Pathophysiology of motor symptoms, cognitive impairments, and psychosis in Parkinson's disease (PD) was reviewed. To understand pathophysiology of motor symptoms in PD, two major models have been proposed. In firing rate model, depletion of striatal dopamine decreases neural activity in the direct pathway from striatum to GPi/SNr and increases neural activity in the indirect pathway via GPe and STN, resulting in greater inhibition of motor thalamus that facilitate corticospinal motor output. This model has led to a new surgical treatment for PD, though there is emerging evidence that criticize the model. In a new model, called oscillation (firing pattern) model, loss of dopamine develops or enhances pathological oscillations in the beta band in STN and GPi, leading to suppression of movement. This model explains treatment effect of STN stimulation at 130Hz used in the deep brain stimulation since the stimulation should suppress the pathological beta band oscillation and improve motor symptom in PD. Cognitive impairments in PD affect various domains while deficits in visuospatial and executive function are frequent. PD psychosis represents a spectrum of illusions, passage/presence hallucinations, formed visual hallucinations and delusions that often progress over the course of PD.

The diagnosis of Parkinson's disease (PD) is based on clinical features. The UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (UKPDSBB criteria) were proposed in 1988, and have been commonly used around the world. Since publication of UKPDSBB criteria and other previous criteria, knowledge about PD has increased and several limitations have been found. In 2015, The International Parkinson and Movement Disorder Society (MDS) offered novel clinical diagnostic criteria for Parkinson's Disease (MDS–PD criteria). We summarize the main points of the MDS–PD criteria, including the utility and limitations of those.

Parkinson's disease is a neurodegenerative disease cardinally showing movement disorders. Motor symptoms are manifested by magnification of Lewy pathology into the substantia nigra pars compacta, which induces dopaminergic neuronal loss and dopamine deficiency in the nigro–striatal dopaminergic projection. Therefore, dopamine replacement therapy is the gold standard in pharmacotherapy in Parkinson's disease. Now a days, dopaminergic agonists, dopamine economizers as well as non–dopaminergic agents are clinically available in Japan. Drug delivery systems have also been improving. Transdermal and intrajejunal formulations are available in Japan, whereas subcutaneous continuous injection, inhaler and sublingual film are available and developing in foreign countries. Most of them are based on the therapeutical concept of continuous dopaminergic stimulation. Neuromodulation and exercise are also important therapeutic interventions in motor treatment in Parkinson's disease. Deep brain stimulation and L–dopa carbidopa intestinal gel are categorized as device–aided therapy, which are applicable to advanced stage. Next to the advanced stage, late stage will inevitably come and variable refractory problems in this stage can deteriorate qualities of life. The qualities of life in the late stage can come at the expense of pharmacotherapy of motor symptoms, which should be established on the well–organized communication and an advanced adherence among patients, physicians, and care givers.

Nonmotor symptoms (NMS) have increasingly been recognized as an important part of Parkinson disease (PD). Although NMS are very common across all stages of PD, NMS are frequently undeclared from the patients, often under–recognized by the clinicians and remain untreated. The burden of NMS can define a patient's health–related quality of life. The management of NMS has been recognized as an important area of unmet needs in PD. There is a broad spectrum of NMS in PD, which include neuro–psychiatric disturbance (hallucination, delirium, delusion, impulse control disorders, cognitive dysfunction, dementia), autonomic dysfunction (orthostatic hypotension, constipation, urinary dysfunction, sexual dysfunction, hyperhydrosis), sleep disturbance (insomnia, excessive daytime sleepiness, sudden onset of sleep, REM sleep behavior disorders, restless legs syndrome), mood disorders (depression, anxiety, apathy), fatigue and sensory disturbance (pain, smell loss). Although the importance of a dopaminergic contribution to NMS in PD has been highlighted, the NMS of PD include a multitude of clinical systems derived from complex multi–neurotransmitter dysfunction involving not just the dopaminergic pathways but also noradrenergic, serotonergic and cholinergic pathways in the brain. In addition to the evolution of NMS as an intrinsic part of the disease, treatment used in PD can trigger, worsen, or even be the primary cause of symptoms. The symptoms and treatments of NMS in PD are often multiple and complex. The Japanese “PD clinical guideline 2018” updates the previous PD treatment guideline 2011 and incorporates new data on efficacy, safety, and implications for clinical practice of treatments for NMS of PD. By using the current evidence in the medical literature, evidence–based medicine helps to provide the best possible care to patients. Although there has been a number of placebo–controlled randomized trials of treatments of PD–related NMS and the evidence base for treating a range of NMS in PD has grown substantially in recent years, many nonmotor areas still lack an adequate evidence base of high–quality studies.

