Brain & Development 29 (2007) 167–170 www.elsevier.com/locate/braindev Case report Epilepsy surgery in a patient with Lennox–Gastaut syndrome and cortical dysplasia Su Jeong You a, Jung-Kyo Lee b, Tae-Sung Ko c,* a Department of Pediatrics, Epilepsy Center, Inje University College of Midicine, Sanggye Paik Hospital, Republic of Korea b Department of Neurosurgery, College of Medicine, Ulsan University, Asan Medical Center, Seoul, Republic of Korea c Department of Pediatrics, College of Medicine, Ulsan University, Asan Medical Center, Seoul, Republic of Korea Received 16 March 2006; received in revised form 28 July 2006; accepted 31 July 2006 Abstract Lennox–Gastaut syndrome (LGS) is classified as a generalized epilepsy, and is often intractable to antiepileptic drugs. Although corpus callosotomy may sometimes control drop attacks, curative epilepsy surgery is rarely possible in LGS. We report, here, a patient with LGS and focal cortical dysplasia, who became seizure-free after epilepsy surgery. The patient was a 24-month-old boy without perinatal insult in whom seizures began 7 days after birth and who experienced development delay. Brain magnetic resonance imaging (MRI) showed focal cortical lesion with calcification in the right frontal area. At age 13 months, his seizure type changed from tonic seizures to head drops (atonic types) and atypical absence seizures. His interictal electroencephalogram (EEG) showed generalized slow spike and wave discharges, and he was diagnosed with LGS. His seizures were intractable to medical treatment, and a ketogenic diet was not effective. He was evaluated prior to surgery by long-term video-EEG monitoring, which detected many seizures consisted of a sudden onset of falling attacks (atonic type) intermittently followed by atypical absence seizures with diffuse slow wave bursts followed by slow spike and wave discharges in ictal EEG, brain positron emission tomography (PET) and MRI. A right frontal lesionectomy with intra-operative electrocorticography (EcoG) was performed. From the time of lesionectomy to the present, the patient has been seizure free and has been developing normally. Our results suggest that focal resective surgery should be considered in patients with LGS and focal epileptic lesions. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Lennox–Gastaut syndrome (LGS); Surgery; Secondary bilateral synchrony (SBS) 1. Introduction LGS is most often defined as an epileptic syndrome characterized by multiple seizure types, including brief tonic, atonic, myoclonic and atypical absence seizures. These seizures are associated with an interictal EEG pattern of diffuse, slow spike–wave complexes, and LGS is classified as a generalized seizure syndrome [1]. The etiology of LGS is heterogeneous and has been found to be related to different genetic and acquired factors. However, in about one-third of cases, the etiology * Corresponding author. Tel.: +82 2 3010 3390; fax: +82 2 473 3725. E-mail address: tsko@amc.seoul.kr (T.-S. Ko). 0387-7604/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2006.07.013 of LGS is unknown. Several patients with atypical LGS have been shown to have focal anatomical lesions with secondary bilateral synchrony [2]. Surgery for LGS generally includes palliative corpus callosotomy to treat drop attacks, which are the most incapacitating type of seizure. Recently, it has been reported that vagus nerve stimulation (VNS) was an effective treatment for intractable epilepsy in LGS [3,4]. In addition, resective surgery has been used in several patients with focal lesions. We report, here, a case of LGS with a focal cortical dysplasia, studied with video-EEG monitoring and brain PET, which was successfully treated by lesionectomy of a dysplasia in the right frontal cortex. 168 S.J. You et al. / Brain & Development 29 (2007) 167–170 2. Case The patient was a 24-month-old boy without a family history of epilepsy or focal neurologic signs, who was born after an uncomplicated pregnancy and delivery. His first seizure, a generalized tonic seizure, occurred 7 days after birth, and he was started on antiepileptic drugs(AEDs). These drugs were not effective in controlling his seizures, and the patient experienced delays in global development. At 6 months of age, he began to experience atypical absence seizures, and, at 13 months of age, his main seizure type changed from tonic seizures to head drops and atypical absence seizures. His interictal EEG showed generalized slow spike and wave discharges, and he was diagnosed as having LGS. Medical therapy included phenobarbital, vigabatrin, topiramate, clobazam, and lamotrigine, either as monoor add-on therapy, all of which gave unsatisfactory results. In addition, a ketogenic diet was not effective in controlling his seizures. Presurgical evaluation included long-term video-EEG monitoring, PET with F18-labeled fluorodeoxyglucose (FDG), and