often the head deviate to one side (60%), or the eyes gaze wide open (12%). Other symptoms in order of prevalence are speech arrest (8%), hemi-facial spasms (6%), visual hallucinations (6%), oropharyngolaryngeal movements (3%), unilateral drooping of the mouth (3%), eyelid jerks (1%), myoclonic jerks (1%) or automatisms (1%). These probably reflect the primary area of the seizure discharge generation. The seizures commonly end with hemi-convulsions often with Jacksonian march (19%) or generalized convulsions (21%). An unusual and important ictal feature of Panayiotopoulos syndrome is that in at least one fifth of the seizures the child becomes unresponsive and flaccid (ictal syncope), before or without convulsions. Ictal syncope may be the only clinical manifestation of a seizure. Hemi-convulsive (2%) or generalized convulsive status (2%) is exceptional. The same child may have seizures with marked autonomic manifestations, and seizures in which autonomic manifestations may be inconspicuous. The clinical seizure manifestations are roughly the same irrespective of inter-ictal EEG spike localizations, although there may be slightly fewer autonomic and slightly more focal motor features at onset in children without occipital spikes. An important feature of Panayiotopoulos syndrome is that nearly half (44%) of the seizures last for more than 30 min and up to 7 h (mean ~ 2 h) constituting autonomic status epilepticus. Of the other half (54%), duration varies from 1-30 min with a mean of 9 min. Lengthy seizures are equally common in sleep and wakefulness. Even after the most severe seizures and status, the patient is normal after a few hours' sleep. There is no record of residual neurological or mental abnormalities. The same child may have brief and lengthy seizures [6].

EEG aspects

The EEG of Panayiotopoulos syndrome is commonly a multifocal EEG with great variability [1, 3, 6, 11]. In the original study of Panayiotopoulos [11], only 12 had occipital spikes, another 9 had extra-occipital spikes, brief generalized discharges or normal EEG [11]. Occipital and frontal spikes predominate, but all brain locations, with different degrees of severity, fluctuation and combination may be involved. One third of patients never have an EEG with occipital spikes. EEG with multifocal spikes in more than 2 and often many brain locations occur in one third (30%) of patients; single spike foci are rare (9%). Cloned-like, repetitive, multifocal spike-wave complexes may be a characteristic feature when they occur (19%). Spikes are usually of high amplitude but small and even inconspicuous spikes may appear in the same or previous EEG of children with giant spikes. Brief generalised discharges of slow waves intermixed with small spikes may occur either alone (4%), or more often with, focal spikes (15%) [6, 11]. These are often asymptomatic or rarely, associated with inconspicuous impairment of consciousness; they are markedly different to those of generalised, symptomatic or idiopathic, epilepsies with absences. Conversely, they are similar to those recorded in children with Rolandic epilepsy [6, 17], a point that once more signifies the links between these two clinical phenotypes of the benign childhood seizure susceptibility syndrome. Occipital photosensitivity is an exceptional finding. Functional spikes at whatever location, are accentuated by sleep. If a routine EEG is normal, a sleep EEG should be performed. There is no particular relationship between the likehood of an abnormal EEG and the interval since the last seizure. EEGs soon or a long time after a seizure are equally likely to manifest with functional spikes, which may occur only once in serial routine and sleep EEGs. The background EEG is usually normal, but diffuse or localized slow wave abnormalities may also occur in at least one EEG in 20% of patients and particularly post-ictally. EEG abnormalities, particularly functional spikes, may persist for many years after clinical remission until the mid-teens. Conversely, spikes may appear only once in one of series of EEGs. Frequency, location and persistence of functional spikes do not determine clinical manifestations, duration, severity and frequency of seizures, or prognosis [6].

Atypical evolutions

The patient in this report initially had a single episode of autonomic status epilepticus, characteristic of Panayiotopoulos syndrome which was mistaken for encephalitis; a common error [6, 24, 25]. Autonomic manifestations such as cephalic auras, pallor, nausea, retching, coughing, hypersalivation and ictal syncope (flaccid and unresponsive) predominated. Emetic symptoms (nausea and retching) did not culminate in vomiting, which is a common occurrence in this syndrome (30%). The EEG had random extra-occipital and occipital spikes.

Subsequently, the patient developed seizures with mainly Rolandic features, which is encountered in 13% of children with Panayiotopoulos syndrome [2, 26]. When, at this stage, carbamazepine was added, a dramatic deterioration occurred, with frequent atypical absences and atonic seizures. This was initially considered as an adverse effect of carbamazepine as reported in a few cases of Rolandic epilepsy [17, 21, 27]. However, her condition did not improve when carbamazepine was replaced by sodium valproate alone or with add-on clonazepam. On the contrary, she became worse, having episodes of absence status ending with GTCS. This indicated that the child had an atypical evolution as reported in Rolandic epilepsy [18], the Gastaut type of idiopathic childhood occipital epilepsy [20], and most recently in Panayiotopoulos syndrome by Caraballo et al. [22].

The two cases of Caraballo et al. [22] presented initially with typical features of Panayiotopoulos syndrome, but later had a severe form of atypical evolution, with marked behavioural and neuropsychological impairment, probably as the result of EEG "continuous spike wave during slow sleep" that was demonstrated in both [22]. One of their cases was severely affected with some residual learning deficit while the other had features similar to those of "atypical benign partial epilepsy of childhood" described by Aicardi and Chevrie [28]. Conversely, our patient represents an atypical evolution of intermediate severity. She did not have behavioural problems, and the EEG during sleep was well organised, without "continuous spike-wave pattern during slow sleep". Her scholastic performance was only mildly affected, probably as the result of frequent atypical absences (video). Significant improvement was achieved when small doses of lamotrigine were added to sodium valproate and clonazepam. Clobazam or ethosuximide that are considered effective in such cases have not been tried.

Clinicians, whilst rightly stressing the benign nature of Panayiotopoulos syndrome, should be aware that occasional patient with atypical evolutions will be encountered. Further, this case report illustrates the links between Panayiotopoulos and Rolandic syndromes. Both can be considered as part of the benign childhood seizure susceptibility syndrome [6, 16, 17].

Received November 12, 2001 ; Accepted February 4, 2002