A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs.

The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy-kainic acid and pentylenetetrazole-induced model of seizures-and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood-brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.

Topiramate treatment in Wistar rats during childhood induces sex-specific vascular dysfunction in adulthood.

The present study determined whether treatment during childhood with topiramate (TPM), a new generation antiepileptic drug, results in altered aortic reactivity in adult male and female rats. We also sought to understand the role of endothelium-derived contractile factors in TPM-induced vascular dysfunction. Male and female Wistar rats were treated with TPM (41 mg/kg/day) or water (TPM vehicle) by gavage during childhood (postnatal day, 16-28). In adulthood, thoracic aorta reactivity to phenylephrine (phenyl), as well as aortic thickness and expression of cyclooxygenases (COX-1 and COX-2), NOX2, and p47phox were evaluated. The aortic response to phenyl was increased in male and female rats from the TPM group when compared with the control group. In TPM male rats, the hyperreactivity to phenyl was abrogated by the inhibition of NADPH oxidase and COX-2, while in female rats, responses were restored only by inhibition of COX-2. In addition, TPM male rats presented aortic hypertrophy and increased expression of NOX-2 and p47phox, while TPM female rats showed increased COX-2 aortic expression. Taken together, for the first-time, the present study provides evidence that treatment with TPM during childhood causes vascular dysfunction in adulthood, and that the mechanism underlying the vascular effects of TPM is sex-specific.

The Impact of Oral-Gut Inflammation in Cerebral Palsy.

Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL). We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy. Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis. Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1ß levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292). Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.

Single antiepileptic drug levels do not predict adherence and nonadherence.

OBJECTIVES: To investigate the significance of "subtherapeutic" vs "therapeutic" antiepileptic drug (AED) plasma levels with respect to treatment adherence. MATERIAL AND METHODS: One hundred and seventy patients with refractory temporal lobe epilepsy who underwent video-EEG monitoring in view of a surgical indication had their AEDs (carbamazepine, phenobarbital, phenytoin, and valproate) rapidly withdrawn following a standardized schedule. Plasma levels were measured at admission, and during the 2 days of drug withdrawal. Adherence and nonadherence were identified by the development of plasma levels from day 1 through day 3. Frequencies of an initial level below the reference range in both groups were compared. RESULTS: Adherence was found in 73.2% of cases, and nonadherence in 26.8%. Low levels were seen equally often (about 1/4 of cases) in adherent and nonadherent cases. The vast majority (73.7%) of low levels had another explanation than nonadherence (eg low-dose treatment or enzyme induction). Of 42 nonadherent cases, the vast majority of 76.2% had unsuspicious plasma levels at admission. CONCLUSIONS: "Subtherapeutic" AED plasma levels only rarely are caused by nonadherence whereas levels in the "therapeutic range" by no means prove that the patient is adherent to treatment. For meaningful interpretation, any level needs to be compared with other levels of the same patient. Our findings strongly emphasize the principle of individualized therapeutic AED monitoring as promoted by the Therapeutic Strategies Commission of the ILAE.

Who are the individuals diagnosed with epilepsy using the Public Health System in the city of Pelotas, southern Brazil?

The aim of this study was to describe sociodemographic, clinical, behavioral, nutritional, and health-related variables from people with epilepsy. A descriptive observational study was carried out in the city of Pelotas, southern Brazil. Sociodemographic, clinical, behavioral, nutritional, and health-related variables were collected. A univariate analysis was performed, calculating the measures of central tendency for continuous variables and proportions for categorical ones. The sample consisted of 101 people, age ranging from 12 to 75years, mostly male (50.5%) and white (59.4%). Only 37.2% from the sample was employed, and the average income was R$ 788.00 Brazilian Reais (US$ 245.90 at the moment of the interview). From all the subjects, 65.6% was in treatment with monotherapy, 62.9% presented more than 15 seizures during the life, 67.3% showed active epilepsy, 64.6% were physically inactive, 52.5% presented normal body mass index, and 50% showed generalized seizures. The most used antiepileptic drug was the carbamazepine. The average score of depression was 12.6±4.1 points and 34.6% showed severe depressive symptoms (equal or higher than 15 points). The mean score of trait and state anxiety was 12.2±3.6 and 15.1±3.4 points, respectively (ranging from 6 to 24 points). The mean score of quality of life and stress was 63.2±18.2 (ranging from 0 to 100 points) and 21.2±7.1 points (ranging from 0 to 40 points), respectively. Considering the medication side effects, the mean score was 42.4±8.9 points, 38.5% showing high rates (higher than 45 points), and only 16% showing good sleep quality. In conclusion, these results are important to improve understanding of these individuals' disease and to subsidize the specific public policies in countries of low and middle income.

