7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 16

Clinical Study Evaluation of the Effects of Charged Amino Acids onUncontrolled Seizures

Hossein Ali Ebrahimi and Saeed Ebrahimi

Neurology Research Center Kerman University of Medical Sciences Kerman Iran

Correspondence should be addressed to Hossein Ali Ebrahimi ebrahimihagmailcom

Received 983089983091 March 983090983088983089983093 Revised 983089983093 June 983090983088983089983093 Accepted 983090983093 June 983090983088983089983093

Academic Editor Changiz Geula

Copyright copy 983090983088983089983093 H A Ebrahimi and S Ebrahimi Tis is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Introduction Epilepsy is one o the most common diseases o the central nervous system Te prevalence o epilepsythroughout theworld is 983088983093 to 983089 and the same rate is 983095983096 per 983089983088983088983088 in Kerman Almost 983090983088 to 983091983088 o epileptic patients do not respond properly tocommon medications Te present study investigated patients who did not respond to common and even in some cases adjuvanttherapies with two seizures or more per week regardless o the type o the in1047298icted epilepsy Methodology Te participants o the present double-blind study were randomly selected into three 983089983088-member groups o uncontrolled epileptic patients (arginineglutamic acid and lysine) Te patients used amino acid powder dissolved in water (three times the daily need) every day or twoweeks beore breakast Te number o seizures was recorded one week prior to commencing amino acid use as well as the 1047297rst

and the second weeks subsequent to use Results A total o 983091983090 patients were studied in three groups Te decline rates o seizureswere 983093983091 983092983089 and 983089983091 and the P value was 983088983088983089983091 983088983088983090983095 and 983088983095983090983088 respectively Conclusion Administration o the charged aminoacids arginine and glutamic acid can decrease the seizures o patients suffering rom uncontrolled epilepsy

1 Introduction

Epilepsy is one o the most prevalent diseases o the centralnervous system with a prevalence o 983088983093 to 983089 percent o theworld population [983089] An estimated 983093983088 million individualssuffer rom epilepsy worldwide [983090 983091] According to theconducted studies 983095983096 per thousand individuals suffer romepilepsy in Kerman Iran and are in need o anticonvulsantmedication [983092] Despite the considerable advances in the

treatment o epilepsy especially production o new moretolerable anticonvulsants 983090983088 to 983091983088 o the patients sufferrom uncontrolled seizures reerred to as medically resistant[983093ndash983096]

Besides uncontrolled seizures side effects o the admin-istered anticonvulsants are important in treating the men-tioned patients which may hinder the administration o certain anticonvulsants Unavailability as well as unreason-able prices o some anticonvulsant drugs may also addto the problems Another impediment is the psychologicalcomplications caused by the long-term use o anticonvulsants(besides their side effects) causing untimely discontinuationo the drug and ailed treatment [983097 983089983088]

In addition to medical therapies adjuvant therapieslike avoiding acilitating actors (light stress and sleepwithdrawal) as well as psychiatric therapies have receivedattention by scholars [983089983089ndash983089983092]

Among the challenging issues is the diet concerningwhich different views have been reported in terms o theefficacy and positive or negative in1047298uence o certain oodsKetogenic diet has long been proposed and used by themedically resistant patients or many years Atkins diet

which leads to ketosis has also received attention [983089983093ndash983089983095]Consumption o oods containing protein chains has beenproposed as well [983089983096]

A study on rat showed that charged amino acids are capa-ble o elongating the seizure latency induced by intraperi-toneal injection o pentylenetetrazole (PZ) as well asshortening seizure duration [983089983097]

Charged amino acids are o two types acidic or basicdependingon their Ph in the physiological environment Glu-tamic and aspartic amino acids are acidic while arginine andlysine are basic Besides being a stimulator neurotransmitterglutamic acid as an acidic charged amino acid plays a greatrole in the brain metabolism [983090983088 983090983089] present in different

Hindawi Publishing CorporationNeurology Research InternationalVolume 2015 Article ID 124507 5 pageshttpdxdoiorg1011552015124507

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 26

983090 Neurology Research International

brain parts and synapses which unctions via ionotropicor metabotropic receptors [983090983090ndash983090983093] Another property o theglutamate brain metabolism is its close association with thecitric acid cycle and energy metabolism [983090983092 983090983094]

Arginine is a basic amino acid and according to exten-sive studies o 983089983097983093983088 through to 983089983097983095983088 it is considered as a

nonessential amino acid or the health o adults [983090983095] and anessential amino acid or the growth o human beings andanimals [983090983096 983090983097] However upon the in1047298ection o diseases aswell as physical traumas it turns into an essential amino acid[983091983088] Te sources o ree arginine within the body are dietary protein endogenous synthesis and turnover o body proteins[983091983089ndash983091983092]

Te importance o lysine is due to its involvement in thecollagen construction It is also among the most importantcomponents o the conjunctival tissue essential or growthLysine is important or carnitine synthesis Te daily amounto lysine intake is 983092983088ndash983089983096983088 mg per kilogram o body weighthowever there have been reports o up to 983091983088983088ndash983092983088983088 mg intake[983091983093]

Te present study investigated the effects o chargedamino acids on the seizures o uncontrolled epilepsy patients

2 Methodology

As an interventional study the present research investigatedepilepsy patients who reerred to the Neurology Clinic o Shaa Medical Center a subsidiary o Kerman University o Medical Sciences Kerman Iran as well as private clinicsregardless o the type o the in1047298icted epilepsy and whodespite using multiple anticonvulsant regimens still expe-rienced seizures though drug side effects were observableo allow or a better assessment patients with at least twoseizures in a week entered the study

Prior to inclusion the entire necessary examinationsincluding sel-report ollow-ups EEG and imaging wereconducted by a neurologist to ensure the presence o epilepsyIt wasensured that the patients who entered the study or theircompanions were made aware o the act that the mentionedsubstances have never been administered or such cases andalso the possibility that it was probably the 1047297rst time theyor their patients were going to have an examination Sub-sequently the participants declared their inormed consentand were included Te patients were allowed to leave theprogram whenever they demanded

It should be mentioned that use o these substances is

embedded in humans daily diet and urthermore there havebeen no reports concerning associated complications andthey do not seem to induce certain disorders as the toxicdosage o the utilized substances is 983093983088ndash983093983088983088 times the daily required amount [983091983094]

Patients who suffered rom diseases other than epilepsy (aprimary brain disease) were reused to enter the study Preg-nant women and breasteeding mothers [983091983095ndash983091983097] psychoticpatients [983091983096 983091983097] and patients suffering rom inectionsparticularly viral inections were excluded

Duration o the treatment was two weeks Te patientsor their companions were asked to record the number o the seizures Te number o the seizures was recorded one

week prior to amino acid use Te patients used amino acidpowder dissolved in water three times the daily need andevery day beore breakast Te number o seizures was onceagain recorded one week later In case any complications(nausea vomit) were reported the patient was excluded romthe study

Charged amino acids are o 983092 types three o which wereinvestigated in the present study Aspartic acid was lef out asit could not be procured andsince it canreplace glutamic acidin the body

Te amount o administered glutamic acid was a daily dosage o 983089983088 grams or adults and 983090 grams or children under983090 years o age Te administered lysine was a daily dosage o 983094grams or adults and 983097983088 mg or children per kilogram o body weight And arginine was administered at a daily dosage o 983089983093 grams or adults and 983090983092983088 mg or children per kilogram o body weight [983092983088]

Te patients were divided into three groups o 983089983088 (withregard to the available patients) and each group was puton one o the oregone amino acids Te participants wererandomly selected and appointed to a group Allocating anamino acid to oneo the three groupswas doubleblinded thatis neither the patient nor the attending physicians were awareo the type o the amino acid administered Te pertinentamino acids were already placed in packets o 983089983092 handed tothe patient bearing only a number Te packaging was carriedout prior to prescription as a result the treating physicianswere unaware o the contents

Te collected data went through statistical analysis Teresults were compared to the recorded data prior to com-mencement o the study and the results rom the threegroups were compared Te recorded 1047297ndings rom the twoprevious stages as well as one and two weeks subsequent toadministration as well as the number o seizures in the threegroups were compared

3 Results

A number o 983092983093 patients were studied o whom 983089983091 individualswere excluded due to experiencing nausea and vomit andreusing cooperation resulting rom tastelessness or unde-sirable taste o arginine which lef us with the remainingcooperative 983091983090 patients

able 983089 shows the number o patients in each groupalong with the average weekly seizures one week prior to

amino acid administration and the 1047297rst and second weeksafer treatment commencement respectively as well as theproportion o the seizures o the second week compared tothose o the week leading to treatment

