Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with...

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Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures G. Goiz-Marquez a , S. Caballero a , H. Solis b , C. Rodriguez a , H. Sumano a, * a Departamento de Fisiologı ´a y Farmacologı ´a, Facultada de Medicina Veterinaria y Zootecnial, Universidad Nacional Auto ´noma de Me ´xico, Avenida Universidad No. 3000, Delegacio ´ n Coyoacan, Ciudad de Me ´xico, C.P. 04510, Mexico b Departamento de Neurofisiologı ´a – Anatomı ´a, Facultad de Medicina, Universidad Nacional Auto ´noma de Me ´xico, Avenida Universidad No. 3000, Delegacio ´ n Coyoacan, Ciudad de Me ´xico, C.P. 04510, Mexico Accepted 26 May 2008 Abstract The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wire implants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled in the study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1 mg/kg) and propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence available through EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test. There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in the EEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established as follow-up of this treatment. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Epilepsy; Dogs; EEG; Acupuncture 1. Introduction Canine epilepsy is the most common neurologic disorder of dogs, representing 14% of neurological cases. Eighty percent of these cases are diagnosed as idiopathic epilepsy (IE) (Heynold et al., 1997). It has been calculated that IE is diagnosed in 0.5–5.7% of consultations for small animal clinicians; yet, it is incompletely understood, and most of the knowledge gathered has been extrapolated from human studies. Treatment of IE requires, in most cases, long-term or life-long treatment and close follow-up. Specific diag- nostic tests for epilepsy are lacking; therefore diagnosis lar- gely relies on exclusion of other potential causes of seizures (Knowles, 1998; Thomas, 2000; Chang et al., 2006). Idiopathic epilepsy (IE) can be defined as a disorder characterized by periodic and unpredictable seizures medi- ated by the rhythmic firing of large groups of neurons (Pur- ves et al., 2004). In general the neuronal activity is excessive and synchronic, and produces characteristic paroxistic dis- charges in electroencephalographic recordings during sei- zure activity (March, 1998). Electroencephalography (EEG) has been recognized as an essential part of the evaluation of seizures and epilepsy (Novotny, 1998). The electroencephalographic abnormali- ties on the interictal EEG recording are referred to as inter- ictal paroxysmal discharges (Holliday and Williams, 1998) and are the spike, the sharp wave and the spike and slow- wave complex (Novotny, 1998; Holliday and Williams, 0034-5288/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.rvsc.2008.05.019 * Corresponding author. Tel.: +52 55 56 22 59 80; fax: +52 55 56 22 59 80. E-mail address: [email protected] (H. Sumano). www.elsevier.com/locate/rvsc Available online at www.sciencedirect.com Research in Veterinary Science 86 (2009) 152–161

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Research in Veterinary Science 86 (2009) 152–161

Electroencephalographic evaluation of gold wire implants insertedin acupuncture points in dogs with epileptic seizures

G. Goiz-Marquez a, S. Caballero a, H. Solis b, C. Rodriguez a, H. Sumano a,*

a Departamento de Fisiologıa y Farmacologıa, Facultada de Medicina Veterinaria y Zootecnial, Universidad Nacional Autonoma de Mexico,

Avenida Universidad No. 3000, Delegacion Coyoacan, Ciudad de Mexico, C.P. 04510, Mexicob Departamento de Neurofisiologıa – Anatomıa, Facultad de Medicina, Universidad Nacional Autonoma de Mexico,

Avenida Universidad No. 3000, Delegacion Coyoacan, Ciudad de Mexico, C.P. 04510, Mexico

Accepted 26 May 2008

Abstract

The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wireimplants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled inthe study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1 mg/kg) and propofol (6 mg/kg) before thetreatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence availablethrough EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test.There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in theEEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatmentperiods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established asfollow-up of this treatment.� 2008 Elsevier Ltd. All rights reserved.