The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum.

Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic levels under pathological conditions. Since increased neuronal excitability induced by QUIN recruits degenerative events in the brain, and novel AED is also expected to exert neuroprotective effects in their pharmacological profiles, in this work the effect of LVT (54 mg/kg, i.p., administered for seven consecutive days) was tested as a pretreatment against the toxicity evoked by the bilateral intrastriatal injection of QUIN (60 nmol/µl) to adult rats. QUIN increased the striatal levels of peroxidized lipids and carbonylated proteins as indexes of oxidative damage 24 h after its infusion. In addition, in synaptosomal fractions isolated from QUIN-lesioned rats 24 h after the toxin infusion, γ-aminobutyric acid (GABA) release was decreased, whereas glutamate (Glu) release was increased. QUIN also decreased motor activity and augmented the rate of cell damage at 7 days post-lesion. All these alterations were significantly prevented by pretreatment of rats with LVT. The results of this study show a neuroprotective role and antioxidant action of LVT against the brain damage induced by excitotoxic events.

Lamotriginium crotonate and lamotriginium salicylate ethanol monosolvate: the role of solvent molecules in the packing organization.

Two lamotriginium salts, namely lamotriginium crotonate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium but-2-enoate, C9H8Cl2N5+·C4H5O2-, (III)] and lamotriginium salicylate [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium 2-hydroxybenzoate ethanol monosolvate, C9H8Cl2N5+·C7H5O3-·C2H5OH, (IV)] present extremely similar centrosymmetric hydrogen-bonded A...L...L...A packing building blocks (L is lamotriginium and A is the anion). The fact that salicylate salt (IV) is (ethanol) solvated, while crotonate salt (III) is not, has a profound effect on the way these elemental units aggregate to generate the final crystal structure. Possible reasons for this behaviour are analyzed and the hypothesis raised checked against similar structures in the literature.

Neurobehavioral effects of vigabatrin and its ability to induce DNA damage in brain cells after acute treatment in rats.

RATIONALE: Vigabatrin (VGB) is a drug indicated mostly for the treatment of spasms in childhood and West's syndrome patients. This drug inhibits irreversibly the enzyme GABA-transaminase (GABA-T), increasing GABA concentrations and enhancing GABAergic neurotransmission in the brain, which is known to induce behavioral changes. OBJECTIVES: The aims of this study were to evaluate the effects of VGB in the short-term memory (STM), long-term memory (LTM), motivation, locomotion, and exploratory behavior tests and to detect deleterious or protective effects on DNA in target tissues of the drug. METHODS: Male Wistar rats were treated with a single dose of VGB (100, 250, or 500 mg/kg) or saline solution before the inhibitory avoidance and open-field tasks. DNA damage was evaluated using the alkaline comet assay in peripheral blood, cerebral cortex, and hippocampus after behavioral testing. RESULTS: There was no significant difference in the inhibitory avoidance task between the treated groups and the saline group. In all tested doses, VGB reduced the number of rearings in the open-field task. Besides, VGB 500 mg/kg affected locomotion, though it was not able to induce any DNA damage. CONCLUSIONS: VGB did not affect STM and LTM, but the drug impaired the exploration and locomotion likely associated with its sedative effect. In addition, no DNA damage in cortex and hippocampus was detected after behavioral testing, when brain GABA levels are already increased.

Neurologist knowledge about interactions between antiepileptic drugs and contraceptive methods.

