RESUMEN
BACKGROUND: Epilepsy is a common neurological disease that affects people all over the world, but it is rarely described in indigenous peoples. OBJECTIVE: To study the epilepsy characteristics and risk factors for seizure control in people from an isolated indigenous population. METHODS: This is a retrospective and historical cohort study conducted from 2003 to 2018 (15 years), at a neurology outpatient clinic, of 25 Waiwai tribes' indigenous individuals with epilepsy, inhabitants of an isolated forest reserve in the Amazon. Clinical aspects, background, comorbidities, exams, treatment, and response were studied. Factors that impacted seizure control over 24 months were identified using Kaplan-Meier curves and Cox and Weibull regression models. RESULTS: The majority of cases started in childhood, with no difference regarding gender. Focal epilepsies were predominant. Most patients had tonic-clonic seizures. A quarter of them had a family history, and 20% had referred febrile seizures. There was intellectual disability in 20% of patients. Neurological examination and psychomotor development were altered in one third of the participants. The treatment controlled 72% of the patients (monotherapy in 64%). Phenobarbital was the most prescribed anti-seizure medication, followed by carbamazepine and valproate. The most relevant factors that impacted seizure control over time were abnormal neurological exam and family history. CONCLUSION: Family history and abnormal neurological exam were predicted risk factors for refractory epilepsy. Even in an isolated indigenous tribe, the partnership between the indigenous people and the multidisciplinary team ensured treatment adherence. The public healthcare system must guarantee modern anti-seizure medications, mainly for this vulnerable population, which has no other source of treatment.
ANTECEDENTES: A epilepsia é uma doença neurológica que afeta povos do mundo todo, mas raramente é descrita em povos indígenas. OBJETIVOS: Estudar as características da epilepsia e os fatores de risco para o controle das crises em pessoas de uma população indígena isolada. MéTODOS: Este é um estudo de coorte retrospectivo e histórico, conduzido de 2003 a 2018 (15 anos) no ambulatório de neurologia, de 25 indígenas Waiwai com epilepsia, habitantes de uma reserva florestal na Amazônia. Aspectos clínicos, antecedentes, comorbidades, exames, tratamento e resposta foram estudados. Identificou-se os fatores que afetaram o controle das crises ao longo de 24 meses usando curvas de Kaplan-Meier e modelos de regressão de Cox e Weibull. RESULTADOS: A maioria dos casos teve início na infância, sem diferença quanto ao gênero. Predominavam as epilepsias focais. A maioria dos pacientes apresentava crises tônico-clônicas. Um quarto deles tinha história familiar e 20% referiram convulsões febris. Vinte por cento dos pacientes apresentava deficiência intelectual. Um terço tinha exame neurológico e desenvolvimento psicomotor alterados. O tratamento controlou 72% dos pacientes (monoterapia em 64%). Fenobarbital foi o medicamento mais prescrito, seguido por carbamazepina e valproate, e os fatores que mais impactaram o controle das crises ao longo do tempo foram exame neurológico anormal e história familiar. CONCLUSãO: História familiar e exame neurológico anormal foram fatores de risco preditores para epilepsia refratária. Mesmo em uma tribo indígena isolada, a parceria entre os indígenas e a equipe multidisciplinar garantiu a adesão ao tratamento. O sistema público de saúde deve garantir medicamentos modernos anticrise, principalmente para essa população vulnerável, que não tem outra fonte de tratamento.
Asunto(s)
Epilepsia Generalizada , Epilepsia , Humanos , Anticonvulsivantes/uso terapéutico , Epilepsia Generalizada/inducido químicamente , Epilepsia Generalizada/tratamiento farmacológico , Brasil/epidemiología , Estudios de Cohortes , Estudios de Seguimiento , Estudios Retrospectivos , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamenteRESUMEN
The lateral-posterior thalamic nuclei (LP) have been shown to play an important role in controlling epileptic activity. In addition, thalamic atrophy and neuronal loss have been observed in epilepsy. The objective of this study was to investigate whether lateral-posterior neuronal activation may be observed shortly after a single generalized seizure in rats submitted to the pilocarpine model of epilepsy. The results showed an increased lateral-posterior activation as soon as the seizure occurred, suggesting that neuronal loss in the thalamus is not only the consequence of chronic epilepsy.
Asunto(s)
Epilepsia Generalizada/patología , Núcleos Talámicos Posteriores/patología , Animales , Modelos Animales de Enfermedad , Epilepsia Generalizada/inducido químicamente , Masculino , Agonistas Muscarínicos/toxicidad , Neuronas/metabolismo , Pilocarpina/toxicidad , Núcleos Talámicos Posteriores/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas WistarRESUMEN
In the PTZ animal model of epilepsy, electrical stimulation applied to the amygdaloid complex may result in either pro-convulsive or anticonvulsant effect, depending on the temporal pattern used (i.e. periodic-PS and non-periodic-NPS electrical stimulation). Our hypothesis is that the anatomical target is a determinant factor for the differential effect of temporally-coded patterns on seizure outcome. The threshold dose of PTZ to elicit forelimb clonus and generalized tonic-clonic seizure behavior was measured. The effect of amygdaloid complex PS on forelimb clonus threshold showed a pro-convulsive effect while NPS was anticonvulsant. NPS also significantly increased generalized tonic-clonic threshold; while PS, although at lower threshold levels, did not present statistical significance. Thalamus stimulation did not affect forelimb clonus threshold and showed similar anticonvulsant profiles for both PS and NPS on generalized tonic-clonic threshold. In summary, the anatomical target is a determinant factor on whether temporally-coded ES differentially modulates seizure outcome.
