RARE DISEASE
Hot water reflex epilepsy
Hot water reflex epilepsy
Hot water reflex epilepsy
Drug discovery
36
papers
On emerging therapies
Overview
Hot Water Reflex Epilepsy (HWE) is a rare form of reflex epilepsy triggered by cutaneous exposure to hot water (≥37°C), typically during head bathing. Predominantly reported in Southern India, it affects males more frequently (2–3:1 ratio) and spans infancy to adulthood. Seizures range from focal to generalized tonic-clonic, often with normal interictal EEG. Pathophysiology involves aberrant thermoregulation and genetic susceptibility. Management includes reducing water temperature, intermittent clobazam prophylaxis, or antiseizure medications. Prognosis is favorable, with spontaneous remission common by adolescence [1][3][6][10].
Burden
Generally benign: 60–80% achieve remission by adolescence; 16–38% develop spontaneous non-reflex seizures [2][3][10].
Comorbid anxiety disorders reported in 20–30% due to fear of bath-related seizures [7][16].
Low economic burden with non-pharmacological interventions, but cultural resistance to temperature reduction may complicate management [1][6].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
36 drug discovery papers about Hot water reflex epilepsy. Recent publications:
36 drug discovery papers about Hot water reflex epilepsy. Recent publications:
categories:
Small molecules
small molecules
2022-11-30 | The anti-seizure and anti-nociceptive potential of hexane fraction from the leaves of Detarium senegalense
Detarium senegalense, J.F. Gmelin (Fabaceae) is used in Nigerian folk medicine to treat different diseases including epilepsy, microbial infections, gastrointestinal diseases and inflammation; its efficacy is widely acclaimed among communities in South Eastern Nigeria. This study aimed to evaluate the anti-seizure and anti-nociceptive potential of hexane fraction from the leaves of D. senegalense The hexane fraction of D. senegalense leaf was evaluated to determine the effect of the oral administration of the extract (100 – 400 mg/kg) against seizure using the pentylenetetrazole (PTZ), brucine, isoniazid (INH) induced seizure models and analgesic activity using the writhing and water tail immersion tests in mice. The hexane fraction of the extract significantly (p<0.05) increased the latency period in seizures induced by PTZ, brucine and isoniazid, and significantly reduced the duration of seizures induced by these three inducing agents. The extract also protected 67 % of animals against death. In acetic acid-induced writhing models and tail immersion models, the fraction showed a good analgesic effect characterized by a significant (p<0.05 – p<0.01) reduction in the number of writhes when compared to the control and a significant (p<0.05 – p<0.01 increase in the latency in a dose-related manner. The findings of the present study validated the folkloric use of Detarium senegalense leaves in seizure disorders as well as painful conditions.
2021-08-17 | Clinical, Demographic, and Electroencephalographic Profile of Hot-Water Epilepsy in Children.
The study attempts to characterize the clinical, demographic, risk factors, electroencephalographical, and neuroimaging features of hot-water epilepsy (HWE) in children. This is a hospital-based observational study in the pediatric neurology clinic and who met the clinical definition of hot-water epilepsy were studied from January 2017 to October 2018. Clinical history, demographic data, and examination findings were recorded in a pre-structured proforma. Electroencephalography (EEG) and neuroimaging were carried out. A total of 68 children with male to female ratio of 2.4:1 were studied. The most common age of onset of seizures was between 1 and 5 y. Focal seizures with impaired awareness were the most common semiology (48.5%). Abnormal EEG was detected in 13.2% and abnormal neuroimaging in 4.4% which consisted of incidental abnormalities. Nonreflex seizures occurred in 35.3% of the children with HWE and the risk factors associated with this were not statistically significant. Clobazam before taking bath helped to achieve seizure control in 85.7% of the children. Hot-water epilepsy should be suspected in children who develop seizures following a hot-water bath. The most common age of onset is 1-5 y. EEG and neuroimaging are normal in the majority of cases. Nonreflex seizures occurred in 35.3% of the children.
