Japanese clinical practice guideline for Parkinson's disease was released in 2018. In this guideline, the importance of levodopa therapy during both early and advanced stage of PD is stressed. Further, MAO–B inhibitors became a one of first–line treatment for the early stage of PD. It is also mentioned about the characteristics of Device Aided Therapy. To state recommendations of each therapy, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was employed. The recent development of devices which is used in Deep brain stimulation enable us to control PD symptoms more precisely. From 2016, Levodopa–carbidopa intestinal gel therapy became available in Japan. We have many therapeutic options for PD treatment, however, we must start to consider the cost and benefit of each therapy in the future.

Precision medicine is a medical model that provides each patient with more customized medical decision, treatments and practices based on detailed information including individual genetic information using the latest technology, instead of a one–drug–fits–all model. We report the current status and prospects of precision medicine for monogenic form of Parkinson's disease (PD).

The outcome of deep brain stimulation (DBS) is generally favorable, with improved motor function and decreased levodopa equivalent daily dose in PD patients with PRKN, LRRK2 mutations. Around 30% of PD patients with GBA mutations had poor outcomes in motor function and progressive cognitive decline was reported after DBS.

A clinical trial (MOVES–PD) using Venglustat, a small–molecule glucosylceramide synthase inhibitor, has begun in PD patients with GBA mutations. The Phase II trial of venglustat failed to meet its primary endpoint and this study was discontinued.

In PLA2G6 (PARK14) deficient Drosophila, lipid replacement therapy corrected the brain lipid composition suppressed dopaminergic neurodegeneration and α–synuclein aggregation, and improved motor function in Drosophila. The dietary manipulation of fatty acids over a long time period could change brain lipid components to prevent α–synuclein aggregation in PD patients with PLA2G6 mutations.

In CHCHD2 (PARK22) deficient Drosophila, the light–dependent activation of mitochondrial proton–motive force using Delta–rhodopsin to recover the function of mitochondria, improved α–synuclein aggregation, DA neuronal loss, and motor behaviors, suggesting that maintaining the mitochondrial proton–motive force may serve as a therapeutic strategy for PD.

Finally, we introduce “PD Registry” in our department. We are planning to recruit hundreds of PD patients, and register a clinical information with many clinical scales, advanced MRI information and genetic information, and started to create a database. Using network science and artificial intelligence, we aim to elucidate the objective evaluation method of clinical subtypes of PD, and to develop precision medicine.

We review reports published in 2018 providing new information on the management of Parkinson's disease (PD) and its related disorder. Adjunct zonisamide to levodopa improved parkinsonism in dementia with Lewy body, without worsening cognitive function or psychiatric symptoms. Camicinal, a gastroprokinetic resulted in significant reduction of off–time and significant decrease in motor symptom in patients with PD, which occurred in parallel with more rapid absorption of levodopa. Subcutaneous apomorphine infusion during waking hours (16 hour a day) significantly reduced off–time. Sodium oxybate, a first–line treatment in narcolepsy, improved excessive daytime sleepiness (EDS) and Epworth Sleepiness Scale (ESS) score in patients with PD. Rasagiline also showed beneficial effects on sleep quality in patients with PD with sleep disturbances. Safinamide improved PD chronic pain in the long term (2–year). Subthalamic nucleus (STN) deep brain stimulation (DBS) slowed rest tremor progression in early PD. STN–DBS decreased restless legs syndrome symptoms in patients with PD and the improvement was sustained over a 2–year period. STN–DBS was effective in improving impulse control disorders and neuropsychiatric fluctuations in the long term. The first randomised blinded evaluation of DBS in the caudal zona incerta (cZi) showed its efficacy on PD symptoms, especially for tremor. The doses of dopaminergic medications did not decrease. PRX002 is a humanized monoclonal antibody designed to target aggregated forms of α–synuclein. Multicenter, randomized, double–blind, placebo–controlled, multiple ascending–dose trial (phase Ib) in 80 patients with PD showed that single and multiple doses of PRX002 were generally safe and well tolerated and resulted in robust binding of peripheral α–synuclein. ProSavin is a lentiviral vector–based gene therapy that delivers local and continuous dopamine. Long–term follow up of a Phase I/II Study of ProSavin showed a significant reduction of off–time in patients with PD. ProSavin continued to be safe and well tolerated.

Movement disorders are defined as neurological states presenting with abnormal speed, fluency, quality, and ease of movement. To categorized patients with abnormal involuntary movements, movement disorders should be divided into those with too little movement, hypokinetic and those with too much movement, hyperkinetic. Mainly six movement disorders are recognized and include parkinsonism, chorea/ballismus, tremor, dystonia, myoclonus and tic. However, some movement disorders show very similar, e.g. dystonic tremor v.s. tremor, and some patients may have mixed movement disorders, e.g. dystonia with myoclonus. For understanding the movement disorders, neurologist should be aware need to focus on the speed, frequency, rhythm and localization of involuntary movements. In this chapter, we review how to diagnosis the movement disorders.