Jin Whan Cho

Background: Image-guided programming (IGP) enables optimization and personalization of deep brain stimulation (DBS) for patients with Parkinson's disease. Although its role in initial programming has been examined, evidence for its value in chronic stimulation remains limited. We aimed to evaluate the effectiveness of IGP in individuals with Parkinson's disease receiving chronic subthalamic nucleus (STN)-DBS with conventional programming (CP). Methods: We reviewed optimal stimulation configurations using IGP with STIMVIEW™ XT in 30 patients with PD implanted with directional DB2202 electrodes. When discrepancies were identified between CP- and IGP-derived configurations, stimulation parameters were adjusted. Motor outcomes were assessed using the Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Parts III and IV and levodopa equivalent daily dose (LEDD) at baseline and 1 month after switching to IGP. Results: Discrepancies between CP- and IGP-selected configurations were found in at least one electrode in 20 patients (66.7%), and 18 were included in the analysis. Of these, 11 (61.1%) showed improvement in MDS-UPDRS Part III and/or IV scores, 4 (22.2%) showed no change, and 3 (16.7%) worsened. Mean MDS-UPDRS Part III scores significantly decreased from 20.7 ± 16.5 to 16.9 ± 13.3 ( p = 0.008), and LEDD from 655.2 ± 326.6 mg to 609.9 ± 311.1 mg ( p = 0.046). Discrepancies occurred more often in stimulation direction than level, and IGP-based stimulation was applied bilaterally in most individuals. Conclusion: IGP for STN-DBS can improve motor symptom control in patients with Parkinson's disease. It may benefit those with suboptimal outcomes under CP and represent a practical approach for individualized DBS management.

Pathogenic variants in GBA1 are a significant genetic risk factor for Parkinson disease (PD). Owing to high sequence homology between GBA1 and its pseudogene GBAP1, short-read NGS (srNGS) is susceptible to read misalignment, particularly in the presence of recombinant alleles. A targeted short-read NGS (srNGS) panel was applied to 175 selected Korean patients with PD, including those with early-onset disease, family history, preoperative assessment, or atypically rapid progression, identifying GBA1 copy-number loss in five patients. Confirmatory testing using MLPA, long-range PCR followed by Sanger sequencing, and long-read sequencing demonstrated that these findings represented recombinant alleles rather than simple deletions in four cases, while confirmatory analysis could not be performed in one case due to insufficient DNA. Thus, recombinant alleles were identified in at least 2.3% (4/175) of patients. We further evaluated whether GBAP1 copy-number analysis could aid interpretation of srNGS findings. GBAP1 copy-number patterns were concordant with confirmatory results in all four cases, indicating gene conversion events; in the remaining case, for which confirmatory testing could not be performed due to insufficient DNA, the pattern was suggestive of a fusion allele. Our findings demonstrate that recombinant alleles may present as exon-level deletions on targeted srNGS. We propose that concurrent GBAP1 copy-number analysis provides a practical interpretive aid for distinguishing recombinant rearrangements from simple copy-number alterations and for guiding confirmatory test selection in routine diagnostics.

Objective Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD.Methods Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention.Results The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η2=0.28).Conclusion SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

Objective Delayed ON is a condition in which Parkinson’s disease (PD) patients do not experience the effect of levodopa in time after taking the dosage. The ability of various oral levodopa regimens to overcome this problem has been poorly investigated. To evaluate the efficacy of levodopa/benserazide dispersible tablets in PD patients with delayed ON to the first morning dose.Methods This multicenter, randomized, crossover trial involved 40 eligible PD patients with delayed ON. The participants were randomized to receive either levodopa/benserazide 100 mg dispersible or regular tablets for 4 weeks, followed by a one-week wash-out interval and an alternate drug for another 4 weeks. Participants took the investigational drug with the first morning dose of their antiparkinsonian medications. Other medications were not changed during the trial. The primary outcome was changes in time-to-ON after the first-morning dose recorded in a special diary before and after each therapy. We also evaluated changes in parkinsonism, motor fluctuations, and dyskinesia using the Unified PD Rating Scale and the Unified Dyskinesia Rating Scale. Finally, we investigated whether efficacy was affected by Helicobacter pylori status via baseline serum samples from every participant.Results Nine patients dropped out during the trial. The time-to-ON was significantly reduced by the dispersible tablet compared with the regular tablet (-34.72 vs. -23.81 minutes, p=0.014). There were no significant changes in parkinsonian severity or dyskinesia with either drug. The dispersible formulation was beneficial for both Helicobacter pylori-positive and -negative groups.Conclusion Levodopa/benserazide dispersible formulations can improve time-to-ON without exacerbating dyskinesia in PD patients suffering from delayed ON.

Spinocerebellar ataxias (SCAs) represent a diverse group of neurodegenerative disorders characterized by progressive cerebellar ataxia. In South Korea, diagnostic laboratories typically focus on common SCA subtypes, leaving the prevalence of rare SCAs uncertain. This study aimed to explore the frequency of rarer forms of SCA, including SCA10, 12, 31, and 36 utilizing molecular techniques including long-read sequencing (LRS). Patients from ataxia cohorts who remained undiagnosed after testing for common genetic ataxias (SCA1, 2, 3, 6, 7, 8 17, and dentatorubral-pallidoluysian atrophy) were analyzed, along with unselected ataxia patients referred for screening of common SCAs. Expanded alleles for SCA10, 12, 31, and 36 were investigated through allele-length PCR, repeat-primed PCR, and LRS. Among 78 patients from 67 families with undiagnosed cerebellar ataxia, SCA36 was identified in 8 families (11.9%), while SCA10, 12, or 31 were not found. In unselected ataxia, SCA36 was present in 1.0% (1/99). Korean SCA36 patients exhibited clinical characteristics similar to global reports, with a higher incidence of hyperreflexia. The haplotype of expanded alleles identified in LRS was consistent among SCA36 patients. The findings indicate that SCA36 accounts for 11.9% of diagnoses after excluding common SCAs and 1.0% in unselected ataxia patients. The study underscores the prevalence of SCA36 in South Korea and emphasizes the potential of LRS as a diagnostic tool for this condition. Integrating LRS into diagnostic protocol could enhance diagnostic efficacy, particularly in populations with a high prevalence of SCA36 like South Korea. Further research is necessary to standardize LRS for routine clinical application.

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.

Chang KW, et al. J Korean Med Sci. 2025 Aug;40:e256. https://doi.org/10.3346/jkms.2025.40.e256

The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing, repeat-primed PCR and Cas9-mediated nanopore sequencing were applied to suspected short tandem repeat disorders. Probands were classified into probable genetic (n = 128) or uncertain (n = 104) origins. The study found genetic causes in 66 individuals (28.4%) and non-genetic causes in 12 (5.2%), with a longer diagnostic journey for those in the probable genetic group or with pediatric symptom onset, emphasizing the need for increased efforts in these populations. Genetic diagnoses facilitated effective surveillance, cascade screening, drug repurposing, and pregnancy planning. This study demonstrates that integrating sequencing technologies improves diagnostic accuracy, may shorten the time to diagnosis, and enhances personalized management for adults with undiagnosed diseases.