Nihon Rinsho. Japanese Journal Of Clinical Medicine[JOURNAL]
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200 papers
Gene therapy for Parkinson's disease.
Muramatsu SI
Nihon Rinsho · 2017 Jan · PMID 30566309
Clinical studies of gene therapy for Parkinson's disease are based on three kinds of strategies. 1. Restoration of dopamine production in the putamen by introducing genes of dopamine-synthesizing enzymes. 2. Protection o...
Clinical studies of gene therapy for Parkinson's disease are based on three kinds of strategies. 1. Restoration of dopamine production in the putamen by introducing genes of dopamine-synthesizing enzymes. 2. Protection of nigrostriatal projections by gene transfer of neurotrophic factors into the putamen and substantia nigra. 3. Modulation of subthalamic nucleus neural activity by gene delivery of an enzyme to synthesize inhibitory transmitter y-aminobutyric acid. In all studies, procedures were well tolerated and no adverse effects attributed to viral vectors were reported. The beneficial effects of putaminal gene transfer on motor symptoms have also been confirmed in children with aromatic L-amino acid decarboxylase deficiency. For a neuroprotective strategy, early intervention is necessary before degeneration has proceeded too far.
Cell-based therapies for Parkinson's disease.
Sakaguchi H, Takahashi J
Nihon Rinsho · 2017 Jan · PMID 30566308
Parkinson's disease (PD) is one of the most common neurodegenerative disorders that is characterized by the loss of A9 midbrain dopaminergic neurons. Recently, cell replacement therapy for PD using iPS cell-derived dopam...
Parkinson's disease (PD) is one of the most common neurodegenerative disorders that is characterized by the loss of A9 midbrain dopaminergic neurons. Recently, cell replacement therapy for PD using iPS cell-derived dopaminergic neurons is attracting public attention, because it is getting closer to clinical application. In this review, we introduce both of the history of cell replacement therapy for PD using fetal ventral mesencephalic tissues and future perspective using iPS cell-derived midbrain dopaminer- gic neurons. Although we must overcome multitude issues including elimination of undifferentiated cells, graft-induced dyskinesia, guarantee of quality of transplanted cells and so on, from there on, we will bring the new generation of stem cell-based cell therapy for PD.
Anti-parkinsonian drugs today.
Nagai M
Nihon Rinsho · 2017 Jan · PMID 30566307
The current pharmacotherapeutic options for Parkinson's disease is described in this article. Newly formulations of levodopa developed to date. Levodopa / carbidopa intestinal gel (Duodopa) was approved recently in Japan...
The current pharmacotherapeutic options for Parkinson's disease is described in this article. Newly formulations of levodopa developed to date. Levodopa / carbidopa intestinal gel (Duodopa) was approved recently in Japan. Duodopa permits to maintain plasma concentrations of levodopa at steady levels and prolongs ON time without dyskinesia. IPX066 is a newly developed oral formulation of levodopa, and launched in US. It contains both an immediate-release and a sustained-release levodopa component. Safinamide has an inhibitory activity of glutamate release and antagonism of sodium channel activity in addition to MAO-B inhibitor. Opicapone is a novel third generation COMT inhibitor. Rasagiline is a widely used MAO-B inhibitor in many countries. Clinical trials of the both agents are performed in Japan. Pimavanserin, a 5-HT2A inverse agonist, is the first and only medication approved by FDA for the treatment of psychosis associated with Parkinson's disease.
Detection and management of sleep disturbances in Parkinson's disease.
Suzuki K, Mivamoto M, Matsubara T
Nihon Rinsho · 2017 Jan · PMID 30566306
In Parkinson's disease (PD), sleep disturbances are major non-motor symptoms, interfering patients' quality of life. Multifactorial factors such as, PD-related pathology, motor/nonmotor symptoms and medications, influenc...
In Parkinson's disease (PD), sleep disturbances are major non-motor symptoms, interfering patients' quality of life. Multifactorial factors such as, PD-related pathology, motor/nonmotor symptoms and medications, influence sleep problems in PD. Patients with PD may complain of difficulty in initiating and maintaining sleep, daytime sleepiness, nocturia, nocturnal abnormal movement and vocalization, nocturnal pain, akinesia and leg restlessness. When nocturnal symptoms are related to wearing off phenomenon, adding dopaminergic drugs at bedtime is effective. In this section, we address these PD-related nocturnal problems including rapid eye movement sleep behavior disorder, restless legs syndrome and sleep apnea syndrome.