Sex distribution o the patients according to the usedamino acid is presented in able 983090 Tere were no signi1047297cantdifferences between the three study groups ( = 028)

Age distribution o the patients according to the usedamino acid is presented in able 983091 Tere were no signi1047297cantdifferences between the three study groups ( = 07)

able 983092 portrays the requency o the different types o uncontrolled epilepsies in terms o the administered aminoacid

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

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Neurology Research International 983091

983137983138983148983141 983089 Te rate o seizure attacks (one week beore starting amino acid 1047297rst week afer starting second week and ratio o second week tobeore starting)

Amino acid Number Beore starting First week Second week Ratio beoresecond 1038389-test value

Arginine 983089983088 983090983091983094 plusmn 983089983094983090 983090983089983094 plusmn 983089983092983090 983089983089983090 plusmn 983089983089983093 983088983092983095 983091983089983091983097 983088983088983089983091

Glutamic acid 983089983089 983091983089983091 plusmn 983091983094983090 983091983089983092 plusmn 983091983094983093 983089983096983093983092 plusmn 983090983089983089 983088983093983097 983090983094983092983094 983088983088983090983095

Lysine 983089983089 983089983089983092 plusmn 983097983097 983089983090983090 plusmn 983089983091983095 983089983088 plusmn 983089983093983093 983088983096983095 983088983091983094983096 983088983095983090983088

983137983138983148983141 983090 Te rate o sex o patients

Sexaminoacid

Arginine Glutamic

acid Lysine otal

Male 983096 983093 983095 983090983088

Female 983090 983094 983092 983089983090

otal 983089983088 983089983089 983089983089 983091983090

= 983088983090983096

983137983138983148983141 983091 Mean age o patients

Amino acidmean age Number Mean o agesArginine 983089983088 983089983094983090 plusmn 983089983088983092

Glutamic acid 983089983089 983089983090983090983095 plusmn 983089983090983096

Lysine 983089983089 983089983091983090983095 plusmn 983089983088983095

= 983088983095

4 Discussion

Amino acids are vital or brain activity the general de1047297ciency o which may cause apathy impaired concentration loss o motivation insomnia mood disorders anxiety depressionsel-harm and aggression Tey are essential in the construc-tion o necessary and important proteins or the productiono neurotransmitters required or the nervous system Poordiets may lead to amino acid shortage and give rise to agenetic potentiality or amino acid de1047297ciency [983092983089]

Use o amino acids is greatly in1047298uential on paroxysmaldisorders and the psychopathologic components o epilepsyAs or inants administration o amino acids contributesto the mental and verbal development Te positive effectso amino acids in children will take 983095ndash983089983088 days to unctionwhich may remain or a long time despite discontinuationAmino acids may urthermore be effective in changinggeneralized epilepsy into ocal epilepsy as well as decreasingthe requency o epileptic seizures [983092983090]

Acid glutamic managed to reduce the seizure requency

( = 0027) in uncontrolled epilepsy patients by morethan 983092983088 (able 983089) Studies conducted in the past ew decades are evidence or the role o glutamic acid in epilepsy [983092983091] which depends on the glutamate receptors some o which have intensiying effects (type 983089) and some otheranticonvulsant effects (types 983090 and 983091) [983092983092] Effects o thesereceptors are mainlycorrective rather than directly stimulantor prohibitory [983092983093] It is assumed that oral amino acids may reinorce the roles o receptors in the natural course andaccordingly improve controlling epileptic seizures

Arginine could also reduce the seizure requency ( =

0013) in uncontrolled epilepsy patients by 983093983091 (able 983089)L-arginine is an amino acid commonly sold in supplement

orm andobtained naturally in the diet L-arginine-richoodsinclude plant and animal proteins such as dairy Arginine isa nonessential amino acid the internal production o whichis however insufficient and needs to be compensated ororally [983091983088 983092983094 983092983095] Arginine regulation is a subject o theextent o oral use and its internal production hence arginineneeds to be viewed as a semiessential amino acid [983091983089] Teultimate metabolism o arginine leads to three substanceso nitrous oxide agmatine and glutamic acid Nitric oxide(NO) is a highly reactive and unstable substance with a very short hal-lie which is a potent vasodilator acting via the

intracellular second-messenger cGMP In healthy humans l-arginine induces peripheral vasodilation and inhibits plateletaggregation due to an increased NO production [983092983096] butacute L-arginine supplementation does not increase plasmaconcentration o NOx in healthy individuals with normalplasma concentrations o ADMA [983092983097]

Agmatine a product o arginine decarboxylation in1047298u-ences multiple physiologic and metabolic unctions Te1047297ndings suggest that AGM elevated the synthesis and levelso cAMP thereby mimicking the effects o caloric restrictionwith respect to metabolic reprogramming [983093983088] Te effectso injected agmatine in animals include anticonvulsant-antineurotoxic- and antidepressant-like actions [983093983089] Agma-

tine has neuroprotective effects [983093983090]Te effectiveness o arginine in reducing seizure re-quency may be due to the increase o glutamate level ratherthan the direct intervention o arginine itsel as the partic-ipants o the present study in the two groups o glutamicacid and arginine show no signi1047297cant difference in terms o age (able 983091) and sex distribution (able 983090) wo products o arginine glutamic acid and agmatine may be involved oranticonvulsant effects o arginine

Concerning lysine no signi1047297cant decrease ( = 0720)was observed in reducing seizure requency in uncontrolledepilepsy patients (983089983091) A study has reported that theintraperitoneal injection o lysine reduces the severity o PZ-induced seizures [983093983091 983093983092] As or the present study modeo lysine administration was oral In another study on ratswith oral lysine administered similar results were reported[983089983097]

In this study we could not evaluate the effect o chargedamino acid on different types o epilepsy due to our limitedcases (able 983092)

5 Conclusion

Administration o arginine and glutamic acid can be effectivein reducing the seizure requency o uncontrolled epilepsy patients without triggering considerable complications

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

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983092 Neurology Research International

983137983138983148983141 983092 Te type o seizures in this study

Aminotype o seizure onic-clonic F-G Atypical Lennox-Gastaut CPS Myoclonic otal

Arginine 983091 983091 983089 983089 983090 983088 983089983088

Glutamic acid 983088 983091 983090 983090 983089 983091 983089983089

Lysine 983090 983090 983089 983090 983090 983090 983089983089

otal 983093 983096 983092 983093 983093 983093 983091983090F-G secondary generalized CPS complex partial seizure and LGS Lennox-Gastaut syndrome

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Te authors would like to thank Mahmoud Reazi whoassisted in the editing

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[983090] J W A S Sander and S D Shorvon ldquoEpidemiology o theepilepsiesrdquo Journal of Neurology Neurosurgery and Psychiatry vol 983094983089 no 983093 pp 983092983091983091ndash983092983092983091 983089983097983097983094

[983091] P N Banerjee D Filippi and W Allen Hauser ldquoTe descriptiveepidemiology o epilepsymdasha reviewrdquo Epilepsy Research vol 983096983093no 983089 pp 983091983089ndash983092983093 983090983088983088983097

[983092] H Ebrahimi M A Shaa and S Hakimzadeh Asl ldquoPrevalenceo active epilepsy in Kerman Iran a house based surveyrdquo ActaNeurologica aiwanica vol 983090983089 no 983091 pp 983089983089983092ndash983089983090983092 983090983088983089983090

[983093] K Radhakrishnan and M B Rao in Epilepsy in India BS Singhal and D Nag Eds pp 983091983092983091ndash983091983094983090 Indian Epilepsy Association Mumbai India 983090983088983088983088

[983094] G Regesta and P anganelli ldquoClinical aspects and biologicalbases o drug-resistantepilepsiesrdquo Epilepsy Research vol 983091983092 no983090-983091 pp 983089983088983097ndash983089983090983090 983089983097983097983097

[983095] J A French ldquoReractory epilepsy clinical overviewrdquo Epilepsia vol 983092983096 supplement 983089 pp 983091ndash983096 983090983088983088983095

[983096] O Devinsky ldquoPatients with reractory seizuresrdquo Te NewEngland Journal of Medicine vol 983091983092983088 pp 983089983093983094983093ndash983089983093983095983088 983089983097983097983097

[983097] K Radhakrishnan ldquoChallenges in the management o epilepsy in resource-poor countriesrdquo Nature Reviews Neurology vol 983093no 983094 pp 983091983090983091ndash983091983091983088 983090983088983088983097

[983089983088] S U Schuele and H O Luders ldquoIntractable epilepsy manage-ment and therapeutic alternativesrdquo Te Lancet Neurology vol 983095no 983094 pp 983093983089983092ndash983093983090983092 983090983088983088983096

