Clinical manifestations

Presentation and course

Hot water epilepsy is predominantly seen in children and young adults with a male preponderance of approximately 2 to 3:1 (05). Among the cohort of 70 patients reported in a prospective clinical series, 55 were men (17). The exact cause for the clustering of cases in men is poorly understood. The majority of the reported cases may be classified as epilepsies of unknown cause with a clinical course similar to presumed genetic epilepsies of adolescence and adult onset (also known as idiopathic generalized epilepsies). A significant proportion of these patients have spontaneous seizures apart from those triggered by the hot water bath. In a series, 25 out of 70 patients had spontaneous seizures. Spontaneous seizures were seen more in patients who had an earlier onset of hot water epilepsy. The onset of spontaneous seizures had a variable interval after the onset of reflex seizures (17). Hot water epilepsy syndrome seen in infancy has been shown to have a strong association with Dravet syndrome (08). In a study from Japan, 5 of 7 children with Dravet syndrome showed an exacerbation in the frequency of seizures after hot water immersion. However, there was no difference in the rate of elevation in rectal temperature in these patients compared to control group (04).

The clinical features of the hot water epilepsy reported from south India have been well characterized (29). Older children are more frequently affected, although it has also been reported in adults (31). Age of onset varies from 10 to 50 years (17). In a pediatric series, the age of onset of seizures was between 1 to 5 years in the majority (06). Temperature of the hot water used for bathing ranges between 40°C and 50°C. Usually water is collected in a bucket, and is poured over the body or head by using a bowl. The frequency of the seizures depends on the frequency of the head baths. A small proportion of people had seizures only on body bath without head bath. The episodes may be characterized as focal seizures with impairment of consciousness. Seizures usually start with intense fear, behavior arrest, irrelevant speech, and complex automatisms. Some of the patients showed a tendency for self-induction of seizures by continuously pouring water over the head until they lost consciousness. Occasionally, secondary generalization occurs, resulting in generalized tonic clonic seizures. Spontaneous nonreflex epilepsy has been reported to occur a few years later in 16% to 38% of patients. A history of epilepsy among the family members has been reported in 7% to 22.6% of cases (14; 31).

In hot water epilepsy of infancy, the temperature of the water is usually close to body temperature (around 37.5°C). The seizures are predominantly characterized by autonomic features. Affected infants have often been described as becoming quiet with staring, apnea, pallor, blue lips, and limpness (20).

Neurologic examination, interictal EEG, and imaging are usually normal. However, focal epilepsies with structural cortical malformations have been reported, presenting initially with reflex seizures triggered by hot water bath (10; 27). A case of macrocephaly-capillary malformation syndrome presenting with hot water epilepsy has also been reported (41). In view of the technical considerations, ictal EEG recordings are difficult in hot water epilepsies induced by head bath (34). In the infantile form of hot water epilepsy induced by immersion of the inferior part of the body, ictal EEG showed a focal onset in the temporal areas (23). Multimodal imaging studies with SPECT and EEG-fMRI were also reported in the literature (22; 28).

Prognosis and complications

The natural course for hot water epilepsy cases reported in older children and adults was usually favorable. A majority of patients outgrow their epilepsy. Five percent to 10% of patients develop seizures in hot water body baths alone at a later stage of their course (34). Spontaneous nonreflex seizures have been seen in around 16% to 38% of patients after few years of onset of hot water epilepsy. Bharathi and colleagues reported nonreflex seizures in around 35.3% of their pediatric cohort, which included both fever-triggered seizures (16.2 %) and unprovoked seizures (19.1%) (06).

The natural course for hot water epilepsy in infancy is also usually benign. All of the 5 patients reported by Plouin and Vigevano were seizure-free at 3 years follow-up (23). However, hot water epilepsy in infancy was found to be one of the strong clinical predictors for future development of Dravet syndrome (11). In cases of hot water epilepsy with associated history of severe early onset febrile seizures, a genetic testing for SCN1A mutation may be useful for prognostication.