2021-03-12 | Synthesis, Anticonvulsant, and Antinociceptive Activity of New 3-(2-Chlorophenyl)- and 3-(3-Chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides
The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug—valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds—namely, 6 and 19—was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.
2020-08-11 | Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione
The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole (scPTZ) seizure tests). To determine the mechanism of action of the most active anticonvulsant compounds (3, 4, 6, 9), their influence on the voltage-gated sodium and calcium channels as well as GABA transporter (GAT) was assessed. The most promising compound 3-(3-methylthiophen-2-yl)-1-(3-morpholinopropyl)pyrrolidine-2,5-dione hydrochloride (4) showed higher ED50 value than those of the reference drugs: valproic acid (VPA) and ethosuximide (ETX) (62.14 mg/kg vs. 252.7 mg/kg (VPA) in the MES test, and 75.59 mg/kg vs. 130.6 mg/kg (VPA) and 221.7 mg/kg (ETX) in the 6 Hz test, respectively). Moreover, in vitro studies of compound 4 showed moderate but balanced inhibition of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Additionally, the antinociceptive activity of the most active compounds (3, 4, 6, 9) was also evaluated in the hot plate test and writhing tests, and their hepatotoxic properties in HepG2 cells were also investigated. To determine the possible mechanism of the analgesic effect of compounds 3, 6, and 9, the affinity for the TRPV1 receptor was investigated.
2020-07-31 | Clinical and EEG features, treatment, and outcome of hot water epilepsy in pediatric patients
Background: Hot water epilepsy is a type of reflex epilepsy which generally occurs with pouring water on the body during bath. Objective: The aim of this study is to evaluate the clinical and electrophysiological features, treatment, and outcome of the pediatric patients with diagnosis of hot water epilepsy. Methods: Patients were followed and treated at Erciyes University, between January 2010 and January 2016. Results: There were 15 patients total, included 9 (60%) boys and 6 (40%) girls. The average age at diagnosis was 30 months (range: 13-60 months). The follow-up period was 16 months (range: 12-48 months). Seven patients (46.6%) had focal seizures with impaired consciousness, four (26.7%) had focal seizure and four (26.7%) had focal starting and generalized tonic-clonic continuing seizures. Seven patients (46.6%) had abnormal interictal EEG findings, ranged from unilateral slowing of the background activity to bilateral sharp wave. Intermittent clobazam treatment (0.8-1.2 mg/kg) was given to 13 patients (86.7%). Other epileptic treatments were used in 5 (33.3%) patients. Three patients (20.0%) developed nonreflex seizures during followup period. Conclusions: Intermittent clobazam prophylaxis prior to hot water bath, as well as changing bathing habits can be effective in pediatric patients with hot water epilepsy.
small molecules
2022-11-30 | The anti-seizure and anti-nociceptive potential of hexane fraction from the leaves of Detarium senegalense
Detarium senegalense, J.F. Gmelin (Fabaceae) is used in Nigerian folk medicine to treat different diseases including epilepsy, microbial infections, gastrointestinal diseases and inflammation; its efficacy is widely acclaimed among communities in South Eastern Nigeria. This study aimed to evaluate the anti-seizure and anti-nociceptive potential of hexane fraction from the leaves of D. senegalense The hexane fraction of D. senegalense leaf was evaluated to determine the effect of the oral administration of the extract (100 – 400 mg/kg) against seizure using the pentylenetetrazole (PTZ), brucine, isoniazid (INH) induced seizure models and analgesic activity using the writhing and water tail immersion tests in mice. The hexane fraction of the extract significantly (p<0.05) increased the latency period in seizures induced by PTZ, brucine and isoniazid, and significantly reduced the duration of seizures induced by these three inducing agents. The extract also protected 67 % of animals against death. In acetic acid-induced writhing models and tail immersion models, the fraction showed a good analgesic effect characterized by a significant (p<0.05 – p<0.01) reduction in the number of writhes when compared to the control and a significant (p<0.05 – p<0.01 increase in the latency in a dose-related manner. The findings of the present study validated the folkloric use of Detarium senegalense leaves in seizure disorders as well as painful conditions.