OBJECTIVE: To evaluate neurologists' knowledge of contraceptive counseling for women receiving antiepileptic drugs (AEDs). METHODS: An interview-based survey was conducted from February 2 to June 30, 2015, among neurologists working in Ribeirão Preto, Brazil. Direct interviews were conducted using a questionnaire that assessed knowledge of the pharmacological interactions between various contraceptive methods and six AEDs (carbamazepine, phenobarbital, topiramate, phenytoin, lamotrigine, and valproate) on the basis of WHO medical eligibility criteria for contraceptive use. RESULTS: Among 42 neurologists who participated, 32 (76%) stated that they treated women with epilepsy and provided them with counseling for family planning. Overall, 34 (81%) recommended the use of a copper intrauterine device irrespective of the AED used, and 26 (60%) stated that they co-prescribed AEDs and hormonal contraceptives. Although 39 (93%) neurologists had knowledge that AEDs might contraindicate the use of some contraceptives, their knowledge regarding the specific drug interactions was lacking. Furthermore, 34 (81%) had no knowledge of WHO medical eligibility criteria for contraceptive use. CONCLUSION: Although most neurologists interviewed had knowledge of interactions between AEDs and hormonal contraceptives, they did not know which specific AEDs interacted with these agents.

Antiepileptic drug therapy and recommendations for withdrawal in patients with seizures and epilepsy due to neurocysticercosis.

INTRODUCTION: Neurocysticercosis (NCC) is a leading causes of secondary epilepsy worldwide. There is increasing evidence on the epileptogenic role of NCC, and the presence of edema, calcified scars, gliosis and hippocampal sclerosis support this phenomenon. AREAS COVERED: We summarized principles of antiepileptic drug (AED) therapy as well as risk factors associated with seizure recurrence after AED withdrawal in patients with NCC. Expert commentary: First-line AED monotherapy is effective as a standard approach to control seizures in most NCC patients. Risks and benefits of AED withdrawal have not been systematically studied, and this decision must be individualized. However, a seizure-free period of at least two years seem prudent before attempting withdrawal. Risk factors for seizure recurrence after AED withdrawal include a history of status epilepticus, poor seizure control during treatment, neuroimaging evidence of perilesional gliosis, hippocampal sclerosis and calcified lesions, as well as persistence of paroxysmal activity in the EEG.

Epilepsy care in the southern Caribbean.

Very little has been reported about the health resources available for patients with epilepsy in the five English-speaking southern Caribbean countries of Trinidad and Tobago, Barbados, Grenada, Saint Vincent and the Grenadines, and Saint Lucia. There is no comprehensive resource describing their health systems, access to specialty care, antiepileptic drug (AED) use, and availability of brain imaging and EEG. The purpose of this study was to profile epilepsy care in these countries as an initial step toward improving the standard of care and identifying gaps in care to guide future policy changes. In each southern Caribbean country, we conducted study visits and interviewed health-care providers, government health ministers, pharmacy directors, hospital medical directors, pharmacists, clinic staff, radiologists, and radiology and EEG technicians. Health-care providers completed extensive epilepsy care surveys. The five countries all have integrated government health systems with clinics and hospitals that provide free or heavily subsidized care and AEDs for patients with epilepsy. Only Trinidad and Tobago and Barbados, however, have neurology specialists. The three smaller countries lack government imaging and EEG facilities. Trinidad had up to one-year waits for public MRI/EEG. Government formularies in Grenada, Saint Vincent and the Grenadines, and Saint Lucia are limited to first-generation AEDs. One or more second-line agents are formulary in Trinidad and Barbados. Nonformulary drugs may be obtained for individual patients in Barbados. Grenada, Saint Lucia, and Saint Vincent and the Grenadines participate in an Organization of Eastern Caribbean States formulary purchasing system, which added levetiracetam following the survey. Newer generic AED formulations with the lowest risks for pregnancy malformation were not in use. In conclusion, patients with epilepsy in the southern Caribbean have excellent access to government clinics and hospitals, but AED choices are limited. Local medical providers reported that the major limitations in care were lack of specialty care, lack of imaging and EEG services, financial barriers to care, long wait times for care, and limited access to additional AEDs.

HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican Mestizo patients.