Olfactory dysfunction.
Taniguchi S, Takeda A
Nihon Rinsho · 2017 Jan · PMID 30566305
Patients with Parkinson's disease (PD) are known to suffer from a variety of non-motor symptoms, such as olfactory dysfunction. In fact, the impaired sense of smell is suggested to precede clinically detectable motor sig...
Patients with Parkinson's disease (PD) are known to suffer from a variety of non-motor symptoms, such as olfactory dysfunction. In fact, the impaired sense of smell is suggested to precede clinically detectable motor signs by several years. Furthermore, several studies demonstrated that the earliest neuropathological changes in PD brain appeared in the olfactory-related brain regions including olfactory bulb. Such an early involvement of olfactory-related areas can explain the hyposmia as one of early signs in PD. On the other hand, recent studies suggested that severe olfactory dysfunction might be a prodromal symptom of dementia associated with PD. Thus, the smell tests seem to be not only a feasible diagnostic tool for the early PD, but also a potentially useful biomarker for the Parkinson disease dementia (PDD).
Bowel and bladder disorders in Parkinson's disease.
Sakakibara R, Tateno F, Yamamoto T … +1 more , Uchiyama T
Nihon Rinsho · 2017 Jan · PMID 30566304
Bladder and gastrointestinal (GI) dysfunction are one of the most common in non-motor disorder of Parkinson's disease (PD). GI dysfunction consists of delayed gastric emptying and constipation, which occur in 70 percent...
Bladder and gastrointestinal (GI) dysfunction are one of the most common in non-motor disorder of Parkinson's disease (PD). GI dysfunction consists of delayed gastric emptying and constipation, which occur in 70 percent of patients and often predate motor disorder. Delayed gastric emptying, slow colonic transit, decreased phasic rectal contraction, weak abdominal strain and paradoxical sphincter contraction on defecation are all features of GI dysfunction in PD, reflecting mostly myenteric plexus pathology. Bladder dysfunction (overactive bladder [OAB]) occurs in 70 percent of patients. This reflects central pathology, particularly in the prefrontal-nigrostriatal DI dopaminergic pathways. The dysfunction needs particular care in order to prevent delayed absorption of levodopa and emergency intestinal pseudo-obstruction.
Neuropsychiatric symptoms in patients with Parkinson's disease.
Kashihara K
Nihon Rinsho · 2017 Jan · PMID 30566303
Neuropsychiatric symptoms that occur in patients with Parkinson's disease (PD) include depression, anxiety, apathy, hallucinations, delusions, and behavioral disorders such as pathological gambling, hypersexuality, dopam...
Neuropsychiatric symptoms that occur in patients with Parkinson's disease (PD) include depression, anxiety, apathy, hallucinations, delusions, and behavioral disorders such as pathological gambling, hypersexuality, dopamine dysregulation syndrome, and punding. The risk factors consist of intrinsic, extrinsic, and inducing factors. Intrinsic factors include aging and PD pathology-related neurodegeneration of the central nervous system. Extrinsic factors include the drugs used to manage Parkinsonian symptoms and concomitant medical conditions. Inducing factors include complicated medical conditions such as fever and dehydration, and psychosocial stress such as that following the death of a spouse, moving homes, or hospitalization. Psychiatric symptoms may lower the quality of life of patients and their caregivers. Better management may be attained by understanding risks associated with the patient's background and dealing with them appropriately.
Cognitive Impairments in Parkinson's disease.
Nakashima K
Nihon Rinsho · 2017 Jan · PMID 30566302
In Parkinson's disease (PD), cognitive impairment is often observed. The clinical diagnostic criteria of dementia associated with PD (PDD) was reported by the Movement Disorder Society Task Force. In PDD, cognitive impai...
