The Bidirectional Relationship Between the Cerebellum and Seizure Networks: a Double-edged Sword

Overview

Journal Curr Opin Behav Sci

Date 2024 May 27

PMID 38800711

Authors

M L Streng

Affiliations

Soon will be listed here.

Abstract

Epilepsy is highly prevalent and notoriously pharmacoresistant. New therapeutic interventions are urgently needed, both for preventing the seizures themselves as well as negative outcomes and comorbidities associated with chronic epilepsy. While the cerebellum is not traditionally associated with epilepsy or seizures, research over the past decade has outlined the cerebellum as a brain region that is uniquely suited for both therapeutic needs. This review discusses our current understanding of the cerebellum as a key node within seizure networks, capable of both attenuating seizures in several animal models, and conversely, prone to altered structure and function in chronic epilepsy. Critical next steps are to advance therapeutic modulation of the cerebellum more towards translation, and to provide a more comprehensive characterization of how the cerebellum is impacted by chronic epilepsy, in order to subvert negative outcomes.

References

Rochefort C, Lefort J, Rondi-Reig L . The cerebellum: a new key structure in the navigation system. Front Neural Circuits. 2013; 7:35. PMC: 3595517. DOI: 10.3389/fncir.2013.00035. View

NORMAN R . THE NEUROPATHOLOGY OF STATUS EPILEPTICUS. Med Sci Law. 1964; 4:46-51. DOI: 10.1177/002580246400400112. View

Stieve B, Richner T, Krook-Magnuson C, Netoff T, Krook-Magnuson E . Optimization of closed-loop electrical stimulation enables robust cerebellar-directed seizure control. Brain. 2022; 146(1):91-108. PMC: 10202393. DOI: 10.1093/brain/awac051. View

Shin W, Hong S, Tae W, Seo D, Kim S . Ictal hyperperfusion of cerebellum and basal ganglia in temporal lobe epilepsy: SPECT subtraction with MRI coregistration. J Nucl Med. 2001; 42(6):853-8. View

Crooks R, Mitchell T, Thom M . Patterns of cerebellar atrophy in patients with chronic epilepsy: a quantitative neuropathological study. Epilepsy Res. 2000; 41(1):63-73. DOI: 10.1016/s0920-1211(00)00133-9. View

Laich E, Kuzniecky R, Mountz J, Liu H, Gilliam F, Bebin M . Supplementary sensorimotor area epilepsy. Seizure localization, cortical propagation and subcortical activation pathways using ictal SPECT. Brain. 1997; 120 ( Pt 5):855-64. DOI: 10.1093/brain/120.5.855. View

Leifer D, Cole D, Kowall N . Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. J Neurol Sci. 1991; 103(2):127-35. DOI: 10.1016/0022-510x(91)90155-z. View

Bohne P, Schwarz M, Herlitze S, Mark M . A New Projection From the Deep Cerebellar Nuclei to the Hippocampus the Ventrolateral and Laterodorsal Thalamus in Mice. Front Neural Circuits. 2019; 13:51. PMC: 6695568. DOI: 10.3389/fncir.2019.00051. View

Kros L, Lindeman S, Eelkman Rooda O, Murugesan P, Bina L, Bosman L . Synchronicity and Rhythmicity of Purkinje Cell Firing during Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence Epilepsy. Front Cell Neurosci. 2017; 11:346. PMC: 5671558. DOI: 10.3389/fncel.2017.00346. View

10.

Heiney S, Kim J, Augustine G, Medina J . Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity. J Neurosci. 2014; 34(6):2321-30. PMC: 3913874. DOI: 10.1523/JNEUROSCI.4547-13.2014. View

11.

Sisterson N, Wozny T, Kokkinos V, Constantino A, Richardson R . Closed-Loop Brain Stimulation for Drug-Resistant Epilepsy: Towards an Evidence-Based Approach to Personalized Medicine. Neurotherapeutics. 2018; 16(1):119-127. PMC: 6361057. DOI: 10.1007/s13311-018-00682-4. View

12.

Ibdali M, Hadjivassiliou M, Grunewald R, Shanmugarajah P . Cerebellar Degeneration in Epilepsy: A Systematic Review. Int J Environ Res Public Health. 2021; 18(2). PMC: 7827978. DOI: 10.3390/ijerph18020473. View

13.

Aiba I, Noebels J . Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models. Sci Transl Med. 2015; 7(282):282ra46. PMC: 4852131. DOI: 10.1126/scitranslmed.aaa4050. View

14.

Han V, Magnus G, Zhang Y, Wei A, Turner E . Bidirectional modulation of deep cerebellar nuclear cells revealed by optogenetic manipulation of inhibitory inputs from Purkinje cells. Neuroscience. 2014; 277:250-66. PMC: 5862060. DOI: 10.1016/j.neuroscience.2014.07.006. View

15.

Wang G, Liu X, Zhang M, Wang K, Liu C, Chen Y . Structural and functional changes of the cerebellum in temporal lobe epilepsy. Front Neurol. 2023; 14:1213224. PMC: 10435757. DOI: 10.3389/fneur.2023.1213224. View

16.

Bohnen N, OBrien T, Mullan B, So E . Cerebellar changes in partial seizures: clinical correlations of quantitative SPECT and MRI analysis. Epilepsia. 1998; 39(6):640-50. DOI: 10.1111/j.1528-1157.1998.tb01433.x. View

17.

Chen C, Newman L, Stark A, Bond K, Zhang D, Nardone S . A Purkinje cell to parabrachial nucleus pathway enables broad cerebellar influence over the forebrain. Nat Neurosci. 2023; 26(11):1929-1941. PMC: 11348979. DOI: 10.1038/s41593-023-01462-w. View

18.

Kros L, Eelkman Rooda O, Spanke J, Alva P, van Dongen M, Karapatis A . Cerebellar output controls generalized spike-and-wave discharge occurrence. Ann Neurol. 2015; 77(6):1027-49. PMC: 5008217. DOI: 10.1002/ana.24399. View

19.

Eelkman Rooda O, Kros L, Faneyte S, Holland P, Gornati S, Poelman H . Single-pulse stimulation of cerebellar nuclei stops epileptic thalamic activity. Brain Stimul. 2021; 14(4):861-872. DOI: 10.1016/j.brs.2021.05.002. View

20.

Fujita H, Kodama T, du Lac S . Modular output circuits of the fastigial nucleus for diverse motor and nonmotor functions of the cerebellar vermis. Elife. 2020; 9. PMC: 7438114. DOI: 10.7554/eLife.58613. View