Jin-Mo Park

Charcot-Marie-Tooth disease (CMT) comprises a genetically and clinically heterogeneous group of inherited peripheral neuropathies and remains a major indication for gene-based diagnostic evaluations in neuromuscular practice. Although supportive management has traditionally been applied across most subtypes, there has recently been a notable expansion of disease-modifying approaches due to advances in molecular diagnostics and accumulating preclinical and early clinical evidence. Improved genetic classification, including the recognition of metabolically defined and potentially treatable subtypes, has increased diagnostic precision and the development of subtype-specific therapeutics, with an increasing emphasis on mechanism-based stratification. This review summarizes recent progress in inherited neuropathies from a clinical perspective. We describe ongoing developments in clinical interventions, including combination pharmacotherapy for Charcot-Marie-Tooth disease type 1A (CMT1A), pathway-targeted therapy for CMT associated with sorbitol dehydrogenase deficiency and related metabolic neuropathies, and early biological and gene-based approaches that are being applied in selected subtypes. We also review the evolving preclinical approaches aimed at normalizing the peripheral myelin protein 22 dosage in CMT1A and gene-replacement and other precision therapies for loss-of-function and dominant-negative conditions. Because many subtypes of CMT progress slowly and conventional clinical scales have low sensitivity, we further discuss recent advances in the approaches used in clinical trials, including the refinement of clinical outcome assessments and the identification of candidate biomarkers such as the magnetic resonance imaging-based muscle fat fraction and the circulating level of neurofilament light chain. Collectively these developments are making subtype-specific therapeutic approaches increasingly feasible, although continued progress will depend on aligning disease biology, therapeutic approaches, and outcome measurements.

Introduction: Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG trinucleotide repeat expansion in the dystrophia myotonica-protein kinase (DMPK) gene and is characterized by progressive muscle weakness with multisystemic involvement, including the central nervous system (CNS). Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in various neurological conditions. This study aimed to evaluate plasma NfL as a biomarker of disease severity by examining its association with motor function in ambulatory patients with DM1. Methods: Thirty-three DM1 patients and 31 controls were enrolled. Plasma NfL levels were measured, and clinical variables including age, sex, age at onset, and disease duration were collected. Motor function was assessed using the Muscular Impairment Rating Scale (MIRS) and the 6-min walk test (6MWT). Associations between NfL levels and clinical measures were analyzed using partial correlation based on Kendall's Tau with adjustment for age. Results: Age-adjusted analyses demonstrated a significant positive correlation between NfL levels and MIRS scores (τ = 0.387, p = 0.002) and a significant negative correlation with 6MWT performance (τ = −0.344, p = 0.014). Disease duration was also positively associated with age-adjusted NfL levels (τ = 0.334, p = 0.007). Although NfL levels showed a negative correlation with peroneal CMAP amplitudes, this association was not significant after age adjustment. Conclusion: Plasma NfL levels were associated with disease duration and motor function severity in DM1. These findings suggest that NfL may serve as a biomarker reflecting not only neuroaxonal damage but also motor impairment in DM1. Larger longitudinal studies are warranted to validate these findings.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment, which is more common in patients with ovarian cancer who are receiving paclitaxel and carboplatin treatment. Although prior studies have explored the association between obesity and CIPN, most relied on subjective grading systems. This study aims to evaluate the relationship between being overweight and CIPN using the Total Neuropathy Score (TNS), a more objective and comprehensive assessment tool. The purpose of this study is to investigate the relationship between being overweight and the onset and severity of CIPN in a cohort of South Korean patients with ovarian cancer who were treated with paclitaxel and carboplatin. Methods: The study was conducted retrospectively at a single tertiary hospital in South Korea from March 2013 to February 2022. Included in this study were forty-two individuals who were diagnosed with epithelial ovarian cancer and who had developed neuropathic symptoms following chemotherapy. Patient characteristics, laboratory findings, and disease-specific TNS were analyzed. Results: Overweight patients showed significantly more severe CIPN, with higher Total Neuropathy Scores (TNS; p = 0.019) and earlier symptom onset (p < 0.05) compared to normal-weight patients. Causal mediation analysis also revealed a significant direct effect of BMI on TNS (p = 0.006). However, no significant correlation was found between BMI and TNS using Kendall’s rank correlation, and other neuropathic symptoms or laboratory parameters did not show statistically significant group differences. Conclusions: The study suggests that overweight may be associated with the severity and onset of CIPN in patients with ovarian cancer who are receiving paclitaxel and carboplatin chemotherapy. While the results are preliminary, they underscore the importance of addressing this modifiable risk factor in clinical care. Further research is needed to better understand the underlying mechanisms and to inform future therapeutic strategies.

This study aimed to analyze the trends and characteristics of hospitalized Guillain-Barré syndrome (GBS) incidence and management in South Korea before and during the coronavirus disease 2019 pandemic, assessing potential impacts of nonpharmaceutical interventions and shifts in public health dynamics. We conducted a retrospective analysis using data from the Health Insurance Review and Assessment Service database from 2013 to 2021, divided into prepandemic (2013–2019) and pandemic (2020–2021) periods. Incident GBS cases were identified based on the G61.0 code with hospital admissions. A total of 10,596 hospitalized patients with GBS were identified, with 8537 cases in the prepandemic period and 2059 during the pandemic. While the overall GBS incidence did not show a statistically significant change during the pandemic (P = .056), the mean age of patients increased. Notably, a significant rise in the proportion of patients receiving intravenous immunoglobulin was observed during the pandemic (P < .001), with older patients showing higher mean ages (P = .007). However, the proportion of patients requiring mechanical ventilation remained stable (P = .240). The findings suggest that while hospitalized GBS incidence remained stable amidst the pandemic and reduced respiratory infection admissions, the increase in intravenous immunoglobulin use points to more severe presentations, particularly among older patients. This highlights the multifactorial nature of GBS triggers and the need for continued investigation into how evolving public health measures and infectious disease patterns influence GBS incidence and management.

Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the ATN1 gene, characterized by diverse neurological and psychiatric symptoms. We report a 23-year-old patient with juvenile-onset seizures, cognitive decline, and ataxia, progressing to psychosis by age 31. Initial brain MRI showed minimal cerebellar atrophy, with prominent atrophy evident on follow-up imaging. Genetic testing confirmed DRPLA with expanded CAG repeats. Family history revealed anticipation, with varying presentations across generations. This case highlights DRPLA's complexity, diagnostic challenges due to symptom overlap, and the critical role of genetic testing in identifying this rare disorder.

Background and purpose Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder characterized by myotonia and progressive muscle weakness. Beyond the primary symptoms, there is growing concern regarding a higher incidence of certain comorbidities in DM1 patients, including cancer, diabetes, thyroid dysfunction, and cataracts. This study was designed to examine the occurrence of these conditions among patients diagnosed with DM1 in South Korea, using data from the National Health Insurance Service database. Methods The study undertook a comprehensive review of 3,842 patients diagnosed with DM1 between 2012 and 2018. We assessed the incidence of cancer and the prevalence of diabetes, thyroid dysfunction, and cataracts among these patients, comparing their rates to those in the general population. Results In the study cohort, 463 out of 3,842 DM1 patients (12.04%) were diagnosed with cancer, indicating a substantial elevation in cancer risk with an overall standard incidence ratio of 1.9 (95% CI = 1.6–2.3, p < 0.01) when compared to the expected rates in the general population. Moreover, the prevalence of diabetes (15.2%) and thyroid dysfunction (17.6%) was noteworthy in the DM1 population. The mean age at which DM1 patients underwent cataract surgery was 55.07 years, noticeably younger than the mean age of 69.25 years for cataract surgery in the general population. Conclusions DM1 patients have a noteworthy occurrence of several comorbidities such as cancer, diabetes, thyroid dysfunction, and earlier cataract surgery. This highlights the importance of a comprehensive and integrative approach to the management and treatment of DM1, going beyond addressing only the primary neuromuscular symptoms. More research is required to understand the underlying mechanisms contributing to these comorbidities in DM1 patients, which may inform preventative measures and guide improvements in patient care.

Erectile dysfunction in patients who underwent radical prostatectomy was evaluated with pudendal somatosensory evoked potentials (PSEP) to measure and predict erectile dysfunction objectively. Fifty-seven patients who completed requirements were included in the study. Patients were divided into 2 groups (potency/non-potency). Erectile function recovery was defined as question 2 and 3 on the IIEF-5 questionnaire at 12 months after surgery. The two-channel PSEP test was performed at the day before RP and 3–6 months after RP. Twenty patients were assigned to the potency group and 37 to the non-potency group. Mean age was less in the potency group. Other clinical variables were similar in two groups. The non-potency group had prolonged lumbar and cortical latencies in postoperative PSEP, and the mean differences of latencies between pre- and postoperative PSEP in lumbar and cortical regions were also greater in the non-potency group. Logistic regression analysis showed that age, lumbar post-operative latency, cortical post-operative latency, and difference of latency in lumbar region were associated with non-potency; odds ratios were 1.292 (p = 0.018), 0.425 (p = 0.047), 1.637 (p < 0.001), and 3.272 (p = 0.010), respectively. This study suggests that PSEP is an effective means of evaluating erectile dysfunction in prostate cancer patients after surgery.

Background and Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Materials and Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.

Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.

Objectives Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue. Our objective was to investigate the incidence of MG using the National Health Insurance database of South Korea. Materials and methods We conducted a retrospective cohort analysis of patients with the G70.0 code designated as MG and administered with MG medications for >3 months from 2007 to 2018 using nationwide data from South Korea. Results A total of 8,376 patients with MG during the period of 2010–2018 were identified. There were 3,862 (46.1%) male and 4,517 (53.9%) female patients. The standardized incidence rate was 1.18/100,000 in 2010, and increased to 1.81/100,000 in 2018. The standardized prevalence was 7.50/100,000 in 2010, and changed to 11.15/100,000 in 2018. Pyridostigmine was used to treat 82.3 ± 1.2% of patients with MG during 2010–2018. Among MG patients, 85.7 ± 0.9% used steroids, 31.6 ± 4.8% used azathioprine, 12.9 ± 9.5% used tacrolimus, 7.2 ± 2.1% used cyclosporine, 6.2 ± 1.8% used mycophenolate mofetil, and 0.4 ± 0.1% used methotrexate. Thymectomy was performed in 1,130 MG patients, and the time from MG diagnosis to thymectomy decreased from 2010 to 2018. Conclusion Based on the national registry data from 2010 to 2018, the incidence and prevalence rate in South Korea has increased. Whereas the use of IVIG has remained stable, thymectomy is performed earlier than before, and the distribution of immunosuppressant therapies has changed over the years with an increase in tacrolimus and mycophenolate mofetil. We expect that this study will serve as a basis for future South Korean MG epidemiological studies.