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Deep Brain Stimulation for Epilepsy: an Update

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Deep Brain Stimulation for Epilepsy: an Update Deep Brain Stimulation for Epilepsy: an Update Claudio Pollo1 and Kaspar Schindler2 1 Neurosurgery and 2 Neurology Departments, University Hospital Bern, Inselspital, Bern Summary Keywords: Deep brain stimulation, epilepsy, anterior nu- cleus, centro-median nucleus, hippocampus, closed-loop Deep brain stimulation (DBS) has shown efficacy in stimulation achieving significant seizure reduction in patients with refractory epilepsy not suitable for resective surgery. Based on the identification of several cortico-subcor- Tiefe Hirnstimulation bei Epilepsie: ein Update tical networks involved in epilepsy, several anatomi- cal targets have been proposed for different epileptic Die Tiefe Hirnstimulation (THS) erzielt eine effek- syndromes. Among these targets, the most exten- tive Reduktion der Anfallshäufigkeit bei Patienten, die sively investigated and also showing the most prom- nicht für resezierende chirurgische Massnahmen geeig- ising results are the anterior nucleus (ANT) as well as net sind. Verschiedene anatomische Zielpunkte wurden the centro-median (CMT) nucleus of the thalamus, and aufgrund der Identifizierung von neuronalen kortikalen the hippocampus (Hipp). This paper provides a review und subkortikalen Netzwerken als Grundlage für unter- of the literature in DBS for epilepsy focused on these schiedliche epileptische Syndrome vorgeschlagen. Unter targets with available data on efficacy as well as side diesen Zielpunkten wurden die anteriore Thalamuskern- effects. Technological advancements like responsive gruppe (ANT), der Nucleus centromedianus (CMT) sowie stimulation (RNS) are also underlined. der Hippokampus (Hipp) umfangreich untersucht und Although promising results were reported for these zeigen dabei zudem die vielversprechendsten Ergebnis- different targets in specific epileptic syndromes, only se. Diese Arbeit liefert einen Literaturüberblick über die ANT and RNS were tested on larger series of patients THS zur Behandlung von Epilepsie mit Augenmerk auf and could reach class I evidence level of efficacy. More- diese drei Zielstrukturen unter Berücksichtigung von over, overall data suggest that seizure outcome im- Daten über die Wirksamkeit als auch Nebenwirkungen. proves over time. Innovative Technologien wie die responsive Neurostimu- We suggest that Hipp stimulation should be re- lation (RNS) werden ebenfalls thematisiert. stricted to MTLE, whereas ANT stimulation could be Obwohl vielversprechende Ergebnisse für alle drei properly performed also in multifocal seizures with Zielpunkte für verschiedene spezifische Epilepsiesyndro- predominant limbic involvement and CMT in general- me berichtet wurden, gibt es lediglich zur Stimulation ized epilepsy. RNS should be proposed in focal epilepsy des ANT und für die RNS grössere Untersuchungen und especially from extratemporal origin, even if closed- eine Klasse-1-Evidenz der Wirksamkeit. Darüber hinaus loop technology could be applied to propagation nodes, deuten die Zahlen darauf hin, dass sich die Anfallsergeb- such as ANT, Hipp or CMT, thus extending its use to nisse über die Zeit verbessern. multifocal or even generalized epilepsy. Wir schlagen vor, dass eine Stimulation des Hipp The complex physiopathology of seizure onset and auf Fälle einer mesialen Temporallappenepilepsie be- propagation justifies further electrophysiologic and schränkt werden sollte, wohingegen die Stimulation clinical research for the better understanding of the des ANT im Falle einer multifokalen Epilepsie mit über- precise correlations existing between clinical manifes- wiegender Beteiligung des limbischen Systems ange- tations and the structural and functional networks in- wendet und die Stimulation des CMT bei generalisier- volved in the control of epileptogenicity. Together with ter Epilepsie durchgeführt werden sollte. RNS sollte für a deeper understanding of the mechanisms of action fokale Epilepsieformen mit überwiegendem Anfalls- of DBS at cortico-subcortical, this will certainly be help- ursprung ausserhalb des Temporallappens vorgesehen ful for the refinement of patient selection criteria, ana- werden, auch im Falle der Anwendung der adaptiven tomical targets and stimulation parameters. Stimulation im Bereich von Knotenpunkten der Anfalls- ausbreitung wie zum Beispiel der ANT, Hipp und CMT Epileptologie 2017; 34: 19 – 24 und damit einer möglichen Erweiterung der Anwen- dung im Bereich der generalisierten Epilepsie. Deep Brain Stimulation for Epilepsy: an Update | C. Pollo, K. Schindler Epileptologie 2017; 34 19 Schlüsselwörter: Tiefe Hirnstimulation, Epilepsie, Nu- Introduction kleus anterior, zentro-medianer Nukleus, Hippokam- pus, „closed-loop“-Stimulation Epilepsy is a potentially devastating