The aim of the article is to describe the revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) in 2017. The criteria for the clinical diagnosis of DLB were first published as the first consensus report in 1996, and were revised in the third consensus report in 2005. After discussion in the International DLB Conference in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017. The 2017 revised criteria distinguish clearly between clinical features and diagnostic biomarkers and give guidance about optimal methods to establish and interpret these. Diagnostic weighting of REM sleep behaviour disorder (RBD) and iodine–123–metaiodobenzylguanidine (MIBG) myocardial scintigraphy was increased. Future directions include development of the criteria for early diagnosis (prodromal and preclinical DLB) and pathological evaluation of diagnostic accuracy of the 2017 revised diagnostic criteria.

Dementia with Lewy bodies (DLB) causes various symptoms such as psychiatric symptoms, parkinsonism, and failures of autonomic nervous system in addition to cognitive impairment, all of which are clinical and care problems. This review provides evidence–based commentary on treatment of DLB. Donepezil has been the central means since its approval in 2014 for the treatment of cognitive impairment of DLB, and evidence of it is accumulating and gives clues of the usage of it. Although there is insufficient evidence on the efficacy of donepezil for BPSD, it is still the first choice before antipsychotics. On the other hand, motor disorders due to parkinsonism are also important therapeutic targets. Levodopa is the mainstay of treatment. Recently, multicenter, placebo–controlled, randomizeouble–blind, controlled trials have shown the efficacy of adding zonisamide over levodopa treatment for parkinsonism in DLB. Unfortunately, there is no high level of evidence of treatment for a variety of other conditions, and individual patients will be treated with knowledge of other diseases.

症例は前兆のない片頭痛の既往のある37歳男性．左耳閉感で発症し，第3病日に浮動性めまい，起立時に増悪する頭痛，嘔吐が出現．rizatriptanは無効．頭部MRIに特記すべき異常なく，第7病日に耳鼻科受診．眼振はなかったがオージオグラムで左低音難聴あり，Ménière病疑いでisosorbideが開始された．徐々に浮遊感を伴う頭痛は改善し，第13病日に聴力検査は正常化し，第20病日に症状も寛解した．7か月後に難聴が再燃するも頭痛はなく，adenosine triphosphate内服にて症状は寛解し，以後再発はない．鑑別診断として，当初前庭性片頭痛が挙げられたが，結果的に頭痛は72時間以上持続したことから除外された．頭痛はMénière病による症状と考えられた．片頭痛はMénière病を合併するとされている．片頭痛の患者において頭痛にめまいを伴った場合，前庭性片頭痛の他に，Ménière病を鑑別する必要があると考えられた．

薬剤抵抗性の本態性振戦（essential tremor：ET）10例（男性8例，女性2例，67.1±17.5歳，全例右利き）に対してMRガイド下集束超音波（MR–guided focused ultrasound：MRgFUS）による左視床中間腹側核（ventral intermediate nucleus：Vim）破壊術を行い，12か月後までの有効性と安全性を検討した．治療直後から全例で右上肢の振戦が改善し，2例で振戦が再増悪したものの，右上肢のClinical Rating Scale for Tremorの平均値は12か月後まで約60%の低下が持続した．しかし，Quality of Life in Essential Tremor QuestionnaireのGlobal Impression Scoreの平均値は有意な改善を認めなかった．有害事象の大部分は軽微かつ一過性であり，治療から6か月後以降に新規の有害事象は生じなかった．MRgFUSによる片側Vim破壊術は薬剤抵抗性のETに対する治療選択肢の1つであるが，振戦の改善効果を高めるとともに，より多数例を長期に検討する必要がある．

重心動揺リアルタイムフィードバック装置（Balance Adjustment System：BASYS）は，立位姿勢調整における随意運動と反射調整のバランスを調整する姿勢リハビリテーション用のプラットホーム型の機器である．われわれはParkinson病患者と脊髄小脳変性症患者にBASYSを用いたリハビリテーション実施した結果，10m歩行における歩数，時間及び歩行速度が改善し，その効果が5日から7日の間は維持することを確認した．立位姿勢を維持するために下腿筋群が活動した結果生じる，筋紡錘からの固有感覚情報による下位運動中枢の活性化と，伸張反射による神経回路の賦活化が歩行機能の改善に寄与した可能性がある．