Version May 2024
INTRODUCTION AND DEFINITION — At its essence, epilepsy is a disease of the brain characterized by an enduring predisposition to epileptic seizures [1,2]. A practical definition of epilepsy, proposed in 2014 by the International League Against Epilepsy (ILAE), considers epilepsy to be defined by any of the following conditions [1]:
●At least two unprovoked (or reflex) seizures occurring >24 hours apart
●One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60 percent) after two unprovoked seizures, occurring over the next 10 years
●Diagnosis of an epilepsy syndrome
Reflex epilepsies are characterized by epileptic seizures that are evoked by specific external sensory stimuli, internal cognitive and emotional processes, or activity of the patient [3-5].
This review will focus on hot water and bathing epilepsy, reading epilepsy, and startle epilepsy. Photosensitive epilepsies are reviewed separately. (See "Photosensitive epilepsies".)
CLASSIFICATION
Syndromes — Reflex seizures can occur in both generalized and focal types of epilepsies. In certain epilepsy syndromes, all or nearly all seizures are reflex seizures, including the following [6]:
●Photosensitive epilepsies (see "Photosensitive epilepsies")
●Reading epilepsy (see 'Reading epilepsy' below)
●Startle epilepsy (see 'Startle epilepsy' below)
●Hot water epilepsy and bathing epilepsy (see 'Hot water epilepsy and bathing epilepsy' below)
The most prevalent type is photosensitivity epilepsy, which is found in all types of epilepsy, but more often in females with idiopathic generalized types of epilepsy [7]. Photosensitive epilepsies are reviewed separately. (See "Photosensitive epilepsies".)
Reflex seizures may also occur along with spontaneous seizures in generalized idiopathic and genetic epilepsy syndromes; examples include [3]:
●Dravet syndrome (see "Dravet syndrome: Genetics, clinical features, and diagnosis")
●Childhood absence epilepsy (see "Childhood absence epilepsy")
●Epilepsy with eyelid myoclonia (Jeavons syndrome) (see "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)')
●Juvenile myoclonic epilepsy (see "Juvenile myoclonic epilepsy")
●Progressive myoclonic epilepsy (see "Symptomatic (secondary) myoclonus", section on 'Progressive myoclonic epilepsy and progressive myoclonic ataxia')
In genetic disorders, reflex seizures are usually combined with spontaneous occurring seizures, as is found in Dravet syndrome and other encephalopathic developmental disorders [8]. At the onset of these epilepsies, reflex seizures are often the first symptom, becoming less prominent with further progression of the disease.
Triggers and provoking factors — Sensory (afferent, external) seizure triggers include visual stimuli (eg, lights and patterns), somatosensory stimulation (eg, hot water immersion), and sounds (eg, sudden noise). Other seizure triggers may involve more complex sensory stimuli along with internal states and input processing; examples include speaking, writing, eating, and playing cards, board games, or video games.
When seizures are exclusively provoked by activities such as drawing, flickering sunlight, or hot water immersion, it is easier to recognize the reflex nature of the epilepsy. More complex stimuli like reading, thinking, eating, or listening to music are more difficult to recognize as seizure precipitants; cognitive and emotional factors also play a role in provoking seizures in these types of stimuli.
Thanks to video-electroencephalography (EEG) monitoring and home videos, novel types of stimuli that provoke seizures have been detected, including movement [9], vigorous exercise [10], diaper changing [11], vacuum cleaning [12], and toothbrushing [13].
Etiology — The cause of most reflex epilepsies is uncertain but is likely heterogeneous, with presumed polygenetic susceptibility as a factor in several types including reading epilepsy, photosensitive epilepsies, and hot water epilepsy [3,14]. Familial cases of reflex epilepsies with concordance among first-degree relatives have been reported [15]. No monogenetic causes have been identified.
As shown by the variety of triggering factors, evoked epileptiform discharges have their onset in different focal and localized areas of the brain; generalization of the discharges can eventually occur, which is often what leads the patient to seek help. In some cases, the brain area that is sensitive to a stimulus enlarges. This is illustrated by a case of a complex reflex mechanism described in a female who started having seizures at five years of age when wrapped up by her mother in a towel [16]. Thereafter, towels played an important role as a seizure trigger. At age 37 years, approximately one-half of her focal seizures were related to not only touching or feeling towel fabric but also to smelling and even thinking about towels [16].