[983089983089] J Parra S N Kalitzin and F H Lopes da Silva ldquoPhotosensitiv-ity andvisually induced seizuresrdquo CurrentOpinionin Neurology vol 983089983096 no 983090 pp 983089983093983093ndash983089983093983097 983090983088983088983093

[983089983090] S S Seshia and L Carmant ldquoVisual-sensitive epilepsies classi-1047297cation and reviewrdquo Canadian Journal of Neurological Sciences vol 983091983090 no 983091 pp 983090983097983096ndash983091983088983093 983090983088983088983093

[983089983091] P D Singhi and D Bansal ldquoSel induced photosensitiveepilepsyrdquo Te Indian Journal of Pediatrics vol 983095983089no 983095 pp 983094983092983097ndash983094983093983089 983090983088983088983092

[983089983092] H Ebrahimi ldquoPhotoconvulsive epilepsyrdquo Iranian Journal of Epilepsy vol 983089983088 pp 983091983089983091ndash983091983089983092 983089983091983096983092

[983089983093] D C De Vivo R R ri1047297letti R I Jacobson G M RonenR A Behmand and S I Harik ldquoDeective glucose transportacrossthe blood-brain barrier as a cause o persistent hypoglyc-orrhachia seizures and developmental delayrdquo Te New England Journal of Medicine vol 983091983090983093 no 983089983088 pp 983095983088983091ndash983095983088983097 983089983097983097983089

[983089983094] I D Wexler S G Hemalatha J McConnell et al ldquoOutcome o pyruvatedehydrogenase de1047297ciency treated with ketogenic dietsstudies in patients with identical mutationsrdquo Neurology vol 983092983097no 983094 pp 983089983094983093983093ndash983089983094983094983089 983089983097983097983095

[983089983095] E H Kossoff G L Krauss J R McGrogan and J M Freeman

ldquoEfficacy o the Atkins diet as therapy or intractable epilepsyrdquoNeurology vol 983094983089 no 983089983090 pp 983089983095983096983097ndash983089983095983097983089 983090983088983088983091

[983089983096] A Evangeliou M Spilioti V Doulioglou et al ldquoBranched chainamino acids as adjunctive therapy to ketogenic diet in epilepsypilot study and hypothesisrdquo Journal of Child Neurology vol 983090983092no 983089983088 pp 983089983090983094983096ndash983089983090983095983090 983090983088983088983097

[983089983097] H Ebrahimi and M Asadi ldquoEffect o charged amino acids onconvulsion due to penthylentetrazol in male adult ratrdquo Iranian Journal of Neurology vol 983092 no 983089983090 983090983088983088983093

[983090983088] J Vaquero and R F Butterworth ldquoTe brain glutamate systemin liverailurerdquo Journal of Neurochemistry vol983097983096no983091pp983094983094983089ndash983094983094983097 983090983088983088983094

[983090983089] F Blandini R H P Porter and J Greenamyre ldquoGlutamateand Parkinsonrsquos diseaserdquo Molecular Neurobiology vol 983089983090 no 983089pp 983095983091ndash983097983092 983089983097983097983094

[983090983090] S M Rothman and J W Olney ldquoGlutamate and the pathophys-iology o hypoxic-ischemic brain damagerdquo Annals of Neurology vol 983089983097 no 983090 pp 983089983088983093ndash983089983089983089 983089983097983096983094

[983090983091] R J Tomas ldquoExcitatory amino acids in health and diseaserdquo Journal of the American Geriatrics Society vol 983092983091 no 983089983089 pp983089983090983095983097ndash983089983090983096983097 983089983097983097983093

[983090983092] A Lau and M ymianski ldquoGlutamate receptors neurotoxicity and neurodegenerationrdquo P1047298ugers Archiv European Journal of Physiology vol 983092983094983088 no 983090 pp 983093983090983093ndash983093983092983090 983090983088983089983088

[983090983093] M Erecinska andI A Silver ldquoMetabolismand role o glutamatein mammalian brainrdquo Progressin Neurobiology vol983091983093no983092pp983090983092983093ndash983090983097983094 983089983097983097983088

[983090983094] L F Obel K M H Andersen L K Bak A Schousboeand H S Waagepetersen ldquoEffects o adrenergic agents onintracellular Ca2+ homeostasis and metabolism o glucose inastrocytes with an emphasis on pyruvate carboxylation oxida-tive decarboxylation and recycling implications or glutamateneurotransmission and excitotoxicityrdquo Neurotoxicity Research vol 983090983089 no 983092 pp 983092983088983093ndash983092983089983095 983090983088983089983090

[983090983095] W C Rose W J Haines and D Warner ldquoTe aminoacid requirements o man V Te role o lysine arginine andtryptophanrdquo Te Journal of Biological Chemistry vol 983090983088983094 no 983089pp 983092983090983089ndash983092983091983088 983089983097983093983092

[983090983096] E Mertz W M Beeson and H D Jackson ldquoClassi1047297cationo essential amino acids or the weanling pigrdquo Archives of Biochemistry and Biophysics vol 983091983096 no 983089 pp 983089983090983089ndash983089983090983096 983089983097983093983090

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

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Neurology Research International 983093

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[983091983088] A Barbul ldquoArginine biochemistry physiology and therapeuticimplicationsrdquo Journal of Parenteral and Enteral Nutrition vol983089983088 no 983090 pp 983090983090983095ndash983090983091983096 983089983097983096983094

[983091983089] G Wu and S M Morris Jr ldquoArginine metabolism nitric oxideand beyondrdquo Biochemical Journal vol 983091983091983094 no 983089 pp 983089ndash983089983095 983089983097983097983096

[983091983090] S M Morris Jr ldquoArginine metabolism boundaries o ourknowledgerdquo Te Journal of Nutrition vol 983089983091983095 no 983094 supplement983090 pp 983089983094983088983090Sndash983089983094983088983097S 983090983088983088983095

[983091983091] H Eagle ldquoAmino acid metabolism in mammalian cell culturesrdquoScience vol 983089983091983088 no 983091983091983095983091 pp 983092983091983090ndash983092983091983095 983089983097983093983097

[983091983092] S M Morris Jr ldquoArginine synthesis metabolism and transportregulators o nitric oxide synthesisrdquo in Cellular and Molecular Biology of Nitric Oxide J D Laskin and D L Laskin Eds pp983093983095ndash983096983093 Marcel Dekker New York NY USA 983089983097983097983097

[983091983093] C Vianey-Liaud P Divry C Poinas and M Mathieu ldquoLysinemetabolism in manrdquo Annales de Biologie Clinique vol 983092983097 no 983089pp 983089983096ndash983090983094 983089983097983097983089

[983091983094] E R Braverman Te Healing Nutrients Within Keats Publish-ing New Canaan Conn USA 983089983097983097983095

[983091983095] M P H Cooper and H Kenneth Advanced Nutritional Tera- pies Tomas Nelson Nashville enn USA 983089983097983097983094

[983091983096] M D Balch F James C NC Balchand A Phyllis Prescription for Nutritional Healing Avery Publishing Group Garden City Park NY USA 983090nd edition 983089983097983097983095

[983091983097] M D Hendler and S Saul Te Doctorrsquos Vitamin and Mineral Encyclopedia Fireside New York NY USA 983089983097983097983088

[983092983088] Johns Hopkins University Johns Hopkins Family Health BookHarper Collins Publishers New York NY USA 983089983097983097983097

[983092983089] C Collard Amino Acids How Tey Affect the Brain and NervousSystem 983090983088983088983097

[983092983090] S A Nikolayeva ldquoUse o amino acid compounds in treatingepilepsy patientsrdquo REHA-Zentrum inoaminocurecz

[983092983091] N A Janjua H Kabuto and A Mori ldquoIncreased plasmaglutamic acid in a genetic model o epilepsyrdquo Neurochemical Research vol 983089983095 no 983091 pp 983090983097983091ndash983090983097983094 983089983097983097983090

[983092983092] R X Moldrich A G Chapman G De Sarro and B SMeldrum ldquoGlutamate metabotropic receptors as targets ordrug therapy in epilepsyrdquo European Journal of Pharmacology vol 983092983095983094 no 983089-983090 pp 983091ndash983089983094 983090983088983088983091

[983092983093] J A Saugstad and S L Ingram ldquoGroup I metabotropicglutamate receptors (mGlu983089 and mGlu983093)rdquo in Te GlutamateReceptors Te Receptors pp 983091983096983095ndash983092983094983091 Humana Press 983090983088983088983096

[983092983094] N Flynn C J Meininger E Haynes and G Wu ldquoTemetabolic basis o arginine nutrition and pharmacotherapyrdquoBiomedicine and Pharmacotherapy vol 983093983094 no 983097 pp 983092983090983095ndash983092983091983096983090983088983088983090

