Long-term prognosis of patients with photosensitive idiopathic generalized epilepsy.

OBJECTIVE: The long-term prognosis of photosensitive idiopathic generalized epilepsy (p-IGE) is generally considered favorable; however, its specific characteristics remain unclear. Our objective was to investigate the extended prognosis of p-IGE. METHODS: We analyzed the demographics, clinical, and electroencephalographic (EEG) data of consecutive patients who were diagnosed as having p-IGE, who were under follow-up for a minimum of 10 years and exhibited a photoparoxysmal response (PPR) in their EEGs. Prognostic data, epilepsy course types, and electroclinical variables were compared using appropriate statistical methods. RESULTS: The mean follow-up duration for 108 consecutive patients with p-IGE (74.1 % female) was 16.8 ± 6.5 years. The main syndromes within this cohort included juvenile myoclonic epilepsy (37 %), juvenile absence epilepsy (15.7 %), and epilepsy with eyelid myoclonia (EEM) (14.8 %). In terms of epilepsy course types, 27.8 % were in the relapse-remission group, and 13.9 % had never experienced remission. A low early remission rate (5.6 %) was evident, with the remaining half of the cohort categorized as the late remission group. Several significant poor prognostic factors were identified including self-induction, clinical symptoms accompanying PPR, asynchrony and focal findings in EEG discharges, a wide frequency range of PPR, the coexistence of three seizure types, the presence of accompanying focal seizure features, and a history of convulsive status epilepticus. CONCLUSIONS: Our long-term follow-up study, conducted within a substantial p-IGE group, unveiled newly proposed course types within this epilepsy category and highlighted significant poor prognostic factors related to photosensitivity. These findings furnish valuable insights for precise prognosis counselling and effective management strategies for patients with p-IGE.

A novel GABRG2 variant in Sunflower syndrome: A case report and video EEG monitoring.

OBJECTIVE: Sunflower syndrome is a unique photosensitive epilepsy, characterized by heliotropism and stereotyped seizures associated with handwaving. These handwaving events (HWE) are thought to be an ictal phenomenon, although current data are contrasting. Photosensitive epilepsy occurs in 2%-5% of the epilepsy forms and several pathogenic gene variants have been associated with photosensitive epilepsy. However, the genetic etiology of Sunflower syndrome remains unknown. Antiseizure medications (ASM) efficacious in treating photosensitive epilepsy are valproic acid (VPA) and levetiracetam (LEV) although some forms, such as Sunflower syndrome, can be drug-resistant. METHODS AND RESULTS: Here, we report an 8-year-old boy with an early onset of episodes of HWE that was initially categorized as behavioral problems for which risperidone was started. However, the medical history was suggestive of Sunflower syndrome, and subsequent video EEG showed focal mostly temporal and frontotemporal (right and left) epileptiform activity and confirmed the epileptic nature of the HWE. Thus, VPA was started and initially led to seizure frequency reduction. Molecular analyses showed a pathogenic variant in GABRG2 (c.1287G>A p.(Trp429Ter)), which has been associated with photosensitive and generalized epilepsy. SIGNIFICANCE: Overall, clinicians worldwide should be cautious by interpreting HWE and/or other tic-like movements, since an epileptic origin cannot be ruled out. A prompt and correct diagnosis can be made by performing a video EEG early on in the diagnostic process when epileptic seizures are part of the differential diagnosis. Even though the genetic etiology of Sunflower syndrome remains poorly understood, this constellation supports further genetic testing since the detection of a pathogenic variant can help in making correct decisions regarding ASM management.

Photosensitive occipital lobe epilepsy: Delineation of an under-recognized reflex epilepsy syndrome according to the new ILAE criteria and long-term follow-up.

