Epilepsies with typical absence seizures (TASs) constitute a genetically determined group of epileptic disorders whose classification, diagnosis, and therapy have been problematic in some cases, especially in adulthood (1,2). The association of photosensitivity with TASs has been shown to be a poor prognostic factor (3). However, no detailed report focuses on photosensitive TASs (PTASs). Our aim was to elucidate the characteristics of the patients with PTASs in which photosensitivity was a consistent and unequivocal seizure-triggering mechanism.
Summary: Purpose: To describe the characteristics of patients with typical absence seizures (TASs), consistently triggered by photosensitivity.
Methods: Consecutive patients having TAS induced by intermittent photic stimulation were included in the study. All clinical parameters, EEG, and video-EEG data were assessed during the long-term follow-up. Statistical analyses were performed with SPSS 10.0 software.
Results: Nine female and two male patients with a mean age at onset of 14 ± 5.9 years (range, 7–27 years) and with a mean follow-up of 9 ± 7.56 years had photosensitive TASs. They constituted 7.64% of absence epilepsies and 0.4% of all patients seen in our tertiary center. The seizures were usually subtle and had a reported frequency of 1 to 9 times daily. Seven patients were clinically photosensitive and reported that some of their TASs were induced by photic stimuli in daily life. All patients also had spontaneous TASs, and four of them had generalized tonic–clonic seizures. EEG results did not show any distinctive features when compared with those of other cases with TASs. Remission could not be achieved in five patients with antiepileptic drug treatments, and we always observed relapses after drug discontinuation or dose reduction in the remaining six cases in remission. Spontaneous remission did not occur even in the five patients older than 30 years.
Conclusions: TASs triggered by photosensitivity are a rare and heterogeneous clinical condition with a marked female preponderance. It is notable that TASs do not remit in these cases.
Consecutive patients admitted to our epilepsy outpatient clinic between April 1997 and 2002, with a diagnosis of TASs based on International League Against Epilepsy (ILAE) criteria (4) were prospectively followed up. We included the patients with PTASs defined as having more than two TASs present only during intermittent photic stimulation (IPS) in the routine screening EEG. Where TASs were recorded during resting and hyperventilation (HV), PTASs were assumed if a twofold or more increase in the number of TASs during IPS was present compared with the number of TASs in the resting and HV periods. These data were assessed with Fisher's t test for statistical significance.
All patients were questioned in a standardized manner about triggering factors for their seizures. Patients who reported that all or some of their TASs were induced by photic stimuli in daily life were defined as clinically photosensitive.
Additional inclusion criteria were as follows: No evidence of neurologic deficit or mental retardation; and computed tomography (CT) and/or magnetic resonance imaging (MRI) scans had to be normal or nonspecific/unrelated to epilepsy. Finally, cases with visually triggered seizures starting with an aura indicating of an occipital lobe onset and patients with eye closure–related epileptiform discharges in the resting EEG were excluded.
Our standard IPS protocol in performing screening EEGs started with eyes open for 5 s and then eyes closed for 5 s; the stimulus trains of 5-10-15-20-25-30-35 Hz were given in screening phase at a distance of 30 cm in a normally illuminated room. A photic stimulator with a granular diffuser and lamp housing reflector capable of delivering a flash from 1 to 50 Hz at a constant intensity (Medelec DG Compact 32; Vickers Medical, Surrey, U.K.) was used for all cases. If photosensitivity was found or suspected, the highest and lowest frequency ranges were established with manual stimulation. HV was done for 5 min, and patients were randomly asked to open and close their eyes ≥7 times during the resting EEG to find the cases with eye-closure sensitivity.
After the patients' informed consent, they underwent synchronous video-EEG investigations (1–6 h, depending on the number of the recorded absences). The level of consciousness was tested by an experienced technologist by giving brief orders and a short phrase to remember after the event and by counting during IPS. The patients were tested without modification of the antiepileptic drug (AED) treatment during the follow-up investigations.
All of the available EEGs and video data were analyzed independently by three investigators in two separate sessions, by using the parameters listed in Table 1. The characteristics of the study group with PTAS were compared with those of other patients with TASs considered as the “main absence epilepsy” group, followed by the same team. Statistical analyses were performed with SPSS 10.0 software. Mann–Whitney U test was applied to calculate the significance of clinical and electroencephalographic differences between the group of PTASs and the “main absence epilepsy” group and some subgroups like the syndromes of eyelid myoclonia with absences (EMA) and of juvenile myoclonic epilepsy (JME).
|Current age and sex||24 M||25 F||35 F||17 F||42 M||56 F||32 F||25 F||30 F||18 F||16 F|
|Age at onset (yr)||11||23||27||9||13||13||12||11||8||11||7|
|Other seizures||FC||GTCS||−||−||FC, GTCS||−||−||GTCSa||FC||GTCS||FC|
|Remission||Rm with||No Rm with||No Rm with||No Rm with||Rm with||Rm with||No Rm with||Rm with||Rm with||Rm with||No Rm with|
|Relapse||Yes (IPS+)||Nob||Nob||No||Yes (IPS+)||Yes||No||Yes (in pregnancy)||Yes||Yes (GTCS)||No|
|Interictal EEG findings in IPS|
|IPS range (Hz)||20–25||10–25||13–20||8–20||5–23||5–30||10–20||8–30||15–30||9–27||10–15|
|PPR eyes open||−||−||+||+||−||+||−||+||−||−||−|
|PPR eye closed||+||+||+||+||+||+||+||+||+||+||+|
|Prolonged IPS r.||+||+||+||+||−||−||−||+||−||+||−|
|Ictal EEG findings: Characteristics of GSW discharges|
|Start frequency (Hz)||4||4||3.5||3,5||3||3.5||4||4||4||3||3.5|
|Median duration (s)||7||7||10||13||20||8||30||10||4||6||6|
|Ictal semiology (video data)|
|Change in consciousness||Moderate||Mild||Moderate||Moderate||Mild||Moderate||Moderate||Moderate to severe|
|Eye deviation||+ (mild)||+||+|
|Other||Urinary incontinence||Self-induction||Nose wiping|
Of 2,697 cases seen in the epilepsy outpatient clinic, 144 (5.34%) were diagnosed as having TASs according to ILAE criteria (4) during the study period. Of these, 11 cases have PTASs by our criteria. They were 7.64% of absence epilepsies and 0.4% of all patients assessed by our epilepsy outpatient clinic. The remaining cases with TASs were considered the “main absence epilepsy group.”
The nine female and two male patients had a mean age of 29.09 ± 11.98 and a mean follow-up period of 9 ± 7.56 years. Clinical photosensitivity was reported by seven patients of the group, whereas none of the cases in the “main absence epilepsy” group reported this feature. The most common trigger was television in six cases, followed by sunlight in four cases, and other electric lights in three cases. Pattern sensitivity could be demonstrated in one case with a checked fabric already known as a trigger, but not in a second patient who reported this feature. The seizure frequency was reported as one to nine seizures/day in 10 cases and 10–25 seizures/day in one case. Four patients had a family history of epilepsy, and the group included a mother and her daughter. Other clinical characteristics and prognostic data are summarized in Table 1. None of the other clinical features differed significantly from the “main absence epilepsy” group, and all patients with PTASs also had either history or EEG evidence of spontaneous TASs. All patients with PTASs were gainfully employed. Four of the patients had migraine without aura.
At least one baseline EEG was obtained without medication in all patients included in the group and in all but 11 of 133 patients from the main absence epilepsy group. A mean of 5.18 ± 3.46 EEGs were done in the PTASs group. Ictal EEG features shown in Table 1 did not show any distinctive parameters when compared with the “main absence epilepsy” group, other than long-lasting photosensitivity (Fig. 1). The background activity was normal in all but one case with a history of coincidental tuberculosis meningitis. None of the 11 cases showed rhythmic occipital slow waves.
A prolonged generalized spike-and-wave (GSW) response in IPS (photoparoxysmal response (PPR) that persisted >100 ms beyond the termination of the flashes) was present in six of the patients in interictal EEGs and in 10 of the ictal records. The ictal GSW discharges were prominent over the anterior regions in six cases, prominent over the posterior regions in one case, and prominent over the central region in one patient. In the remaining three cases, the GSW discharges were purely generalized. Additional focal findings as described by Lombroso (5) were seen in six cases as a consistent interictal finding.
Ten video-EEG investigations were performed in eight of the patients (Table 1). The clinical manifestations of PTASs were usually subtle and could easily have escaped notice without specific testing. The patient, who was considered to have severe impairment of consciousness, was the youngest. We did not observe tonic, clonic, myoclonic, or atonic components during the seizures. Only one patient had a history of self-induction of PTASs. Diagnosis and therapy were delayed in five cases for >1 year. Spontaneous TASs as well as PTASs continued despite increasing valproate (VPA) to 2,000–3,000 mg/day with therapeutic blood levels and despite rational combination therapies used in five cases. We observed relapses after drug discontinuation or dose reduction in the other six cases with remission with VPA. In two of them, IPS could induce PTASs although the patients reported clinical remission for PTASs and TASs at that time. Finally, spontaneous remission did not appear even in the five patients older than 30 years.
It is established that patients with visually evoked seizures have mainly tonic–clonic and myoclonic seizures (6). In some studies, a few cases having PTASs triggered by visual stimuli were described briefly (1,2,7,8). One of the pioneering video-EEG studies reported that duration and semiologic categories did not differ between spontaneous TASs and PTASs. However, no further clinical and prognostic details were provided (7). Wolf and Goossess (9) emphasized that TASs were rarely induced by IPS. One case with frequent television-induced PTASs was mentioned in a study describing TASs in adulthood (2). No detailed study focuses on PTASs.
The presence of photosensitivity during EEG examination does not always coexist with the occurrence of visually induced seizures in daily life (10), as seen in four cases in our group. Doose and Gerken (11) elucidated that GSWs present at rest and accentuated by HV are inherited independent of photosensitive discharges, although both may be present in one patient. Ictal accompaniments as well as interictal EEG characteristics of the PTASs group were not distinctive when compared with those of other cases with absence epilepsies, underlining the coexistence of different but related EEG traits.
Self-induced seizures are encountered in some photosensitive epilepsy patients and are induced by either hand waving or eye blinking (12). Although asked specifically, we could detect only one case with this particular feature among the PTASs group.
EMA is a distinctive syndrome with brief TASs occurring with prominent rhythmic eyelid myoclonia associated with GSW discharges after eye closure (13). Photosensitivity is also seen in close relation with eye-closure sensitivity, and TASs in cases with EMA persist usually into adult life. We diagnosed EMA syndrome in 13 (9%) other cases in our main absence epilepsy group. None of our 11 cases reported here had the typical eyelid myoclonia related to eye closure, and EEG characteristics were not similar.
Harding et al. (14) reported that photosensitivity persists in at least two thirds of 100 patients with photosensitive epilepsy and that VPA is effective in controlling this photosensitivity. Our small series with PTASs showed that photosensitivity persisted in five patients older than 30 years, and some cases with PTASs could not achieve remission although treated with VPA and rational combination therapies.
As a whole, the group with PTASs had a heterogeneous epileptic phenotype but with an unremitting course. Many differences are found in the group with respect to the ages at onset of seizures (7–27 years), association with generalized tonic–clonic convulsions (GTCSs), presence or absence of remission under treatment, and IPS frequency ranges. These differences may be consistent with intrasyndromic variability observed for many epileptic syndromes as well as absence epilepsies. Although absence epilepsies are, at first glance, a seemingly homogeneous group of epileptic disorders with a high remission rate, within-group differences are manifest in various features (1,2,4,8), association with photosensitivity being one of the clues of unremitting course according to our results.
A separate category was proposed under idiopathic generalized epilepsy (IGE) called visual-sensitive IGE, which includes patients with absences with eyelid myoclonia and pure PTASs without associated spontaneous TASs (6,15). We did not observe any case with pure PTASs in our study. Apart from our observations, the category of visual-sensitive IGE seems to include mainly cases with GTCSs and myoclonia, exclusively triggered with visual stimuli. At the moment, it is not clear whether this entity corresponds to the coincidence of different closely related genetic traits or to a single mechanism. Further genetic research with scrutiny of clinical data is required to unravel this clinical entity.
In conclusion; typical absence seizures triggered by photosensitivity are rare and show a heterogeneous phenotype with a marked female preponderance. It is noteworthy that clinical seizures in form of TASs as well as PTASs do not remit in these cases.
Acknowledgment: We thank Dr. Alastair Sutcliffe for reviewing the manuscript. We also thank our hard-working EEG technologists, Mr. Nazmi Aslan, Mr. Mehmet Ali Carik, and Ms. Emirzade Dagdas for careful EEG recordings and Mr. Yavuz Nural for secretarial assistance. This study was supported by the research fund of Istanbul University (T-1124/18062001).