AIM: Several HLA alleles have been associated with antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) in different populations; however, this has not been investigated in Mexican Mestizos (MM). Thus, the purpose of this preliminary study was to determine the association of HLA class I alleles with AED-induced cADRs in MM patients. MATERIALS & METHODS: This case-control association study included 21 MM patients with phenytoin (PHT)-, carbamazepine (CBZ)-, or lamotrigine (LTG)-induced maculopapular exanthema (MPE) or Stevens-Johnson syndrome (SJS); 31 MM patients tolerant to the same AEDs; and 225 unrelated, healthy MM volunteers. HLA class I genotyping was performed. Differences in HLA allele frequencies between AED-induced cADR patients and AED-tolerant patients were assessed. Frequencies of alleles possibly associated with AED-induced cADRs in MM patients were compared with those in MM population. RESULTS: The frequency of HLA-C*08:01 allele in PHT-induced MPE was higher than that in the PHT-tolerant group (pc=0.0179) or in the MM population (pc<0.0001). For the first time, HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype was associated with LTG-induced MPE (pc=0.0048 for LTG-tolerant groups and pc<0.0001 for MM population). CONCLUSION: Our data suggest the HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype may be a biomarker for LTG-induced MPE and the HLA-C*08:01 allele for PHT-induced MPE. We also identified HLA-A*01:01:01 and -A*31:01:02 as candidates alleles associated with CBZ-induced MPE in MM patients. However, further investigations are necessary to confirm these findings.

Estado epiléptico convulsivo en adultos atendidos en el Instituto Nacional de Ciencias Neurológicas de Lima, Perú 2011-2013. / Convulsive status epilepticus in adults attending the Instituto Nacional de Ciencias Neurológicas in Lima, Perú 2011-2013.

Objetivos: describir las características clínicas y la evolución del estado epiléptico convulsivo (EEC) en pacientes adultos admitidos en el Servicio de Emergencia del Instituto Nacional de Ciencias Neurológicas de Lima, Perú entre los años 2011 y 2013. Métodos: Se realizó un estudio prospectivo de serie de casos. Resultados: Se incluyeron 28 pacientes mayores de 17 años, la mediana de edad fue 31 años. El 57% fueron hombres y el 89% tenían antecedentes de epilepsia. La principal causa del EEC fue el incumplimiento de la medicación antiepiléptica (54%). El diazepam seguido de la fenitoína fue el tratamiento antiepiléptico más empleado (75%) y la frecuencia de EEC refractario fue del 4%. Conclusiones: los pacientes fueron mayoritariamente varones, adultos jóvenes, con antecedentes de epilepsia que presentaron un EEC debido el incumplimiento de la medicación antiepiléptica y respondieron favorablemente al tratamiento con diazepam seguido de fenitoína.

Objectives: to describe the characteristics features and outcome of convulsive status epilepticus (CSE) in adult patients admitted to the Emergency Department at the Instituto Nacional de Ciencias Neurológicas in Lima, Peru between 2011 and 2013. Methods: a prospective study was conducted. Results: twenty-eight patients older than 17 years were included, the median age was 31 years old. 57% were male and 89% had a history of epilepsy. Main cause of CSE was antiepileptic medication noncompliance (54%). Diazepam followed by phenytoin was the most used therapeutic regimen (75%) and the frequency of refractory CSE was 4%. Conclusion: patients were mostly male, young adults with a history of epilepsy who presented a CSE caused by the antiepileptic medication noncompliance and the response to treatment based on diazepam followed by phenytoin was positive.

Injuries in adolescents with childhood-onset epilepsy compared with sibling controls.

OBJECTIVE: To compare the occurrence of injuries in adolescents with childhood-onset epilepsy and matched sibling controls. STUDY DESIGN: Retrospective case-control lifetime injury assessments were obtained from a community-based cohort of adolescents with childhood-onset epilepsy diagnosed 9 years earlier and their siblings. The children with epilepsy (n = 501; mean age, 15.3 years) included those with complicated (abnormal neurologic examination or IQ <80; n = 133) and uncomplicated (normal neurologic examination and IQ ≥80; n = 368) epilepsy. Children with uncomplicated epilepsy were matched to sibling controls (n = 210 pairs). The children reported whether or not they had ever (before and after epilepsy diagnosis) experienced injuries "serious enough to require medical attention" and if so, the type of treatment required. RESULTS: Almost one-half (49.1%) of the children with epilepsy experienced injury, of whom 8.9% required surgery/hospitalization and 17.1% had injury related to a seizure. Fewer children with uncomplicated epilepsy had seizure-related injuries versus those with complicated epilepsy (13.6% vs 27.4%; P ≤ .01). The proportion of children with epilepsy with any injury by type (not mutually exclusive) were: 25.2% with fractures (n = 126); 24.4% with head injuries (n = 122); 10.2% with other injuries (n = 51); 8.4% with dental injuries (n = 42); and 8% with burns/scalds (n = 40). A similar proportion of children with uncomplicated epilepsy experienced any injury (overall and by type) compared to matched sibling controls, with the exception that more children with uncomplicated epilepsy had head injuries (30.0% vs 19.5%; P < .02). CONCLUSION: With the exception of head injuries, we found no evidence of an increased risk of injury in a representative cohort of children with epilepsy compared with matched sibling controls. This finding may reflect the fact that the sample was not biased to more severe cases, or that safety precautions to prevent injury were widely used.

