Visual cortex hyperexcitability in idiopathic generalized epilepsies with photosensitivity: A TMS pilot study Francesco Brigo a, b, ⁎ , 1 , Luigi Giuseppe Bongiovanni a, 1 , Raffaele Nardone b, c , Eugen Trinka c , Frediano Tezzon b , Antonio Fiaschi a , Paolo Manganotti a a Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy b Department of Neurology, Franz Tappeiner Hospital, Meran/o, Italy c Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria abstract article info Article history: Received 15 December 2012 Revised 11 February 2013 Accepted 13 February 2013 Available online xxxx Keywords: Idiopathic generalized epilepsy Motor threshold Phosphene threshold Photosensitivity Transcranial magnetic stimulation Background: The current understanding of the mechanisms underlying photosensitivity is still limited, although most studies point to a hyperexcitability of the visual cortex. Methods: Using transcranial magnetic stimulation, we determined the resting motor threshold (rMT) and the phosphene threshold (PT) in 33 patients with IGEs (8 with photosensitivity) compared with 12 healthy controls. Results: Eleven controls (92%) reported phosphenes compared with fifteen (46%) patients with idiopathic gener- alized epilepsy (p = 0.015). Phosphenes were reported more frequently among patients with epilepsy with photosensitivity (87.5%) than in patients with active epilepsy without photosensitivity (30.8%) (p = 0.038) and patients with epilepsy in remission without photosensitivity (33.3%) (p = 0.054); no differences were found between patients with epilepsy with photosensitivity and controls (p = 0.648). Resting motor threshold and phosphene threshold were significantly higher among patients with epilepsy (active epilepsy or epilepsy in remission without photosensitivity) compared to healthy controls (p b 0.01). Conversely, patients with active epilepsy and photosensitivity had significantly lower values than controls (p = 0.03). Conclusions: The marked decrease in PT and the high phosphene prevalence in patients with IGE with photosen- sitivity indicate a regional hyperexcitability of the primary visual cortex. Results of this study also suggest that the PT may serve as a biomarker for excitability in patients with IGE and photosensitivity. © 2013 Elsevier Inc. All rights reserved. 1. Introduction Idiopathic generalized epilepsies (IGEs) include many distinct epi- leptic syndromes and are thought to be the expression of a widespread hyperexcitability involving subcortical and cortical structures in both hemispheres, especially in thalamo-cortical circuitry. However, each seizure type characterizing an epileptic syndrome (typical absences, myoclonic jerks, and generalized tonic-clonic seizures, alone or in vary- ing combinations and severity) involves a distinct hyperexcitable cir- cuitry, which, in most instances, does not involve the whole brain [1]. The circuits involved may even change with age [1]. Photosensitivity is an abnormal sensitivity of the human brain in reaction to visual stimulation. It is a highly heritable electroenceph- alographic (EEG) trait characterized by the occurrence of spikes, spike–waves, and intermittent slow waves in response to visual stimulation [2]. Photosensitivity is a frequent feature of IGEs, with positive response to IPS reported to range from 7.5% in juvenile ab- sence epilepsy to 100% in pure photosensitive epilepsy [3]. The cur- rent understanding of the mechanisms underlying photosensitivity is still limited, although most studies point to a hyperexcitability of the visual cortex [4–7]. Transcranial magnetic stimulation (TMS) has been used to noninva- sively and directly assess cortical physiology and excitability in vivo, thus representing a fascinating method to study pathophysiological mechanisms underlying epilepsy in general and IGE in particular. Transcranial magnetic stimulation of the motor cortex in epilepsy can assess cortical excitability by determining different parameters. Motor threshold (MT) represents the most easily recorded parameter. It reflects the excitability and the local density of a central core of excit- atory interneurons and corticospinal neurons in the muscle representa- tion at the primary motor cortex level, as well as the excitability of the target spinal motoneurons [8,9]. Resting MT (rMT) represents the phys- iological and methodological bases for more complex TMS assessments of cortical excitability, such as the evaluation of intra-cortical inhibition Epilepsy & Behavior 27 (2013) 301–306 ⁎ Corresponding author at: Department of Neurological, Neuropsychological, Morpho- logical and Movement Sciences, Section of Clinical Neurology, University of Verona, Piazzale L.A. Scuro, 10-37134 Verona, Italy. Fax: +39 0458124873. E-mail address: dr.francescobrigo@gmail.com (F. Brigo). 1 These authors contributed equally to the manuscript. 1525-5050/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yebeh.2013.02.010 Contents lists available at SciVerse ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh