Brain & Development 29 (2007) 243–246 www.elsevier.com/locate/braindev
Intractable reﬂex audiogenic seizures in Aicardi syndrome S. Grosso *, M.A. Farnetani, E. Bernardoni, G. Morgese, P. Balestri Department of Pediatrics, Pediatric Neurology Section, University of Siena, Italy Received 3 July 2006; received in revised form 20 August 2006; accepted 2 September 2006
Abstract Aicardi syndrome (AS) is a rare disorder which includes the triad of total or partial agenesis of the corpus callosum, infantile spasms, and chorioretinal anomalies. Seizures and electroencephalogram ﬁndings observed in AS are polymorphic with both focal and generalized seizures. We ﬁrst report on a patient aﬀected by AS who presented with reﬂex audiogenic seizures speciﬁcally triggered by the starting tune of a popular television news. No other type of stimuli, either simple or complex, were able to precipitate the seizures in the patient. The severe cortical-subcortical lesions commonly observed in AS are associated with hyperexcitability of the cortices and may well account for the broad electroclinical patterns noted in this group of patients. From our report, the context of these patterns should be extended to include reﬂex audiogenic seizures. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Reﬂex seizures; Audiogenic epilepsy; Startle epilepsy; Brain malformation
2. Case report
Aicardi syndrome (AS) was ﬁrst recognized in 1965 . Further detailed were reported in 1969 . The syndrome classically includes the triad of total or partial agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae’ [3,4]. Other cerebral malformations include cerebellar hypoplasia, cortical polymicrogyria, periventricular heterotopia, and cysts of the choroid plexus and/or the pineal. Abnormalities such as congenital defects of the eyes, abnormal vertebrae are often observed [4,5]. Although normal neurological development has been reported in a few patients , severe psychomotor retardation is usually present . Here we report on a patient aﬀected by AS who presented with reﬂex audiogenic seizures speciﬁcally provoked by the starting tune of a popular television news.
This 18-year-old female patient was the ﬁrst child of non consanguineous, healthy parents. She was born after an uneventful pregnancy and delivery. Weight and length at birth were normal. Her head circumference was 30 cm (below the third percentile). At four months of age, she presented with frequent episodes (up to 30 per day) of symmetric and asymmetric ﬂexor spasms. Physical examination at that time revealed profound generalized hypotonia and delayed development. EEGs showed bilateral, independent bursts of asynchronous high-voltage irregular slow waves and fast waves that alternated with low-voltage interburst periods. Hyps arrhythmia developed two months later. MRI detected partial agenesis of the corpus callosum, marked cerebral asymmetry, enlarged lateral and third ventricles, diﬀuse pachigyria, and a 5 cm diameter arachnoid cyst in the posterior fossa. Ophthalmologic examination showed chorioretinal ‘‘lacunae’’. A diagnosis of Aicardi syndrome was therefore made. At the clinical follow-up she presented with severe mental retardation, generalized
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S. Grosso et al. / Brain & Development 29 (2007) 243–246
hypotonia and spasticity. She never acquired the ability to walk, and language was absent. Several types of seizures, including asymmetric epileptic spasms, myoclonic, and partial seizures, occurred thereafter. The seizures were poorly controlled by various combinations of antiepileptic drugs (AEDs). Cycles of ACTH therapy were able to control seizures for periods of 2–3 months. At 15 years of age, a further brain MRI conﬁrmed the presence of the previously detected lesions (data not shown). Brainstem auditory evoked response was normal. At the latter examination the child had fortnightly, uncontrolled episodes of asymmetric epileptic spasms both singly and in series. Interictal EEG showed multifocal spikes and irregular spike-waves. Sleep structure was extremely poor. Flash visual evoked response was normal. At the age of 15 years, the mother also noted seizures that were invariably evoked by the starting tune of a popular Italian television news program. The patient underwent several video-EEG recordings that substantiated the reﬂex nature of the seizures. Seizures were almost invariably provoked by the tune which was characterized by a roll of drum-like sounds followed by a wind instrument section. Between one and two seconds after the start of the tune, the patient had a seizure characterized by a massive myoclonic jerk with an abrupt anti-ﬂexion of the head and abduction of upper limbs, followed by a prolonged bilateral tonic phase lasting 20–40 s (Fig. 1). The ictal EEG showed a low-voltage, fast activity pattern, preceded by an initial movement artifact with a frontal maximum (Fig. 2). Although the onsets of seizures were commonly abrupt, termination of the tonic phase was often unclear. Systematic testing revealed that the seizures were specifically precipitated by the starting tune of the television program. The patient had seizures provoked by the tune
even when she was not watching the TV program. Other audiogenic stimuli, either simple or complex, were unable to precipitate seizures. Visual or nonauditory sensory stimuli were also ineﬀective. Changing TV channel just before the onset of the tune avoided the occurrence of seizures in the patient. It was impossible to establish how long the child had been exposed to the tune before presenting with provoked seizures. Moreover, because of the severe mental retardation presented by the patient, we were unable to evaluate the possibility of an emotional anticipation component in the evocation of the seizures. Several AEDs were ineﬀective in controlling these audiogenic seizures.
