Abstract
Genetic brain channelopathies result from inherited or de novo mutations of genes encoding ion channel subunits within the central nervous system. Most neurological channelopathies arise in childhood with paroxysmal or episodic symptoms, likely because of a transient impairment of homeostatic mechanisms regulating membrane excitability, and the prototypical expression of this impairment is epilepsy. Migraine, episodic ataxia and alternating hemiplegia can also occur, as well as chronic phenotypes, such as spinocerebellar ataxias, intellectual disability and autism spectrum disorder. Voltage-gated and ligand-gated channels may be involved. In most cases, a single gene may be associated with a phenotypical spectrum that shows variable expressivity. Different clinical features may arise at different ages and the adult phenotype may be remarkably modified from the syndrome onset in childhood or adolescence. Recognizing the prominent phenotypical traits of brain channelopathies is essential to perform appropriate diagnostic investigations and to provide the better care not only in the paediatric setting but also for adult patients and their caregivers. Herein, we provide an overview of genetic brain channelopathies associated with epilepsy, highlight the different molecular mechanisms and describe the different clinical characteristics which may prompt the clinician to suspect specific syndromes and to possibly establish tailored treatments.
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EEG changes at different ages in an adult patient with Dravet syndrome and drug-resistant seizures (personal observation, routine EEG bipolar montage, high-pass filter 1.6 Hz, low-pass filter 70 Hz, amplitude sensitivity 100 microV/cm). A. Mild slowing of background activity at 7–7.5 Hz, short electrographic seizure arising in the right frontotemporal regions (20 years of age). B. Bilateral diffuse slow activity at 5.5–6 Hz with rare sharp waves in the right frontotemporal regions (25 years of age). C. Slow background activity at 6–7 Hz with abundant interictal discharges, especially in frontotemporal regions bilaterally and over the midline channels (26 year of age). D. Mild slowing of background activity at 7–7.5 Hz, persisting sharp waves in the right temporal regions (32 years of age) (PNG 3612 kb)
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Bartolini, E., Campostrini, R., Kiferle, L. et al. Epilepsy and brain channelopathies from infancy to adulthood. Neurol Sci 41, 749–761 (2020). https://doi.org/10.1007/s10072-019-04190-x
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DOI: https://doi.org/10.1007/s10072-019-04190-x