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Autoimmune nodopathy (AN) is a rare immune-mediated neuropathy characterized by autoantibodies against nodal or paranodal proteins. Patients with AN generally respond poorly to immunoglobulin therapy, and as a newly defined condition, there are currently no established treatment guidelines. Although rituximab shows potential as a therapeutic option, its high cost, limited availability, and the need for infusion monitoring hinder its use as a first-line treatment in many countries. In this report, we identified AN antibodies in five of 106 serum samples (4.7%) prospectively collected from patients initially diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): anti-neurofascin 155 (NF155) in 2 patients, anti-contactin-1 (CNTN1) in 1, anti-contactin associated protein 1 (CASPR1), and anti-NF186/140 in 1. Notably, we observed favorable long-term outcomes in these patients following treatment with mycophenolate mofetil (MMF) and corticosteroids. Given that these patients had not responded to immunoglobulin therapy and/or experienced relapses with corticosteroid monotherapy in their prior episodes, we propose MMF as a cost-effective treatment strategy for AN. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Despite treatment, a considerable proportion of patients with Guillain–Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS. Methods: We performed a retrospective study of 136 IVIg‐treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS‐DS) and the degree of improvement from nadir (∆GBS‐DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1‐week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre‐treatment serum albumin levels were adjusted as covariates. Results: Shorter time to IVIg was independently associated with better GBS‐DS, greater ∆GBS‐DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset. Discussion: Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients. [ABSTRACT FROM AUTHOR]

Deregulated cyclin‐dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild‐type superoxide dismutase 1 (SOD1) or SOD1G93A and primary neuronal cultures from SOD1G93A transgenic (TG) mice or non‐TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5‐small interfering RNA or Cdk5‐short hairpin RNA (shRNA). For the in vivo study, SOD1G93A mice and non‐TG mice were intrathecally injected with adeno‐associated virus 9 (AAV9)‐scramble (SCR)‐shRNA or AAV9‐Cdk5‐shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90‐day‐old or 120‐day‐old mice. Neurons with SOD1G93A showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non‐TG and SOD1G93A mice with or without Cdk5 silencing. SOD1G93A mice treated with AAV9‐Cdk5‐shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9‐SCR‐shRNA. The brain and spinal cord of SOD1G93A mice intrathecally injected with AAV9‐Cdk5‐shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1G93A mice injected with AAV9‐SCR‐shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS. [ABSTRACT FROM AUTHOR]

As persistent elevation of transforming growth factor‐β (TGF‐β) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF‐β would be effective against both exacerbations. The effects of TGF‐β and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF‐β inhibitor in ameliorating the pathogenic role of TGF‐β in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF‐β causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF‐β in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro‐inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF‐β inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell‐induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF‐β inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival. [ABSTRACT FROM AUTHOR]

Introduction/Aims: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea. Methods: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire‐9 (PHQ‐9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not. Results: Ninety‐eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8–20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10–24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8–15) and 8/20 (8–11), respectively), and both were lower in those caring for patients without than with tracheostomy (p <.001 and p <.02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home. Discussion: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill‐prepared. Designing home‐based medical care is necessary for pALS to thrive at home. [ABSTRACT FROM AUTHOR]

Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [ ≥ 80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09–1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50–0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32–0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to present the results of our investigation of the prognostic value of adipopenia and sarcopenia in patients with amyotrophic lateral sclerosis (ALS). Methods: Consecutive patients with ALS with abdominal computed tomography (CT) were retrospectively identified at a single tertiary hospital between January 2010 and July 2021. Deep learning‐based volumetric CT body composition analysis software was used to obtain abdominal waist fat volume, fat attenuation, and skeletal muscle area at the L3 level, then normalized to the fat volume index (FVI) and skeletal muscle index (SMI). Adipopenia and sarcopenia were defined as the sex‐specific lowest quartile and SMI reference values, respectively. The associations of CT‐derived body composition parameters with clinical variables, such as body mass index (BMI) and creatinine, were evaluated by Pearson correlation analyses, and associations with survival were assessed using the multivariable Cox regression analysis. Results: Eighty subjects (40 men, 65.5 ± 9.4 years of age) were investigated (median interval between disease onset and CT examination = 25 months). The mean BMI at the CT examination was 20.3 ± 4.3 kg/m2. The BMI showed a positive correlation with both FVI (R = 0.70, p < 0.001) and SMI (R = 0.63, p < 0.001), and the serum creatinine level was associated with SMI (R = 0.68, p < 0.001). After adjusting for sex, age, King's stage, BMI, creatinine, progression rate, and sarcopenia, adipopenia was associated with shorter survival (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 1.01, 35.0, p = 0.049). In a subgroup analysis for subjects with nutritional failure (stage 4a), the HR of adipopenia was 15.1 (95% CI = 2.45, 93.4, p = 0.003). Interpretation: Deep learning‐based CT‐derived adipopenia in patients with ALS is an independent poor prognostic factor for survival. ANN NEUROL 2023;94:1116–1125 [ABSTRACT FROM AUTHOR]