Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects 1–2% of people by the age of 70 years. Age is the most important risk factor, and most cases are sporadic without any known environmental or genetic causes. Since the late 1990s, mutations in the genes SNCA, PRKN, LRRK2, PINK1, DJ-1, VPS35, and GBA have been shown to be important risk factors for PD. In addition, common variants with small effect sizes are now recognized to modulate the risk for PD. Most studies in genetic PD have focused on finding new genes, but few have studied the long-term outcome of patients with the specific genetic PD forms. Patients with known genetic PD have now been followed for more than 20 years, and we see that they may have distinct and different prognoses. New therapeutic possibilities are emerging based on the genetic cause underlying the disease. Future medication may be based on the pathophysiology individualized to the patient’s genetic background. The challenge is to find the biological consequences of different genetic variants. In this review, the clinical patterns and long-term prognoses of the most common genetic PD variants are presented.
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The etiology of Parkinson’s disease (PD) is not fully understood, but environmental toxin overexposure, increased intestinal permeability, and dysbiosis related to nutrition and lifestyle habits are thought to be contributors. Considering these nutrition and lifestyle implications, there is a lack of practice-based programs utilizing interventions for managing symptoms or slowing the progression of the disease. The purpose of this narrative review was to identify relevant research related to nutrition and lifestyle interventions for PD, evaluate the research utilizing the evidence analysis process of the Academy of Nutrition and Dietetics to assess the quality of each research article, and group the research into categories. A grading of recommendations assessment, development and evaluation (GRADE) of either good, fair, limited, or not assignable was allocated to each category of research, including diet patterns, vitamin D, B-complex, omega-3 fatty acids, coenzyme Q10, probiotics, physical activity, stress, and sleep. An intervention based on the research presented in the review may be utilized for coaching people with PD on symptom management.
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While many infectious disorders are unknown to most neurologists, COVID-19 is very different. It has impacted neurologists and other health care workers, not only in our professional lives but also through the fear and panic within our own families, colleagues, patients and their families, and even in the wider public. COVID-19 affects all sorts of individuals, but the elderly with underlying chronic conditions are particularly at risk of severe disease, or even death. Parkinson’s disease (PD) shares a common profile as an age-dependent degenerative disorder, frequently associated with comorbidities, particularly cardiovascular diseases, so PD patients will almost certainly fall into the high-risk group. Therefore, the aim of this review is to explore the risk of COVID-19 in PD based on the susceptibility to severe disease, its impact on PD disease severity, potential long-term sequelae, and difficulties of PD management during this outbreak, where neurologists face various challenges on how we can maintain effective care for PD patients without exposing them, or ourselves, to the risk of infection. It is less than six months since the identification of the original COVID-19 case on New Year’s Eve 2019, so it is still too early to fully understand the natural history of COVID-19 and the evidence on COVID-19-related PD is scant. Though the possibilities presented are speculative, they are theory-based, and supported by prior evidence from other neurotrophic viruses closely related to SARS-CoV-2. Neurologists should be on high alert and vigilant for potential acute and chronic complications when encountering PD patients who are suspected of having COVID-19.
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Objective Non-motor symptoms (NMSs) significantly contribute to increased morbidity and poor quality of life in patients with parkinsonian disorders. This study aims to explore the profile of NMSs in patients with progressive supranuclear palsy (PSP) using the validated Non-Motor Symptom Scale (NMSS).
Methods Seventy-six patients with PSP were evaluated in this study. Motor symptoms and NMSs were evaluated using the PSP Rating Scale (PSPRS), Unified Parkinson’s Disease Rating Scale-III, Montreal Cognitive Assessment, Hamilton Depression (HAMD) and Anxiety Rating Scales, Parkinson’s Disease Sleep Scale (PDSS) and NMSS. NMS severity and prevalence were also compared between patients with PSP-Richardson syndrome (PSP-RS) and those with PSP-parkinsonism.
Results All subjects in this cohort reported at least 2 NMSs. The most prevalent NMSs in patients with PSP were in the domains of sleep/fatigue, mood/cognition, and sexual function. The least prevalent NMSs were in the domains of cardiovascular including falls, and perceptual problems/hallucinations. Significant correlations were observed between the NMSS scores and HAM-D, PDSS, PSPRS scores and PSPRS sub-scores. The severity of NMSs was unrelated to the duration of illness. Patients with PSP-RS reported a higher severity of drooling, altered smell/taste, depression and altered interest in sex and a higher prevalence of sexual dysfunction.