Keywords: Epilepsy; Dogs; EEG; Acupuncture

1. Introduction

Canine epilepsy is the most common neurologic disorderof dogs, representing 14% of neurological cases. Eightypercent of these cases are diagnosed as idiopathic epilepsy(IE) (Heynold et al., 1997). It has been calculated that IE isdiagnosed in 0.5–5.7% of consultations for small animalclinicians; yet, it is incompletely understood, and most ofthe knowledge gathered has been extrapolated from humanstudies. Treatment of IE requires, in most cases, long-termor life-long treatment and close follow-up. Specific diag-nostic tests for epilepsy are lacking; therefore diagnosis lar-

0034-5288/$ - see front matter � 2008 Elsevier Ltd. All rights reserved.

doi:10.1016/j.rvsc.2008.05.019

* Corresponding author. Tel.: +52 55 56 22 59 80; fax: +52 55 56 22 5980.

E-mail address: [email protected] (H. Sumano).

gely relies on exclusion of other potential causes of seizures(Knowles, 1998; Thomas, 2000; Chang et al., 2006).

Idiopathic epilepsy (IE) can be defined as a disordercharacterized by periodic and unpredictable seizures medi-ated by the rhythmic firing of large groups of neurons (Pur-ves et al., 2004). In general the neuronal activity is excessiveand synchronic, and produces characteristic paroxistic dis-charges in electroencephalographic recordings during sei-zure activity (March, 1998).

Electroencephalography (EEG) has been recognized asan essential part of the evaluation of seizures and epilepsy(Novotny, 1998). The electroencephalographic abnormali-ties on the interictal EEG recording are referred to as inter-ictal paroxysmal discharges (Holliday and Williams, 1998)and are the spike, the sharp wave and the spike and slow-wave complex (Novotny, 1998; Holliday and Williams,

G. Goiz-Marquez et al. / Research in Veterinary Science 86 (2009) 152–161 153

1998). The spike is defined as a transient discharge having asharp morphology with duration of 70 ms or less. Thesharp wave discharge is transient (70–200 ms) and typicallystands out from the background (Novotny, 1998).

To date, there is no cure, means of prevention or idealtreatment for epilepsy; yet, it is of paramount importanceto control seizures to prevent permanent plastic changesin the central nervous system (Purves et al., 2004). Whileantiseizure drugs are the conventional treatment for sei-zures, they reduce the clinical signs but do not treat thecause (Bollinger-Schmitz and Kline, 2000), and not alltreatments provide absolute control of seizures (Janssens,1993). In approximately 50% of cases, seizures control isdefective at best (Podell and Fenner, 1993; Podell, 1998;Trepanier et al., 1998; Bollinger-Schmitz and Kline, 2000;Pellegrino, 2003). Dogs die eventually because of complica-tions caused by recurrent seizures (Shell, 1993). Approxi-mately 20–40% of epileptic dogs have seizures which arerefractory to phenobarbital and close to 40% are also resis-tant to potassium bromide which are the most commonlyanticonvulsants (O’Brien et al., 1997).

Pharmacologic therapy is not the only treatment so farimplemented. Thomas (2000) suggests the use of non-con-ventional therapies in refractory epilepsy and there arereports that claim that acupuncture can be used as a treat-ment to control seizures in dogs (Sumano et al., 1987; VanNiiekerk, 1988; Durkes, 1992; Janssens, 1993). Differentmodalities of acupuncture have been used to stimulate acu-puncture points to treat epilepsy, including needle insertion(Janssens, 1993) electrostimulation (Huang, 1999; Yang,2000), injection of substances (Sumano et al., 1987) andgold bead/wire implants on acupuncture points (Durkes,1992). Nevertheless, there are no studies that evaluate theeffect of acupuncture on EEG recordings in dogs affectedwith IE. Hence, the purpose of this study was to evaluatethe effect of acupuncture by means of gold bead implantson EEG recordings of dogs with epileptic seizures and todetermine whether or not this is an effective treatment tocontrol seizures in dogs.

Table 1Patient information

Patient Breed Age (years) Sex Medicati

1 Labrador retriever 4 M Phenoba2 Dachshund 4 F None3 Chihuahua 6 M None4 Labrador retriever 6 M None5 Cocker spaniel 6 M None6 Miniature dachshund 5.5 NM None7 Cocker spaniel 6 F None8 Poodle 7 M None9 Poodle 3 M Phenoba10 Cocker spaniel 2 M Phenytoi11 Cocker spaniel 6 F Phenoba12 Cocker spaniel 4 M Phenoba13 Cocker spaniel 5 NM Oxicarba14 Poodle 10 M None15 Dachshund 4 F Phenoba

F, female; M, male; NM, neutered male; bid, twice a day.

