Tuberous sclerosis: Localizing the epileptogenic tuber with synthetic aperture magnetometry with excess kurtosis analysis Leonides Canuet a,b, * , Ryouhei Ishii a , Masao Iwase a , Ryu Kurimoto a , Koji Ikezawa a , Michiyo Azechi a , Mari Wataya-Kaneda c , Masatoshi Takeda a a Departments of Clinical Neuroscience and Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan b Department of Neurology, ‘‘Saturnino Lora’’ Provincial Hospital, Santiago de Cuba, Cuba c Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan Received 19 January 2007; accepted 18 March 2007 Abstract The hallmark of tuberous sclerosis is the presence of multiple cortical tubers. Identifying the epileptogenic tubers is difficult and often requires invasive intracranial electroencephalograph (EEG) monitoring. We report on a patient with tuberous sclerosis upon whom the novel magnetoencephalography (MEG) technique of synthetic aperture magnetometry (SAM) with excess kurtosis (g2) analysis was per- formed for localization of the epileptogenic tuber. Simultaneous electroencephalography (EEG) was also performed. MEG data, as ana- lyzed by SAM(g2), were superimposed on the patient’s MRIs. In the fluid attenuated inversion recovery MRIs, several tubers and subependymal nodules could be identified, with the largest tubers being located in the right frontal and left anteriotemporal regions. Despite multiple cortical lesions existing, the SAM(g2) images showed a single large tuber and surrounding epileptogenic tissue in the left temporal cortex. We suggest that MEG with SAM(g2) analysis may be clinically useful for the accurate identification of epileptogenic tubers in patients with tuberous sclerosis. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Tuberous sclerosis; Magnetoencephalography; Synthetic aperture magnetometry; Kurtosis; Epileptogenic tuber 1. Introduction Multimodality neuroimaging has improved the detection of epileptogenic foci, allowing an increasing number of indi- viduals to be evaluated for surgery. 1 However, because localization of epileptic foci remains challenging, there is an urgent need to improve the methods by which epilepto- genic tubers are detected. Synthetic aperture magnetometry (SAM) 2,3 with excess kurtosis (g2) 4,5 is a recently developed analysis technique that transforms magnetoencephalogra- phy (MEG) data into a functional image of spike-like activ- ity, giving the source waveforms for those locations. This technique seems to be appropriate for localizing epilepto- genic tubers in tuberous sclerosis. In the current study we illustrate the value of the combination of MEG and SAM(g2) for the accurate interictal localization of an epi- leptogenic tuber in a patient with focal epilepsy as a symp- tom of tuberous sclerosis. 2. Clinical presentation A 29-year-old female patient was diagnosed with tuber- ous sclerosis, in accordance with the revised clinical diagnostic criteria for tuberous sclerosis complex. 6 Symp- tomatic focal epilepsy was also diagnosed, with age of on- set being 14 years. After epilepsy appeared, the patient was followed up at the outpatient clinic of psychiatry, Osaka University Hospital, Japan. The patient experienced fre- quent partial complex seizures, suggestive of a temporal fo- cus. Seizures were characterized by behavioral arrest and staring, usually accompanied by fear, nausea, mild cyano- sis, and, rarely, secondary generalized seizures. Previous electroencephalography (EEG) recordings often showed bilateral epileptic discharges in the temporal regions. The patient underwent an MEG measurement using a 64-chan- nel whole head magnetometer (NeuroSQUID Model 100, CTF Systems Inc., Port Coquitlam, BC, Canada). The data sample rate was 250 Hz per channel. To assist in spike detection, simultaneous EEG data were recorded using 19 electrodes (International 10–20 system). MEG demon- strated clear spike activity over the left temporal region (Fig. 1). MEG data were analyzed by using synthetic SAM(g2). This functional imaging analysis technique combines a three-dimensional functional image of excess kurtosis, g2, considered a measure of spike-like activity, and the estima- tion of source waveforms at the coordinates identified in the functional image by SAM virtual sensors. The presence of spike activity yields a large positive kurtosis, whereas normal cortical activity exhibits a small kurtosis, and noise * Corresponding author. Present address: Department of Psychiatry, Osaka University Graduate School of Medicine, Yamadaoka 2–2, D-3, Suita City 565–0871, Japan. Tel.: +81 6 6879 3051; fax: +81 6 6879 3059. E-mail address: leocanon2002@yahoo.com.mx (L. Canuet). 1296 Case Reports / Journal of Clinical Neuroscience 15 (2008) 1296–1298