[983092983095] N N Abumrad and A Barbul ldquoTe use o arginine in clinicalpracticerdquo in Metabolic and Terapeutic Aspects of Amino Acidsin Clinical Nutrition L A Cynober Ed pp 983093983097983093ndash983094983089983089 CRCPressBoca Raton Fla USA 983090983088983088983092

[983092983096] S M Bode-Boger R H Boger H Ale et al ldquoL-arginineinduces nitric oxidemdashdependent vasodilation in patients withcritical limb ischemia a randomized controlled studyrdquo Circu-lation vol 983097983091 no 983089 pp 983096983093ndash983097983088 983089983097983097983094

[983092983097] S Alvares C A Conte-Junior J Silva and V MF Paschoalin ldquoAcute L-arginine supplementation does notincrease nitric oxide production in healthy subjectsrdquo Nutritionamp Metabolism vol 983097 article 983093983092 983090983088983089983090

[983093983088] I Nissim O Horyn Y Daikhin et al ldquoTe molecular andmetabolic in1047298uence o long term agmatine consumptionrdquo Te Journal of Biological Chemistry vol 983090983096983097 no 983089983092 pp 983097983095983089983088ndash983097983095983090983097983090983088983089983092

[983093983089] A Halaris and J Plietz ldquoAgmatine metabolic pathway andspectrum o activity in brainrdquo CNS Drugs vol 983090983089 no 983089983089 pp983096983096983093ndash983097983088983088 983090983088983088983095

[983093983090] M Moretti F C Matheus P A de Oliveira et al ldquoRole o agmatine in neurodegenerative diseases and epilepsyrdquo Frontiersin BiosciencemdashElite vol 983094 no 983090 pp 983091983092983089ndash983091983093983097 983090983088983089983092

[983093983091] Y-F Chang and N R Myslinski ldquoEffects o l-lysine andits metabolites on pentylenetetrazol-induced seizuresrdquo Neuro-science Letters vol 983093983097 no 983089 pp 983095983097ndash983096983092 983089983097983096983093

[983093983092] Y E Chang V Hargest and J S Chen ldquoModulation o ben-zodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizuresrdquo Life Sciences vol 983092983091 no 983089983093 pp 983089983089983095983095ndash983089983089983096983096

983089983097983096983096

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 66

Submit your manuscripts at

httpwwwhindawicom

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 36

Neurology Research International 983091

983137983138983148983141 983089 Te rate o seizure attacks (one week beore starting amino acid 1047297rst week afer starting second week and ratio o second week tobeore starting)

Amino acid Number Beore starting First week Second week Ratio beoresecond 1038389-test value

Arginine 983089983088 983090983091983094 plusmn 983089983094983090 983090983089983094 plusmn 983089983092983090 983089983089983090 plusmn 983089983089983093 983088983092983095 983091983089983091983097 983088983088983089983091

Glutamic acid 983089983089 983091983089983091 plusmn 983091983094983090 983091983089983092 plusmn 983091983094983093 983089983096983093983092 plusmn 983090983089983089 983088983093983097 983090983094983092983094 983088983088983090983095

Lysine 983089983089 983089983089983092 plusmn 983097983097 983089983090983090 plusmn 983089983091983095 983089983088 plusmn 983089983093983093 983088983096983095 983088983091983094983096 983088983095983090983088

983137983138983148983141 983090 Te rate o sex o patients

Sexaminoacid

Arginine Glutamic

acid Lysine otal

Male 983096 983093 983095 983090983088

Female 983090 983094 983092 983089983090

otal 983089983088 983089983089 983089983089 983091983090

= 983088983090983096

983137983138983148983141 983091 Mean age o patients

Amino acidmean age Number Mean o agesArginine 983089983088 983089983094983090 plusmn 983089983088983092

Glutamic acid 983089983089 983089983090983090983095 plusmn 983089983090983096

Lysine 983089983089 983089983091983090983095 plusmn 983089983088983095

= 983088983095

4 Discussion

Amino acids are vital or brain activity the general de1047297ciency o which may cause apathy impaired concentration loss o motivation insomnia mood disorders anxiety depressionsel-harm and aggression Tey are essential in the construc-tion o necessary and important proteins or the productiono neurotransmitters required or the nervous system Poordiets may lead to amino acid shortage and give rise to agenetic potentiality or amino acid de1047297ciency [983092983089]

Use o amino acids is greatly in1047298uential on paroxysmaldisorders and the psychopathologic components o epilepsyAs or inants administration o amino acids contributesto the mental and verbal development Te positive effectso amino acids in children will take 983095ndash983089983088 days to unctionwhich may remain or a long time despite discontinuationAmino acids may urthermore be effective in changinggeneralized epilepsy into ocal epilepsy as well as decreasingthe requency o epileptic seizures [983092983090]

Acid glutamic managed to reduce the seizure requency

( = 0027) in uncontrolled epilepsy patients by morethan 983092983088 (able 983089) Studies conducted in the past ew decades are evidence or the role o glutamic acid in epilepsy [983092983091] which depends on the glutamate receptors some o which have intensiying effects (type 983089) and some otheranticonvulsant effects (types 983090 and 983091) [983092983092] Effects o thesereceptors are mainlycorrective rather than directly stimulantor prohibitory [983092983093] It is assumed that oral amino acids may reinorce the roles o receptors in the natural course andaccordingly improve controlling epileptic seizures

Arginine could also reduce the seizure requency ( =

0013) in uncontrolled epilepsy patients by 983093983091 (able 983089)L-arginine is an amino acid commonly sold in supplement

orm andobtained naturally in the diet L-arginine-richoodsinclude plant and animal proteins such as dairy Arginine isa nonessential amino acid the internal production o whichis however insufficient and needs to be compensated ororally [983091983088 983092983094 983092983095] Arginine regulation is a subject o theextent o oral use and its internal production hence arginineneeds to be viewed as a semiessential amino acid [983091983089] Teultimate metabolism o arginine leads to three substanceso nitrous oxide agmatine and glutamic acid Nitric oxide(NO) is a highly reactive and unstable substance with a very short hal-lie which is a potent vasodilator acting via the

intracellular second-messenger cGMP In healthy humans l-arginine induces peripheral vasodilation and inhibits plateletaggregation due to an increased NO production [983092983096] butacute L-arginine supplementation does not increase plasmaconcentration o NOx in healthy individuals with normalplasma concentrations o ADMA [983092983097]

Agmatine a product o arginine decarboxylation in1047298u-ences multiple physiologic and metabolic unctions Te1047297ndings suggest that AGM elevated the synthesis and levelso cAMP thereby mimicking the effects o caloric restrictionwith respect to metabolic reprogramming [983093983088] Te effectso injected agmatine in animals include anticonvulsant-antineurotoxic- and antidepressant-like actions [983093983089] Agma-

tine has neuroprotective effects [983093983090]Te effectiveness o arginine in reducing seizure re-quency may be due to the increase o glutamate level ratherthan the direct intervention o arginine itsel as the partic-ipants o the present study in the two groups o glutamicacid and arginine show no signi1047297cant difference in terms o age (able 983091) and sex distribution (able 983090) wo products o arginine glutamic acid and agmatine may be involved oranticonvulsant effects o arginine

Concerning lysine no signi1047297cant decrease ( = 0720)was observed in reducing seizure requency in uncontrolledepilepsy patients (983089983091) A study has reported that theintraperitoneal injection o lysine reduces the severity o PZ-induced seizures [983093983091 983093983092] As or the present study modeo lysine administration was oral In another study on ratswith oral lysine administered similar results were reported[983089983097]

In this study we could not evaluate the effect o chargedamino acid on different types o epilepsy due to our limitedcases (able 983092)

5 Conclusion

Administration o arginine and glutamic acid can be effectivein reducing the seizure requency o uncontrolled epilepsy patients without triggering considerable complications

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 46

983092 Neurology Research International

983137983138983148983141 983092 Te type o seizures in this study

Aminotype o seizure onic-clonic F-G Atypical Lennox-Gastaut CPS Myoclonic otal

Arginine 983091 983091 983089 983089 983090 983088 983089983088

Glutamic acid 983088 983091 983090 983090 983089 983091 983089983089

Lysine 983090 983090 983089 983090 983090 983090 983089983089

otal 983093 983096 983092 983093 983093 983093 983091983090F-G secondary generalized CPS complex partial seizure and LGS Lennox-Gastaut syndrome

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Te authors would like to thank Mahmoud Reazi whoassisted in the editing

References

[983089] G S Bell and J W Sander ldquoTe epidemiology o epilepsy thesize o the problemrdquo Seizure vol 983089983088 pp 983091983088983094ndash983091983091983089 983090983088983088983089

