Adjunctive oral electrolyte therapy for uncontrolled seizures in children
Abstract. Experimental studies in animals have suggested that alteration of extra cellular volume, ion concentration and osmolarity may affect the epileptic process. We report persistent beneficial effects of add-on oral electrolyte therapy (OET) in seven children with uncontrolled epilepsy. Three patients treated with OET remained seizure free, one patient became free of absence seizures but persisted with generalized convulsions and two other patients had improved seizure control. One patient did improve and discontinued treatment after 3 weeks. No significant side affects or complication was observed. Rice-based OET, used alone or in addition to standard antiepileptic drugs, may provide a therapeutic effect in children with uncontrolled epilepsy. Larger controlled studies are needed to validate this finding.
1. Introduction
Epilepsy affects approximately 1% of the general population. Ten to 30% of children with epilepsy continue to have seizures despite the appropriate use of standard antiepileptic drugs (AEDs). It is currently thought that children who fail to respond to two AEDs have a low likelihood of responding to further medication. Use of multiple AEDs is frequently complicated by intolerable cognitive side effects. Patients refractory to AEDs, who are not surgical candidates available to them, aside from new ADE drug trials, vagus nerve stimulation therapy, or the ketogenic diet. There remains a need for new antiepileptic therapies in children that prevent seizures, without significant interference with normal brian function.
There are many factors that influences brain excitability and affect neuronal epileptic process. The mechanism of action of currently available medications, as well as many of action of the new drug in development, mainly focuses on altering the predominance of excitatory vs. inhibitory synaptic interaction. There is evidence however, that osmolarity changes can also affect neuronal excitability and animal studies have demon strated that alterations in extracellular versus intracellular ion gradients may directly or indirectly affect neuronal discharges. Brain function and neuronal excitability can also be affected by alterations in cerebral blood flow. It is known that blood pressure dysregulation has been associated with cognitive dysfunction in elderly patients, and children with familial dysautonomia have been reported to have seizures presumably due to abrupt hemodynamic changes. Water drinking and salt loading result in a positive systemic blood pressure response and improve cerebral blood flow regulation; this effect could be achieved by drinking a slightly hypotonic oral solution to provide volume restoration, without significantly changing serum osmolarity. We have previously reported good short-term results with oral electrolyte therapy (OET) in a few selected patients with uncontrolled epilepsy (typical absence) associated with familial dysautonomia. In this report, we describe the effects of hypotonic oral solution on seizure control in seven children with uncontrolled epilepsy.
2. Materials and methods
The medical records of 12 children with uncontrolled epilepsy and who received OET were reviewed for evidence of seizure control and effects. These 12 children, identified over a 6-year period (2000-2006), received OET as add on therapy to standard AEDs. Seven out of the 12 patients are presented in this paper (Table1). The other five patients were excluded because of intolerance to the solution’s taste. Agematched controls were not used because the particular patient clinical characteristics were not possible to match among our epilepsy patient population. However, all patients served as their own control, and developmental control of seizure was excluded by clinical and electroencephalography (EEG) evidence of persistent active epileptic disease. Placebo control was not used because the nature of the treatment and the taste of the solution were not possible to mask. All patients has normal routine laboratory investigation including basic chemistries obtained within 6 months prior to starting therapy. Osmolarity was calculated using a standard formula. Seizure frequency was recorded in the chart according to standard patient seizure dairies. Institutional review board waiver was obtained to review clinical records from our epilepsy clinic.
OET is rice based oral hydrating solution. OET 90 has an osmolarity of 275 mOsm/L and contains sodium 90 mEq/L, potassium 20 mEq/L (1.3g), chloride 80 mEq/L, rice based as carbohydrate substrate, and total proteins 0.5g. OET 70 has a lower osmolarity (260 mOsm/L) and lower sodium concentration (70 mEq/L). A rice based oral hydration solution was used instead of a glucose-based sulotion because the complex carbohydrates in the former solution minimize rapid changes in insulin release and plasma glucose levels. In addition rice, based solution quickly reach the small intestine, promoting early recovery and faster restoration of blood volume. The higher level of carbohydrates in this particular solution (40 g vs. 20-25 g in typical oral hydration solutions) facilitates a greater of absorption.
