Refractory Epilepsy: A Clinically Oriented Review

Abstract

About one third of patients with newly diagnosed epilepsy do not achieve seizure control despite medical therapy and should be assessed in detail to confirm the diagnosis, to determine the epilepsy syndrome and to plan treatment strategy. Refractory epilepsy is established when there is inadequate seizure control despite using potentially effective antiepileptic drugs (AEDs) at tolerable levels for 1–2 years, and excluding nonepileptic events and poor compliance. An overview of patient management in everyday clinical practice is given. Risk factors for refractoriness include (1) generalized epilepsy with lesions; (2) focal epilepsy with hippocampal sclerosis, cortical dysplasia or hemorrhages; (3) early epilepsy onset; (4) high seizure frequency; (5) absence of response to the first 2 AEDs; (6) high frequency of interictal spikes, and (7) multifocal spikes. The efficacy of surgery ranges from curative (resection) to palliative (vagus nerve stimulation, callosotomy, multiple subpial transections) depending on the epilepsy syndrome and etiology. Using a new antiepileptic drug benefits about one third of patients. Refractoriness is constitutive in most patients and shows a progressive or remission-relapse course in others. As the transporter and target hypotheses do not entirely explain refractoriness, other hypotheses are emerging. New treatments under investigation are described.

Effect of Aqueous Extract Withania somnifera on Tolerance to Antiepileptic Effect of Phenobarbitone in Mice

“…But, even these have limited utility and search is on for newer more effective AEDs. 21 Pharmacoresistance is explained intrinsic severity hypothesis, the target hypothesis and the transporter hypothesis. 22 Drug related factors like tolerence have also been involved in development of pharmacoresistance.…”

Avaliação de métodos de análises não lineares em sinais eletroencefalográficos na presença de oscilações de alta frequência em pacientes portadores de epilepsia refratária

“…A investigação e determinação da provável ZE dentro deste plano pode ser realizada através de algumas abordagens, incluindo análise de semiologia, história clínica, imagens de ressonância magnética, imagens funcionais (PET e SPECT), e eletroencefalografia [14]. Todavia, mesmo com o uso de todas essas técnicas, a determinação da ZE nem sempre é possível, e nestes casos, o paciente é impedido de realizar a cirurgia.…”

“…Considerando m=1 e o vetor x1={u(1)}, seu padrão é repetido três vezes em {u(7)},{ u(14)}, {u(31)}. Ao considerar o vetor x2={u(1),u(2)} para m+1=2, nota-se que somente dois dos padrões anteriores ainda se repetem, em {u (14),u(15)} e {u (31),u(32)}. O xii mesmo pode ser observado considerando o vetor x2={u(1),u(2)} para o caso m=2.…”

Prenatal Environmental Exposure and Neurodevelopmentally Important Gene Expression in Malformed Brain Tissue from Pediatric Intractable Epilepsy Patients

“…According to Beleza (2009), refractory epilepsy is established when there is inadequate seizure control despite using potentially effective AEDs at tolerable levels for 1 to 2 years. Refractory epilepsy patients show increased risk of psychiatric, psychosocial, and medical morbidities.…”

“…Various studies have suggested that onset of early intractable seizures may be a significant risk factor for impairment of intellectual functioning and adaptive abilities (Saneto and Wyllie, 2000). Resective surgery, based on the removal of the entire epileptogenic area without causing permanent neurological deficit, is one of the treatment forms for refractory epilepsy (Beleza, 2009). In surgical series, focal cortical malformations and low-grade tumors were the most common in infants with intractable epilepsy.…”