Conclusion NMSs are commonly observed in patients with PSP, and the domains of sleep, mood and sexual function are most commonly affected. These symptoms contribute significantly to disease morbidity, and clinicians should pay adequate attention to identifying and addressing these symptoms.
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Objective The long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on postural instability and gait difficulty (PIGD) in patients with Parkinson’s disease (PD) remain unclear. In this study, we aimed to evaluate the longterm effects of STN-DBS surgery on PIGD symptoms in patients with advanced-stage PD. Methods This study included 49 consecutively included patients with PD who underwent bilateral STN-DBS. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and subscores for PIGD were assessed at baseline and at 1, 3, and 5 years postoperatively. The PIGD subscore was divided into PIGD-motor and PIGD-activities of daily living (ADL) scores according to parts III and II of the UPDRS, respectively. Results The PIGD-motor and PIGD-ADL scores at the “medication-off” state improved at 3 and 5 years, respectively. Overall, the UPDRS III and II scores at “medication-off” improved at 5 years. The UPDRS IV score also significantly improved and the levodopa equivalent daily dosage decreased at all follow-ups. Finally, the PIGD-motor score at baseline was able to predict long-term improvement in the PIGD-motor score at the 5-year follow-up. Conclusion The STN-DBS has both short- and long-term effects on PIGD, as well as overall motor function, in patients with advanced PD. The degree of PIGD at the preoperative evaluation can be used to predict long-term outcomes after STN-DBS surgery.
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The Role of Microelectrode Recording in Deep Brain Stimulation Surgery for Parkinson’s Disease: A Systematic Review and Meta-Analysis R. Saman Vinke, Martin Geerlings, Ashok K. Selvaraj, Dejan Georgiev, Bastiaan R. Bloem, Rianne A.J. Esselink, Ronald H.M.A. Bartels Journal of Parkinson's Disease.2022; 12(7): 2059. CrossRef
Axial impairment and falls in Parkinson’s disease: 15 years of subthalamic deep brain stimulation Alessandro Zampogna, Francesco Cavallieri, Francesco Bove, Antonio Suppa, Anna Castrioto, Sara Meoni, Pierre Pélissier, Emmanuelle Schmitt, Amélie Bichon, Eugénie Lhommée, Andrea Kistner, Stephan Chabardès, Eric Seigneuret, Valerie Fraix, Elena Moro npj Parkinson's Disease.2022;[Epub] CrossRef
Objective To investigate whether baseline olfactory dysfunction in Parkinson’s disease (PD) patients is associated with baseline and longitudinal motor and cognitive function.
Methods We recruited 228 drug-naïve PD patients who were followed for a mean of 6 years. Patients underwent the Cross-Cultural Smell Identification Test (CCSIT), a neuropsychological test, and N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography within 6 months of the baseline evaluation. Olfactory dysfunction was categorized as normosmia (CCSIT score ≥ 9), hyposmia (CCSIT score 5–8), and anosmia (CCSIT score ≤ 4). During the follow-up period, we investigated changes in the levodopa-equivalent dose (LED) and the occurrence of wearing-off, levodopa-induced dyskinesia, and dementia.
Results Among the PD patients, 80.7% were hyposmic at the time of diagnosis, and 26.1% were anosmic. Baseline olfactory dysfunction was not associated with either initial parkinsonian motor symptoms or with the longitudinal LED increment and motor complications. Meanwhile, the anosmic group had lower baseline scores on the Korea version of the Boston Naming Test and Stroop color reading test than the normosmic and hyposmic groups. The anosmic group exhibited a higher rate of conversion to dementia than the normosmic [adjusted hazard ratio (HR) 3.99, 95% confidence interval (CI) 1.08–14.72] and hyposmic (adjusted HR 2.48, 95% CI 1.15–5.32) PD groups, regardless of baseline motor deficits and cognitive status.
Conclusion Baseline olfactory dysfunction was not associated with motor deficits and complications, but it was associated with cognitive dysfunction and prognosis, suggesting that severe olfactory impairment may reflect early cortical involvement, probably in the frontotemporal region, and rapid spreading of Lewy body pathology.
