Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures
| Autor: | Régis C. Lambert, Nathalie Leresche, Vincenzo Crunelli, Cian McCafferty, François David, Giuseppe Di Giovanni, Magor L. Lőrincz |
|---|---|
| Přispěvatelé: | Neuroscience Division [Cardiff, UK] (School of Bioscience), Cardiff University, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta, University College Cork (UCC), Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Malta [Malta], Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Petit mal epilepsy -- Animal models
Adolescent [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Thalamus Petit mal epilepsy -- Drug therapy Substantia nigra Comorbidity Review Article 03 medical and health sciences Epilepsy 0302 clinical medicine Limbic system limbic system Seizures Basal ganglia medicine Animals Humans Ictal Child anti-absence drugs 030304 developmental biology 0303 health sciences Thalamic reticular nucleus Valproic Acid AcademicSubjects/SCI01870 business.industry Basal ganglia -- Pathophysiology Petit mal epilepsy -- Alternative treatment medicine.disease 3. Good health medicine.anatomical_structure nervous system attention deficits Petit mal epilepsy -- Treatment basal ganglia cortico-thalamo-cortical loop AcademicSubjects/MED00310 Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Brain-A Journal of Neurology Brain-A Journal of Neurology, Oxford University Press (OUP), 2020, ⟨10.1093/brain/awaa072⟩ Brain |
| ISSN: | 0006-8950 1460-2156 |
| DOI: | 10.1093/brain/awaa072⟩ |
| Popis: | What causes absence seizures and are they really benign? Crunelli et al. review the pathophysiology, pharmacotherapy and neuropsychiatric comorbidities of absence seizures, and highlight the key role of cortical, thalamic and basal ganglia mechanisms in driving absence seizure ictogenesis. Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|