Epilepsy and NREM-parasomnia: A complex and reciprocal relationship

Sleep Medicine 13 (2012) 442–444

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Epilepsy and NREM-parasomnia: A complex and reciprocal relationship Alessandro Pincherle a,⇑, Paola Proserpio c, Giuseppe Didato a, Elena Freri b, Suela Dyljgeri a, Tiziana Granata b, Lino Nobili c, Roberto Spreafico a, Flavio Villani a a b c

Clinical Epileptology and Experimental Neurophysiology Unit, Neurological Institute Foundation ‘‘C. Besta’’, Milan, Italy Department of Pediatric Neuroscience, Neurological Institute Foundation ‘‘C. Besta’’, Milan, Italy Epilepsy Surgery Centre ‘‘C. Munari’’ and Sleep Medicine Centre, Niguarda Hospital, Milan, Italy

a r t i c l e

i n f o

Article history: Received 31 May 2011 Received in revised form 5 August 2011 Accepted 8 September 2011 Available online 28 January 2012 Keywords: Epilepsy Arousal Sleepwalking Parasomnia

1. Introduction The differential diagnosis between sleep-related epilepsies and NREM parasomnias may be difficult because of the possible clinical similarities between the two disorders, particularly when affective symptoms or ambulatory behaviours characterize the paroxysmal episodes [1]. Several attempts have been made to define specific and reliable clinical diagnostic criteria [1–3] and to describe peculiar semeiological patterns recognizable by Video-Polysomnographic (V-PSG) recordings [4]; however, the differential diagnosis still remains challenging in some cases, especially if epilepsy and parasomnia coexist in the same subject. In such cases, the epileptic ⇑ Corresponding author. Address: Clinical Epileptology and Experimental Neurophysiology Unit, National Neurological Institute ‘‘C. Besta’’, Via Celoria 11, Milan, Italy. Tel.: +39 02 23 94 22 42; fax: +39 02 23 94 27 31. E-mail address: alex.pincherle@infinito.it (A. Pincherle). 1389-9457/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2011.09.011

condition may facilitate the occurrence of NREM disturbances and vice versa [1,4,5]. Here we describe two patients in which a V-PSG demonstration of the coexistence of parasomnia and epilepsy suggests the presence of opposite bidirectional influences between the two disturbances.

2. Case 1 A 13-year-old right-handed girl was referred to the Sleep Centre of the Niguarda Hospital, Milan, Italy, for the assessment of nocturnal paroxysmal episodes. The girl had a normal psychomotor development and absence of personal antecedents. Her family history was positive for epilepsy and sleepwalking. The patient reported a two-year history of at least one episode a week of nocturnal walking of a few minutes’ duration, and of sleep talking. In some of these episodes sudden segmental movements were noticed when trying to wake the patient. Nocturnal V-PSG recording showed rare and isolated bilateral centro-temporal sharp-waves and spikes during wakefulness and diffuse spike/ polyspike and wave complexes at sleep onset. A typical paroxysmal episode was recorded (Video 1): it occurred during slow-wave sleep and the electro-clinical pattern was clearly suggestive of an NREM parasomnia (Fig. 1). The electroencephalogram (EEG) preceding the episode was characterized by a periodical occurrence of delta burst (cyclic alternating pattern sequencies). During the behavioural arousal, lasting about 20 s, the EEG showed a hypersynchronous delta activity. The episode stopped when the technician entered the room and called the patient; at that moment, the EEG showed a brief discharge of

A. Pincherle et al. / Sleep Medicine 13 (2012) 442–444

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Fig. 1. On the left: a confusional arousal occurring during NREM sleep (Video 1, first part). Notice the hypersynchronous delta activity, mainly expressed over the anterior regions. At the end of the episode, immediately after the awakening, a poly-spike and wave discharge is visible within the artefacts. On the right: Poly-spike and waves accompanied by myoclonic jerks (arrow in figure; Video 1, second part).

Fig. 2. On the top: NREM sleep. An epileptic discharge occurring over the left central derivation accompanied and followed by a sustained increase in delta activity and by the appearance of confusional arousal (see Video 2).

