Second-line treatment of Parkinson’s disease

When Parkinson’s disease evolves with the arrival of motor and non-motor fluctuations with escape from conventional drug treatment (L-dopa and oral dopaminergic agonist), the question arises of an optimization of treatment. This is called “second line” processing. It includes more complex techniques to use and is based on the principle of continuous dopaminergic stimulation (closest to the physiological state) compared to discontinuous dopaminergic stimulation represented by oral treatment (with hazards related to digestive absorption, hepatic metabolism and the passage of the blood-brain barrier). The reference technique remains deep brain stimulation (mainly subthalamic nuclei) more rarely of the thalamus (isolated trembling form). Initially reserved for patients with a long duration of disease progression and with fluctuations, it can be proposed earlier in the course (while respecting a duration of disease progression of at least 5 years to be certain of the dopa-sensitive nature of the disease). There is a risk of increased post-operative apathy to be taken into account especially in young patients. The second technique is the Apomorphine pump (APOKINON) which has undergone significant expansion in the last ten years. Easy to use subcutaneously, it can be started at home by providers and no longer requires hospitalization. We use a pump system that administers a fixed flow rate during the day with the possibility of making boluses in case of blockage. The treatment is used during the day or even at night (often half a dose of the day). Some skin tolerance problems are possible (nodules). The big advantage is that the system is reversible and can be removed easily in case of intolerance (rare) or in case of lack of efficiency. Administration of Apomorphine is often (but not always) accompanied by a decrease in oral dopaminergic therapy. The third system is based on continuous gastro-jejunal infusion by Duo-dopa pump : it can be used in patients at the early stage of motor fluctuations but requires close collaboration between neurologist and gastroenterologist given the technical problems related to the administration of the product directly by digestive tract (a test administration of the product by nasogastric tube is proposed before the realization of the endoscopic gesture and the implementation of the pump). Apart from the role of Tolcapone (TASMAR), a potent COMT inhibitor that was withdrawn from the market a few years ago following the occurrence of severe hepatitis. It can be used under conditions in fluctuating patients in combination with L-dopa with strict hepatic monitoring in case of insufficiency of other conventional drug treatments called first-line.