ORIGINAL RESEARCH Low-Frequency Photoparoxysmal Response in Adults: An Early Clue to Diagnosis Julie Guellerin,* Sophie Hamelin,† Cecile Sabourdy,*† and Laurent Vercueil*† Summary: Intermittent photic stimulation is performed during an EEG to evoke photoparoxysmal response. When they appear triggered by low- frequency stimulation in children, they are suggestive of rare diagnosis, that is, neuronal ceroid lipofuscinosis. Among adults, their significance is less well understood. Low-frequency (,5 Hz) intermittent photic stimulation was performed over a period of 5 years during adult standard EEG. This retro- spective study included all patients exhibiting low-frequency photoparoxys- mal response. Five cases were identified. Three of them presented with active epilepsy (two progressive myoclonus epilepsy, one unclassifiable), two had visual deficiency, and three had dementia. The etiologies were MELAS (two), Creutzfeldt–Jakob disease (one), Kufs disease (one), and remained undeter- mined for one patient. In all patients, low-frequency photoparoxysmal response was observed years or months before the final diagnoses have been reached. Low-frequency photoparoxysmal response, classically associated with childhood progressive myoclonus epilepsy, seems to have a wider eti- ological spectrum in adult population. Moreover, this neurophysiological feature could be present before the final diagnosis in most cases. Systemat- ically testing low frequencies during intermittent photic stimulation even during adult EEG seems warranted, particularly in a context of severe pro- gressive neurologic deterioration. Key Words: Photosensitivity, Low frequency, MELAS, Creutzfeldt–Jakob disease, Kufs disease. (J Clin Neurophysiol 2012;29: 160–164) P hotosensitivity is defined as abnormal EEG activity induced by visual stimuli (Kasteleijn–Nolst Trenité et al., 2001). In photosen- sitive patients, intermittent photic stimulation (IPS) induces epilepti- form discharges in the occipital cortex that may propagate to more rostral areas. Different classifications of EEG response to IPS have been proposed. One of them is from Kasteleijn–Nolst Trenité et al. (2001): grade I: photic following (or photic driving); grade II: orbito- frontal photomyoclonus; grade III: posterior stimulus-dependent response; grade IV: posterior stimulus-independent response; grade V: generalized photoparoxysmal response (PPR); and grade VI: acti- vation of preexisting epileptogenic area. Grade III to V are commonly known as PPR and include the four types of the classification of Waltz et al. (1992). It has been proposed that photosensitivity may originate from an increased excitability of the occipital cortex (Parra et al., 2003; Siniatchkin et al., 2007). Usually, photosensitivity is observed at frequencies varying from 10 to 30 Hz. Using stimulation frequencies below 5 Hz, photosensitivity is very unusual, but in children, it may provide clues to diagnosis, especially in patients with progressive myoclonus epilepsy [neuronal ceroid lipofuscinosis (Binelli et al., 2000), Lafora disease (Roger et al., 1983), and mitochondrial disease (Canafoglia et al., 2001)]. Little is known about its diagnostic value in adults, despite occasional reports (Gourfinkel–An et al., 2007). In this study, we report on the occurrence of low-frequency PPR (LFPPR) in a consecutive series of five adult patients presenting with various diagnoses. METHOD In the neurologic functional exploration unit at the Grenoble University Hospital, IPS, including low frequencies (1, 2, and 4 Hz), was systematically performed from 2003 to 2007 during adult stan- dard EEGs. All patients with LFPPR, according to the following criteria, on at least one EEG recording were retrospectively included in this study. Clinical and electrophysiological data and etiologies were retrieved from medical charts. EEG recordings were reex- amined to confirm the diagnosis. EEGs were recorded with scalp electrodes placed according to the international 10-20 system with both bipolar and referential montages (Deltamed, Bordeaux, France). All patients had undergone routine EEG usually lasting .20 minutes, including activating pro- cedures (i.e., hyperventilation and IPS). The IPS was performed using a photostimulator (Deltamed or Braintronics; Almere, the Netherlands) with white flash. The flash lamp was placed 30 cm from the nasion. The IPS was performed using flash frequencies ranging from 1 to 50 Hz lasting 5 seconds after the closure of the eyes. The recordings were then reviewed to determine the back- ground activity, the presence of spontaneous epileptiform discharges, and to characterize the PPR type, frequency, and location. Patients were considered for inclusion if IPS induced a paroxysmal EEG response according to the three following criteria: (1) time-locked response (starting with IPS), (2) generalized spikes or diffuse epileptiform discharges, and (3) IPS frequency lower than 5 Hz. RESULTS Five patients (four women) were identified: the mean age was 37.4 years at the time of the LFPPR (range, 19–66 years). Three of the patients presented with active epilepsy (two progressive myoc- lonus epilepsies, one unclassifiable), two had visual deficiency, and three with severe and rapidly progressive dementia. Three patients had antiepileptic drugs. The clinical features and final diagnosis are described in Table 1. Brain MRI showed diffuse subcortical atrophy in two patients, and diffuse fluid-attenuated inversion recovery image showed uptake spreading cortically in one. The paraclinical findings are described in Table 2. From the *EFSN, Grenoble University Hospital, Grenoble, France; and †INSERM U836, Grenoble Institute of Neuroscience, Grenoble, France. Address correspondence and reprint requests to Julie Guellerin; e-mail: jguellerin@ yahoo.fr. Copyright Ó 2012 by the American Clinical Neurophysiology Society ISSN: 0736-0258/12/2902-0160 160 Journal of Clinical Neurophysiology  Volume 29, Number 2, April 2012