Sleep-related hyperkinetic seizures: always a frontal onset

Neurol Sci (2005) 26:s220–s224 DOI 10.1007/s10072-005-0491-9 R. Mai • I. Sartori • S. Francione • L. Tassi • L. Castana • F. Cardinale • M. Cossu • A. Citterio N. Colombo • G. Lo Russo • L. Nobili Sleep-related hyperkinetic seizures: always a frontal onset? Abstract Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleeprelated seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy. Introduction Hyperkinetic automatisms [1], such as pelvic thrusting, bimanual/bipedal activity, body rocking and ballistic movements, are commonly considered typical manifestations of seizures originating in the frontal lobe [2–4]. Indeed, in nocturnal frontal lobe epilepsy (NFLE), seizures are frequently characterised by the occurrence of hyperkinetic automatisms often associated with affective symptoms [5, 6]. We have recently described three drugresistant epileptic patients with sleep-related hyperkinetic seizures in which stereo-EEG (SEEG) investigation and surgical outcome demonstrated a temporal lobe origin of the attacks [7]. In this study we have conducted a retrospective analysis of our population of drug-resistant epileptic patients who were operated on, in order to define the distribution of sleep-related hyperkinetic seizures with respect to the site of origin. Key words Hyperkinetic automatisms • Sleep • Nocturnal frontal lobe epilepsy • Epilepsy surgery Patients and methods R. Mai (쾷) • I. Sartori • S. Francione • L. Tassi • L. Castana F. Cardinale • M. Cossu • G. Lo Russo • L. Nobili “C. Munari” Epilepsy Surgery Centre Niguarda Hospital Piazza Ospedale Maggiore 3, I-20163 Milan, Italy e-mail: roberto.mai@ospedaleniguarda.it A. Citterio • N. Colombo Service of Neuroradiology Niguarda Hospital, Milan, Italy We have evaluated all the consecutive patients affected by drug-resistant epilepsy operated on in the “C. Munari” Epilepsy Surgery Centre between January 1996 and January 2004. All the patients were submitted to video-EEG (VEEG) investigation before the operation. Patients with hyperkinetic seizures occurring exclusively or predominantly during sleep (>95%) were selected on the basis of video-EEG analysis of the seizures. The site of the seizure onset was determined on the basis of the anatomo-electroclinical correlations. When the VEEG analysis of seizures was not sufficient to localise the ictal onset zone, patients were studied with stereotactically implanted intracerebral electrodes stereo-EGG (SEEG) [8]. All patients underwent magnetic resonance imaging (MRI) examination. Of the extracted population we have evaluated the main clinical and EEG features, the neuroradiological aspects and the results of histopathological examinations. The classification of R. Mai et al.: Sleep-related hyperkinetic seizures s221 dysplastic tissues was done according to Tassi et al. [9]. The postoperative seizure outcome was determined according to the classification proposed by Engel et al. [10]. All the patients had a post-operative follow-up of at least one year. Results Among 442 consecutive patients affected by drug-resistant epilepsy we found 25 patients with sleep-related seizures as previously defined. Eighteen patients had a frontal origin of the seizures (NFLE) and in seven the ictal onset zone was within the temporal lobe (nocturnal temporal lobe epilepsy, NTLE). In Table 1 the main clinical features of the patients are reported. Epilepsy mainly started during infancy. Frequency of family history for epilepsy was relatively high in both frontal and temporal epileptic patients. No patient reported febrile convulsions or other remarkable antecedents. Only two patients with frontal epilepsy had mild mental retardation, all the others had a normal neurological examination. Seizure frequency was high in all patients. Patients with NFLE frequently reported a disturbed sleep with frequent awakenings. Bed partners reported agitated sleep; moreover some patients complained of excessive daytime sleepiness. These features were not reported by NTLE. Neuroimaging MR examinations were positive in 8/18 patients with NFLE and in most patients (6/7 patients) with NTLE. In only one NTLE patient MR suggested a hippocampal sclerosis. Anamnestic characteristics All NFLE patients reported an aura preceding the onset of the seizures even if frequency of occurrence was extremely variable within subjects. Auras could be characterised by forced thinking (5 patients), diffuse shiver (5 patients), fear (5 patients), dizziness (2 patients) and epigastric aura (1 patient). These subjective manifestations were reported merely during the rare diurnal seizures while they were rare during the nocturnal ones. NTLE epileptic patients (6/7) reported rare warning sensations that awakened them or occurred after awakening. These were characterised by fear associated with an epigastric sensation or breathless feeling (2 patients), isolated epigastric sensation (1 patient), acoustic sensations (1 patient), déjà vu (1 patient) and cephalic aura (1 patient). In all patients seizures were described by bed partners as a hyperkinetic motor behaviour, without remarkable differences between NFLE and NTLE. Electrophysiological investigations In NFLE background activity was generally normal (Table 2) while in NTLE it was slow and/or asymmetric. Focal spikes during wakefulness were constantly evident in NTLE patients while they were rarer in NFLE patients. Sleep induced an activation of spikes in most patients. In 5 NFLE patients focal spikes were evident only during sleep. Ictal EEG did not show clear-cut epileptic discharges in 5 patients with NFLE and in one with NTLE. In the others a fast activity discharge localised over the frontal (bilaterally or monolaterally) or fronto-temporal regions was detected (Table 2). In 4 patients the good coherence among interictal/ictal EEG, clinical ictal semeiology and brain MRI findings allowed the localisation of the epileptogenic zone (EZ) Table 1 Main clinical features of the patients Patients, n (sex) Mean age onset, years Age range, years Neurological examination Family history, n (%) Epilepsy, n Febrile convulsions, n Personal antecedents, n Febrile convulsion, n Side, n Frequency of seizures, median seizures/month NFLE NTLE 18 (10 M, 8 F) 6.3 1–24 2 with low I.Q. 7 (38.8) 6 1 0 0 9 right, 9 left 35 7 (2 M, 5 F) 5.6 1–17 Normal 2 (28.5) 2 0 0 0 5 right, 2 left 42 s222 R. Mai et al.: Sleep-related hyperkinetic seizures Table 2 Interictal and ictal EEG features Background activity Normal, n (%) Slow, n Asymmetric, n Focal abnormalities, n (%) Sharp waves, spike Sleep activation Ictal EEG, n Negative Frontal monolateral fast activity Frontal bilateral fast activity Fronto-temporal fast activity, n NFLE (n=18) NTLE (n=7) 14 (77.8) 2 2 1 (14.3) 3 3 7 (38.8) 14 (77.8) 7 (100) 7 (100) 5 2 3 8 and resective surgery was carried out. The other 21 patients underwent a stereo-EEG investigation before the operation (16/18 NFLE patients, 5/7 NTLE patients). In six NFLE patients, all with non-invasive data positive for a seizure involving the frontal lobe, SEEG monitoring limited to the frontal lobe was indicated for one of the following reasons: (a) electroclinical findings suggested that the EZ involved only a portion of the frontal cortex in the absence of a localising MRI; (b) with a circumscribed MRI lesion, electroclinical evidence indicated that the EZ extended to frontal extralesional areas; (c) anatomo-electroclinical data suggested that either a lesion and/or the EZ involved highly eloquent areas of the fronto-central region. In the remaining patients intracerebral electrodes were placed within both the temporal and frontal lobes. Surgery, histopathological findings and follow-up Sites of surgical resection are summarised in Table 3. Three patients with NFLE underwent two operations. In 2 of these, both resections involved the frontal lobe; in the remaining case the temporal pole was removed in the first operation. In 16/18 NFLE patients the frontal portion of the cingulated gyrus was removed and 16/18 had a more or less extended resection of the first frontal gyrus (Mes in Table 3). Six out of the 7 cases with NTLE had an anteromesial temporal lobectomy, which was extended to posterior-basal temporal cortex in 3 cases and to the whole temporal lobe (as far as the temporo-occipital junction) in one. The remaining patient had a resection limited to the antero-lateral neocortex only. Taylor’s dysplasia and architectural dysplasia were the most common findings at the histopathological examination (Table 4). Patients with Taylor’s dysplasia had the more favourable follow-up with 16/16 patients being seizure-free after the operation. 1 0 0 3 Table 3 Resected structures in NFLE and NTLE patients Cases, n NFLE DL DL+Mes+Cg Mes+Cg Mes+OrbPol+Cg Mes+OrbPol+Cg (+ATL) Mes OrbPol+Cg Olofrontal 18 1 6 6 1 1 1 1 1 NTLE ATL ATL+Postbas Olotemporal Neocort 7 2 3 1 1 DL, dorsolateral; Mes, mesial; Cg, cingulated gyrus; OrbPol, orbito-polar; ATL, antero-mesial temporal lobectomy; Postbas, postero-basal; Neocort, neocortical Table 4 Histopathological and follow-up results (Engel’s Classification) after the operation Neoplasia Pilocytic astrocytoma Malformations Taylor’s dysplasia Architectural dysplasia NFLE (n=18) NTLE (n=7) n n Engel’s Class 0 1 1: IVa 13: Ia 3: IIa 1: III 1: IV 0 3 0 3: Ia 0 1 1: Ia 0 2 1: IIb 1: IVa 0 13 5 Architectural dysplasia 0 plus hippocampal sclerosis