Current and Future Management of Temporal Lobe Epilepsy

Educational Objectives

The goal of this program is to improve management of temporal lobe epilepsy. After hearing and assimilating this program, the clinician will be better able to:

1. Use alternative palliative treatments in patients with epilepsy.
2. Select therapies for treatment of essential tremor.

Summary

Surgery for epilepsy: patients with new diagnoses of epilepsy receive first line treatment with anti-seizure medications; 33% of patients with epilepsy have drug-resistant epilepsy; surgery may be considered for patients with drug-resistant temporal lobe epilepsy; robust clinical trials have shown that procedures, eg, resective surgery, laser ablation, can be highly effective (leading to, eg, seizure freedom, significant reduction) if the seizure origin is precisely identified; laser thermal ablation of the hippocampus is highly effective in treating epilepsy; studies have shown that thermal ablation for lesional mantle epilepsy can result in seizure freedom (Engel Class 1) in >60% of cases; removing both temporal lobes may lead to severe anterograde amnesia; surgeries affecting the dominant hemisphere can result in language impairments

Neurostimulation: vagal nerve stimulation, deep brain stimulation, and responsive neurostimulation are increasingly used as alternative treatment options; patients may be treated with multiple devices to optimize seizure control; neurostimulation devices are palliative, and outcomes are heterogeneous across patients; no prognostic biomarkers exist that can predict the most effective device

Role of the thalamus: seizure localization has traditionally relied on recording brain activity from the cortex using subdural or depth electrodes; recent studies have explored placing electrodes directly into the thalamus (stereo electroencephalography) to better understand its role in epilepsy; early studies have shown different thalamic nuclei engage differently during seizures arising from different cortical areas; the anterior nucleus of the thalamus is involved with limbic seizures in the temporal cortex, insula, and cingulate cortex; the central median nucleus of the thalamus is involved in frontoparietal seizure networks; the pulvinar nuclei are involved in parietal, occipital, or posterior quadrant seizures; 2 devices can stimulate specific thalamic nuclei and reduce seizures; the requirement of placing electrodes into small nuclei deep in the brain is a significant impediment to research

Transcranial focused ultrasonography (US): high intensity focused US (HIFU) has a thermal ablative effect and is approved by the Food and Drug Administration for thalamotomy for essential tremor; the low intensity version has pleotropic effects, eg, disrupts the blood brain barrier, disrupts neuromodulation; the exact mechanism by which low-intensity focused US (LIFU) achieves its effects is unclear, but brain activity appears to be influenced by heat, bubble formation, or mechanical effects; Brinker et al (2020) showed that LIFU targeting the hippocampus was well-tolerated and reduced seizures

Stem cell therapy: the medial ganglionic eminence (MGE) in the developing brain gives rise to progenitor cells which become inhibitory inner neurons and migrate to the cortex and hippocampus and secrete gamma-aminobutyric acid to provide adequate balance between excitation and inhibition; embryonic stem cells or induced pluripotent stem cells could be made to differentiate into MGE progenitors for injection into the epileptic hippocampus; 77% of animals treated with stem cells had a ≥75% reduction in seizures, and ≈66% animals became seizure free compared with 4% in controls; an ongoing multi-center trial in humans is underway; immunosuppression is required for several months post-transplant to ensure the grafted cells are not rejected; epilepsy types may be linked to autoimmune conditions; the immunosuppression itself has been hypothesized as the cause of seizure reduction

Readings

Brinker ST, Preiswerk F, White PJ, et al. Focused ultrasound platform for investigating therapeutic neuromodulation across the human hippocampus. Ultrasound Med Biol. 2020;46(5):1270-1274. doi:10.1016/j.ultrasmedbio.2020.01.007; Fisher RS. Deep brain stimulation of thalamus for epilepsy. Neurobiol Dis. 2023;179:106045. doi:10.1016/j.nbd.2023.106045; Fishman PS. Thalamotomy for essential tremor: FDA approval brings brain treatment with FUS to the clinic. J Ther Ultrasound. 2017;5:19. Published 2017 Jul 13. doi:10.1186/s40349-017-0096-9; Hill CE, Lin CC, Terman SW, et al. Definitions of drug-resistant epilepsy for administrative claims data research. Neurology. 2021;97(13):e1343-e1350. doi:10.1212/WNL.0000000000012514; Li D, Wu Q, Han X. Application of medial ganglionic eminence cell transplantation in diseases associated with interneuron disorders. Front Cell Neurosci. 2022;16:939294. Published 2022 Jul 5. doi:10.3389/fncel.2022.939294; Rugg-Gunn F, Miserocchi A, McEvoy A. Epilepsy surgery. Pract Neurol. 2020;20(1):4-14. doi:10.1136/practneurol-2019-002192; Vakilna YS, Chaitanya G, Hafeez MU, et al. Pulvinar neuromodulation for seizure monitoring and network modulation in temporal plus epilepsy. Ann Clin Transl Neurol. 2023;10(7):1254-1259. doi:10.1002/acn3.51815.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Rao has received research support from NeuroPace, Inc. and Medtronic; has been on the medical advisory board at NeuroPace, Inc.; has been on the strategic neuromodulation advisory board at LivaNova, PLC; has been the chief neurology advisor at Myndscape, Inc.; has been a scientific advisor at EnlitenAI, Inc.; and has been a consultant at Encephalogix, Inc. and Novela Neurotechnologies. Members of the planning committee reported nothing relevant to disclose. Dr. Rao's lecture contains information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Rao was recorded at the 57th Annual Recent Advances in Neurology, held February 14-16, 2024, in San Francisco, CA, presented by the University of California, San Francisco, School of Medicine. For more information about the upcoming CME activities from this presenter, please visit cme.ucsf.edu. Audio Digest thanks the speakers and University of California, San Francisco, School of Medicine, for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

NE151903

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.