Clinical vignette

A 2-year-old girl presented with reported recurrent events during bathing. She was born of nonconsanguineous parents with a normal birth history. Birth weight was 3.5 Kg. Neonatal period was uneventful. She had the first episode of generalized tonic clonic seizures after DPT vaccination on day 42. EEG and MRI brain were normal. Subsequently, she developed recurrent myoclonic jerks and generalized tonic clonic seizures. By the age of 6 months, she developed frequent seizures during febrile illnesses. She was on multiple antiepileptic drugs without much response. Her mother also noted frequent episodes during bathing of the body with hot water during which child became pale initially, then became unresponsive with tonic posturing of the limbs and up rolling of the eyes. Examination showed no dysmorphic features. She had significant global developmental delay and symmetric hypotonia. Video-EEG telemetry demonstrated 2 habitual clinical events on immersion of the body in hot water. The EEG showed a sudden burst of high amplitude diffuse asymmetrical delta slow waves that were maximum over both temporal regions. No events were noted spontaneously or on immersion in cold water. The possibility of Dravet syndrome with symptomatic hot water epilepsy in infancy was considered clinically. The family was advised to avoid hot water baths. SCN1A mutation study was not carried out because of the lack of availability.

Biological basis

Etiology and pathogenesis

The etiology of hot water epilepsy is not known. It is predominantly seen in children and adults with no identified etiologies. A high proportion of the infants with hot water epilepsy also had febrile seizures (37), suggesting a common pathophysiology. Hot water epilepsy in infancy is one of the strong clinical predictors for future development of Dravet syndrome (04; 08; 11).

The exact pathogenesis of hot water epilepsy is unknown. Although it was possible to provoke seizures in the laboratory by pouring hot water over the heads of patients, hot-water towels, sauna, or blowing hot air on the head failed to induce seizures, suggesting that the triggering stimulus is complex and would involve a combination of factors such as contact of scalp with hot water, temperature of water, and specific cortical area of stimulation (35). The warmth receptors are most active in the temperature range between 40°C and 50°C, which is most often associated with precipitation of seizures. Above this range of temperature, pain fibers are activated (noxious heat). None of the reported cases reported pain on pouring of hot water; rather, some of them described a pleasurable sensation before the development of frank seizures. This may suggest that a specific range of temperature is an important trigger (12). A defective inhibitory influence over afferent volleys of somatosensory stimuli, such as warm or hot water over large body surfaces, with an additive effect from the specific temperature range described, might be acting as the final trigger.

A hypothesis based on the hyperthermic kindling model has also been suggested (38). According to this model, an aberrant thermoregulatory system is postulated in patients with hot water epilepsy, along with an increased sensitivity of the brain to rapid surges in body temperature. Satishchandra and colleagues experimentally demonstrated that people with hot water epilepsy had a rapid spurt in body temperature compared to their normal peers (33). This higher body temperature also persisted for prolonged periods compared to the controls. Another study reported impaired autonomic system balance in drug naive patients with hot water epilepsy (16). A subsequent study from the same group showed a different pattern of autonomic dysfunction in patients who had both hot water epilepsy and spontaneous seizures compared to those with hot water epilepsy alone (18). In another clinical series from south India, a significant proportion of patients had features suggestive of nonepileptic psychogenic events during hot water baths, suggesting the possibility of a nonepileptic condition, pseudo hot water epilepsy (39).

A high proportion of the infants with hot water epilepsy also had febrile seizures (09). Eleven percent to 27% of the older children and adults with hot water epilepsy reported from India also had history suggestive of febrile seizures before the development of epilepsy (36; 14). Children with Dravet syndrome with severe febrile convulsions also showed an increased tendency for seizures stimulated by hot water baths. There was no difference in the rate of elevation in rectal temperature between the patients with Dravet syndrome and controls, suggesting that the brain is exquisitely sensitive to elevation in body temperature in children with this disorder (03).

The genetic mechanism underlying the expression of hot water epilepsy in humans is not known. Eighteen percent of Indian patients had at least 1 family member affected by hot water epilepsy. Two genetic loci have been described from India (25; 24). SCN1A mutations, pathognomonic of Dravet syndrome, may possibly contribute to the expression of hot water epilepsy in infancy. A distinct genetic epileptic syndrome called “X-linked focal epilepsy with reflex bathing seizures” has been reported in a French–Canadian family (21). Q555X mutation of synapsin 1 (SYN1) on chromosome Xp11-q21 was documented in this cohort. SYN1 mutations were identified in 12 individuals from 10 different Caucasian families with bathing epilepsy (01). However, none of the patients with pure hot water epilepsy in this cohort had this variation.

Epidemiology

Population-based data for hot water epilepsy are available only from south India. In the Yelandur study, a large epidemiologic study in a rural population, the prevalence rate was as high as 255 per 100,000 population (15). A house-to-house Bangalore urban-rural neuroepidemiologic survey (BURN) of 102,557 population from south India reported that hot water epilepsy accounted for 6.9% of all epilepsies in that community, giving a prevalence rate of 60 per 100,000 (29). Males were affected more frequently than females. Family history of hot water epilepsy was seen in 18% of patients.