2. Materials and methods

The study design was approved by the Ethics Committeeof the Postgraduate Studies Division at the Facultad deMedicina Veterinaria of the Universidad Nacional Autono-ma de Mexico. The clinical trial was carried out in a 22month period and 15 dogs were included in the study. Allpatients were referrals from animal hospitals in Mexico Cityand all had reasonably well documented clinical files. Thegeneral description of the patients is presented in Table 1.

Selection criteria of patients were based on a thoroughphysical and neurologic examination. Diagnosis of IEwas made based upon age of onset of seizures (between 1and 5 years), frequency, type and duration of seizure, fam-ily history, absence of interictal neurological abnormalities,absence of abnormalities in biochemical and hematologicprofiles and exclusion of other causes (Thomas, 2000).Electrocardiograms and chest survey radiographs were alsoperformed in all patients. The animals were evaluated for15 weeks by the owners as the control for the study, beforethey received the treatment.

An electroencephalographic recording (EEG) was obtai-ned from all patients under anaesthesia with xylazine(Procin�; Pisa Agropecuaria; 1 mg/kg) and propofol(Recofol�; Pisa Agropecuaria; 6 mg/kg) similar to the anes-thetic protocol proposed by Jaggy and Bernardini (1998). Areferential montage with 12 needle electrodes (DisposableLow Profile Needle Electrodes 12 mm � 28 ga, ChalgrenEnterprises Inc.) using the nose as reference was carriedout as proposed by Pellegrino (2003). This setting allows acomplete coverage of electric activity in cerebral hemi-spheres, even in animals with atypical types of skull. Toobtain the EEG recordings computerized EEG softwarewas used (Akonic EEG, Bio-PC) with a simultaneous 12channel recording (see Table 2), using 60 Hz filter a high fre-quency filter of 50 Hz and a low frequency filter of 0.5 Hzand an impedance <10 KX. In addition, photic stimulationwas used as an activation method. Each recording wascomposed of three different stages: pre-stimulation, photic

on Type of seizure

rbital 100 mg bid Partial with secondary tonic-clonic generalizationGeneralized tonicGeneralizad tonicGeneralized tonicGeneralized tonic-clonic with automatismsMyoclonic and generalized tonic-clonicGeneralizad tonicGeneralizad tonic-clonic

rbital 50 mg bid Partial with secondary tonic generalizationn 30 mg/week Generalizad tonicrbital 25 mg sid Generalizad tonicrbital 75 mg bid Generalizad tonicmezepine Generalizad tonic

Generalizad tonic-clonicrbital 12.5 mg bid Generalizad tonic

Table 2Electrode placement according to Pellegrino (2003)

Fp1 and Fp2 (left and rightfrontoparietal)

� Transverse plane: lateral canthus of the eye� Sagittal plane: in line with the frontal electrodes

F3 and F4 (left and right frontal) � Transverse plane: cranial to the union of the temporal lines, forming the base of a scalenous triangle (where thetemporal lines loose their curvature)� Sagittal plane: 25% of the distance between the midline and the zygomatic

P3 y P4 (left and right parietal) � Transverse plane: half the distance between the frontal and occipital electrodes� Sagittal plane: in line with the frontal electrodes

O1 y O2 (left and right occipital) � Transverse plane: at the level of the mastoid process, at the base of the auricular portion of the temporal bone� Sagittal plane: in line with the frontal and parietal electrodes

T3 y T4 (left and right temporal) At the dorsal border of the caudal portion of the zygomatic arch, cranial to the beginning of the temporal crest. Theneedle is introduced obliquely towards the orbital cavity of the opposite side until it reaches the ventral portion of thetemporal fossa

Cz (central) At the dorsal midline, level with the occipital electrodesOz (occipital medio) At the dorsal midline, level with the parietal electrodesReference Nose

154 G. Goiz-Marquez et al. / Research in Veterinary Science 86 (2009) 152–161

stimulation and post-stimulation; lasting 7–10 min, 30 s and7–10 min, respectively.