In Parkinson's disease (PD), cognitive impairment is often observed. The clinical diagnostic criteria of dementia associated with PD (PDD) was reported by the Movement Disorder Society Task Force. In PDD, cognitive impairments including memory, visuospatial function and executive function have been reported. The diagnostic criteria of mild cognitive impairment in PD (PD-MCI) was also reported by the Movement Disorder Society Task Force. The number of patients with PD, PD-MCI and PDD are growing. Using these criteria, studies of cognitive impairment in PD are progressing, including epidemiology, assessment, neurobiology, diagnostic biomarkers, prevention and treatment.
Autonomic dysfunction.
Nakamura T, Sobue G
Nihon Rinsho · 2017 Jan · PMID 30566301
Autonomic symptoms affect most patients with Parkinson's disease (PD) and often have a profound impact on their prognosis. Symptoms include orthostatic hypotension, gastroparesis, constipation, excessive sweating, and se...
Autonomic symptoms affect most patients with Parkinson's disease (PD) and often have a profound impact on their prognosis. Symptoms include orthostatic hypotension, gastroparesis, constipation, excessive sweating, and sexual dysfunction, however, these symptoms are frequently unrecognised by clinicians and remain untreated. The mechanism of autonomic dysfunction is attributed to the involvement of the central and peripheral postganglionic nervous system. It is now well established some autonomic symptoms have a diagnostic value because they appear early in the course of PD and may precede the onset of motor symptoms. Early recognition of autonomic symptoms is essential because it will help to expand our knowledge of the nature the neurodegenera- tive process. It is important that physicians both recognize and treat theses complications in an effort to improve quality of life.
Rehabilitation for patients with Parkinson's disease.
Chuma T
Nihon Rinsho · 2017 Jan · PMID 30566300
Parkinson's disease (PD) is a progressive neurodegenerative disorder. In our research for patients with PD, they were having trouble with posture disorder, gait disorder, fatigue and constipation. And almost of them have...
Parkinson's disease (PD) is a progressive neurodegenerative disorder. In our research for patients with PD, they were having trouble with posture disorder, gait disorder, fatigue and constipation. And almost of them have gotten some exercise to keep their health and felt beneficial effect of exercise. Rehabilitation for patients with PD is one of standard therapies of PD and includes stretching, muscle training, exercise using external cueing strategies and walking. Recently, the exercise effect includes the report of the effect on PD progression. It is important that we confirm the needs of patients with PD and start rehabilitation at an early stage to prevent movement disorder.
Deep brain stimulation for Parkinson's disease.
Umemura A, Oyama G, Shimo Y … +1 more , Hattori N
Nihon Rinsho · 2017 Jan · PMID 30566299
There is a long history of surgical treatment for Parkinson's disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment...
There is a long history of surgical treatment for Parkinson's disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. In this review, we summarize accumulated findings concerning patient selection, clinical outcomes, complications, target selection, long-term outcomes, manage- ment of axial symptoms, and timing of surgery in DBS for PD. We also describe new technologies of DBS device.
The therapy of the motor symptoms in the advanced stage of Parkinson's disease.
Takahashi K
Nihon Rinsho · 2017 Jan · PMID 30566298
This review focuses on the medical treatment strategies for the advanced stages of Parkinson disease (PD), according to the therapeutic guideline for PD by the committee of Japanese Society of Neurology in 2011. Levodopa...
This review focuses on the medical treatment strategies for the advanced stages of Parkinson disease (PD), according to the therapeutic guideline for PD by the committee of Japanese Society of Neurology in 2011. Levodopa still remains the gold standard for the treatment of motor symptoms of PD in advanced stage, but dopamine agonists, monoamine oxidase B inhibitors and catechol-O-methyltransferase inhibitors have--also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to prevent and improve levodopa-induced motor complications, including wearing off phenomenon and peak-dose dyskinesia. A number of non-dopaminergic receptors are expressed on different parts of the basal ganglia motor circuits and have become targets of PD drug development. Zonisamide, which has multimodal effects on the dopaminergic and non-dopaminergic systems, and istradefylline, the first adenosine A2A antagonist, have shown positive evidence for improved motor fluctuations.
Pharmacological treatment of early Parkinson's disease.
Yamamoto M
Nihon Rinsho · 2017 Jan · PMID 30566297
Initiation of medical treatment of early stage of Parkinson's disease (PD) is consisted of pharmacological and no-pharmacological treatment. When and which drug is rationale for initial treatment is still controversial e...