OBJECTIVE: Photosensitive occipital lobe epilepsy (POLE) should be suspected in patients with occipital lobe seizures triggered by photic stimuli, who have normal motor-mental development and brain imaging. We aimed to examine the clinical, electrophysiological, and prognostic features of POLE, which is a rare and under-investigated syndrome. METHODS: Archives from two tertiary epilepsy centers were retrospectively scanned and patients with normal neurological examination and cranial imaging were identified with POLE if they had: (1) seizures consistently triggered by photic stimuli; (2) non-motor seizures with visual symptoms; and (3) photosensitivity documented on EEG. The clinical and electrophysiological features and prognostic factors were evaluated for patients who had follow-up ≥5 years. RESULTS: We identified 29 patients diagnosed with POLE with a mean age of 20.1 ± 7.6 years. In one-third of the patients, POLE syndrome overlapped with genetic generalized epilepsy (GGE). The overlap group had higher rates of febrile seizure history and self-induction; when compared to pure POLE patients, their EEGs showed more frequent interictal generalized epileptic discharges and posterior multiple spikes during intermittent photic stimulation. During long-term follow-up, the remission rate for POLE was 80%, but EEG photosensitivity persisted in three quarters of patients despite clinical remission, and more than half had relapsed after clinical remission. SIGNIFICANCE: This first long-term follow-up study, utilizing newly suggested criteria of the International League Against Epilepsy, showed that POLE syndrome shows a notable overlap with GGE but also has distinctive features. POLE has a good prognosis; however, relapses are common, and photosensitivity persists as an EEG finding in the majority of patients.

Epilepsia refleja por agua caliente. Estrategias de diagnóstico y tratamiento / Hot water reflex epilepsy. Management and treatment

Las epilepsias reflejas son un grupo de trastornos epilépticos desencadenados por determinados estímulos (luces, agua caliente, música…). Por la semiología de los episodios pueden confundirse con algunos trastornos paroxísticos no epilépticos comunes como los síncopes. Es importante en la anamnesis dirigida preguntar acerca del estímulo desencadenante y de la cronología de la resolución del mismo para poder distinguirlos (AU)

Reflex epilepsies are a group of diseases induced by identifiable stimuli (light flashes, hot water, music…). They can be confused with non-epileptic paroxysmal events like syncope. It is important to ask about the identifiable trigger and about how the event is resolved to make a right differential diagnosis. (AU)

Psychophysiological interaction analysis for the detection of stimulus-specific networks in reflex epilepsy.

We report detailed functional MRI (fMRI) analyses in a patient with reflex seizures elicited by driving along a specific rural crossroad or by watching a video thereof. Semiology consisted of epigastric aura, followed by a sensory seizure of the left hand and sporadic automotor seizures. The right amygdala-region (rh-amygdala) was surgically and electroclinically confirmed as the epileptogenic zone. Presurgical task-fMRI was performed, during which videos of the driving along that specific crossroad (IC), of another crossroad (NC) or noise were presented. Independent component analysis was conducted, and one component was used to aid in selection of a seed region within the rh-amygdala for subsequent psychophysiological interaction analysis (PPI). Here, the following regions showed stronger connectivity with the rh-amygdala seed during the IC condition compared to NC: right > left visual cortex, bilateral insulae, and right secondary somatosensory cortex (S2), potentially explaining epigastric aura and left somatosensory seizure semiology. Contralateral analyses did not reproduce these results. Overall, the ictogenic stimulus elicited enhanced connectivity of the epileptogenic rh-amygdala with visual cortex and further regions of potential seizure spread (S2, insula) as a putative mechanism of ictogenesis. Our results highlight the potential of PPI in the analysis of stimulus-dependent networks in patients with reflex epilepsies to gain insight into seizure generation.

A Computational Biomarker of Photosensitive Epilepsy from Interictal EEG.