[983090] J W A S Sander and S D Shorvon ldquoEpidemiology o theepilepsiesrdquo Journal of Neurology Neurosurgery and Psychiatry vol 983094983089 no 983093 pp 983092983091983091ndash983092983092983091 983089983097983097983094

[983091] P N Banerjee D Filippi and W Allen Hauser ldquoTe descriptiveepidemiology o epilepsymdasha reviewrdquo Epilepsy Research vol 983096983093no 983089 pp 983091983089ndash983092983093 983090983088983088983097

[983092] H Ebrahimi M A Shaa and S Hakimzadeh Asl ldquoPrevalenceo active epilepsy in Kerman Iran a house based surveyrdquo ActaNeurologica aiwanica vol 983090983089 no 983091 pp 983089983089983092ndash983089983090983092 983090983088983089983090

[983093] K Radhakrishnan and M B Rao in Epilepsy in India BS Singhal and D Nag Eds pp 983091983092983091ndash983091983094983090 Indian Epilepsy Association Mumbai India 983090983088983088983088

[983094] G Regesta and P anganelli ldquoClinical aspects and biologicalbases o drug-resistantepilepsiesrdquo Epilepsy Research vol 983091983092 no983090-983091 pp 983089983088983097ndash983089983090983090 983089983097983097983097

[983095] J A French ldquoReractory epilepsy clinical overviewrdquo Epilepsia vol 983092983096 supplement 983089 pp 983091ndash983096 983090983088983088983095

[983096] O Devinsky ldquoPatients with reractory seizuresrdquo Te NewEngland Journal of Medicine vol 983091983092983088 pp 983089983093983094983093ndash983089983093983095983088 983089983097983097983097

[983097] K Radhakrishnan ldquoChallenges in the management o epilepsy in resource-poor countriesrdquo Nature Reviews Neurology vol 983093no 983094 pp 983091983090983091ndash983091983091983088 983090983088983088983097

[983089983088] S U Schuele and H O Luders ldquoIntractable epilepsy manage-ment and therapeutic alternativesrdquo Te Lancet Neurology vol 983095no 983094 pp 983093983089983092ndash983093983090983092 983090983088983088983096

[983089983089] J Parra S N Kalitzin and F H Lopes da Silva ldquoPhotosensitiv-ity andvisually induced seizuresrdquo CurrentOpinionin Neurology vol 983089983096 no 983090 pp 983089983093983093ndash983089983093983097 983090983088983088983093

[983089983090] S S Seshia and L Carmant ldquoVisual-sensitive epilepsies classi-1047297cation and reviewrdquo Canadian Journal of Neurological Sciences vol 983091983090 no 983091 pp 983090983097983096ndash983091983088983093 983090983088983088983093

[983089983091] P D Singhi and D Bansal ldquoSel induced photosensitiveepilepsyrdquo Te Indian Journal of Pediatrics vol 983095983089no 983095 pp 983094983092983097ndash983094983093983089 983090983088983088983092

[983089983092] H Ebrahimi ldquoPhotoconvulsive epilepsyrdquo Iranian Journal of Epilepsy vol 983089983088 pp 983091983089983091ndash983091983089983092 983089983091983096983092

[983089983093] D C De Vivo R R ri1047297letti R I Jacobson G M RonenR A Behmand and S I Harik ldquoDeective glucose transportacrossthe blood-brain barrier as a cause o persistent hypoglyc-orrhachia seizures and developmental delayrdquo Te New England Journal of Medicine vol 983091983090983093 no 983089983088 pp 983095983088983091ndash983095983088983097 983089983097983097983089

[983089983094] I D Wexler S G Hemalatha J McConnell et al ldquoOutcome o pyruvatedehydrogenase de1047297ciency treated with ketogenic dietsstudies in patients with identical mutationsrdquo Neurology vol 983092983097no 983094 pp 983089983094983093983093ndash983089983094983094983089 983089983097983097983095

[983089983095] E H Kossoff G L Krauss J R McGrogan and J M Freeman

ldquoEfficacy o the Atkins diet as therapy or intractable epilepsyrdquoNeurology vol 983094983089 no 983089983090 pp 983089983095983096983097ndash983089983095983097983089 983090983088983088983091

[983089983096] A Evangeliou M Spilioti V Doulioglou et al ldquoBranched chainamino acids as adjunctive therapy to ketogenic diet in epilepsypilot study and hypothesisrdquo Journal of Child Neurology vol 983090983092no 983089983088 pp 983089983090983094983096ndash983089983090983095983090 983090983088983088983097

[983089983097] H Ebrahimi and M Asadi ldquoEffect o charged amino acids onconvulsion due to penthylentetrazol in male adult ratrdquo Iranian Journal of Neurology vol 983092 no 983089983090 983090983088983088983093

[983090983088] J Vaquero and R F Butterworth ldquoTe brain glutamate systemin liverailurerdquo Journal of Neurochemistry vol983097983096no983091pp983094983094983089ndash983094983094983097 983090983088983088983094

[983090983089] F Blandini R H P Porter and J Greenamyre ldquoGlutamateand Parkinsonrsquos diseaserdquo Molecular Neurobiology vol 983089983090 no 983089pp 983095983091ndash983097983092 983089983097983097983094

[983090983090] S M Rothman and J W Olney ldquoGlutamate and the pathophys-iology o hypoxic-ischemic brain damagerdquo Annals of Neurology vol 983089983097 no 983090 pp 983089983088983093ndash983089983089983089 983089983097983096983094

[983090983091] R J Tomas ldquoExcitatory amino acids in health and diseaserdquo Journal of the American Geriatrics Society vol 983092983091 no 983089983089 pp983089983090983095983097ndash983089983090983096983097 983089983097983097983093

[983090983092] A Lau and M ymianski ldquoGlutamate receptors neurotoxicity and neurodegenerationrdquo P1047298ugers Archiv European Journal of Physiology vol 983092983094983088 no 983090 pp 983093983090983093ndash983093983092983090 983090983088983089983088

[983090983093] M Erecinska andI A Silver ldquoMetabolismand role o glutamatein mammalian brainrdquo Progressin Neurobiology vol983091983093no983092pp983090983092983093ndash983090983097983094 983089983097983097983088

[983090983094] L F Obel K M H Andersen L K Bak A Schousboeand H S Waagepetersen ldquoEffects o adrenergic agents onintracellular Ca2+ homeostasis and metabolism o glucose inastrocytes with an emphasis on pyruvate carboxylation oxida-tive decarboxylation and recycling implications or glutamateneurotransmission and excitotoxicityrdquo Neurotoxicity Research vol 983090983089 no 983092 pp 983092983088983093ndash983092983089983095 983090983088983089983090

[983090983095] W C Rose W J Haines and D Warner ldquoTe aminoacid requirements o man V Te role o lysine arginine andtryptophanrdquo Te Journal of Biological Chemistry vol 983090983088983094 no 983089pp 983092983090983089ndash983092983091983088 983089983097983093983092

[983090983096] E Mertz W M Beeson and H D Jackson ldquoClassi1047297cationo essential amino acids or the weanling pigrdquo Archives of Biochemistry and Biophysics vol 983091983096 no 983089 pp 983089983090983089ndash983089983090983096 983089983097983093983090

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 56

Neurology Research International 983093

[983090983097] W C Heird J F Nicholson J M Driscoll Jr J N Schullingerand R W Winters ldquoHyperammonemia resulting rom intra- venous alimentation using a mixture o synthetic L-aminoacids a preliminary reportrdquo Te Journal of Pediatrics vol 983096983089no 983089 pp 983089983094983090ndash983089983094983093 983089983097983095983090

[983091983088] A Barbul ldquoArginine biochemistry physiology and therapeuticimplicationsrdquo Journal of Parenteral and Enteral Nutrition vol983089983088 no 983090 pp 983090983090983095ndash983090983091983096 983089983097983096983094

[983091983089] G Wu and S M Morris Jr ldquoArginine metabolism nitric oxideand beyondrdquo Biochemical Journal vol 983091983091983094 no 983089 pp 983089ndash983089983095 983089983097983097983096

[983091983090] S M Morris Jr ldquoArginine metabolism boundaries o ourknowledgerdquo Te Journal of Nutrition vol 983089983091983095 no 983094 supplement983090 pp 983089983094983088983090Sndash983089983094983088983097S 983090983088983088983095

[983091983091] H Eagle ldquoAmino acid metabolism in mammalian cell culturesrdquoScience vol 983089983091983088 no 983091983091983095983091 pp 983092983091983090ndash983092983091983095 983089983097983093983097