After the EEG, the acupuncture treatment protocol wascarried out by implanting 2–3 mm gold wire pieces into thefollowing acupuncture points: GB-20, GV-23, GV-21, GV-20, GV-14, GV-16, auricular Shen men, Yin Tang, LI-4,LIV-3, ST-40 as reported by Sumano et al. (1987), Klide(1987), Van Niiekerk (1988), Durkes (1992), Janssens(1993), Xinnong (1999), Xie (2003). Implants were placedsubcutaneously or intramuscularly (depending on thepoint) using a 20 gauge needle and a plunger.

All patients received the same treatment. There was nountreated control group because of ethical considerations.Antiseizure medication remained unchanged in patientsalready receiving it. Treatment and pre-treatment assess-ment of seizures lasted 15 weeks each. Then, a secondEEG was performed following the same protocol. Individ-ual seizures were counted separately in dogs that had clus-ter seizures. If the number of seizures per cluster was notclear each cluster was counted as a single seizure episode.

The number of seizures before and after treatment wascompared as well as seizure severity on a 0–20 scale. Own-ers participating in this trial were trained to grade severityas outlined in Table 3.

Relative frequency power and intrahemispheric coher-ence available through the EEG software were comparedin both control and post-treatment EEG’s. EEG abnormal-ities were also recorded.

Results were analyzed using SPSS (Statistical Productand Service Solutions 10.0 for Windows SPSS Inc., Chi-cago, USA, 2000) statistical software by use of a Wilcoxonsigned-rank test. The response variables were the reductionin seizure frequency, reduction in seizure severity and dif-

Table 3Grades of seizure severity

0 1–5 6–10 11–

Absence ofseizures

Single seizurelasting <30 s

Single seizure lasting between30 s and 1 min

Sin1 a

ferences in relative power and intrahemispheric coherencebefore and after seizures.

3. Results

No side effects attributable to the acupuncture proce-dure were noted in any of the dogs. The second record-ing was not performed in patients #1 and #5. Theformer was euthanized following uncontrolled status epi-lepticus 5 days before the second recording. Patient #5was presented with a 5/6 heart murmur on the date ofthe second EEG recording and the owner refused theprocedure.

Table 4 shows the number of seizures and the grade ofseizure severity before and after the treatment. Twelve dogshad reduction of seizure frequency during the treatmentperiod relative to the control period, 2 dogs had no changein seizure number and 1 dog had an increase in seizure num-ber with two additional seizures. Of the 15 dogs, ten had areduction in seizure severity, four dogs had no change inseizure severity and one dog had an increase in seizureseverity. The decrease in mean seizure frequency was38.7% and seizure severity was reduced 33.4%. Figs. 1and 2 show the percentage reduction in seizure frequencyand seizure severity for each patient (Figs. 3–9).

Concerning the EEG, a Wilcoxon signed-rank testcomparing the 15 patients showed no significant statisti-cal differences before and after treatment in any of thefrequency ranges for the intrahemispheric coherence andthe relative power among channels before and after treat-ment (Table 5 shows P values for intrahemispheric coher-ence and relative power for each frequency). In additionthere were spike waves detected on the recordings of

15 16–20

gle seizure lasting betweennd 3 min

Generalized tonic-clonic seizure lasting>3 min or cluster seizures

Table 4Seizure frequency and seizure severity before and after treatment

Patient Seizure frequency Seizure severity

Beforetreatment

Aftertreatment

Beforetreatment

Aftertreatment

1 32 4 10 72 2 0 5 03 6 3 10 104 5 2 10 155 4 2 12 56 7 3 20 137 3 3 15 108 3 2 20 129 15 8 17 1210 5 0 7 011 1 4 7 712 11 6 20 1513 3 0 5 014 20 10 20 2015 7 7 15 15X ± SD 8.27 8.35 3.53 2.99

P 0.003 0.015

Change in seizure severity

-60

-40

-200

20

40

6080

100

120

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Patients

Per

cen

tag

e ch

ang

e

Fig. 1. Change in seizure frequency after treatment.

