Convection-Enhanced Delivery of Muscimol in Patients with Drug-Resistant Epilepsy
| Autor: | John D. Heiss, Omar I. Khan, Davis P. Argersinger, John A. Butman, Susumu Sato, William H. Theodore |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Drug Resistant Epilepsy Electroencephalography Convection 03 medical and health sciences Epilepsy chemistry.chemical_compound 0302 clinical medicine Infusion Procedure medicine Humans Epilepsy surgery Research—Human—Clinical Trials medicine.diagnostic_test Muscimol business.industry GABAA receptor Brain medicine.disease Magnetic Resonance Imaging Crossover study Infusions Intraventricular chemistry 030220 oncology & carcinogenesis Anesthesia Anticonvulsants Female Surgery Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Neurosurgery |
| ISSN: | 1524-4040 0148-396X |
| Popis: | Background Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist, was previously completed in non-human primates. Objective To investigate the safety and anti-epileptic effects of intracerebral muscimol infusion into the epileptic focus of patients with DRE. Methods In this phase 1 clinical trial, 3 adult patients with DRE underwent CED into the seizure focus of artificial CSF vehicle followed by muscimol for 12 to 24 h each using a crossover design. Basic pathophysiology of the epileptic focus was examined by assessing the infusions' effects on seizure frequency, electroencephalogram (EEG) spike-wave activity, and power-spectral EEG frequency. Results Inter-ictal neurological function remained normal in all patients. Pathological examination of resected specimens showed no infusion-related brain injuries. Seizure frequency decreased in 1 of 3 patients during muscimol infusion but was unchanged in all patients during vehicle infusion. Mean beta frequencies did not differ significantly before, during, or after infusion periods. Infused fluid provided insufficient MRI-signal to track infusate distribution. In the 2 yr after standard epilepsy surgery, 1 patient had temporary reduction in seizure frequency and 2 patients were seizure-free. Conclusion CED of muscimol into the epileptic focus of patients with DRE did not damage adjacent brain parenchyma or adversely affect seizure surgery outcome. This study did not confirm that intracerebral muscimol infusion effectively suppressed seizures. A surrogate tracer is recommended to track infusion distribution to the epileptic focus and surrounding structures in future studies using CED to suppress the seizure focus. |
| Databáze: | OpenAIRE |
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