[983091983092] S M Morris Jr ldquoArginine synthesis metabolism and transportregulators o nitric oxide synthesisrdquo in Cellular and Molecular Biology of Nitric Oxide J D Laskin and D L Laskin Eds pp983093983095ndash983096983093 Marcel Dekker New York NY USA 983089983097983097983097

[983091983093] C Vianey-Liaud P Divry C Poinas and M Mathieu ldquoLysinemetabolism in manrdquo Annales de Biologie Clinique vol 983092983097 no 983089pp 983089983096ndash983090983094 983089983097983097983089

[983091983094] E R Braverman Te Healing Nutrients Within Keats Publish-ing New Canaan Conn USA 983089983097983097983095

[983091983095] M P H Cooper and H Kenneth Advanced Nutritional Tera- pies Tomas Nelson Nashville enn USA 983089983097983097983094

[983091983096] M D Balch F James C NC Balchand A Phyllis Prescription for Nutritional Healing Avery Publishing Group Garden City Park NY USA 983090nd edition 983089983097983097983095

[983091983097] M D Hendler and S Saul Te Doctorrsquos Vitamin and Mineral Encyclopedia Fireside New York NY USA 983089983097983097983088

[983092983088] Johns Hopkins University Johns Hopkins Family Health BookHarper Collins Publishers New York NY USA 983089983097983097983097

[983092983089] C Collard Amino Acids How Tey Affect the Brain and NervousSystem 983090983088983088983097

[983092983090] S A Nikolayeva ldquoUse o amino acid compounds in treatingepilepsy patientsrdquo REHA-Zentrum inoaminocurecz

[983092983091] N A Janjua H Kabuto and A Mori ldquoIncreased plasmaglutamic acid in a genetic model o epilepsyrdquo Neurochemical Research vol 983089983095 no 983091 pp 983090983097983091ndash983090983097983094 983089983097983097983090

[983092983092] R X Moldrich A G Chapman G De Sarro and B SMeldrum ldquoGlutamate metabotropic receptors as targets ordrug therapy in epilepsyrdquo European Journal of Pharmacology vol 983092983095983094 no 983089-983090 pp 983091ndash983089983094 983090983088983088983091

[983092983093] J A Saugstad and S L Ingram ldquoGroup I metabotropicglutamate receptors (mGlu983089 and mGlu983093)rdquo in Te GlutamateReceptors Te Receptors pp 983091983096983095ndash983092983094983091 Humana Press 983090983088983088983096

[983092983094] N Flynn C J Meininger E Haynes and G Wu ldquoTemetabolic basis o arginine nutrition and pharmacotherapyrdquoBiomedicine and Pharmacotherapy vol 983093983094 no 983097 pp 983092983090983095ndash983092983091983096983090983088983088983090

[983092983095] N N Abumrad and A Barbul ldquoTe use o arginine in clinicalpracticerdquo in Metabolic and Terapeutic Aspects of Amino Acidsin Clinical Nutrition L A Cynober Ed pp 983093983097983093ndash983094983089983089 CRCPressBoca Raton Fla USA 983090983088983088983092

[983092983096] S M Bode-Boger R H Boger H Ale et al ldquoL-arginineinduces nitric oxidemdashdependent vasodilation in patients withcritical limb ischemia a randomized controlled studyrdquo Circu-lation vol 983097983091 no 983089 pp 983096983093ndash983097983088 983089983097983097983094

[983092983097] S Alvares C A Conte-Junior J Silva and V MF Paschoalin ldquoAcute L-arginine supplementation does notincrease nitric oxide production in healthy subjectsrdquo Nutritionamp Metabolism vol 983097 article 983093983092 983090983088983089983090

[983093983088] I Nissim O Horyn Y Daikhin et al ldquoTe molecular andmetabolic in1047298uence o long term agmatine consumptionrdquo Te Journal of Biological Chemistry vol 983090983096983097 no 983089983092 pp 983097983095983089983088ndash983097983095983090983097983090983088983089983092

[983093983089] A Halaris and J Plietz ldquoAgmatine metabolic pathway andspectrum o activity in brainrdquo CNS Drugs vol 983090983089 no 983089983089 pp983096983096983093ndash983097983088983088 983090983088983088983095

[983093983090] M Moretti F C Matheus P A de Oliveira et al ldquoRole o agmatine in neurodegenerative diseases and epilepsyrdquo Frontiersin BiosciencemdashElite vol 983094 no 983090 pp 983091983092983089ndash983091983093983097 983090983088983089983092

[983093983091] Y-F Chang and N R Myslinski ldquoEffects o l-lysine andits metabolites on pentylenetetrazol-induced seizuresrdquo Neuro-science Letters vol 983093983097 no 983089 pp 983095983097ndash983096983092 983089983097983096983093

[983093983092] Y E Chang V Hargest and J S Chen ldquoModulation o ben-zodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizuresrdquo Life Sciences vol 983092983091 no 983089983093 pp 983089983089983095983095ndash983089983089983096983096

983089983097983096983096

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 66

Submit your manuscripts at

httpwwwhindawicom

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 46

983092 Neurology Research International

983137983138983148983141 983092 Te type o seizures in this study

Aminotype o seizure onic-clonic F-G Atypical Lennox-Gastaut CPS Myoclonic otal

Arginine 983091 983091 983089 983089 983090 983088 983089983088

Glutamic acid 983088 983091 983090 983090 983089 983091 983089983089

Lysine 983090 983090 983089 983090 983090 983090 983089983089

otal 983093 983096 983092 983093 983093 983093 983091983090F-G secondary generalized CPS complex partial seizure and LGS Lennox-Gastaut syndrome

Conflict of Interests

Te authors declare that there is no con1047298ict o interestsregarding the publication o this paper

Acknowledgment

Te authors would like to thank Mahmoud Reazi whoassisted in the editing

References

[983089] G S Bell and J W Sander ldquoTe epidemiology o epilepsy thesize o the problemrdquo Seizure vol 983089983088 pp 983091983088983094ndash983091983091983089 983090983088983088983089

[983090] J W A S Sander and S D Shorvon ldquoEpidemiology o theepilepsiesrdquo Journal of Neurology Neurosurgery and Psychiatry vol 983094983089 no 983093 pp 983092983091983091ndash983092983092983091 983089983097983097983094

[983091] P N Banerjee D Filippi and W Allen Hauser ldquoTe descriptiveepidemiology o epilepsymdasha reviewrdquo Epilepsy Research vol 983096983093no 983089 pp 983091983089ndash983092983093 983090983088983088983097

[983092] H Ebrahimi M A Shaa and S Hakimzadeh Asl ldquoPrevalenceo active epilepsy in Kerman Iran a house based surveyrdquo ActaNeurologica aiwanica vol 983090983089 no 983091 pp 983089983089983092ndash983089983090983092 983090983088983089983090

[983093] K Radhakrishnan and M B Rao in Epilepsy in India BS Singhal and D Nag Eds pp 983091983092983091ndash983091983094983090 Indian Epilepsy Association Mumbai India 983090983088983088983088

[983094] G Regesta and P anganelli ldquoClinical aspects and biologicalbases o drug-resistantepilepsiesrdquo Epilepsy Research vol 983091983092 no983090-983091 pp 983089983088983097ndash983089983090983090 983089983097983097983097

[983095] J A French ldquoReractory epilepsy clinical overviewrdquo Epilepsia vol 983092983096 supplement 983089 pp 983091ndash983096 983090983088983088983095

[983096] O Devinsky ldquoPatients with reractory seizuresrdquo Te NewEngland Journal of Medicine vol 983091983092983088 pp 983089983093983094983093ndash983089983093983095983088 983089983097983097983097

[983097] K Radhakrishnan ldquoChallenges in the management o epilepsy in resource-poor countriesrdquo Nature Reviews Neurology vol 983093no 983094 pp 983091983090983091ndash983091983091983088 983090983088983088983097

[983089983088] S U Schuele and H O Luders ldquoIntractable epilepsy manage-ment and therapeutic alternativesrdquo Te Lancet Neurology vol 983095no 983094 pp 983093983089983092ndash983093983090983092 983090983088983088983096

[983089983089] J Parra S N Kalitzin and F H Lopes da Silva ldquoPhotosensitiv-ity andvisually induced seizuresrdquo CurrentOpinionin Neurology vol 983089983096 no 983090 pp 983089983093983093ndash983089983093983097 983090983088983088983093

[983089983090] S S Seshia and L Carmant ldquoVisual-sensitive epilepsies classi-1047297cation and reviewrdquo Canadian Journal of Neurological Sciences vol 983091983090 no 983091 pp 983090983097983096ndash983091983088983093 983090983088983088983093

