Abstract
About 50% of patients with newly diagnosed epilepsy become seizure-free (for at least one year) with the first antiepileptic drug (AED). From those patients who are switched to a second antiepileptic drug because of inadequate seizure or adverse events, 13% respond satisfactorily, in particular if adverse events were the reason. About 40% have difficulties treating or are pharmacoresistant. The response to the first antiepileptic drug is the most important prognostic factor. Pharmacoresistance is a prerequisite for epilepsy surgery and is usually clinically defined as non-response to two antiepileptic drugs of first choice in successive monotherapy and in combination. Non-compliance is a frequent reason for non-response to prescribed antiepileptic drug. In true pharmacoresistance several biological factors have to be considered: severity and type of the syndrome and underlying neuropathology, abnormal neuronal circuits (e.g. hippocampal sclerosis, cortical dysplasia), hyperexcitable or disinhibited network reorganisation, alterations of neurotransmitter receptors, pathologies of ion channels, reactive autoimmune processes and altered penetration of antiepileptic drugs into the focus, e.g. P-glycoprotein (Pgp) expression at the blood-brain barrier. Lipophilic antiepileptic drugs are potential substrates for P-glycoprotein. Over-expression of P-glycoprotein in the endothelia of the blood-brain barrier has been found in pharmacoresistant epilepsy patients who underwent surgery and indicates that this might be the cause for diminished antiepileptic drug uptake into the brain. If pharmacoresistance is established, the patient should be considered a candidate for epilepsy surgery and undergo presurgical evaluation, which has to answer the following questions: (1) Is the patient suffering from a surgically amenable syndrome? (2) Can the seizure-generating zone be delineated with the precision and certainty necessary for a resective surgical intervention? (3) Can the seizure-generating zone be resected without the risks of intolerable neurological or neuropsychological deficits? And (4) if curative surgery with the aim of postoperative freedom of is not possible, can epilepsy surgery be offered, with the aim of improving the patient's seizure situation and quality of life? From a methodological point of view the presurgical evaluation aims to define several conceptual of an epileptic focus: (a) the epileptogenic lesion, (b) the seizure-generating or epileptogenic (c) the irritative zone and (d) the symptomatogenic zone. It is obvious that these various zones are not the same but can overlap. The mode of propagation of seizure discharges (seizure spread) via preferential pathways is of great importance for the definition of the symptomatogenic zone, but is also important for the definition of the resection borders. In certain palliative surgeries the inaccessible primary seizure-generating zone is only partly removed or even left behind and the secondary epileptogenic pacemaker is removed or preferential pathways for seizure spread are disrupted, such as is the case in corpus callosotomy (CCT). Curative epilepsy surgery is not only able to control seizures in a high proportion of patients but has the potential to cure in the sense that a considerable proportion of patients can discontinue their antiepileptic drugs. In the Zurich selective amygdalohippocampectomy series 90% of those patients who achieved complete seizure and aura freedom since operation (ILAE outcome class la) were without antiepileptic drugs in the 8th postoperative year. Neurobehavioural and psychiatric aspects of the epilepsies in general, and of temporal lobe epilepsy in particular play an important role in the discussion whether some epilepsy syndromes, such as the mesial temporal lobe epilepsy, may show a disease-related progressive course.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.