MRI. Long-term video EEG (Telefactor Cop, Conshohoken, PA) was carried out for 24 h. We observed continuous, almost generalized slow spike and wave discharges, with several focal spike discharges from the right frontal area, during the interictal period (Fig. 1). Many seizures were captured. His semiology consisted of a sudden onset of falling attacks (atonic type) intermittently followed by atypical absence seizures. Ictal EEG showed diffuse slow wave bursts followed by slow spike and wave discharges. Brain MRI showed focal cortical lesion with calcification in the right frontal area (Fig. 2). FDG-PET demonstrated glucose hypometabolism at the right anterior frontal lobe (Fig. 3). We performed a right frontal lesionectomy with preand post-operative EcoG and neuronavigation system (VectorVision2, BrainLab, Germany). Macroscopically, the resected cortical area had relatively small gyral convolutions, mottled calcification and rubbery hard gliotic tissue. The excision biopsy showed an ill-defined cortical lesion consisting of cytomegalic neurons, balloon cells, and abnormal cytoskeletons. At 13 month follow-up, the patient was seizure-free without any change of AEDs, and his development is progressing. 3. Discussion LGS is a catastrophic epileptogenic encephalopathy, identified by three sets of signs or symptoms. The first consists of multiple seizures, such as axial tonic, atonic, atypical absence, myoclonic, generalized tonic–clonic, and partial seizures. The second consists of an interictal EEG characterized by abnormal, slow background rhythm, diffuse 2–5 Hz spike and wave complexes, and paroxysmal fast discharges during sleep. The third consists of diffuse cognitive dysfunction, which may not become apparent until later, and is often associated with personality disorders [2,5]. Several patients with LGS, however, show focal anatomical, clinical or EEG features that constitute an atypical form of this disease. In particular, atypical LGS may be associated with focal brain lesions in the frontal or temporal lobes [6,7]. In these cases, a cortical mechanism of secondary bilateral synchrony (SBS) may play an important role in the development of LGS [8]. SBS consists of bursts of high-amplitude synchronous slow spike and wave complexes symmetric over both hemispheres, and is thought to be due to a unilateral Fig. 1. Interictal EEG showing diffuse, generalized slow spike and wave patterns. S.J. You et al. / Brain & Development 29 (2007) 167–170 169 Fig. 2. Brain MRI scans showing focal cortical dysplasia with calcification in the right frontal area. T2 weighted and FLAIR axial sections. Fig. 3. FDG-PET during the interictal period showing glucose hypometabolism in the right anterior frontal lobe. epileptogenic lesion of the mesial surface of the frontal or temporal lobe [9]. Many attempts have been made to establish the difference between epilepsy with SBS and LGS. For example, epilepsy with SBS is thought to develop later; to be more frequently associated with focal neurologic signs; and to be less frequently associated with obvious mental retardation. Moreover, previous studies indicate that in epilepsy with SBS, seizure frequency is lower; there is a lower frequency of multiple seizure types in the same patient; partial seizures are more frequent; astatic seizures are less frequent; atypical absence seizures are not observed; and there is a constant, localized epileptic focus [9]; SBS may be considered as a good prognostic factor [10]. And it has been suggested that patients with partial seizure with SBS characterized by the predominance of atonic drop attacks should be differentiated from LGS, which is classified as a generalized epilepsy [11]. 170 S.J. You et al. / Brain & Development 29 (2007) 167–170 However, although the patient described here had a focal epileptogenic lesion with SBS, he showed findings similar to those observed in typical LGS. That is, our patient had atypical absence seizures, obvious mental retardation, no focal seizures and no definite focal neurologic signs. Thus, our results suggest that typical LGS and partial seizure with SBS may lie on a spectrum, rather than being clearly separate diseases. LGS including partial seizure with SBS is generally resistant to medical therapy, and social life and development are severely disrupted in patients with this disorder. It is important to recognize above situation, because surgery may be the treatment of choice, especially when the primary lesion can be removed. Thorough investigations using PET may be useful in diagnosing this condition and in determining whether the patient is amenable to surgery [12]. References [1] Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489–501. [2] Farrel KE. Symptomatic generalized epilepsy and Lennox– Gastaut syndrome. In: Wyllie E, editor. The treatment of epilepsy. Principles and practice. 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