People with photosensitive epilepsy (PSE) are prone to seizures elicited by visual stimuli. The possibility of inducing epileptiform activity in a reliable way makes PSE a useful model to understand epilepsy, with potential applications for the development of new diagnostic methods and new treatments for epilepsy. A relationship has been demonstrated between PSE and both occipital and more widespread cortical hyperexcitability using various types of stimulation. Here we aimed to test whether hyperexcitability could be inferred from resting interictal electroencephalographic (EEG) data without stimulation. We considered a cohort of 46 individuals with idiopathic generalized epilepsy who underwent EEG during intermittent photic stimulation: 26 had a photoparoxysmal response (PPR), the PPR group, and 20 did not, the non-PPR group. For each individual, we computed functional networks from the resting EEG data before stimulation. We then placed a computer model of ictogenicity into the networks and simulated the propensity of the network to generate seizures in silico [the brain network ictogenicity (BNI)]. Furthermore, we computed the node ictogenicity (NI), a measure of how much each brain region contributes to the overall ictogenic propensity. We used the BNI and NI as proxies for testing widespread and occipital hyperexcitability, respectively. We found that the BNI was not higher in the PPR group relative to the non-PPR group. However, we observed that the (right) occipital NI was significantly higher in the PPR group relative to the non-PPR group. Other regions did not have significant differences in NI values between groups.

Long-term clinical course and prognosis of hot water epilepsy: 15-Year follow-up.

OBJECTIVE: Hot water epilepsy (HWE) is a type of reflex epilepsy triggered by bathing with hot water. Hot water epilepsy is generally considered as a self-limiting benign disease although its long-term course and prognosis remains unknown. In this study, we aimed to determine the long-term clinical course and prognosis of hot water epilepsy and possible factors affecting them. METHODS: The diagnosis of HWE was made based on the clinical history obtained from patients and their first degree relatives witnessing to the seizures and video recordings of seizures if available; then, the type of seizure was identified. Good prognosis was defined as patients whose seizures were controlled with or without preventive measures and who did not require antiepileptic treatment. The poor prognosis was defined as patients whose seizures continued despite preventive measures and required antiepileptic treatment. RESULTS: The study included 50 (31 male and 19 female) patients with a mean follow-up of 17.63 ±â€¯10.46 (median, 15.0) years. The age at onset of seizure was 14.52 ±â€¯12.71 (median: 10.0) years. There were 38 (76%) patients in the good prognosis group. 18 (36%) of them achieved complete remission, who did not require preventive measures. In the remaining 20 (40%) patients, seizures could be controlled with only preventive measures. Seizures could be controlled with antiepileptic treatment in only 1 (2%) of 12 (24%) patients in the poor prognosis group. A significant relationship was found between the frequency of hot water seizures (HWSs) and poor prognosis (p = 0.019), as well as the presence of spontaneous seizures outside of bathing and poor prognosis (p = 0.000). SIGNIFICANCE: Hot water epilepsy, as previously known, is not a self-limiting benign disease. Approximately ¾ of the cases have a good prognosis, but the rest are in the case of chronic epilepsy. The low response rate to antiepileptics' treatment suggests that the pathogenesis of the HWE may differ from other epilepsies.

Musicogenic epilepsy in paraneoplastic limbic encephalitis: a video-EEG case report.

Musicogenic epilepsy (ME), a peculiar form of reflex epilepsy, represents a neurological rarity and yet another demonstration of the extraordinary power of music on the human brain. Despite the heterogeneity of the reported musical triggers, patients' emotional response to music is thought to play a crucial role in provoking seizures. Accordingly, the mesial temporal structures (especially of the non-dominant hemisphere) appear most involved in seizure generation, although a more complex fronto-temporal epileptogenic network was documented in some cases. Autoimmune encephalitis has been recently included among the many possible aetiologies of ME based on a few reports of music-induced seizures in patients with anti-glutamic acid decarboxylase 65 antibodies. Here, we describe the case of a 25-year-old man, educated in music over a long period of time, who had suffered from drug-resistant temporal lobe epilepsy following seronegative limbic encephalitis related to non-Hodgkin lymphoma. Along with spontaneous events, the patient also developed musicogenic seizures later in the disease course. After detecting five music-induced episodes via 24-hour ambulatory EEG, we performed prolonged video-EEG monitoring during which the patient presented a right temporal seizure (characterized by déjà-vu, piloerection and gustatory hallucinations) while listening to a hard rock song through headphones (which he had not previously heard). This observation allowed us to confirm the provoking effect of the music on our patient's seizures, despite the lack of any emotional drive, which suggests that a "cognitive" trigger was more likely in this case. Our report further highlights that autoimmune encephalitis should be investigated as a novel potential cause of musicogenic epilepsy, regardless of autoantibody status.