GENERAL APPROACH
Evaluation and diagnosis — A standard question is necessary when patients present with a history of seizures: "In what circumstances did your seizures occur?" It can help to give examples of possible evoking factors, because patients are not always aware of the specific and sometimes exotic triggering factors for reflex seizures.
If a potential provocative stimulus is recognized, we obtain video-EEG diagnostics using intermittent photic stimulation (see "Photosensitive epilepsies") or using the potential trigger to help with confirmation of the reflex nature of the seizure. As an example, in a case of suspected musicogenic epilepsy, the patient can bring the specific music piece to be tested during video-EEG recording.
When the stimulus repeatedly and consistently evokes epileptiform discharges (not to be confused with epileptiform activity that occurs spontaneously), with or without clinical symptomatology, the diagnosis of reflex epilepsy is confirmed.
More patients with reflex seizures may be identified when this approach is followed up.
Management considerations — Avoidance of the provocative stimulus is the best prevention for reflex epilepsy (eg, for bathing epilepsy, hand-washing small children rather than immersive bathing). The more specific the trigger, the easier it may be to avoid. However, avoidance is not always possible. This strategy will depend not only on the type of stimulus (eg, drawing, reading, bathing) but also on the feasibility of avoidance (eg, a graphic designer cannot avoid drawing) and the severity of provoked seizures in a particular patient.
Treatment with antiseizure medication (ASM) is often necessary, but seizures are refractory to ASM therapy in many cases (25 percent in those with an unexplained focal epilepsy) [17]. No robust clinical trials exist. Observational data suggest benefit with valproate, lamotrigine, levetiracetam, and clobazam [4]. There is little experience with newer ASMs, but brivaracetam, cenobamate, lacosamide, and perampanel might be good choices [18-21].
Specific management strategies are described separately for photosensitive epilepsies (see "Photosensitive epilepsies", section on 'Management') and in the sections that follow for reading epilepsy (see 'Reading epilepsy' below), startle epilepsy (see 'Startle epilepsy' below), and hot water and bathing epilepsy (see 'Hot water epilepsy and bathing epilepsy' below).
PHOTOSENSITIVE EPILEPSIES — Photosensitive epilepsies are triggered by visual stimuli. They constitute the most important and heterogeneous group of reflex epilepsies. The highest prevalence is found in younger patients, particularly adolescent females. Photosensitive epilepsies are reviewed in detail separately. (See "Photosensitive epilepsies".)
READING EPILEPSY — Reading epilepsy is a reflex epilepsy characterized by seizures triggered by the act of reading or by other activities related to language, including speaking or writing [22,23].
Pathogenesis — Reading-induced seizures are thought to arise from an epileptogenic stimulus that triggers ictal activity in language-related brain regions, with spread of excitation and recruitment of cortical and/or subcortical regions that are activated by reading or the cognitive processes related to the reading material [3,24,25]. As examples, one case report of a patient with seizures that occurred with silent reading identified ictal activity on EEG originating in the left temporo-occipital-parietal region [22]. Another study included six patients with reading epilepsy who had myoclonic seizures induced while being monitored by EEG, electromyography (EMG), and functional magnetic resonance imaging (fMRI); areas of activation were observed variably in the left motor and premotor areas, left striatum, mesiotemporal and limbic areas, and Brodmann area 47 of the frontal cortex [24].
Clinical features — The onset of reading epilepsy is generally from 12 to 20 years of age, with a male predominance of approximately 2:1 [26,27]. Seizures are triggered by reading silently or aloud and, in some patients, by other activities related to language, such as speaking or writing [22,23,26,28]. In most patients, the seizures involve orofacial myoclonus, with other forms including visual symptoms, alexia, absence, or generalized tonic-clonic seizures [27].
Diagnosis — The key to the diagnosis of reading epilepsy is identifying the language stimulus (most often reading) that provokes the ictal phenomenon of seizure (most often orofacial myoclonus). The diagnosis may be confirmed by EEG if epileptiform discharges are provoked by reading or other identified language trigger. However, inability to confirm the reflex epilepsy by routine EEG does not exclude the diagnosis [29]. Reflex seizures may be difficult to provoke and capture by EEG; this may be due in part to the clinical setting with inability to replicate the cognitive and emotional aspects that ordinarily accompany the seizure trigger [23]. Visual black-and-white striped pattern testing is necessary to rule out pattern sensitivity, a subform of photosensitivity [30].