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generalized spike/polyspike and waves. Soon after awakening, the patient presented with myoclonic jerks of the upper and lower limbs, coinciding with a 2.5–3 Hz diffuse discharge of polyspike and wave (Video 1, Fig. 1). A diagnosis of Juvenile Myoclonic Epilepsy (JME) was made and treatment with levetiracetam was started, which resulted in the disappearance of both NREM parasomnia episodes and epileptic jerks. 3. Case 2 A 4-year-old boy was referred to the ‘‘C. Besta’’ Neurological Institute, Milan, Italy, for the investigation of nocturnal paroxysmal episodes. The boy, who had a normal psychomotor development and a negative family history for sleep disorders, presented from the age of 27 months with diurnal episodes characterised by a ‘‘grimace-like smile,’’ followed by tonic flexion of the left arm and hypotonia of the right arm. These episodes disappeared after a low dose regimen of valproate. Nevertheless, the patient continued to present with frequent nocturnal paroxysmal manifestations characterized by apparently sudden awakening followed by exploratory behaviour, itself sometimes followed by smiling or laughing. EEG during wakefulness showed a normal background activity with interictal epileptic abnormalities on the left fronto-central regions. Brain MRI was unrevealing. V-PSG confirmed the presence of epileptic abnormalities located in the left centro-parietal regions. During NREM sleep we recorded a long-lasting (about minutes) paroxysmal episode that could be classified as a confusional arousal (Video 2): the child opened his eyes, sat up in bed, and looked around. He did not interact with his mother, but kept a smiling face, and then went back to sleep. A subclinical focal EEG paroxysm located on the left fronto-central region (Fig. 2) was recorded a few seconds before the onset of a hypersynchronous delta activity that persisted for the entire period of arousal. Upon adjustment of the valproate dosage, a reduction in nocturnal episodes of confusional arousal was reported; later on, the introduction of carbamazepine led to the almost total disappearance of such nocturnal episodes. 4. Brief discussion An increased incidence of NREM parasomnia in patients with either nocturnal or diurnal epilepsy has been reported [6,7]. Our V-PSG recordings revealed a comorbidity between epilepsy and parasomnia in the two study subjects and suggested the presence of a bidirectional relationship between these two disorders. In the first case, the V-PSG recording allowed the formulation of a diagnosis of JME, interestingly documenting the appearance of diffuse spike and wave complex discharges at the end of a NREM parasomnia, coinciding with sudden segmental movements (i.e., myoclonic jerks). The gating effects of arousal could be regarded as the common permissive background for the appearance of both epileptic and non-epileptic motor phenomena in this patient [8].

On the contrary, in the second case, a subclinical focal epileptic discharge may have triggered a parasomnic episode with a sustained (i.e., >5 min) hypersynchronous delta activity EEG pattern, clinically manifested by confusional arousal. This is in accordance with intracerebral EEG studies showing that subclinical EEG paroxysms may induce sleep-related non-epileptic motor events [1,9]. More specifically, the epileptic discharge may have acted as an internal trigger, increasing arousal instability and facilitating the occurrence of the confusional arousal. Interestingly, in both patients the start, or an increase in dosage, of an antiepileptic drug (AED) caused the disappearance of both epileptic and parasomnic episodes. It is conceivable that AEDs, while reducing epileptic intrinsic activity, may have improved arousal instability (i.e., CAP rate, notably high in JME) [10], reducing the facilitating effect of arousal for both epileptic activities and sleep-related motor events. Finally, our data confirm that V-PSG should be regarded as the gold-standard in the differential diagnosis of sleep-related paroxysmal episodes and highlight the relevant therapeutic implications that may be derived. Conflict of Interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.09.011. References [1] Nobili L. Nocturnal frontal lobe epilepsy and non-rapid eye movement sleep parasomnias: differences and similarities. Sleep Med Rev 2007 Aug;11(4): 251–4. [2] Derry CP, Davey M, Johns M, et al. Distinguishing sleep disorders from seizures: diagnosing bumps in the night. Arch Neurol 2006;63:705–9. [3] Manni R, Terzaghi M, Repetto A. The FLEP scale in diagnosing nocturnal frontal lobe epilepsy, NREM and REM parasomnias: data from a tertiary sleep and epilepsy unit. Epilepsia 2008 Sep;49(9):1581–5. [4] Derry CP, Harvey AS, Walker MC, Duncan JS, Berkovic SF. NREM arousal parasomnias and their distinction from nocturnal frontal lobe epilepsy: a video EEG analysis. Sleep 2009;32(12):1637–44. [5] Touchon J, Baldy-Moulinier M, Billiard M, Besset A, Cadilhac J. Sleep organization and epilepsy. Epilepsy Res Suppl 1991;2:73–81. [6] Grigg-Damberger M, Ralls F. Primary sleep disorders and paroxysmal nocturnal nonepileptic events in adults with epilepsy from the perspective of sleep specialists. J Clin Neurophysiol 2011;28(2):120–40. [7] Bisulli F, Vignatelli L, Naldi I, Licchetta L, Provini F, Plazzi G, et al. Increased frequency of arousal parasomnias in families with nocturnal frontal lobe epilepsy: a common mechanism? Epilepsia 2010;51:1852–60. [8] Parrino L, Halasz P, Tassinari CA, Terzano MG. CAP, epilepsy and motor events during sleep: the unifying role of arousal. Sleep Med Rev 2006 Aug;10(4):267–85. [9] Terzaghi M, Sartori I, Mai R, Tassi L, Francione S, Cardinale F, et al. Coupling of minor motor events and epileptiform discharges with arousal fluctuations in NFLE. Epilepsia 2008;49:670–6. [10] Gigli GL, Calia E, Marciani MG, Mazza S, Mennuni G, Diomedi M, et al. Sleep microstructure and EEG epileptiform activity in patients with juvenile myoclonic epilepsy. Epilepsia 1992;33:799–804.