Lancet neurology
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The efficacy of amantadine in the symptomatic treatment of patients with Parkinson's disease, discovered serendipitously more than 50 years ago, has stood the test of time and the drug is still commonly used by neurologists today. Its pharmacological actions are unique in combining dopaminergic and glutamatergic properties, which account for its dual effect on parkinsonian signs and symptoms and levodopa-induced dyskinesias. ⋯ Other uses of amantadine, such as in the treatment of drug-induced parkinsonism, atypical parkinsonism, Huntington's disease, or tardive dyskinesia, lack a strong evidence base. Future trials should examine its role in the management of motor and non-motor symptoms in patients with early Parkinson's disease and those with other movement disorders.
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Three neuromodulation therapies have been appropriately tested and approved in refractory focal epilepsies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation of the epileptogenic zone or zones. These therapies are primarily palliative. Only a few individuals have achieved complete freedom from seizures for more than 12 months with these therapies, whereas more than half have benefited from long-term reduction in seizure frequency of more than 50%. ⋯ Biomarkers to predict response to neuromodulation therapies are not available, and high-level evidence to aid decision making about when and for whom these therapies should be preferred over other antiepileptic treatments is scant. Future studies are thus needed to address these shortfalls in knowledge, approve other forms of neuromodulation, and develop personalised closed-loop therapies with embedded machine learning. Until then, neuromodulation could be considered for individuals with intractable seizures, ideally after the possibility of curative surgical treatment has been carefully assessed and ruled out or judged less appropriate.