Although not widely employed, some authors have proposed the use of an activation protocol that includes reading, writing, arithmetic, and spatial construction to increase the likelihood of detecting correlation with video-EEG [31]. The authors employ such a protocol when reading epilepsy is suspected.
Management — Avoidance of known seizure triggers and provoking factors, along with lifestyle changes, are an important aspect of epilepsy management [3]. With reading epilepsy, strategies may include limiting time reading, avoiding reading aloud, avoiding reading certain triggering forms of text, taking frequent rest breaks while reading, and stopping reading immediately when noticing any myoclonic jerks or discomfort [3,23].
Retrospective studies suggest that antiseizure medication (ASM) therapy with levetiracetam, clonazepam, or valproate may be associated with reduced seizure frequency [3,32-34]. Based on the observation that certain ASMs may exacerbate myoclonic seizures, including carbamazepine, oxcarbazepine, gabapentin, and lamotrigine, some experts have recommended avoiding their use in this setting [3,35]. However, some patients will respond well to these ASMs; carbamazepine treatment has been associated with improved seizure control for patients with atypical reading epilepsy characterized by alexia and/or visual symptoms [22,26].
Outcomes — Data are limited but suggest that acceptable control of reading epilepsy can be attained with ASM therapy [7]. In some cases, reading epilepsy may resolve with age, and withdrawal of ASM can be considered after an appropriate seizure-free duration of two years or longer. (See "Approach to the discontinuation of antiseizure medications".)
STARTLE EPILEPSY — In startle epilepsy, seizures are triggered by sudden, unexpected sensory stimuli, which incite a normal startle response that leads to a seizure [36-38].
Etiology — Nearly all cases of startle epilepsy are associated with a structural brain lesion involving the premotor, motor, and/or sensorimotor cortex caused by an insult in the prenatal period or early life [3,39-43]. The various causes include neonatal encephalopathy, dysplastic brain lesions, porencephalic cyst, meningitis, and perinatal and neonatal stroke. Startle epilepsy has also been reported in patients with Down syndrome [40,44].
Clinical features — The onset of startle epilepsy is generally from 1 to 16 years of age [3]. The seizure trigger is most often a sudden, unexpected auditory stimulus such as a loud sound, and less often a sudden somatosensory or visual stimulus [41,45]. Startle epilepsy is associated with a variety of seizure types, including tonic-myoclonic, myoclonic, atonic, epileptic spasms, or asymmetric tonic posturing, often followed by falls [3,41,42,46,47]. Rarely, startle may trigger focal seizures with impaired awareness (complex seizures) in older patients [3]. Most patients have intellectual disability and a static or progressive encephalopathy [39,41].
Brain imaging may be normal but more commonly shows focal or diffuse brain lesions or focal atrophy [46,48].
Diagnosis — The diagnosis of startle epilepsy is suspected in a child or adolescent with apparent seizure activity following a normal startle response. A video-EEG recording is necessary to confirm startle epilepsy by detecting electrographic seizures that are triggered by an unexpected stimulus. The EEG can help to distinguish startle seizures and epilepsy from nonepileptic paroxysmal disorders, such as hereditary hyperekplexia, which is characterized by an exaggerated startle reflex with hypertonia or tonic spasms that are precipitated by auditory or tactile stimuli.
The most common ictal EEG pattern is a generalized electrodecremental response; some patients have rhythmic ictal activity [3,46].
Management — Startle epilepsy is often resistant to therapy with antiseizure medications (ASMs). Observational data suggest that some patients with startle epilepsy improve with carbamazepine, lamotrigine, valproate, levetiracetam, clobazam, and/or clonazepam, alone or in combination [40,42]. When feasible, surgical treatment should be considered for patients with medically-refractory startle epilepsy [4,36,49,50]. (See "Seizures and epilepsy in children: Refractory seizures", section on 'Epilepsy surgery'.)
Outcomes — The prognosis of startle epilepsy is typically poor since most patients have an underlying static or progressive encephalopathy with drug-resistant epilepsy [42].
HOT WATER EPILEPSY AND BATHING EPILEPSY — Hot water epilepsy (HWE) is characterized by seizures that are triggered when bathing with heated water. Bathing epilepsy (BE) is recognized by some experts as distinct from HWE, as noted in the sections that follow.