[983089983091] P D Singhi and D Bansal ldquoSel induced photosensitiveepilepsyrdquo Te Indian Journal of Pediatrics vol 983095983089no 983095 pp 983094983092983097ndash983094983093983089 983090983088983088983092

[983089983092] H Ebrahimi ldquoPhotoconvulsive epilepsyrdquo Iranian Journal of Epilepsy vol 983089983088 pp 983091983089983091ndash983091983089983092 983089983091983096983092

[983089983093] D C De Vivo R R ri1047297letti R I Jacobson G M RonenR A Behmand and S I Harik ldquoDeective glucose transportacrossthe blood-brain barrier as a cause o persistent hypoglyc-orrhachia seizures and developmental delayrdquo Te New England Journal of Medicine vol 983091983090983093 no 983089983088 pp 983095983088983091ndash983095983088983097 983089983097983097983089

[983089983094] I D Wexler S G Hemalatha J McConnell et al ldquoOutcome o pyruvatedehydrogenase de1047297ciency treated with ketogenic dietsstudies in patients with identical mutationsrdquo Neurology vol 983092983097no 983094 pp 983089983094983093983093ndash983089983094983094983089 983089983097983097983095

[983089983095] E H Kossoff G L Krauss J R McGrogan and J M Freeman

ldquoEfficacy o the Atkins diet as therapy or intractable epilepsyrdquoNeurology vol 983094983089 no 983089983090 pp 983089983095983096983097ndash983089983095983097983089 983090983088983088983091

[983089983096] A Evangeliou M Spilioti V Doulioglou et al ldquoBranched chainamino acids as adjunctive therapy to ketogenic diet in epilepsypilot study and hypothesisrdquo Journal of Child Neurology vol 983090983092no 983089983088 pp 983089983090983094983096ndash983089983090983095983090 983090983088983088983097

[983089983097] H Ebrahimi and M Asadi ldquoEffect o charged amino acids onconvulsion due to penthylentetrazol in male adult ratrdquo Iranian Journal of Neurology vol 983092 no 983089983090 983090983088983088983093

[983090983088] J Vaquero and R F Butterworth ldquoTe brain glutamate systemin liverailurerdquo Journal of Neurochemistry vol983097983096no983091pp983094983094983089ndash983094983094983097 983090983088983088983094

[983090983089] F Blandini R H P Porter and J Greenamyre ldquoGlutamateand Parkinsonrsquos diseaserdquo Molecular Neurobiology vol 983089983090 no 983089pp 983095983091ndash983097983092 983089983097983097983094

[983090983090] S M Rothman and J W Olney ldquoGlutamate and the pathophys-iology o hypoxic-ischemic brain damagerdquo Annals of Neurology vol 983089983097 no 983090 pp 983089983088983093ndash983089983089983089 983089983097983096983094

[983090983091] R J Tomas ldquoExcitatory amino acids in health and diseaserdquo Journal of the American Geriatrics Society vol 983092983091 no 983089983089 pp983089983090983095983097ndash983089983090983096983097 983089983097983097983093

[983090983092] A Lau and M ymianski ldquoGlutamate receptors neurotoxicity and neurodegenerationrdquo P1047298ugers Archiv European Journal of Physiology vol 983092983094983088 no 983090 pp 983093983090983093ndash983093983092983090 983090983088983089983088

[983090983093] M Erecinska andI A Silver ldquoMetabolismand role o glutamatein mammalian brainrdquo Progressin Neurobiology vol983091983093no983092pp983090983092983093ndash983090983097983094 983089983097983097983088

[983090983094] L F Obel K M H Andersen L K Bak A Schousboeand H S Waagepetersen ldquoEffects o adrenergic agents onintracellular Ca2+ homeostasis and metabolism o glucose inastrocytes with an emphasis on pyruvate carboxylation oxida-tive decarboxylation and recycling implications or glutamateneurotransmission and excitotoxicityrdquo Neurotoxicity Research vol 983090983089 no 983092 pp 983092983088983093ndash983092983089983095 983090983088983089983090

[983090983095] W C Rose W J Haines and D Warner ldquoTe aminoacid requirements o man V Te role o lysine arginine andtryptophanrdquo Te Journal of Biological Chemistry vol 983090983088983094 no 983089pp 983092983090983089ndash983092983091983088 983089983097983093983092

[983090983096] E Mertz W M Beeson and H D Jackson ldquoClassi1047297cationo essential amino acids or the weanling pigrdquo Archives of Biochemistry and Biophysics vol 983091983096 no 983089 pp 983089983090983089ndash983089983090983096 983089983097983093983090

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 56

Neurology Research International 983093

[983090983097] W C Heird J F Nicholson J M Driscoll Jr J N Schullingerand R W Winters ldquoHyperammonemia resulting rom intra- venous alimentation using a mixture o synthetic L-aminoacids a preliminary reportrdquo Te Journal of Pediatrics vol 983096983089no 983089 pp 983089983094983090ndash983089983094983093 983089983097983095983090

[983091983088] A Barbul ldquoArginine biochemistry physiology and therapeuticimplicationsrdquo Journal of Parenteral and Enteral Nutrition vol983089983088 no 983090 pp 983090983090983095ndash983090983091983096 983089983097983096983094

[983091983089] G Wu and S M Morris Jr ldquoArginine metabolism nitric oxideand beyondrdquo Biochemical Journal vol 983091983091983094 no 983089 pp 983089ndash983089983095 983089983097983097983096

[983091983090] S M Morris Jr ldquoArginine metabolism boundaries o ourknowledgerdquo Te Journal of Nutrition vol 983089983091983095 no 983094 supplement983090 pp 983089983094983088983090Sndash983089983094983088983097S 983090983088983088983095

[983091983091] H Eagle ldquoAmino acid metabolism in mammalian cell culturesrdquoScience vol 983089983091983088 no 983091983091983095983091 pp 983092983091983090ndash983092983091983095 983089983097983093983097

[983091983092] S M Morris Jr ldquoArginine synthesis metabolism and transportregulators o nitric oxide synthesisrdquo in Cellular and Molecular Biology of Nitric Oxide J D Laskin and D L Laskin Eds pp983093983095ndash983096983093 Marcel Dekker New York NY USA 983089983097983097983097

[983091983093] C Vianey-Liaud P Divry C Poinas and M Mathieu ldquoLysinemetabolism in manrdquo Annales de Biologie Clinique vol 983092983097 no 983089pp 983089983096ndash983090983094 983089983097983097983089

[983091983094] E R Braverman Te Healing Nutrients Within Keats Publish-ing New Canaan Conn USA 983089983097983097983095

[983091983095] M P H Cooper and H Kenneth Advanced Nutritional Tera- pies Tomas Nelson Nashville enn USA 983089983097983097983094

[983091983096] M D Balch F James C NC Balchand A Phyllis Prescription for Nutritional Healing Avery Publishing Group Garden City Park NY USA 983090nd edition 983089983097983097983095

[983091983097] M D Hendler and S Saul Te Doctorrsquos Vitamin and Mineral Encyclopedia Fireside New York NY USA 983089983097983097983088

[983092983088] Johns Hopkins University Johns Hopkins Family Health BookHarper Collins Publishers New York NY USA 983089983097983097983097

[983092983089] C Collard Amino Acids How Tey Affect the Brain and NervousSystem 983090983088983088983097

[983092983090] S A Nikolayeva ldquoUse o amino acid compounds in treatingepilepsy patientsrdquo REHA-Zentrum inoaminocurecz

[983092983091] N A Janjua H Kabuto and A Mori ldquoIncreased plasmaglutamic acid in a genetic model o epilepsyrdquo Neurochemical Research vol 983089983095 no 983091 pp 983090983097983091ndash983090983097983094 983089983097983097983090

[983092983092] R X Moldrich A G Chapman G De Sarro and B SMeldrum ldquoGlutamate metabotropic receptors as targets ordrug therapy in epilepsyrdquo European Journal of Pharmacology vol 983092983095983094 no 983089-983090 pp 983091ndash983089983094 983090983088983088983091

[983092983093] J A Saugstad and S L Ingram ldquoGroup I metabotropicglutamate receptors (mGlu983089 and mGlu983093)rdquo in Te GlutamateReceptors Te Receptors pp 983091983096983095ndash983092983094983091 Humana Press 983090983088983088983096

[983092983094] N Flynn C J Meininger E Haynes and G Wu ldquoTemetabolic basis o arginine nutrition and pharmacotherapyrdquoBiomedicine and Pharmacotherapy vol 983093983094 no 983097 pp 983092983090983095ndash983092983091983096983090983088983088983090

[983092983095] N N Abumrad and A Barbul ldquoTe use o arginine in clinicalpracticerdquo in Metabolic and Terapeutic Aspects of Amino Acidsin Clinical Nutrition L A Cynober Ed pp 983093983097983093ndash983094983089983089 CRCPressBoca Raton Fla USA 983090983088983088983092