The average daily dose used these patients ranged from 20 to 50 mL/kg/day (Table1) OET 90 was used in all but two patients who only tolerated OET 70. The dose was adjusted according to tolerability and seizure control. the target daily dose was at least 20 ml/kg/day. parents were instructed to monitor daily weight to assess for fluid retention. the patients were followed in our epilepsy clinic for clinical response and treatment monitoring. follow up visit intervals varied according to patient response and seizure severity. Re-ports of the seizures were registered on the clinical chart reflecting parents' reports in seizure dairies. Diagnosis of the epileptic syndrome and seizure type was based on the current ILAE classification. Diagnosis was supported with routine EEG before, during, and after therapy in all patients. Four patients had long term EEG monitoring after initiation of therapy. Classification as a "good" response to OET was a reduction of at least 50% in reported seizure frequency, or improvement in the severity of seizure as indicated by the decrease in use of rescue medications, or less frequent seizure induced emergency room visits or hospital admissions.
Results
Six patients treated with OET reported improvement, including three who became totally seizures but persisted with generalized convulsions. Another patient did not improve and discontinued treatment after 1 month of therapy. No significant side effects or complications were observed. Three patients with familial dysautonomia and uncontrolled typical absence epilepsy became seizure free. Follow-up treatment for 4 years demonstrated persistent efficacy, tolerability and good compliance with the OET. Routine chemistry showed no significant changes in the serum electrolyte concentration or serum osmolarity before and during OET.
Patient 1 was a 13-year-old boy with familial dysautonomia who development absence seizures at age four. Topiramate therapy resulted in only partial improvement of clinical seizure, which persisted on a daily basis. He had failed other AEDs, including valproic acid and lamotrigine. He became seizure free within a few days after starting OET, allowing completed discontinuation of AED therapy 1 year later. He has remained seizure free after 4 year of OET (fig. 1A). No
Adjunctive oral electrolyte therapy for uncontrolled seizures in children
Abstract. Experimental studies in animals have suggested that alteration of extra cellular volume, ion concentration and osmolarity may affect the epileptic process. We report persistent beneficial effects of add-on oral electrolyte therapy (OET) in seven children with uncontrolled epilepsy. Three patients treated with OET remained seizure free, one patient became free of absence seizures but persisted with generalized convulsions and two other patients had improved seizure control. One patient did improve and discontinued treatment after 3 weeks. No significant side affects or complication was observed. Rice-based OET, used alone or in addition to standard antiepileptic drugs, may provide a therapeutic effect in children with uncontrolled epilepsy. Larger controlled studies are needed to validate this finding.
1. Introduction
Epilepsy affects approximately 1% of the general population. Ten to 30% of children with epilepsy continue to have seizures despite the appropriate use of standard antiepileptic drugs (AEDs). It is currently thought that children who fail to respond to two AEDs have a low likelihood of responding to further medication. Use of multiple AEDs is frequently complicated by intolerable cognitive side effects. Patients refractory to AEDs, who are not surgical candidates available to them, aside from new ADE drug trials, vagus nerve stimulation therapy, or the ketogenic diet. There remains a need for new antiepileptic therapies in children that prevent seizures, without significant interference with normal brian function.
There are many factors that influences brain excitability and affect neuronal epileptic process. The mechanism of action of currently available medications, as well as many of action of the new drug in development, mainly focuses on altering the predominance of excitatory vs. inhibitory synaptic interaction. There is evidence however, that osmolarity changes can also affect neuronal excitability and animal studies have demon strated that alterations in extracellular versus intracellular ion gradients may directly or indirectly affect neuronal discharges. Brain function and neuronal excitability can also be affected by alterations in cerebral blood flow. It is known that blood pressure dysregulation has been associated with cognitive dysfunction in elderly patients, and children with familial dysautonomia have been reported to have seizures presumably due to abrupt hemodynamic changes. Water drinking and salt loading result in a positive systemic blood pressure response and improve cerebral blood flow regulation; this effect could be achieved by drinking a slightly hypotonic oral solution to provide volume restoration, without significantly changing serum osmolarity. We have previously reported good short-term results with oral electrolyte therapy (OET) in a few selected patients with uncontrolled epilepsy (typical absence) associated with familial dysautonomia. In this report, we describe the effects of hypotonic oral solution on seizure control in seven children with uncontrolled epilepsy.