Etiology and epidemiology — Although HWE occurs worldwide, most reported cases are from southern India or Turkey, which supports a genetic mechanism as a likely cause [3,51,52]. A positive family history of HWE has been found in approximately 25 percent of cases [3]. Although the seizure mechanism is uncertain, HWE may arise from abnormalities involving thermoregulation or temporo-insular and parietal connections [52].
Some authors suggest that HWE and BE are distinct or exist on a spectrum with different or overlapping triggers (eg, hot water being the primary trigger in HWE, and lukewarm water or pouring water over the head the trigger in BE), genetics, clinical features, and associated conditions [53,54]. As an example, one study compared 12 patients with HWE and 23 patients with BE, in whom seizures were triggered by bathing or showering [54]. Pathogenic or likely pathogenic variants in the SYN1 gene were identified in all patients with BE and in none with HWE. By contrast, familial HWE has been linked to loci at 10q12.3-q22.3, 4q24-q28, and 9p23.3-p23 [55-57].
Clinical features — The age at onset of HWE ranges from 1 to 28 years [3] but most commonly occurs from 1 to 5 years of age [51,58]. Males are predominantly affected, with a male-to-female ratio of approximately 2.4:1 [58,59]. Febrile seizures predated the onset of HWE in a minority of patients reported from India [51,59,60].
Seizures in HWE are usually triggered by showering or bathing in warm or hot water that is at or above normal body temperature, generally >37°C. In many reports, the seizure trigger involves pouring hot water over the head, neck, and/or trunk [53,59]. However, a minority of patients develop a seizure with bathing even when water is not poured over the head; this may occur later in the course of HWE [59]. Seizure onset may occur early or late during the bath. Many other triggers have been reported in small studies, including memories of childhood bathing, the sound of water, the smell of soap, and hand immersion in hot water [61].
The most common type of seizure in HWE is focal onset seizures with impaired awareness, accounting for approximately one-half of events [52,59]. Generalized tonic-clonic seizures account for approximately one-third of events. Seizures generally last 30 seconds to two minutes. Some patients with HWE experience pleasure with these seizures and will self-induce seizures by increasing the temperature or amount of water, or by recalling earlier experiences of bathing [59,62]. In addition, unprovoked nonreflex seizures occur in up to one-third of children with HWE [58].
With BE, seizures with BE are focal onset seizures with impaired awareness, accompanied in some patients by autonomic symptoms [52,54].
Neurodevelopment in children with HWE is typically normal, as is neuroimaging [58]. In a study of 64 children from India with HWE, incidental neuroimaging abnormalities were reported in less than 5 percent of patients [58]. Incidental or likely incidental imaging abnormalities have included arachnoidal cysts, pineal cysts, and cavum septum pellucidi. Occasional patients with HWE have epileptogenic structural brain abnormalities on imaging, including hippocampal sclerosis or focal dysplasia [63,64].
Diagnosis — The diagnosis of HWE and/or BE is suspected when children exhibit sudden altered consciousness, cyanosis, loss of motor tone, or convulsive motor activity with bathing.
In cases where the diagnosis is unclear, we obtain a video-EEG while bathing or exposing to hot water; demonstrating ictal activity in response to these stimuli can confirm the diagnosis. In a study of 64 children with HWE, routine EEG showed abnormalities in only 13 percent [58].
Neuroimaging is usually not necessary if there is high confidence of the diagnosis of HWE or BE in a child with normal development and a normal neurologic examination [58].
Nonepileptic paroxysmal disorders (table 1) are considerations in the differential diagnosis of HWE and BE. For infants, these disorders include hyperekplexia, breath holding spells, benign myoclonus of infancy, and shuddering attacks; for children, these include nonepileptic staring spells, syncope, tics, stereotypies, and paroxysmal dyskinesia. (See "Nonepileptic paroxysmal disorders in infancy" and "Nonepileptic paroxysmal disorders in children".)
Management — For most patients with HWE or BE, seizure control can be achieved with nonpharmacologic measures, such as using cooler bath water and avoiding known seizure triggers like water poured over the head [52,65]. If the response is insufficient, prophylactic oral clobazam 5 to 10 mg given 1.5 to 2 hours before bathing may be beneficial [51,65,66].
For patients with inadequate seizure control despite these measures, particularly those who develop nonreflex seizures, adding an antiseizure medication (ASM) can be tried. In various observational reports, carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, phenytoin, phenobarbital, and valproate have been associated with reduced frequency of seizures [7,52,59,62,64,65]. Of these, we typically chose to start ASM with either levetiracetam, lamotrigine, or carbamazepine.