Initiation of medical treatment of early stage of Parkinson's disease (PD) is consisted of pharmacological and no-pharmacological treatment. When and which drug is rationale for initial treatment is still controversial except young-onset PD patient. Initial drug should be decided according to patient state, age of onset and present, severity and cognition. Dopamine agonist is rationale for young-onset PD patient at early stage. Disease modify therapy is not established.
Secondary parkinsonism.
Terashi H, Taguchi T, Aizawa H
Nihon Rinsho · 2017 Jan · PMID 30566296
Although many disorders are included in secondary parkinsonism, the mechanisms underlying parkinsonism vary and have yet to be elucidated. Herein, we introduced a group of diseases included among the forms of secondary p...
Although many disorders are included in secondary parkinsonism, the mechanisms underlying parkinsonism vary and have yet to be elucidated. Herein, we introduced a group of diseases included among the forms of secondary parkinsonism and provide overviews of clinically significant drug-induced parkinsonism (DIP), vascular parkinson- ism (VP), and idiopathic normal pressure hydrocephalus (iNPH) with a focus on pathophysiology and symptoms. Although DIP has the highest frequency among the forms of secondary parkinsonism, it is overlooked in many patients due to lack of knowledge about drugs by the prescribing physicians. Both VP and iNPH present with "lower body parkinsonism, " showing the characteristic gait disturbance. DIP and iNPH are treatable, highlighting the importance of early diagnosis and treatment intervention.
Differential diagnosis of Parkinson's disease and other neurodegenerative disorders.
Koh J, Ito H
Nihon Rinsho · 2017 Jan · PMID 30566295
Parkinson's disease (PD) is a common neurodegenerative disorder. In 2015, The Movement Disorder Society Clinical Diagnostic Criteria for PD was published. In the criteria, the absolute exclusion criteria and red flags we...
Parkinson's disease (PD) is a common neurodegenerative disorder. In 2015, The Movement Disorder Society Clinical Diagnostic Criteria for PD was published. In the criteria, the absolute exclusion criteria and red flags were designed to minimize diagnostic error, in particular to differentiate from neurodegenerative or secondary parkinsonism. Here, we reviewed neurodegenerative disorders that we should differentiate from PD. The common differential diagnoses, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, and essential tremor are important but sometimes difficult to differentiate. We also described the features of rare but important differential diagnoses: neuronal intranuclear inclusion disease, Perry syndrome, Fragile X tremor/ataxia syndrome, Huntington's disease, dopa-responsive dystonia, Wilson disease, and neurodegeneration wit,1 brain iron accumulation.
Diagnostic imaging in Parkinson's disease.
Orimo S
Nihon Rinsho · 2017 Jan · PMID 30566294
Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes (PS). The purpose of performing brain MRI is to exclude other PS. Recently, several new MRI techniques such as functio...
Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes (PS). The purpose of performing brain MRI is to exclude other PS. Recently, several new MRI techniques such as functional MRI and neuromelanin imaging have been introduced in the diagnosis of PD. MIBG cardiac scintigraphy is a sensitive imaging tool to differentiate PD from other PS. Dopamine transporter imaging is a sensitive tool to detect very early neurodegenerative parkinsonism but is difficult to differentiate PD from other neurodegenerative PS. Brain perfusion imaging is sometimes useful to diagnose PD. Transcranial sonography (TCS) of the substantia nigra is useful to differentiate PD from other PS. However the recording failure of TCS in aged, particularly female subjects, may limit the clinical use in Japan.
Animal models for Parkinson's disease.
Ikuno M, Takahashi R
Nihon Rinsho · 2017 Jan · PMID 30566293
Parkinson's disease (PD) is one of the most common degenerative disorders of the CNS, characterized by motor syndrome, for example, tremor, rigidity, bradykinesia, and postural instability. Parkinson's disease was first...