2. Materials and methods
The medical records of 12 children with uncontrolled epilepsy and who received OET were reviewed for evidence of seizure control and effects. These 12 children, identified over a 6-year period (2000-2006), received OET as add on therapy to standard AEDs. Seven out of the 12 patients are presented in this paper (Table1). The other five patients were excluded because of intolerance to the solution’s taste. Agematched controls were not used because the particular patient clinical characteristics were not possible to match among our epilepsy patient population. However, all patients served as their own control, and developmental control of seizure was excluded by clinical and electroencephalography (EEG) evidence of persistent active epileptic disease. Placebo control was not used because the nature of the treatment and the taste of the solution were not possible to mask. All patients has normal routine laboratory investigation including basic chemistries obtained within 6 months prior to starting therapy. Osmolarity was calculated using a standard formula. Seizure frequency was recorded in the chart according to standard patient seizure dairies. Institutional review board waiver was obtained to review clinical records from our epilepsy clinic.
OET is rice based oral hydrating solution. OET 90 has an osmolarity of 275 mOsm/L and contains sodium 90 mEq/L, potassium 20 mEq/L (1.3g), chloride 80 mEq/L, rice based as carbohydrate substrate, and total proteins 0.5g. OET 70 has a lower osmolarity (260 mOsm/L) and lower sodium concentration (70 mEq/L). A rice based oral hydration solution was used instead of a glucose-based sulotion because the complex carbohydrates in the former solution minimize rapid changes in insulin release and plasma glucose levels. In addition rice, based solution quickly reach the small intestine, promoting early recovery and faster restoration of blood volume. The higher level of carbohydrates in this particular solution (40 g vs. 20-25 g in typical oral hydration solutions) facilitates a greater of absorption.
The average daily dose used these patients ranged from 20 to 50 mL/kg/day (Table1) OET 90 was used in all but two patients who only tolerated OET 70. The dose was adjusted according to tolerability and seizure control. the target daily dose was at least 20 ml/kg/day. parents were instructed to monitor daily weight to assess for fluid retention. the patients were followed in our epilepsy clinic for clinical response and treatment monitoring. follow up visit intervals varied according to patient response and seizure severity. Re-ports of the seizures were registered on the clinical chart reflecting parents' reports in seizure dairies. Diagnosis of the epileptic syndrome and seizure type was based on the current ILAE classification. Diagnosis was supported with routine EEG before, during, and after therapy in all patients. Four patients had long term EEG monitoring after initiation of therapy. Classification as a "good" response to OET was a reduction of at least 50% in reported seizure frequency, or improvement in the severity of seizure as indicated by the decrease in use of rescue medications, or less frequent seizure induced emergency room visits or hospital admissions.
Results
Six patients treated with OET reported improvement, including three who became totally seizures but persisted with generalized convulsions. Another patient did not improve and discontinued treatment after 1 month of therapy. No significant side effects or complications were observed. Three patients with familial dysautonomia and uncontrolled typical absence epilepsy became seizure free. Follow-up treatment for 4 years demonstrated persistent efficacy, tolerability and good compliance with the OET. Routine chemistry showed no significant changes in the serum electrolyte concentration or serum osmolarity before and during OET.
Patient 1 was a 13-year-old boy with familial dysautonomia who development absence seizures at age four. Topiramate therapy resulted in only partial improvement of clinical seizure, which persisted on a daily basis. He had failed other AEDs, including valproic acid and lamotrigine. He became seizure free within a few days after starting OET, allowing completed discontinuation of AED therapy 1 year later. He has remained seizure free after 4 year of OET (fig. 1A). No
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