Outcomes — Some experts emphasize that HWE is associated with a good outcome for most children, with normal development and normal neuroimaging [58,65,67]; this knowledge can be used in counseling to relieve anxiety in parents and caregivers [67].
However, other studies illustrate that there is variability in clinical features and outcomes. In a report from Turkey of 50 patients with HWE, with a mean age of onset of 10 years, and a median follow-up of 15 years, approximately one-quarter of affected children developed chronic epilepsy with suboptimal seizure control despite treatment with ASM [63].
Several other reports have found that BE is often accompanied by various disorders, including speech delay, developmental delay, intellectual disability, attention deficit hyperactivity disorder (ADHD), and/or autism spectrum disorder (ASD) [54,68,69].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in children" and "Society guideline links: Seizures and epilepsy in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Seizures (The Basics)" and "Patient education: Epilepsy in adults (The Basics)" and "Patient education: Epilepsy in children (The Basics)")
●Beyond the Basics topics (see "Patient education: Seizures in children (Beyond the Basics)" and "Patient education: Seizures in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Classification – Reflex epilepsies are characterized by epileptic seizures that are predominantly evoked by specific external sensory stimuli, internal cognitive and emotional processes, or activity of the patient. In some cases, a combination of these factors is seen. Reflex seizures can be found in both generalized and focal epilepsies.
In certain epilepsy syndromes, all or nearly all seizures are reflex seizures, including photosensitive epilepsies, reading epilepsy, startle epilepsy, hot water epilepsy, and bathing epilepsy.
Reflex seizures may occur along with spontaneous seizures in generalized idiopathic and genetic epilepsy syndromes; examples include childhood absence epilepsy, juvenile myoclonic epilepsy, myoclonic epilepsy of infancy, and Dravet syndrome. (See 'Classification' above.)
●Evaluation and diagnosis – Key to diagnosing reflex seizures is figuring out the circumstances in which seizures have occurred. Confirmation of the reflex nature of the seizure is done by video-EEG with intermittent photic stimulation or exposure to the potential trigger. (See 'Evaluation and diagnosis' above.)
●Management – The best strategy is avoidance of the seizure trigger, if possible. Antiseizure medications (ASMs) are often necessary, but reflex seizures are often refractory to ASM therapy. (See 'Management considerations' above.)
●Photosensitive epilepsies – Photosensitive epilepsies are triggered by visual stimuli. They constitute the most important and heterogeneous group of reflex epilepsies, as reviewed in detail separately. (See "Photosensitive epilepsies".)
●Reading epilepsy – Reading epilepsy is a reflex epilepsy characterized by seizures triggered by the act of reading or by other activities related to language. The onset of reading epilepsy is generally from 12 to 20 years of age, with a male predominance of approximately 2:1. Seizures are triggered by reading silently or aloud and, in some patients, by other activities related to language, such as speaking or writing. In most patients, the seizures involve orofacial myoclonus; other manifestations include visual symptoms, alexia, and/or generalized tonic-clonic seizures. The key to the diagnosis is identifying the language stimulus (most often reading) that provokes the ictal phenomenon of seizure. Management strategies are described above. (See 'Reading epilepsy' above.)
●Startle epilepsy – In startle epilepsy, seizures are triggered by sudden, unexpected sensory stimuli, which incites a normal startle response that leads to a seizure. Nearly all cases of startle epilepsy are associated with a structural brain lesion caused by an insult in the prenatal period or early life. The onset is generally from 1 to 16 years of age. The seizure trigger is most often a sudden, unexpected auditory stimulus such as a loud sound. A video-EEG recording is necessary to confirm the diagnosis. Startle epilepsy is often resistant to therapy with ASMs. (See 'Startle epilepsy' above.)
●Hot water and bathing epilepsies – Hot water epilepsy (HWE) is characterized by seizures that are triggered by bathing with heated water. Some experts consider bathing epilepsy (BE) to be a distinct entity or to exist on a spectrum with HWE; the two may have different triggers (eg, hot water in HWE and lukewarm water or pouring water over the head in BE), genetics, clinical features, and associated conditions. Most reported cases of HWE come from India or Turkey, suggesting a genetic mechanism. Pathogenic variants in the SYN1 gene have been linked to BE. For most patients with HWE or BE, seizure control can be achieved with nonpharmacologic measures. (See 'Hot water epilepsy and bathing epilepsy' above.)
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