[983092983096] S M Bode-Boger R H Boger H Ale et al ldquoL-arginineinduces nitric oxidemdashdependent vasodilation in patients withcritical limb ischemia a randomized controlled studyrdquo Circu-lation vol 983097983091 no 983089 pp 983096983093ndash983097983088 983089983097983097983094

[983092983097] S Alvares C A Conte-Junior J Silva and V MF Paschoalin ldquoAcute L-arginine supplementation does notincrease nitric oxide production in healthy subjectsrdquo Nutritionamp Metabolism vol 983097 article 983093983092 983090983088983089983090

[983093983088] I Nissim O Horyn Y Daikhin et al ldquoTe molecular andmetabolic in1047298uence o long term agmatine consumptionrdquo Te Journal of Biological Chemistry vol 983090983096983097 no 983089983092 pp 983097983095983089983088ndash983097983095983090983097983090983088983089983092

[983093983089] A Halaris and J Plietz ldquoAgmatine metabolic pathway andspectrum o activity in brainrdquo CNS Drugs vol 983090983089 no 983089983089 pp983096983096983093ndash983097983088983088 983090983088983088983095

[983093983090] M Moretti F C Matheus P A de Oliveira et al ldquoRole o agmatine in neurodegenerative diseases and epilepsyrdquo Frontiersin BiosciencemdashElite vol 983094 no 983090 pp 983091983092983089ndash983091983093983097 983090983088983089983092

[983093983091] Y-F Chang and N R Myslinski ldquoEffects o l-lysine andits metabolites on pentylenetetrazol-induced seizuresrdquo Neuro-science Letters vol 983093983097 no 983089 pp 983095983097ndash983096983092 983089983097983096983093

[983093983092] Y E Chang V Hargest and J S Chen ldquoModulation o ben-zodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizuresrdquo Life Sciences vol 983092983091 no 983089983093 pp 983089983089983095983095ndash983089983089983096983096

983089983097983096983096

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 66

Submit your manuscripts at

httpwwwhindawicom

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 56

Neurology Research International 983093

[983090983097] W C Heird J F Nicholson J M Driscoll Jr J N Schullingerand R W Winters ldquoHyperammonemia resulting rom intra- venous alimentation using a mixture o synthetic L-aminoacids a preliminary reportrdquo Te Journal of Pediatrics vol 983096983089no 983089 pp 983089983094983090ndash983089983094983093 983089983097983095983090

[983091983088] A Barbul ldquoArginine biochemistry physiology and therapeuticimplicationsrdquo Journal of Parenteral and Enteral Nutrition vol983089983088 no 983090 pp 983090983090983095ndash983090983091983096 983089983097983096983094

[983091983089] G Wu and S M Morris Jr ldquoArginine metabolism nitric oxideand beyondrdquo Biochemical Journal vol 983091983091983094 no 983089 pp 983089ndash983089983095 983089983097983097983096

[983091983090] S M Morris Jr ldquoArginine metabolism boundaries o ourknowledgerdquo Te Journal of Nutrition vol 983089983091983095 no 983094 supplement983090 pp 983089983094983088983090Sndash983089983094983088983097S 983090983088983088983095

[983091983091] H Eagle ldquoAmino acid metabolism in mammalian cell culturesrdquoScience vol 983089983091983088 no 983091983091983095983091 pp 983092983091983090ndash983092983091983095 983089983097983093983097

[983091983092] S M Morris Jr ldquoArginine synthesis metabolism and transportregulators o nitric oxide synthesisrdquo in Cellular and Molecular Biology of Nitric Oxide J D Laskin and D L Laskin Eds pp983093983095ndash983096983093 Marcel Dekker New York NY USA 983089983097983097983097

[983091983093] C Vianey-Liaud P Divry C Poinas and M Mathieu ldquoLysinemetabolism in manrdquo Annales de Biologie Clinique vol 983092983097 no 983089pp 983089983096ndash983090983094 983089983097983097983089

[983091983094] E R Braverman Te Healing Nutrients Within Keats Publish-ing New Canaan Conn USA 983089983097983097983095

[983091983095] M P H Cooper and H Kenneth Advanced Nutritional Tera- pies Tomas Nelson Nashville enn USA 983089983097983097983094

[983091983096] M D Balch F James C NC Balchand A Phyllis Prescription for Nutritional Healing Avery Publishing Group Garden City Park NY USA 983090nd edition 983089983097983097983095

[983091983097] M D Hendler and S Saul Te Doctorrsquos Vitamin and Mineral Encyclopedia Fireside New York NY USA 983089983097983097983088

[983092983088] Johns Hopkins University Johns Hopkins Family Health BookHarper Collins Publishers New York NY USA 983089983097983097983097

[983092983089] C Collard Amino Acids How Tey Affect the Brain and NervousSystem 983090983088983088983097

[983092983090] S A Nikolayeva ldquoUse o amino acid compounds in treatingepilepsy patientsrdquo REHA-Zentrum inoaminocurecz

[983092983091] N A Janjua H Kabuto and A Mori ldquoIncreased plasmaglutamic acid in a genetic model o epilepsyrdquo Neurochemical Research vol 983089983095 no 983091 pp 983090983097983091ndash983090983097983094 983089983097983097983090

[983092983092] R X Moldrich A G Chapman G De Sarro and B SMeldrum ldquoGlutamate metabotropic receptors as targets ordrug therapy in epilepsyrdquo European Journal of Pharmacology vol 983092983095983094 no 983089-983090 pp 983091ndash983089983094 983090983088983088983091

[983092983093] J A Saugstad and S L Ingram ldquoGroup I metabotropicglutamate receptors (mGlu983089 and mGlu983093)rdquo in Te GlutamateReceptors Te Receptors pp 983091983096983095ndash983092983094983091 Humana Press 983090983088983088983096

[983092983094] N Flynn C J Meininger E Haynes and G Wu ldquoTemetabolic basis o arginine nutrition and pharmacotherapyrdquoBiomedicine and Pharmacotherapy vol 983093983094 no 983097 pp 983092983090983095ndash983092983091983096983090983088983088983090

[983092983095] N N Abumrad and A Barbul ldquoTe use o arginine in clinicalpracticerdquo in Metabolic and Terapeutic Aspects of Amino Acidsin Clinical Nutrition L A Cynober Ed pp 983093983097983093ndash983094983089983089 CRCPressBoca Raton Fla USA 983090983088983088983092

[983092983096] S M Bode-Boger R H Boger H Ale et al ldquoL-arginineinduces nitric oxidemdashdependent vasodilation in patients withcritical limb ischemia a randomized controlled studyrdquo Circu-lation vol 983097983091 no 983089 pp 983096983093ndash983097983088 983089983097983097983094

[983092983097] S Alvares C A Conte-Junior J Silva and V MF Paschoalin ldquoAcute L-arginine supplementation does notincrease nitric oxide production in healthy subjectsrdquo Nutritionamp Metabolism vol 983097 article 983093983092 983090983088983089983090

[983093983088] I Nissim O Horyn Y Daikhin et al ldquoTe molecular andmetabolic in1047298uence o long term agmatine consumptionrdquo Te Journal of Biological Chemistry vol 983090983096983097 no 983089983092 pp 983097983095983089983088ndash983097983095983090983097983090983088983089983092

[983093983089] A Halaris and J Plietz ldquoAgmatine metabolic pathway andspectrum o activity in brainrdquo CNS Drugs vol 983090983089 no 983089983089 pp983096983096983093ndash983097983088983088 983090983088983088983095

[983093983090] M Moretti F C Matheus P A de Oliveira et al ldquoRole o agmatine in neurodegenerative diseases and epilepsyrdquo Frontiersin BiosciencemdashElite vol 983094 no 983090 pp 983091983092983089ndash983091983093983097 983090983088983089983092

[983093983091] Y-F Chang and N R Myslinski ldquoEffects o l-lysine andits metabolites on pentylenetetrazol-induced seizuresrdquo Neuro-science Letters vol 983093983097 no 983089 pp 983095983097ndash983096983092 983089983097983096983093

[983093983092] Y E Chang V Hargest and J S Chen ldquoModulation o ben-zodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizuresrdquo Life Sciences vol 983092983091 no 983089983093 pp 983089983089983095983095ndash983089983089983096983096

983089983097983096983096

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 66

Submit your manuscripts at

httpwwwhindawicom

7172019 Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures

httpslidepdfcomreaderfullevaluation-of-the-effects-of-charged-amino-acids-on-uncontrolled-seizures 66

Submit your manuscripts at

httpwwwhindawicom