Electroclinical features and long-term outcome of cryptogenic epilepsy in children with Down syndrome.

OBJECTIVE: To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. STUDY DESIGN: Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. RESULTS: A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. CONCLUSION: Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

Atualização em epilepsia canina parte II – Terapia antiepiléptica / Canine epilepsy update part II: antiepileptic therapy

As crises epilépticas são manifestações de distúrbios neurológicos, e ocorrem com grande frequênciana clínica de pequenos animais. O sucesso na terapia antiepiléptica pode ser traduzido por redução emno mínimo 50% da frequência das crises epilépticas. Para isso é de extrema importância definir e tratara causa primária quando ela existir, já que a maioria dos fármacos não possui atividade antiepileptogênica.Novas drogas antiepilépticas, utilizadas em humanos, estão sendo estudadas para uso em cães,porém, até agora, o fenobarbital e o brometo de potássio, associados à correta monitoração do paciente,continuam sendo as melhores opções de tratamento. Quando uma crise não é bem controlada, o animalpode apresentar status epilepticus, situação que requer tratamento emergencial. Busca-se com essa revisãode literatura realizar uma abordagem aplicada e crítica sobre o tratamento de crises epilépticas em cães,sejam elas simples, recorrentes, agrupadas ou contínuas.

The epileptic seizures are manifestations of neurological disorders, and occur with great frequency insmall animals. The success in antiepileptic therapy can be translated by reduction in at least 50% of theepileptic seizure frequency. For this reason is very important to define and treat the primary cause whenit exists, since the majority of drugs has no antiepileptogenic activity. New antiepileptic drugs are beingstudied for use in dogs but up to now none of them replaces or equals the benefits that the phenobarbitaland potassium bromide brings to the patient. When seizure is not well controlled, the animal maypresent status epilepticus, which is a situation of emergency treatment. With this review we pretend togive a practical and critical approach to the treatment of single, recurrent, cluster or continuous epilepticactivity in dogs.

Atualização em epilepsia canina parte II Terapia antiepiléptica / Canine epilepsy update part II: antiepileptic therapy

As crises epilépticas são manifestações de distúrbios neurológicos, e ocorrem com grande frequênciana clínica de pequenos animais. O sucesso na terapia antiepiléptica pode ser traduzido por redução emno mínimo 50% da frequência das crises epilépticas. Para isso é de extrema importância definir e tratara causa primária quando ela existir, já que a maioria dos fármacos não possui atividade antiepileptogênica.Novas drogas antiepilépticas, utilizadas em humanos, estão sendo estudadas para uso em cães,porém, até agora, o fenobarbital e o brometo de potássio, associados à correta monitoração do paciente,continuam sendo as melhores opções de tratamento. Quando uma crise não é bem controlada, o animalpode apresentar status epilepticus, situação que requer tratamento emergencial. Busca-se com essa revisãode literatura realizar uma abordagem aplicada e crítica sobre o tratamento de crises epilépticas em cães,sejam elas simples, recorrentes, agrupadas ou contínuas.(AU)

The epileptic seizures are manifestations of neurological disorders, and occur with great frequency insmall animals. The success in antiepileptic therapy can be translated by reduction in at least 50% of theepileptic seizure frequency. For this reason is very important to define and treat the primary cause whenit exists, since the majority of drugs has no antiepileptogenic activity. New antiepileptic drugs are beingstudied for use in dogs but up to now none of them replaces or equals the benefits that the phenobarbitaland potassium bromide brings to the patient. When seizure is not well controlled, the animal maypresent status epilepticus, which is a situation of emergency treatment. With this review we pretend togive a practical and critical approach to the treatment of single, recurrent, cluster or continuous epilepticactivity in dogs.(AU)