Asunto(s)
Amígdala del Cerebelo/fisiología , Terapia por Estimulación Eléctrica/métodos , Epilepsia Generalizada/terapia , Pentilenotetrazol/uso terapéutico , Animales , Modelos Animales de Enfermedad , Epilepsia Generalizada/inducido químicamente , Epilepsia Generalizada/fisiopatología , Masculino , Pentilenotetrazol/toxicidad , Ratas , Ratas Wistar , Tálamo/fisiologíaRESUMEN
Amado and Cavalheiro [Amado, D., Cavalheiro, E.A., 1998. Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilepsy. Epilepsy Res. 32, 266-274], studying the establishment of the pilocarpine epilepsy model in female rats observed that the estrous cycle was dramatically altered during the three periods of this experimental model. This work was delineated to study the function of sexual hormones in the development of the epilepsy model induced by pilocarpine in ovariectomized rats. Experimental groups were: (a) control animals during estrus phase of the estrous cycle (E) and ovariectomized female rats (OVX) treated with saline instead of pilocarpine in the same volume, (b) experimental animals, that developed status epilepticus (SE) and were studied during the chronic phase of this model: intact chronic rats (CHRON) and ovariectomized chronic rats (OVX+CHRON) and (c) ovariectomized chronic rats, that were submitted to hormonal replacement therapy treated with: medroxyprogesterone (OVX+CHRON+MPA); 17beta-estradiol (OVX+CHRON+E2), or both (OVX+CHRON+E2+MPA). All ovariectomized animals showed genital atrophy 4 days after the surgical procedure. Moreover, all animals that developed SE and survived showed spontaneous recurrent seizures during the chronic phase. Concerning to seizure frequency, animals receiving medroxyprogesterone associated with 17beta-estradiol showed decreased seizures' number. However, animals that received only medroxyprogesterone therapy also showed reduction in the number of seizures. In addition, hormonal treatment was also able to stabilize the mossy fibers sprouting process, showing the importance of these hormones in the development of the epilepsy in female rats.
Asunto(s)
Epilepsia Generalizada/fisiopatología , Estradiol/farmacología , Hormonas Esteroides Gonadales/fisiología , Hipocampo/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Medroxiprogesterona/farmacología , Animales , Epilepsia Generalizada/inducido químicamente , Estradiol/administración & dosificación , Estradiol/uso terapéutico , Estro , Femenino , Hipocampo/fisiopatología , Hipogonadismo/complicaciones , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/etiología , Medroxiprogesterona/administración & dosificación , Medroxiprogesterona/uso terapéutico , Fibras Musgosas del Hipocampo/efectos de los fármacos , Fibras Musgosas del Hipocampo/ultraestructura , Ovariectomía/efectos adversos , Pilocarpina/toxicidad , Ratas , Ratas WistarRESUMEN
For exploring a possible connection between the reduced hearing sensitivity and certain abnormalities in the auditory brainstem responses (ABRs) in generalized epilepsy, the effects of two convulsing agents, namely pentylenetetrazole (PTZ) and of 4-aminopyridine (4-AP), on: (1). the cortical activity (EEG), (2). the hearing threshold and (3). the amplitudes and latencies of the ABR waves evoked by a stimulus of high intensity (100 dB) were investigated in guinea pigs. All animals injected (i.p.) with 100mg/kg PTZ or with 2mg/kg 4-AP developed generalized seizures, followed by characteristic EEG patterns for the post-ictal period, that were accompanied by a marked reduction of the hearing sensitivity (as indicated by the elevated threshold of the ABR), as well as by retro-cochlear changes (as judged by the changes in the later ABR waves in response to 100 dB). For instance, both convulsing agents decreased the amplitude and increased the latency of P4, that is the wave component of the ABRs generated in the lateral superior olivary nucleus and while PTZ increased the latency of P3, the wave component of the ABRs generated in the medial superior olivary nucleus, 4-AP dramatically increased its amplitude. Comparison of recordings taken at specific times for the duration of the post-ictal period (i.e. within about 1h for PTZ and 2h for 4-AP) reveals that the extent of the changes on the EEG matches with the increase in the auditory threshold and with the extent of the changes on the later waves of the ABR elicited by 100 dB. These data indicate that changes in the activity of the lateral and the medial nuclei of the superior olivary complex (SOC) accompany the hearing loss and the post-ictal epileptic cortical activity.