Neuronal ectopia in 0 white matter Engel’s Class R. Mai et al.: Sleep-related hyperkinetic seizures Discussion We found a relatively high incidence (about 6%) of sleeprelated hyperkinetic seizures in a population of drug-resistant epileptic patients; moreover we confirm our previous findings that this kind of epileptic manifestations are not only peculiar to frontal lobe epilepsy [7]. Patients with temporal lobe epilepsy and sleep-related seizures have been described [11, 12], however their attacks were not frequent, lacked hyperkinetic automatisms and were mainly characterised by experiential, autonomic and psychic symptoms [11], thus more resembling typical temporal lobe seizures. Conversely, our 7 patients with NTLE had anamnestic and clinical features striking similar to those of NFLE patients: as in NFLE, seizures were sleep related, were characterised by agitated movements and frequency of occurrence was high. None had a history of febrile convulsions. At the anamnestic evaluation and also after VEEG recording of the episodes, temporal and frontal lobe seizures were hardly distinguishable; however some clinical and electroencephalographic features could suggest a temporal lobe epilepsy. Indeed the reported warning sensations in the NTLE group were more indicative of a temporal onset. Another anamnestic difference was the frequently reported poor quality of sleep, sometimes associated with excessive daytime sleepiness, in the NFLE group. Though in this work we have not analysed all the recorded motor manifestations during sleep but only the major seizures, it is well known that NFLE patients frequently present periodic motor events (lasting 2–4 s) in coincidence with arousal fluctuations during NREM sleep [5, 6, 13–16] leading to sleep fragmentation and consequent possible daytime sleepiness. This seems not to happen in NTLE but further investigations on this aspect are needed. While ictal EEG activity was generally poorly helpful in recognising a frontal or temporal onset, interictal EEG activity could be more informative. Indeed, not surprisingly, in the NTLE group background activity was abnormal while generally normal in the NFLE one. Moreover in NTLE focal spikes during wakefulness were evident. In this paper we have not conducted a detailed analysis of the semeiological features of the attacks recorded during VEEG and stereo-EEG investigation in NFLE and in NTLE; however, in accordance with previous observations [7], it seems that in NTLE complex motor automatisms are more asymmetric, prevailing, at least in the first part of the seizure, on the side ipsilateral to the origin of the epileptic discharge. We do not have enough information to explain why this sub-group of patients affected by temporal lobe epilepsy manifests these kinds of complex epileptic manifestations during sleep. With the aid of SEEG investigation we have observed that hyperkinetic automatisms and complex s223 behaviours appeared when the ictal discharge in the temporal lobe involved extra-temporal structures such as the cingulated, the frontal and parietal regions [7, 17]. The cingulated region, via the hippocampus and para-hippocampus, indeed constitutes a bridge between the temporal and the frontal lobes [18, 19]. Moreover, it is known that the electrical stimulation of the anterior cingulated cortex can be associated with complex bilateral movements [20]. Accordingly a hyperperfusion of the cingulated gyrus has been shown both during epileptic complex manifestations occurring during sleep [21, 22] and during episodes of nonepileptic sleepwalking [23]; the cinguli could be the brain region mainly involved, both primarily and secondarily, in the generation of complex motor behaviours during sleep. Nevertheless, although in most of our patients with NFLE resections included the frontal cingulated gyrus, the two patients with no cingulectomy had a seizure-free outcome after surgery. On the other hand it has been shown that distant brain regions can transiently synchronise their rhythms [24] during seizures, thus indicating that a complex anatomical and functional network could probably participate in the genesis of seizures with these features [25]. Finally the hyperkinetic automatisms might be interpreted not as excitatory phenomena but as the result of the disinhibition of common central pattern generators leading to the emergence of innate behaviours [26]. In our selected population of drug-resistant epileptic patients, cortical dysplasia was the most frequent finding at the histopathological examination, thus suggesting that the histopathological substrate also could play a role in producing particular cerebral involvements during the seizures. Our data show