Publication date: November 2017
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Paul Hwang
Since the 1960s, major neuroscience advances have facilitated the development of new antiepilepsy drugs (AEDs) targeting specific neurotransmitter-receptor systems, particularly the GABAergic, the NMDA-receptors and voltage-gated ion channels. In addition to the classical AEDs, carbamazepine and cogeners act at the voltage-gates sodium channels, while ethosuxumide acts at the calcium channel, improving the treatment of partial and generalized seizures. But approximately 30% of partial complex seizures remain refractory to AEDs, leading to novel AEDs: levetiracetam, tiagabine, lacosamide, perampanel and others. The pharmacoresistant epilepsies are typically dyscognitive partial-onset, arising from limbic structures of mesial temporal lobes, better visualised by improved neuroimaging methods eg. MRI and PET. Together with invasive intracranial monitoring in specialized units with long-term recording of multichannelled EEG and videorecording of behaviour, the localization of the seizure-onset zone has allowed targeted excision of the epileptogenic tissue for better outcome.Functional neurosurgical methods include vagal nerve stimulation and deep brain stimulation of selected targets in affected circuits, mapped by new EEG criteria including gamma rhythm, HFOs, ripples and clusters. Novel intervention in refractory epilepsies include the ketogenic diet and variants, neurosteroids, hormones eg. progestins and ACTH. A number of genetic mutations and copy number variants have been linked to epilepsies. It remains to be seen how expanded knowledge of the genetic bases of the epilepsies and epileptic encephalopathies leads to new intervention improving long-term prognosis and quality of life in persons afflicted with this ancient curse of the human condition, 'The Falling Sickness' also known as 'The Sacred Disease' (Hippocrates).In the words of Sir William Osler: 'He who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all' ('Aequanimitas' by Osler), quoted in Herbert Ho Ping Kong, 'The Art of Medicine: Healing and the Limits of Technology' (ECW Press, 2014 Toronto).
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