neurological disorder affecting more than 50M people world-wide. People with uncontrolled epilepsy are subject to many La stimulation cérébrale profonde: une revue de consequences, such as falls and related injuries, driving la littérature restrictions, work limitations, lack of independence, the need of constant supervision, frequent medical con- La stimulation cérébrale profonde (DBS) a démon- sultations, hospital admissions and medically-related tré son efficacité à réduire la fréquence des crises chez expenses. These result in a significant impact on the les patients souffrant d’épilepsie réfractaire et qui ne quality of life, leading to school absenteism, unemploy- sont pas des candidats à la chirurgie ablative. Basé sur ment, depression and other psychiatric conditions, such l’identification de différents circuits cortico-sous-corti- as generalized anxiety and phobic disorder, often lead- caux impliqués dans le contrôle de l’épilepsie, plusieurs ing to social isolation and even suicide [1]. Antiepileptic cibles anatomiques ont été proposées pour différents drugs (AEDs) remain the first option for treating epi- syndromes épileptiques. Parmi elles, le noyau antérieur lepsy. However, 20% to 40% of patients will suffer poor (ANT) et le noyau centro-médian (CMT) du thalamus, control from best medical treatment [2 - 4]. Standard ainsi que l’hippocampe ont été investiguées de manière of care for drug-resistant epilepsies in case of focal sei- plus extensive et ont démontré les résultats les plus zure onset is resective surgery [5]. Seizure freedom can prometteurs. Ce travail propose une revue de la littéra- be achieved in 60 - 90% of MTLE, glioneuronal tumors, ture concernant la DBS appliquée à l’épilepsie, focalisée vascular malformations and focal cortical dysplasias [6, sur ces cibles anatomiques, d’après les données sur les 7]. The success of resective surgery is highly dependant résultats et les effets secondaires de cette thérapie dis- on the ability to detect and resect a focal epileptogenic ponibles dans la littérature. Les avancées technologiques lesion or epileptogenic brain area as well as to interrupt telles que la stimulation réactive (RNS) sont également an epileptogenic network. Thus, up to 30 - 40% of medi- soulignées. Bien que des résultats encourageants ont cally resistant epileptic patients may not benefit from été rapportées pour ces différents cibles dans des syn- a resective surgical approach, due to multifocal epilep- dromes épileptiques spécifiques, seules les stimulation sy, or high risks of neurological deficits associated with du ANT et la RNS ont été testées à des séries de patients lesion or cortex resection in highly eloquent brain are- plus larges et ont pu ainsi atteindre un niveau d’évidence as. These patients may benefit from vagus nerve stimu- d’efficacité de classe I. De plus, l’ensemble des données lation (VNS) in addition to continued medical therapy. suggère une augmentation de l’efficacité dans le temps. VNS offers a mean seizure reduction of 28% for patients Nous suggérons de réserver la stimulation hippo- in whom it is employed with 23% of patients having a campique aux patients souffrant d’épilepsie réfractaire greater than 50% reduction in seizure frequency (Class d’origine mésio-temporale, alors que la stimulation du 1 evidence) [8, 9]. ANT peut être proposée lors d’épilepsies multifocales Development of EEG signal analysis has improved impliquant principalement le circuit limbique. Enfin la our understanding in the neuronal pathways involved stimulation du CMT pour les épilepsies généralisées. La in seizure propagation, such as the limbic circuit of RNS devrait être proposée pour les épilepsies focales Papez [10 - 11] and the diffuse reticulo-thalamo-corti- d’origine extratemporale, même si cette technologie cal pathway [12 - 14]. Consequently, the anterior tha- pourrait être appliquée à différents nœuds de propaga- lamic nucleus (ANT), the hippocampus (Hipp) and the tion, tels que le ANT, le CMT ou même à l’hippocampe, centromedian nucleus of the thalamus (CMT) have étendant ainsi son indication à l’épilepsie multifocale been proposed and investigated for Deep Brain Stimu- ou voire même généralisée. La physiopathologie com- lation (DBS) in epilepsy. Other targets have been re- plexe de l’origine et de la propagation des crises justifie ported such as the subthalamic nucleus (STN), the cau- la continuation de recherches électrophysiologiques et date nucleus, the mamillothalamic tract, the nucleus cliniques pour permettre de mieux comprendre les cor- ventro-oralis posterior (Vop) of the thalamus, the glo- rélations existant entre les manifestations cliniques et bus pallidus internus and the nucleus accumbens. De- les circuits structurels et fonctionnels impliqués dans le spite increasing interest in DBS for epilepsy, the exact contrôle
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