Prevention

Measures for the prevention of seizures in hot water epilepsy are similar to other reflex epilepsies. Complete avoidance of the precipitating stimuli, the hot water baths, is the most ideal preventative measure. Other modifications, like using lukewarm water for the head bath and using hot towels, have also been advocated (14).

Differential diagnosis

Confusing conditions

Several closely related paroxysmal infantile syndromes induced by bathing, such as aquagenic urticaria, infantile syncope, paroxysmal extreme pain syndrome, hyperekplexia, and alternate hemiplegia of childhood, have been described in the past. A review has addressed the similarities among many of these entities (20). Autonomic manifestations are the defining clinical features in bathing epilepsy, aquagenic urticaria, and infantile syncope induced by bathing. Ictal EEG might be a useful tool to differentiate these entities.

Associated or underlying disorders

Hot water epilepsy in infancy is also one of the strong clinical predictors for future development of Dravet syndrome (11). In cases of hot water epilepsy with associated history of severe early onset febrile seizures, a genetic testing for SCN1A mutation may be warranted. Gastroesophageal reflux is another disorder to be considered in the differential diagnosis.

Diagnostic workup

A proper clinical history with specific thrust to the precipitating factors is the clue to diagnosis. Home videos are useful for characterization of the events.

EEG. Interictal EEG may show nonspecific changes. However, it may help to rule out other epilepsies of genetic origin and those due to structural malformations. In view of the technical considerations, ictal EEG recordings are difficult in hot water epilepsies induced by head bath (34). In the infantile form of hot water epilepsy induced by immersion of the inferior part of the body, ictal EEG showed a focal onset in the temporal areas (23).

MRI. Brain MRI may help to rule out symptomatic causes. Focal epilepsies with cerebral malformations have been reported to present with reflex seizures triggered by hot water bath (10; 27; 41).

Genetic testing. No genetic tests are commercially available for hot water epilepsy. Genetic testing for the SCN1A mutation may be warranted in cases of hot water epilepsy of infancy with associated history of severe early onset febrile seizures (11).

Management

Complete avoidance of the precipitating stimuli, the hot water baths, is considered to be the most ideal step in management. Other modifications, like using lukewarm water for the head bath and using hot towels, have also been advocated (14). Phenytoin and carbamazepine have been used in the past to control the seizures. Follow-up of 208 patients treated with conventional antiepileptic drugs for a mean period of 14 ± 12.9 months (range, 6 to 60 months) showed that 60% could be easily controlled, and 18.3% had a 50% reduction in frequency, but others continued to have seizures at their last follow-up (32). Drugs like phenobarbital, sodium valproate, oxcarbazepine, lamotrigine, and levetiracetam were also used in some cases (42). If the patients are taking head baths infrequently, oral administration of 5 to 10 mg of clobazam about 1.5 to 2 hours before head bath has been found to be effective in preventing the seizures (07). If the hot water epilepsy is associated with other nonreflex seizures, regular intake of antiepileptic dugs may be necessary (30).

Venkataramiah and Ghorpade reported a pilot trial of psychotherapeutic intervention that was found to be successful in preventing the recurrence of events in a cohort of patients with presumed hot water epilepsy. After the characterization of the symptoms and the temperature and volume of the hot water used in an assessment trial bath, the patients underwent a series of therapeutic trial baths, based on the principle of desensitization. To begin with, the hot water used was 1°C less than the temperature at which patients previously experienced the symptoms. During the therapeutic baths, the investigator continuously kept patients engaged in conversation, boosting their confidence to take the bath and also diverting attention away from the anticipatory anxiety. This procedure was repeated over a few days, increasing the temperature of water by 2°C each time until the highest tolerable level was achieved. Out of the 8 patients who were followed up for 1 year, 6 were completely symptom-free and were able to take hot water baths without any recurrence of symptoms (39).

Outcomes

The natural course for hot water epilepsy cases reported in older children and adults was usually favorable. A majority of patients outgrow their epilepsy. Five percent to 10% of patients develop seizures in hot water body baths alone at a later stage of their course (34). Spontaneous nonreflex seizures have been seen in around 16% to 38% of patients after few years of onset of hot water epilepsy. Bharathi and colleagues reported nonreflex seizures in around 35.3% of their pediatric cohort, which included both fever-triggered seizures (16.2 %) and unprovoked seizures (19.1%) (06). In this cohort, 81% attained seizure control within a period of 12 to 24 months.

Special considerations

Pregnancy

One case of hot water epilepsy in pregnancy has been reported from Turkey. The patient had a benign course after the initiation of carbamazepine (19).