Change in seizure frequency

-150-100-50

050

100150200250

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Patients

Per

cent

age

chan

ge

50% reduction in seizure frequency

Fig. 2. Reduction in seizure severity after treatment.

Fig. 3. Spike waves detected in the EEG o

G. Goiz-Marquez et al. / Research in Veterinary Science 86 (2009) 152–161 155

some patients. Number, presence and location of spikewaves before and after treatment are presented on Table6. In contrast, a significant mean difference in seizure fre-quency (P = 0.003) and a significant mean difference inseizure severity (P = 0.015) were observed between con-trol and treatment periods. Table 7 shows the statisticalmeasures for seizure frequency and severity before andafter treatment.

4. Discussion

Even though it is not a generalized diagnostic tool, theelectroencephalogram (EEG) is a confirmatory test of epi-lepsy. It provides evidence about the partial or generalizednature of seizures (Knowles, 1998). In humans, interictalEEG obtained using activation procedures such as photicstimulation, hyperventilation, sleep, and sleep deprivationincreases the diagnostic yield of the procedure (Novotny,1998). Unfortunately, lack of cooperation, pain, anxietyor even aggressive behaviour often prevents EEG examina-tion in animals and chemical restraint or anaesthesia is nec-essary (Bergamasco et al., 2003). For this purpose,

f patient #4–15 weeks after treatment.

Fig. 4. Generalized spike waves detected in the EEG of patient #6, recorded before treatment.

Fig. 5. Generalized spike waves detected in the EEG of patient #6–15 weeks after treatment.

156 G. Goiz-Marquez et al. / Research in Veterinary Science 86 (2009) 152–161

pentobarbitone anaesthesia (Klemm and Mallo, 1966;Klemm, 1968) was first used, but lately propofol was cho-sen as an alternative (Short and Bufalari, 1999). There areconflicting reports that indicate that anesthetic agents masksome features of the EEG due to their antiepileptic proper-ties (Lowson et al., 1990), nevertheless, some authors con-sider propofol as an epileptic inducer (Short and Bufalari,1999). In this trial, propofol was chosen as the anestheticagent because unlike barbiturates, it does not increase theseizure threshold (Short and Bufalari, 1999) and avoidsmarked decreased registration of brain activity and hasnot been linked to artifactual paroxysmal activity (Jaggyand Bernardini, 1998). It has been used previously for

EEG recordings in neurological patients without suppress-ing spontaneous epileptic activity or inducing paroxysmaldischarges (Srenk and Jaggy, 1996; Jaggy and Bernardini,1998). Hence, it was somehow predictable that EEG activ-ity found in patients was similar to that found in previousreports, with delta and theta rhythms having the highestprevalence (Bergamasco et al., 2003). Xylazine was usedbased on suggestions that this drug did not alter EEGrecordings (Jaggy and Bernardini, 1998; Pellegrino, 2003).

Although long electroencephalographic tracings mayincrease the possibility of finding abnormalities (Novotny,1998; Pellegrino, 2003), there are reports that indicate thatEEG recordings lasting 15–30 min suffice to detect interic-

Fig. 6. Localized spike waves detected in the EEG of patient #11, recorded before treatment.

Fig. 7. Localized spike waves detected in the EEG of patient #11–15 weeks after treatment.

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tal paroxysmal discharges in epileptic dogs (Holliday andWilliams, 1998). There are no previous reports that haveused photic stimulation as an activation method in dogswith IE. The aim of using it in this trial was to try toimprove the diagnostic yield of the EEG and additionallythis later criterion was consider safer as it involves less timeunder anaesthesia (15–20 min).

Although the sample size was small (n = 15), all patientssuffered uncontrolled IE and could have revealed a directeffect of gold wire implants on the EEG tracing. Yet, therewere no statistically significant effects of the procedure inthe EEG recordings either in relative power or in intra-hemispheric coherence among frequencies. Further trialscarried out with continuous monitoring may reveal other-

wise and perhaps they could better explain the correlationsbetween EEG and acupuncture.

