Seong-Min Choi

Distinct and Combined Cognitive Profiles associated with Depression and Anxiety in Early Parkinson

Background and Objectives: Head trauma (HT) has been suggested as a risk factor for Parkinson’s disease (PD), but its impact on the motor and non-motor manifestations remains unclear. We investigated whether patients with early PD and a history of HT differ from those without HT in terms of their motor and non-motor symptom profiles. Materials and Methods: We enrolled patients with early PD (disease duration of ≤5 years, modified Hoehn and Yahr stages [mHY] 1–3). HT history was ascertained by structured questionnaire. Motor and non-motor symptoms were evaluated using standardized clinical rating scales. Motor subtypes—tremor-dominant (TD), akinetic-rigid (AR), and mixed—were determined according to established criteria based on the tremor-to-AR score ratio. Subtype distribution and motor scores were compared between HT and non-HT groups using univariate tests, mHY-adjusted ANCOVA, and multivariable models adjusting for age, sex, disease duration, education, mHY stage, MMSE, and BDI score. Results: Of 237 patients, 35 (14.8%) reported HT. The HT group had a higher mHY stage than the non-HT group and showed lower total and rest tremor scores on the Unified Parkinson’s Disease Rating Scale, whereas rigidity scores were similar. Bradykinesia and gait/posture scores tended to be higher in the HT group, but these differences did not persist after adjustment for disease severity. The TD subtype was less frequent in the HT group than in the non-HT group (5.7% vs. 30.2%), whereas the AR subtype was more common (82.9% vs. 61.9%). The categorical subtype redistribution remained significant after multivariable adjustment (adjusted OR for AR vs. TD = 4.61, 95% CI 1.28–16.67). No detectable between-group difference in non-motor symptom burden was observed. Conclusions: In this single-center cross-sectional cohort, a self-reported history of HT in early PD was associated with a redistribution of motor phenotype categories toward AR-predominant presentations, with no detectable difference in non-motor symptom burden. Given the retrospective binary exposure assessment, these findings should be interpreted as hypothesis-generating, and prospective studies with structured exposure ascertainment are needed to clarify how HT may shape PD motor phenotype expression.

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked disorder caused by pathogenic variants in the WDR45 gene. Early diagnosis remains challenging because of nonspecific presentations in childhood. We report six pediatric patients with BPAN identified through genetic testing performed during evaluations of neurodevelopmental disorders. All the participants were female and exhibited early developmental delay, severe language impairment, and varying degrees of motor dysfunction. Seizures occurred in four patients with varying severity. Two patients showed signs of central precocious puberty. Serum neuron-specific enolase levels were elevated in all tested patients. Brain magnetic resonance imaging (MRI) revealed corpus callosum thinning in all the patients. Iron accumulation in the substantia nigra and globus pallidus was observed in only two older patients. WDR45 variants included two nonsense mutations, two splice sites, one in-frame deletion, and one novel frameshift deletion. Our findings highlight early clinical features that may aid in recognizing BPAN prior to the emergence of distinctive MRI abnormalities or degenerative-phase manifestations.

Background and Objectives: Apathy and sleep problems are frequently observed among non-motor symptoms (NMSs) in Parkinson’s disease (PD), but the relationship between the two has not been well investigated. This study aimed to determine the extent to which apathy and sleep disturbances are present in people with early PD and whether apathy affects sleep quality. Materials and Methods: Patients diagnosed with early PD, defined as modified Hoehn and Yahr (mHY) stages 1-3 and a disease duration of no more than 5 years, were included in the study. Demographic characteristics were collected, and motor and NMSs including apathy and sleep disturbance were investigated with relevant scales. Results: Of 302 patients with PD, apathy was found in 97 (32.1%) patients. Patients with apathetic PD had significantly less formal education, a more advanced mHY stage, and higher scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part II, total Non-Motor Symptom Scale (NMSS), Beck Depression Inventory (BDI), Apathy Evaluation Scale (AES), and Pittsburgh Sleep Quality Index (PSQI) global scores than patients with non-apathetic PD. The PSQI global score showed significant associations with years of education, UPDRS-II, total NMSS, Mini-Mental State Examination, BDI, and AES scores. For each component of the PSQI, only sleep latency was different between patients with apathetic and non-apathetic PD. Partial correlation analyses for determining the association between apathy and sleep disturbance revealed a significant positive correlation. Conclusions: Apathy is common and associated with poor sleep quality in patients with early PD. These findings suggest that recognizing and addressing apathy may be relevant for managing sleep disturbances in this population.

Objective We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD).Methods Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks.Results A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05).Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Background/Objectives: A family history of Parkinson’s disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients’ PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.

Background: Increasing levodopa (L‐dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol‐O‐methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing‐off symptoms in Parkinson's disease (PD) patients. Objectives: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing‐off in PD patients. Methods: ADOPTION was a randomized, parallel‐group, open‐label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L‐dopa 100 mg (n = 81) (added to current L‐dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society‐Unified Parkinson's Disease Rating Scale and 8‐item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. Results: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L‐dopa 100 mg (−62.1 vs. −16.7 minutes; P = 0.0015). Opicapone‐treated patients also reported a greater reduction in the percentage of off time ( P = 0.0015), a greater increase in absolute on time ( P = 0.0338) and a greater increase in the percentage of on time ( P = 0.0015). There were no significant differences in other secondary endpoints. The L‐dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. Conclusions: Opicapone 50 mg was more effective than an additional 100 mg L‐dopa dose at decreasing off time in patients with PD and early wearing‐off.

Restless legs syndrome (RLS) is common in Parkinson’s disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. The aim of this study was to identify the clinical factors affected by RLS in patients with PD. We included 369 de novo PD patients. RLS was assessed via face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the cardiovascular, sleep/fatigue, and attention/memory subdomain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.