Cortical stimulation in pharmacoresistant focal epilepsies
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Bioelectronic Medicine
MINI-REVIEW
Open Access
Cortical stimulation in pharmacoresistant focal epilepsies Jens Ellrich1,2
Abstract Pharmacoresistance and adverse drug events designate a considerable group of patients with focal epilepsies that require alternative treatments such as neurosurgical intervention and neurostimulation. Electrical or magnetic stimulations of cortical brain areas for the treatment of pharmacoresistant focal epilepsies emerged from preclinical studies and experience through intraoperative neurophysiological monitoring in patients. Direct neurostimulation of seizure onset zones in neocortical brain areas may specifically affect neuronal networks involved in epileptiform activity without remarkable adverse influence on physiological cortical processing in immediate vicinity. Noninvasive low-frequency transcranial magnetic stimulation and cathodal transcranial direct current stimulation are suggested to be anticonvulsant; however, potential effects are ephemeral and require effect maintenance by ongoing stimulation. Invasive responsive neurostimulation, chronic subthreshold cortical stimulation, and epicranial cortical stimulation cover a broad range of different emerging technologies with intracranial and epicranial approaches that still have limited market access partly due to ongoing clinical development. Despite significant differences, the present bioelectronic technologies share common mode of actions with acute seizure termination by high-frequency stimulation and long-term depression induced by low-frequency magnetic or electrical stimulation or transcranial direct current stimulation. Keywords: Adherence, Anticonvulsant, Chronic subthreshold cortical stimulation, Epicranial cortical stimulation, Long-term depression, Neuromodulation, Responsive neurostimulation, Seizure, Transcranial direct current stimulation, Transcranial magnetic stimulation
Background Epilepsies are characterized by unpredictable seizures and affect more than 70 million people worldwide (Beghi 2020; Ngugi et al. 2010). Focal seizures are the predominant seizure type in children and adults with a proportion of about 68% (Forsgren et al. 1996). Seizures are primarily treated by anticonvulsant drugs (ACD) that typically strengthen inhibition and attenuate excitation of synaptic processing via pre- and postsynaptic mechanisms (Loscher and Schmidt 2012). Nearly two dozen ACDs with different mechanisms of action have been introduced over the past three decades with the aim of providing a better efficacy or safety profile than previous Correspondence: [email protected] 1 Medical Faculty, University of Erlangen-Nuremberg, Erlangen, Germany 2 Precisis AG, Heidelberg, Germany
drugs (Chen et al. 2020). Although these recent drugs have advantages in terms of drug-drug interactions and teratogenicity, still a third of epilepsy patients suffer from recurrent seizures (Janmohamed et al. 2020). This pharmacoresistance is defined as failure of adequate trials of two tolerated, appropriately chosen, and used ACD schedules t
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