3. Discussion Reﬂex epilepsies are a group of disorders in which seizures are triggered by speciﬁc sensory stimuli. Seizures that are related to audiogenic reﬂex stimuli include two main forms [5,8]. In the ﬁrst type, seizures are precipitated by simple stimuli and these coincide with startle epilepsy. The second form is provoked by complex stimuli, including (i) musicogenic seizures (MS), (ii) seizures triggered by musical pitch, and by (iii) complex auditory stimuli . MS are peculiar since emotional and psychodynamic factors play a key role in the pathophysiology . The degree of sensory synesthesia linking musical perception with an emotional impact, along with the prolonged latency between stimulus onset and EEG or clinical seizure, distinguishes MS from simple reﬂex epilepsy [10–12]. The pathophysiology of startle epilepsy is conjectural. Chauvel et al.  reported that the ictal discharge originates in the motor and premotor cortices, with a
Fig. 1. This is a video sample of are ﬂex audiogenic seizure. The sudden antiﬂexion of the head in the second and third frames, and the subsequent bilateral tonic arm postures, with both abduction and ﬂexion, are notable in the fourth frame.
S. Grosso et al. / Brain & Development 29 (2007) 243–246
Fig. 2. The ictal EEG shows a low-voltage fast activity pattern and an initial movement artifact, with the frontal maximum occurring 1.5 s after the onset of the tune (indicated by the arrow). The clinical correlation is a myoclonic jerk followed by bilateral tonic phase.
rapid spread to the mesial frontal area, parietal and contralateral frontal lobes. The direct projection of sensory aﬀerents to the motor areas, including the supplementary motor area, is considered capable of triggering discharges. A possible relay in the primary auditory cortex may be involved in audiogenic startle epilepsy. Alternatively, seizures may originate in the supplementary motor area, and be triggered by the proprioceptive input from the startle reaction to a speciﬁc stimulus (motor, sensory or auditory) . Startle epilepsy is usually associated with large cortical and subcortical lesions. According to Nolan et al. , epileptogenic lesions may be located in the dorsolateral frontal lobe or in the perirolandic area. The startle reaction may trigger nearby epileptogenic tissue, but this does not explain patients with diﬀuse lesions and EEG abnormalities in whom diﬀuse deﬁciencies in cortical inhibition have been suggested [15,16]. Intractable reﬂex audiogenic epilepsy was recently reported in a patient with infantile hemiplegia seizure syndrome in whom seizures were speciﬁcally provoked by sudden and unexpected sounds. Abnormal electrical activity in the right centro-parietal region was demonstrated by EEG tomography using low-resolution electromagnetic multiplanar tomography (LORETA). A peri-insular hemispherotomy led to complete control of seizures . It is well known that AS patients may present with a broad, polymorphic seizures and EEG features, and these patients are rarely free of seizures [7,7–19]. The types of seizures in AS patients include infantile spasms, myoclonic, generalized tonic-clonic, atonic, tonic, atypical absence, and focal/complex partial seizures [7,17– 19]. Our observations extend the electroclinical pattern characterizing AS. We believe this is the ﬁrst report of reﬂex audiogenie seizures in a patient with AS. In particular, the ictal events in our patient were speciﬁcally triggered by the starting tune of a popular television program. Seizures were even triggered at low TV
volume, and changing the TV channel just before the onset of the tune avoided the occurrence of the seizure. Other tunes, music, simple or complex sounds, or diverse visual, and tactile stimuli did not induce seizures. Seizures invariably occurred between one and two seconds after the start of the tune. Because of the severe mental retardation of the patient, it was impossible to establish whether an emotional component was involved in the pathogenesis of reﬂex seizures. However, we believe this is unlikely because of the very short latency period. Video-EEG analysis showed that an initial, abrupt myoclonic jerk, rather than the classic startle reaction characterized these seizures. This jerk was followed by a bilateral tonic phase. In contrast to the previous reports of a high prevalence of focal tonic seizures [21,22], Tibussek et al.  recently found that the ‘‘myoclonic tonic’’ type was the most common seizure in a series of 22 patients with startle-provoked epileptic seizures. That result is consistent with our observations here. Audiogenic seizures linked to television viewing were described in a normal adult woman in whom complex partial seizures were precipitated by the voice of the female co-host of a popular television entertainment program. The cause of the seizures in that patient is unknown . According to Martines-Manas et al. , the fact that only a very speciﬁc audiogenic stimulus was able to trigger seizures suggests that these seizures may be related to a direct auditory reﬂex. The patient’s epileptogenic cortex may be triggered directly by aﬀerents from the primary auditory area. In conclusion, we report on a patient aﬀected by AS who presented with intractable reﬂex audiogenie seizures. The severe cortical-subcortical lesions commonly observed in AS are associated with hyper excitability of the cortices and may well account for the broad electroclinical patterns noted in this group of patients. From our report, the context of these patterns should be extended to include reﬂex audiogenie seizures.
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