Interictal paroxysmal discharges in the form of spikewaves were found in six out of 15 patients (40% of the studysample), so they were regarded as confirmation of epilepsy.Of those six, only four of them had a clear reduction in thenumber of spike waves found in the second EEG recording.These six patients showed 18.2% reduction in the number ofseizure and a 23.2% reduction in seizure severity. These val-ues are not outstanding because one patient had anincreased number of seizures, and evaluation of severity inanother patient was regarded as augmented.

In patients #1 and #12 two doses of phenobarbital werenot administered by the owner during the trial. In patient

Fig. 8. Localized spike waves detected in the EEG of patient #12, recorded before treatment.

Fig. 9. Localized spike wave detected in the EEG of patient #12–15 weeks after treatment.

Table 5P values for intrahemispheric coherence and relative power for eachfrequency and in each of the different EEG stages, comparing meansbefore and 15 weeks after implanting gold wires in acupuncture points

Delta Theta Alpha Beta1 Beta2

Intrahemispheric coherence

Before photic stimulation 0.314 0.441 0.374 0.889 0.441During photic stimulation 0.953 0.374 0.441 0.401 0.086After photic stimulation 0.314 0.066 0.314 0.374 0.260

Relative power

Before photic stimulation 0.515 0.859 0.139 0.374 0.260During photic stimulation 0.953 0.314 0.260 0.314 0.441After photic stimulation 0.066 0.086 0.066 0.066 0.314

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#1 this event precipitated refractory status epilepticus inspite of pentobarbital administration and euthanasia wasperformed. Patient #12 had 3 seizures the following day.Nevertheless, patient #1 had shown a 87.5% reduction inseizures number after the gold wire implants and patient#12 had an overall 45.5% reduction of the same variable.

Six patients were on medication before the study per-iod but seizures were not controlled. Antiepileptic medi-cation was not withdrawn because it was uncertainwhether or not acupuncture could afford some efficacy.In addition, discontinuing drug therapy could inducewithdrawal seizures (Thomas, 2000), thus rendering thisprocedure as unethical. It could be argued that antisei-

Table 6Number and location of spike waves detected before and after treatment

Patient No. ofspikes

Location Amplitude(lV)

Propagation

4 After tx: 2 Right and leftoccipital

81–89 Central occipital

6 Before tx: 30 Right and leftoccipital

162–389 Central occipitalAfter tx: 34 112–467

9 Before tx: 1 Centraloccipital

94 Left parietal

10 Before tx: 18 Leftfrontoparietal

31–50 Left frontal

11 Before tx: 20 Right and leftoccipital

58–135 Central occipitaland right and leftparietal

After tx: 1 Rightfrontoparietal

51 Right frontal

12 Before tx: 19 Right and leftoccipital

74–94 Central occipital

After tx: 1 Righttemporal

62 Central

Table 7Statistical measures for seizure frequency

Paired sample statistics

Mean N Std. deviation Std. error mean

Seizure frequency

PRETx 8.26667 15 8.35350 2.15686POSTTx 3.53333 15 2.99682 0.77378Wilcoxon test for seizure frequency P = 0.003

Seizure severity

PRETx 12.86667 15 5.65517 1.46016POSTTx 9.40000 15 6.15049 1.58805Wilcoxon test for seizure frequency P = 0.015

PRETx, pre-treatment.POSTTx, post-treatment.

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zure medication could alter the EEG recordings, butaccording to Pellegrino (2003) there is no antiseizuremedication capable of suppressing interictal spikes, akey feature to diagnose IE. Most antiepileptic drugs actby avoiding or attenuating the synchronization mecha-nisms of neuronal pools (Pellegrino, 2003), so even ifpatients were receiving antiseizure medication, findinginterictal spikes remained a strong possibility. In fact,of the six patients in which interictal spikes weredetected, four were receiving antiseizure medication.