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Olfactory dysfunction is associated with motor function only in tremor-dominant Parkinson’s disease Fardin Nabizadeh, Kasra Pirahesh, Elham Khalili Neurological Sciences.2022; 43(7): 4193. CrossRef
Novel diagnostic tools for identifying cognitive impairment using olfactory-stimulated functional near-infrared spectroscopy: patient-level, single-group, diagnostic trial Jaewon Kim, Dong Keon Yon, Kyu Yeong Choi, Jang Jae Lee, Namwoo Kim, Kun Ho Lee, Jae Gwan Kim Alzheimer's Research & Therapy.2022;[Epub] CrossRef
The Role of Olfactory System in the Etiogenesis of Parkinson’s Diseases: An Overview Jiju Narayanan Avanipully, Dithu Thekkekkara, Sahyadri M, Vipan K. Parihar, Santhepete Nanjundaiah Manjula Journal of Pharmacology and Pharmacotherapeutics.2022; 13(1): 31. CrossRef
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Impact of Subthalamic Deep Brain Stimulation on Hyposmia in Patients With Parkinson's Disease Is Influenced by Constipation and Dysbiosis of Microbiota Chao Li, Ying Hou, Xu Wang, Yue-xuan Li, Feng Li, Chao Zhang, Wei-guo Li Frontiers in Neurology.2021;[Epub] CrossRef
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Objective We aimed to identify risk factors for falls in patients with de novo Parkinson’s disease (PD). Methods Forty-six patients with de novo PD were retrospectively included in the study. We assessed details on the patients’ motor symptoms as well as non-motor symptoms using several representative scales for global cognition, depression, fatigue, and dysautonomia. Fallers and non-fallers were identified according to their history of falls during the preceding year. Results Twenty-two patients (45.8%) with de novo PD had a history of falls. Compared with the non-faller group, the faller group exhibited higher scores for postural instability/gait difficulty (PIGD), anxiety, fatigue, total dysautonomia, gastrointestinal dysfunction, and thermoregulatory dysfunction. Moreover, logistic regression analysis showed that falling was positively correlated with anxiety and gastrointestinal symptoms but negatively associated with the tremor scores. Conclusion Our findings suggest that falling in patients with de novo PD is significantly associated with PIGD/non-tremor symptoms, anxiety, and gastrointestinal dysfunction.
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Association Between Gait and Dysautonomia in Patients With De Novo Parkinson’s Disease: Forward Gait Versus Backward Gait Seon-Min Lee, Mina Lee, Eun Ji Lee, Rae On Kim, Yongduk Kim, Kyum-Yil Kwon Journal of Movement Disorders.2023; 16(1): 59. CrossRef
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Initial Vestibular Function May Be Associated with Future Postural Instability in Parkinson’s Disease Jeong Ho Park, Min Seung Kim, Suk Yun Kang Journal of Clinical Medicine.2022; 11(19): 5608. CrossRef
Association of fall risk factors and non-motor symptoms in patients with early Parkinson’s disease Kyum-Yil Kwon, Suyeon Park, Eun Ji Lee, Mina Lee, Hyunjin Ju Scientific Reports.2021;[Epub] CrossRef
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Objective Cognitive symptoms of Parkinson’s disease (PD) may be alleviated by moderate-to-vigorous physical activity (MVPA), but no published research has characterized the relationship between objectively measured sedentary behavior and cognitive symptoms of PD. Therefore, the objective of this study was to assess the cross-sectional relationship between sedentary time and cognitive performance in a small pilot sample of individuals with mild-to-moderate PD. Methods Objective measures of sedentary time were obtained using an armband accelerometer. Cognition was assessed with the Parkinson’s Disease Cognitive Rating Scale and a computerized task-switching paradigm. Results The percentage of awake time spent in sedentary activities was negatively correlated with attention (β = -14.20, t(12) = -2.47, p = 0.03) but not other cognitive domains (p > 0.05) after controlling for MVPA and medication dosage. Conclusion Sedentary activity may have unique associations with cognition, particularly attention, over and above MVPA in individuals with PD.
Dopa-responsive dystonia (DRD) is a complex genetic disorder with either autosomal dominant or autosomal recessive inheritance, with autosomal dominant being more frequent. Autosomal dominant DRD is known to be caused by mutations in the GCH1 gene, with incomplete penetrance frequently reported, particularly in males. Here, we report a male patient with DRD caused by exon 1 deletion in the GCH1 gene inherited from the asymptomatic mother. The patient had an atypical presentation, notably with no dystonia, and underwent extensive workup for a myriad of neuromuscular disorders before a low-dose L-dopa trial and confirmatory genetic testing were performed. Our experience with this family highlights an atypical presentation of DRD and prompts us to consider the genetic complexity of DRD.
Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.
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