A single centre prospective study of three device-assisted therapies for Parkinson's disease.

Comparative studies assessing outcomes with the three device-assisted therapies could help to individualise treatment for patients living with Parkinson's disease. We designed a single-centre non-randomised prospective observational study assessing the quality of life (QoL), motor and non-motor outcomes at 6 and 12-months in patients treated with subcutaneous apomorphine continuous 16-hours infusion (APO), levodopa-carbidopa intestinal gel (LCIG) or subthalamic nucleus deep brain stimulation (STN-DBS). In this study, 66 patients were included (13 APO; 19 LCIG; 34 STN-DBS). At baseline, cognitive, non-motor and motor scores were significantly less severe in the STN-DBS group, whereas the LCIG group had a longer disease duration and higher non-motor scores. In the APO group, there were no statistically significant changes in non-motor, motor and QoL scales. The LCIG group had significant changes in QoL and motor scales that were significant after multiple comparison analysis at 6 and 12-months. The STN-DBS group showed improvement in QoL scores and non-motor and motor scores at 6 and 12-months after multiple comparison analysis. In this real-life prospective study, device-assisted therapies showed differences in their effects on QoL and motor and non-motor function at 12-months. However, there were also differences in baseline characteristics of the patient groups that were not based on pre-determined selection criteria. Differences in characteristics of patients offered and/or treatment with different device-assisted therapies may reflect within-centre biases that may, in turn, influence perceptions of treatment efficacy or outcomes. Treatment centres should be aware of this potential confounder when assessing and offering device-assisted treatment options to their patients and potential baseline differences need to be taken into consideration when comparing the results of non-randomised studies.

Transcranial Direct Current Stimulation on Different Targets to Modulate Cortical Activity and Dual-Task Walking in Individuals With Parkinson's Disease: A Double Blinded Randomized Controlled Trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation to modulate cortical activity for improving motor function. However, the information of tDCS stimulation on different brain regions for dual-task walking and cortical modulation in Parkinson's disease (PD) has not yet been compared. OBJECTIVE: The objective of this study was to investigate the effects of different tDCS targets on dual-task gait performance and cortical activity in patients with PD. METHODS: A total of 36 participants were randomly assigned to primary motor cortex (M1) tDCS, dorsal lateral prefrontal cortex (DLPFC) tDCS, cerebellum tDCS, or Sham tDCS group. Each group received 20 min of tDCS stimulation, except for the Sham group. Gait performance was measured by the GAITRite system during dual-task walking and single walking. Corticomotor activity of the tibialis anterior (TA) was measured using transcranial magnetic stimulation (TMS). The functional mobility was assessed using the timed up and go (TUG) test. RESULTS: All participants showed no significant differences in baseline data. Following the one session of tDCS intervention, M1 (p = 0.048), DLPFC (p < 0.001), and cerebellum (p = 0.001) tDCS groups demonstrated significant improvements in dual-task gait speed compared with a pretest. The time × group interaction [F(3, 32) = 5.125, p = 0.005] was detected in dual-task walking speed. The post hoc Tukey's test showed that the differences in gait speed were between the Sham tDCS group and the DLPFC tDCS group (p = 0.03). Moreover, DLPFC tDCS also increased the silent period (SP) more than M1 tDCS (p = 0.006) and Sham tDCS (p = 0.002). CONCLUSION: The results indicate that DLPFC tDCS exerted the most beneficial effects on dual-task walking and cortical modulation in participants with PD. CLINICAL TRIAL REGISTRATION: [http://www.thaiclinicaltrials.org/show/TCTR20200909005], Thai Clinical Trials Registry [TCTR20200909005].

Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.

The AFG3L2 gene encodes AFG3-like protein 2, which is a subunit of human mitochondrial ATPases associated with various cellular protease activities (m-AAA). The clinical spectrum of AFG3L2 mutations is broad. Dominant AFG3L2 mutations can cause autosomal dominant spinocerebellar ataxia type 28 (SCA28), whereas biallelic AFG3L2 mutations may lead to spastic ataxia 5 (SPAX5). However, the role of AFG3L2 mutations in autosomal recessive spinocerebellar ataxia (SCAR) remains elusive. The aim of this study is to delineate the clinical features and spectrum of AFG3L2 mutations in a Taiwanese cohort with cerebellar ataxia. Mutational analyses of AFG3L2 were carried out by targeted resequencing in a cohort of 133 unrelated patients with molecularly undetermined cerebellar ataxia. We identified one single patient carrying compound heterozygous mutations in AFG3L2, p.[R632*];[V723M] (c.[1894C > T];[2167G > A]). The patient has suffered from apparently sporadic and slowly progressive cerebellar ataxia, ptosis, and ophthalmoparesis since age 55 years. These findings expand the clinical spectrum of AFG3L2 mutations and suggest a new subtype of late-onset SCAR caused by biallelic AFG3L2 mutations.