Studies have shown with functional magnetic resonanceimaging (fMRI) that certain acupuncture points activateareas in the cerebral cortex (Cho et al., 1998). It has alsobeen postulated that electracupuncture stimulation can berelated to the extracellular increase of inhibitory aminoac-ids such as taurine, glycine and GABA in the hippocampus(Liu, 1995; Shu, 2004) and that it acts synergically withantagonist of non-NMDA receptors (Liu, 1997) such as

kainate receptors which in turn participate in glutaminergictransmission in granule cells of the hippocampus in animalswith chronic epilepsy and are in charge of nearly half of theexcitation not mediated by NMDA receptors in these cells(Epsztein et al., 2005). This can have relevance since non-NMDA receptors have been implicated in the physiopa-thology of epilepsy as non-NMDA glutaminergic antago-nists potentiate the antiseizure activity of conventionalantiseizure drugs (Czuczwar, 2000). It has also been pro-posed that electroacupuncture might inhibit seizures bydecreasing the transcription of nitric oxide neuronal syn-thase (Huang, 1999; Yang, 2000), which has been foundto increase in rats with experimentally induced epilepsy(Yang, 2000) and which has been suggested to mediateinteractions between GABA and glutamate (Rajasekaranet al., 2003). Another anticonvulsive effect of acupunctureappears to be due to somatovisceral neuronal communica-tions (Shu, 2004). He demonstrated that stimulation ofauricular acupuncture points decreased experimentallyinduced seizure activity in rats, and that this effect disap-peared if the great auricular nerve was severed beforestimulation.

The procedure used here is based on permanent stimula-tion of acupuncture points by gold wire. Gold containingdrugs have also been used as a medical therapy in condi-tions such as rheumatoid arthritis (Chicorian and Barrios,2004) and Jessner’s lymphocytic infiltrate (Hafejee et al.,2004). These gold-containing drugs have a clear effect onantigen processing by T cells, reduce cytokine expressionfrom macrophages (Hayman and Cox, 2004), induce mito-chondrial parameters inducing permeability changes anddecrease cell membrane potential (Bragadin et al., 2004)even in at submicromolar concentrations (Rigobello etal., 2002). It is feasible to speculate that some or all of thesemechanisms are implicated in the effect of gold wireimplants in acupuncture points for seizure control.

Ideally, the purpose of a treatment for IE is to reinstatea normal life for the patient and its family with minimaladverse effects (Knowles, 1998; Thomas, 2000). It is recog-nized for IE that it might not be possible to completelyeliminate seizures with drugs (Podell, 1996; Bollinger-Sch-mitz and Kline, 2000; Thomas, 2000) but some degree ofsuccess is accepted in dogs if seizure frequency, severityand duration are reduced to a point where they are accept-able to the owner (Bollinger-Schmitz and Kline, 2000; Tho-mas, 2000). Yet, in spite of adequate drug treatment, it hasbeen estimated that approximately 30% of dogs with IEeventually die, either by recurrent seizures or by euthanasia(Bollinger-Schmitz and Kline, 2000). It is in this contextthat these results can be of value and reinforce Thomas(2000) remark: ‘‘the role of alternative therapies shouldnot be overlooked”.

According to Platt et al. (2006), in new drug evaluationsin human epilepsy, so few subjects become seizure-free inadd-on trials that complete control is rarely a usefulparameter to monitor. Traditional measurements of effi-cacy of antiepileptic drugs include the percentage reduction

160 G. Goiz-Marquez et al. / Research in Veterinary Science 86 (2009) 152–161

in seizures from baseline period, the percentage of patientsrendered seizure-free and the proportion of subjects whoexperience a defined reduction in the frequency of seizures(Platt et al., 2006). Most authors considered that a singleseizure every 6 to 8 weeks is an acceptable positiveresponse. For example: Knowles, (1998) and Platt et al.(2006) consider that control of seizures means a 100%increase in duration of interictal period and a 50% reduc-tion in seizure frequency without drug adverse effects. Inthis trial, a beneficial effect was observed in nine of the15 dogs (60%) which had at least a 50% reduction in sei-zures frequency during the 15 weeks following treatment.

Summarizing, apparently acupuncture, by means ofgold wire implants, does not modify the basic variablesof the canine EEG; yet this procedure affords sufficientbenefits, and no side effects making it feasible to proposeincorporation into the treatment or control of IE in dogs.

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