Parkinson's disease (PD) is one of the most common degenerative disorders of the CNS, characterized by motor syndrome, for example, tremor, rigidity, bradykinesia, and postural instability. Parkinson's disease was first described in 1817, but the pathogenesis still remains unclear. An animal model is very important, in order to explore the pathogenesis, to search for translatable biomarkers, and verify the efficacy of experimental therapeutic interven- tions. However, there is no perfect animal model of PD. Animal model for PD need 1) clinical symptoms of parkinsonism, 2) selective catecholaminergic neuronal loss, and 3) Lewy bodies and Lewy neurites. We deal here with representative animal models for PD, including drug-induced models (MPTP, Rotenone, 6-OHDA) and genetic models (α-synuclein, PARKIN: PINK1).
Neuroprotective effects of Necdin in the Parkinson's disease.
Sasaki T, Mochizuki H
Nihon Rinsho · 2017 Jan · PMID 30566292
Necdin, a growth suppressor expressed predominantly in postmitotic neurons, interacts with transcription factors E2F1 and p53. Mitochondrial dysfunction plays central roles in the pathophysiology of neurodegenerative dis...
Necdin, a growth suppressor expressed predominantly in postmitotic neurons, interacts with transcription factors E2F1 and p53. Mitochondrial dysfunction plays central roles in the pathophysiology of neurodegenerative disease including Parkinson's disease. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-la) is master regulator in mitochondrial biogenesis. Necdin promotes neuronal mitochondrial biogene- sis induced by enhanced PGC-la expression in neuron. Necdin binds and strongly stabilizes PGC-la by inhibiting its ubiquitin-proteasomal degradation. Necdin KO mice aggravates MPTP-induced dopaminergic neuronal loss. In the adult mice, AAV-mediated overexpression of necdin in the substantia nigra leads to significant neuroprotection in experimental Parkinson's disease. These findings demonstrate that necdin promotes mitochondrial biogenesis mediated by stabilization of endogenous PGC-la protein to enhance neuroprotection against neurodegenerative disease by mitochondriallInsults.
Mitochondrial damages and Parkinson's disease.
Imai Y
Nihon Rinsho · 2017 Jan · PMID 30566291
The mitochondrion is an organelle that regulates a variety of cellular events, including ATP production, lipid and iron metabolism, cellular Ca(2+) concentration buffering and apoptotic and necrotic signaling. Characteri...
The mitochondrion is an organelle that regulates a variety of cellular events, including ATP production, lipid and iron metabolism, cellular Ca(2+) concentration buffering and apoptotic and necrotic signaling. Characterization of neurotoxins that recapitulate parkinsonian phenotypes has suggested that putative environmental factors that endanger mitochondrial activity could be risk factors for Parkinson's disease. Recent advances in the genetic analyses of familial PD cases have provided molecular evidence that a subset of causative and susceptible genes of Parkinson' s disease controls mitochondrial functions. PINKI, Parkin, and Fbxo7 are suggested to be involved in mitochondrial quality control. DJ-1 protects cells from oxidative stress caused by oxidative phosphorylation (OXPHOS) in mitochondria, and CHCHD2 could regulate OXPHOS complexes. PLA2G6 is suggested to regulate phospholipid oxidation and Ca2+ dynamics. These findings contribute to the evidence that midbrain dopamiiergic neurons are particularly sensitive to mitochondrial malfunction. Further research in this area will lead to the identification of new molecular targets for Parkinson's disease therapeutics.
Genes for Parkinson's disease.
Toda T
Nihon Rinsho · 2017 Jan · PMID 30566290
Parkinson's disease (PD) is caused by multiple genetic and environmental factors. ~14 disease causing genes have been identified for familial form of Parkinson's disease studies of which indicate a cell death pathway in...
Parkinson's disease (PD) is caused by multiple genetic and environmental factors. ~14 disease causing genes have been identified for familial form of Parkinson's disease studies of which indicate a cell death pathway in dopaminergic neurons induced by defective protein degradation as a key molecular mechanism underlying the pathogenesis of PD. Yet the majority of PD cases are sporadic, which is a multifactorial genetic disorder. We performed genome-wide association study (GWAS) and identified four PD- susceptibility loci. Now, large-scale meta-analysis of GWAS identifies total of -30 genes. Rare variants, less common yet associated with high risks for the disease onset, are also important, and Gaucher disease mutations are proven to be a definite rare variant risk factor for PD.
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