2021-08-17 | Clinical, Demographic, and Electroencephalographic Profile of Hot-Water Epilepsy in Children.
The study attempts to characterize the clinical, demographic, risk factors, electroencephalographical, and neuroimaging features of hot-water epilepsy (HWE) in children. This is a hospital-based observational study in the pediatric neurology clinic and who met the clinical definition of hot-water epilepsy were studied from January 2017 to October 2018. Clinical history, demographic data, and examination findings were recorded in a pre-structured proforma. Electroencephalography (EEG) and neuroimaging were carried out. A total of 68 children with male to female ratio of 2.4:1 were studied. The most common age of onset of seizures was between 1 and 5 y. Focal seizures with impaired awareness were the most common semiology (48.5%). Abnormal EEG was detected in 13.2% and abnormal neuroimaging in 4.4% which consisted of incidental abnormalities. Nonreflex seizures occurred in 35.3% of the children with HWE and the risk factors associated with this were not statistically significant. Clobazam before taking bath helped to achieve seizure control in 85.7% of the children. Hot-water epilepsy should be suspected in children who develop seizures following a hot-water bath. The most common age of onset is 1-5 y. EEG and neuroimaging are normal in the majority of cases. Nonreflex seizures occurred in 35.3% of the children.
2021-03-12 | Synthesis, Anticonvulsant, and Antinociceptive Activity of New 3-(2-Chlorophenyl)- and 3-(3-Chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides
The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug—valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds—namely, 6 and 19—was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.
2020-08-11 | Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione
The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole (scPTZ) seizure tests). To determine the mechanism of action of the most active anticonvulsant compounds (3, 4, 6, 9), their influence on the voltage-gated sodium and calcium channels as well as GABA transporter (GAT) was assessed. The most promising compound 3-(3-methylthiophen-2-yl)-1-(3-morpholinopropyl)pyrrolidine-2,5-dione hydrochloride (4) showed higher ED50 value than those of the reference drugs: valproic acid (VPA) and ethosuximide (ETX) (62.14 mg/kg vs. 252.7 mg/kg (VPA) in the MES test, and 75.59 mg/kg vs. 130.6 mg/kg (VPA) and 221.7 mg/kg (ETX) in the 6 Hz test, respectively). Moreover, in vitro studies of compound 4 showed moderate but balanced inhibition of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Additionally, the antinociceptive activity of the most active compounds (3, 4, 6, 9) was also evaluated in the hot plate test and writhing tests, and their hepatotoxic properties in HepG2 cells were also investigated. To determine the possible mechanism of the analgesic effect of compounds 3, 6, and 9, the affinity for the TRPV1 receptor was investigated.
2020-07-31 | Clinical and EEG features, treatment, and outcome of hot water epilepsy in pediatric patients
Background: Hot water epilepsy is a type of reflex epilepsy which generally occurs with pouring water on the body during bath. Objective: The aim of this study is to evaluate the clinical and electrophysiological features, treatment, and outcome of the pediatric patients with diagnosis of hot water epilepsy. Methods: Patients were followed and treated at Erciyes University, between January 2010 and January 2016. Results: There were 15 patients total, included 9 (60%) boys and 6 (40%) girls. The average age at diagnosis was 30 months (range: 13-60 months). The follow-up period was 16 months (range: 12-48 months). Seven patients (46.6%) had focal seizures with impaired consciousness, four (26.7%) had focal seizure and four (26.7%) had focal starting and generalized tonic-clonic continuing seizures. Seven patients (46.6%) had abnormal interictal EEG findings, ranged from unilateral slowing of the background activity to bilateral sharp wave. Intermittent clobazam treatment (0.8-1.2 mg/kg) was given to 13 patients (86.7%). Other epileptic treatments were used in 5 (33.3%) patients. Three patients (20.0%) developed nonreflex seizures during followup period. Conclusions: Intermittent clobazam prophylaxis prior to hot water bath, as well as changing bathing habits can be effective in pediatric patients with hot water epilepsy.
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