that, especially for NTLE, most of the patients can be seizure-free after the operation. Considering that drug-resistant epileptic patients with hyperkinetic seizures during sleep are not rare [5, this paper], the correct localisation of the EZ becomes mandatory in a surgical perspective and the information that these manifestations may have an origin outside the frontal lobe could be useful. References 1. Blume WT, Lüders HO, Mizrahi E, Tassinari CA, van Emde Boas W, Engel J (2001) Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 42:1212–1218 2. Geier S, Bancaud J, Talairach J (1976) Automatisms during frontal lobe epileptic seizures. Brain 99:447–458 3. Williamson PD, Spencer DD, Spencer SS, Novelly RA, Mattson RH (1985) Complex partial seizures of frontal lobe origin. Ann Neurol 18:497–504 4. Salanova V, Morris HH, Van Ness P, Kotagal P, Wyllie E, Lüders H (1995) Frontal lobe seizures: electroclinical syndromes. Epilepsia 36:16–24 s224 5. Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P (1999) Nocturnal frontal lobe epilepsy: a clinical and polygraphic overview of 100 consecutive cases. Brain 122:1017–1031 6. Oldani A, Zucconi M, Ferini-Strambi L, Bizzozero D, Smirne S (1996) Autosomal dominant nocturnal frontal lobe epilepsy: electroclinical picture. Epilepsia 37:964–976 7. Nobili L, Cossu M, Mai R et al (2004) Sleep related hyperkinetic seizures of temporal lobe origin. Neurology 62:482–485 8. Munari C, Hoffmann D, Francione S, Kahane P, Tassi L, Lo Russo G, Benabid AL (1994) Stereo-electroencephalography methodology: advantages and limits. Acta Neurol Scand S152:56–67 9. Tassi L, Colombo N, Gabelli R et al (2002) Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain 125:1719–1732 10. Engel J, Van Ness P, Rasmussen T, Ojemann L (1993) Outcome with respect to epileptic seizures. In: Engel J Jr (ed) Surgical treatment of the epilepsies, 2nd edn. Raven Press, New York, pp 609–621 11. Bernasconi A, Andermann F, Cendes F, Dubeau F, Andermann E, Olivier A (1998) Nocturnal temporal lobe epilepsy. Neurology 50:1772–1777 12. Herman ST, Walczak TS, Bazil CW (2001) Distribution of partial seizures during the sleep-wake cycle: differences by seizure onset site. Neurology 56:1453–1459 13. Sforza E, Montagna P, Rinaldi R et al (1993) Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features. Electroencephalogr Clin Neurophysiol 86:161–166 14. Zucconi M, Oldani A, Smirne S, Ferini-Strambi L (2000) The macrostructure and microstructure of sleep in patients with autosomal dominant nocturnal frontal lobe epilepsy. J Clin Neurophysiol 17:77–86 15. Nobili L, Francione S, Mai R et al (2003) Nocturnal frontal lobe epilepsy: intracerebral recordings of paroxysmal motor attacks with increasing complexity. Sleep 26:883–886 16. Nobili L, Sartori I, Terzaghi M et al (2005) Intracerebral R. Mai et al.: Sleep-related hyperkinetic seizures 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. recordings of minor motor events, paroxysmal arousals and major seizures in nocturnal frontal lobe epilepsy. Neurol Sci 26[Suppl 3]:s215–s219 Nobili L, Francione S, Cardinale F, Lo Russo G (2002) Epileptic nocturnal wanderings with a temporal lobe origin: a stereo-EEG study. Sleep 25:669–671 Gloor P (1997) The temporal lobe and limbic system. Oxford University Press, New York Munari C, Bancaud J (1992) Electroclinical symptomatology of partial seizures of orbital frontal origin. In: Chauvel P, Delgado-Escueta AV et al (eds) Advances in neurology. Raven Press, New York, pp 257–265 Talairach J, Bancaud J, Geier S, Bordas-Ferrer M, Bonis A, Szikla G, Rusu M (1973) The cingulate gyrus and human behaviour. Electroencephalogr Clin Neurophysiol 34:45–52 Schindler K, Gast H, Bassetti C et al (2001) Hyperperfusion of anterior cingulate gyrus in a case of paroxysmal nocturnal dystonia. Neurology 57:917–920 Vetrugno R, Mascalchi M, Vella A et al (2005) Paroxysmal arousal in epilepsy associated with cingulate hyperperfusion. Neurology 64:356–358 Bassetti C, Vella S, Donati F, Wielepp P, Weder B (2000) SPECT during sleep walking. Lancet 356:920–924 Bartolomei F, Wendling F, Vignal JP, Chauvel P, LiegeoisChauvel C (2002) Neural networks underlying epileptic humming. Epilepsia 43:1001–1012 Spencer SS (2002) Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia 43:219–227 Tassinari CA, Gardella E, Meletti S, Rubboli G (2003) The neuroethological interpretation of motor behaviours in “nocturnal-hyperkinetic-frontal seizures”: emergence of innate motor behaviours and role of central pattern generators. In: Beaumanoir A, Andermann F, Chauvel P, Mira L, Zifkin B (eds) Frontal seizures and epilepsies in children. Mariani Foundation Pediatric Neurology Series, Vol 11. Libbey Eurotext, Paris, pp 43–48