Bathing epilepsy: a video case report.

Bathing epilepsy is a rare form of reflex epilepsy triggered by bathing in room temperature water. It predominates in boys with a mean age of 15 months and its evolution is benign. Diagnosis of bathing epilepsy requires the exclusion of other paroxysmal disorders triggered by water contact. Video-EEG confirmation of the seizures is necessary to reach a diagnosis of certainty and to allow adequate management. We present the case of a one-year-old boy who experienced recurrent episodes of unresponsiveness and cyanosis while bathing in lukewarm water. The diagnosis of bathing epilepsy was confirmed by the video-EEG recording of a seizure, showing left-sided frontotemporal delta activity with rapid contralateral spread. Therapy with levetiracetam was effective, subsequently allowing bathing without further seizures.

Flash-evoked high-frequency EEG oscillations in photosensitive epilepsies.

OBJECTIVE: To determine the feasibility of measuring scalp-recorded, flash-evoked, high-frequency EEG oscillations (F-HFOs) using a relatively simple technique. Furthermore, to assess whether F-HFOs are enhanced in photosensitive epileptic patients and if they might be proposed as a putative non-provocative biomarker of photosensitivity. METHODS: We studied 19 photosensitive patients with idiopathic generalized epilepsy, and 22 controls matched for demographic features. We extracted F-HFOs from the broadband scalp flash-visual evoked potential (b F-VEP) through appropriate filtering. We measured F-HFO amplitude, number and latency. Also, we carried out a time-frequency domain spectral F-HFO analysis. Inter-group statistics was performed. Within-groups, F-HFO features were correlated to the b F-VEP. RESULTS: The N3-N3I wave of the b F-VEP was significantly (p = 0.01) larger in patients compared to controls. The same was true for the inter-group F-HFO amplitude (p = 0.01). F-HFOs showed two main spectral peaks (∼88 and ∼125 Hz), whose power was greater (p = 0.001) in patients than in controls. The ∼88 Hz peak power exceeded the upper normal range in 15/19 patients. Patients showed a significant (p = 0.04) correlation between the ∼88 Hz peak power and the size of the N3-N3I wave. SIGNIFICANCE: A simplified F-HFO measurement proved feasible. In patients, F-HFOs were enhanced in terms of both size and spectral power, suggesting a role in the generation of the photoparoxysmal response. Some spectral features of the F-HFOs may be proposed as a putative non-provocative marker of epileptic photosensitivity.

SYNGAP1-DEE: A visual sensitive epilepsy.

OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS: Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient. RESULTS: We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures. CONCLUSIONS: Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort. SIGNIFICANCE: Combining these clinical and electroencephalographic features could help guide genetic diagnosis.

Sunflower syndrome: a poorly understood photosensitive epilepsy.

Sunflower syndrome is a rare photosensitive epilepsy which has received little attention in recent medical literature. The historical cases documenting the epilepsy's stereotyped handwaving motion in front of light characterized the behavior as self-inducing seizures via mimic of stroboscopic effect. However, the relationship between handwaving episodes and attendant generalized electroencephalogram abnormalities, and an appreciation of the compulsive attraction the sun and other light sources hold for these patients, suggest the handwaving motion may be a part of the seizure rather than a mechanism of self-induction. The lack of awareness of Sunflower syndrome often leads to misdiagnosis. The seizures are often refractory to traditional anticonvulsant medication, and patients resort to behavioral intervention, such as hats and sunglasses, to reduce handwaving episodes. Further study is required to determine the syndrome's natural history and to identify more effective treatment options. WHAT THIS PAPER ADDS: Sunflower syndrome is a rare condition that is often misdiagnosed. Awareness of the clinical and electroencephalogram characteristics of Sunflower syndromemay reduce the prevalence of misdiagnosis.