Fibroblast Growth Factor 20 Gene Polymorphism in Parkinson's Disease in Asian Population: A Meta-Analysis.

Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3' untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = -3.96; p < 0.0001) and the dominant models (Z = -4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.

COVID-19 Vaccination for Persons with Parkinson's Disease: Light at the End of the Tunnel?

Several COVID-19 vaccines have recently been approved for emergency use according to governmental immunization programs. The arrival of these vaccines has created hope for people with Parkinson's disease (PD), as this can help to mitigate their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can lead to serious, life-threatening disease, at least among those with more advanced PD. However, both persons with PD and physicians looking after these individuals have expressed concerns about the vaccine's efficacy and safety in the specific context of PD and its symptomatic treatment. Here, we discuss our perspective on these concerns, based on our interpretation of the literature plus the unfolding experience with widespread vaccination in the population at large. Because the benefits and risks of COVID-19 vaccines do not appear to be different than in the general population, we recommend COVID-19 vaccination with approved vaccines to persons with PD, unless there is a specific contraindication. Some caution seems warranted in very frail and terminally ill elderly persons with PD living in long-term care facilities.

Colonic Leucine-Rich Repeat Kinase 2 Expression Is Increased and Associated With Disease Severity in Patients With Parkinson's Disease.

BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise a common genetic risk factor for Parkinson's disease (PD) and inflammatory bowel disease (IBD). We investigated the expression of LRRK2 in colonic biopsies obtained from a cohort of PD patients and healthy controls. METHODS: A cohort of 51 PD patients and 40 age- and gender-matched controls who have colonic biopsied samples were recruited. Among these participants, 26 individuals (12 PD patients and 14 controls) had a series of colon biopsies. For the patients with PD, the first biopsies were taken before the PD diagnosis. The colonic expression of LRRK2 was assayed by immunohistochemical staining. RESULTS: The fraction of LRRK2-positive cells among the total cell count in biopsied colonic tissues was significantly higher in PD patients than controls (0.81% ± 0.53% vs. 0.45% ± 0.39%; P = 0.02). Colonic LRRK2 immunoreactivity was higher in those with LRRK2 genetic variants compared to those with wild type LRRK2 (2.44% ± 1.15% vs. 0.21 ± 0.13%, P < 0.01). Age had no effect on LRRK2 expression (P = 0.96). LRRK2 expression correlated with disease severity in regards to motor symptoms measured by the UPDRS part III scores (r = 6335, P < 0.001) and cognitive dysfunction measured by the mini-mental status examination scores (r = -0.5774, P < 0.001). PD patients in the prodromal phase had a steeper increase in colonic LRRK2 expression compared to controls during the serial colon biopsy assessment (P < 0.01). CONCLUSION: Colonic LRRK2 expression was increased in PD patients compared to controls, and the expression level correlated with disease severity.

Tardive syndrome: An update and mini-review from the perspective of phenomenology.

Tardive syndrome (TS) is a group of movement disorders caused by the long-term use of dopamine receptor blocking agents. The phenotypic presentation of TS is diverse, ranging from the most well-characterized symptom of tardive dyskinesia to other symptoms, including dystonia, akathisia, myoclonus, parkinsonism, tremor, and tics. These tardive symptoms are distinct not only in their phenomenology but also in their clinical outcomes. However, our knowledge of the pathophysiology and management of TS is almost exclusively based on tardive dyskinesia. First-generation antipsychotics have a higher risk of inducing TS and have largely been replaced by second-generation antipsychotics with a lower risk of TS. However, patients with off-label use of second-generation antipsychotics are still at risk of developing TS. Thus, the management of TS remains a challenging and important issue for physicians. In this review, we update the information on the epidemiology, phenomenology, and treatment of TS from the perspective of the specific form of TS.

Genetic Analysis of EGLN1 C127S Variant in Taiwanese Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder related to nigrostriatal dopaminergic neuron degeneration and iron accumulation. As a cellular oxygen sensor, prolyl hydroxylase domain containing protein 2 (PHD2, encoded by egl-9 family hypoxia inducible factor 1, EGLN1) modifies hypoxia-inducible factor alpha (HIF-α) protein for proteasomal destruction under normoxic condition. In addition, 2-oxoglutarate- (OG-) dependent dioxygenase activity of PHD2 is involved in the oxygen and iron regulation of iron-responsive element binding protein 2 (IRP2) stability. Previously increased expression of EGLN1 was found in the substantia nigra of the parkinsonian brain. We investigated the possible role of c.380 G > C (p.C127S) of EGLN1 gene in Taiwanese patients with PD. 479 patients and 435 healthy controls were recruited. Polymerase chain reaction and BsmAI restriction enzyme analysis were applied for analysis. An association between CC genotype and reduced PD risk in the recessive model (CC vs. GG + GC) was found. Our study provides a link between EGLN1 c.380 G > C SNP and the development of PD.