Prognostic significance of peripheral neutrophils and lymphocytes in early untreated Parkinson's disease: an 8-year follow-up study.

BACKGROUND: To explore whether peripheral blood neutrophils and lymphocytes are associated with longitudinal motor and cognitive decline in patients with early Parkinson's disease (PD) and, to uncover the disease-specific mechanisms underlying these associations. METHODS: Data were obtained from the Parkinson's Progression Markers Initiative cohort. We included 376 patients with recently diagnosed, drug-naïve PD and 178 matched healthy controls. The patients underwent annual assessments, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 test to measure motor function and the Montreal Cognitive Assessment (MoCA) to measure cognitive function, for up to 8 years of follow-up. Dopamine transporter (DAT) imaging was performed at baseline and the 1-year, 2-year and 4-year follow-up visits. RESULTS: At baseline, patients with PD showed higher neutrophil and lower lymphocyte counts, resulting in a higher neutrophil-to-lymphocyte ratio (NLR) than that in healthy controls. Higher neutrophil counts were associated with a greater increase in MDS-UPDRS part 3 scores in patients with PD (estimate: 0.25, 95% CI: 0.12 to 0.37, p<0.001). Correspondingly, higher neutrophil levels were related to a greater reduction in DAT activity in the caudate (estimate: -0.007, 95% CI: -0.014 to -0.001, p=0.046) and putamen (estimate: -0.0039, 95% CI: -0.0077 to -0.0002, p=0.042). However, there were no significant effects of lymphocyte count and NLR on changes in the MDS-UPDRS part 3 and MoCA scores and striatal DAT uptake over time. CONCLUSION: Among the blood biomarkers, only a higher neutrophil count was associated with faster motor progression along with accelerated nigrostriatal dopaminergic degeneration in patients with PD. The impact of neutrophils and lymphocytes on longitudinal cognitive changes remains unclear. TRIAL REGISTRATION NUMBER: NCT01141023.

Effects of perampanel on cognition and quantitative electroencephalography in patients with epilepsy.

Antiepileptic drugs are well known for their effects on cognition and electrophysiologic changes. However, perampanel is yet to be evaluated for its effects on cognitive function and electroencephalography (EEG). The purpose of the present study was to identify the effect of perampanel on neuropsychological (NP) tests and quantitative EEG (QEEG) and their relationship with the level of the drug in blood. Seventeen patients with epilepsy were enrolled in the study. Electroencephalographic recordings were obtained, and NP tests were conducted before perampanel intake and 6 months after treatment. The relative frequency band power, peak alpha frequency, and NP test scores were compared before and after drug administration. The serum concentration of perampanel was correlated with the QEEG changes. Delayed recall of the Rey Complex Figure showed significant improvement (20.03 vs. 22.94; P = 0.004) following perampanel administration. Other cognitive function tests showed no significant differences before and after drug administration. Theta frequency band power increased in all brain regions (P = 0.001-0.01), and alpha frequency power decreased in all brain regions (P = 0.006-0.03). The theta/alpha ratio, which represents background EEG slowing, increased in all brain areas (P = 0.003-0.02). The peak frequency of the alpha rhythm decreased after perampanel intake (t = 2.45, P = 0.03). Difference of relative alpha power in the central region positively correlated with the blood level of perampanel (r = 0.53, P = 0.03). Perampanel induced electrophysiological slowing, but cognitive decline was not observed. Because the controls were not compared in the study, the results of cognitive function tests should be interpreted conservatively. Background EEG slowing correlated with the serum concentration of perampanel. Our results show the effect of perampanel on cognitive function and background EEG in adult patients with epilepsy.

Characteristics and prognosis of patients with cryptogenic stroke and suggestive of patent foramen ovale.

AIMS: The purpose of this study were to identify the usefulness of screening for PFO using agitated saline echocardiography (ASE) and characteristics and prognosis of patients with suggestive of patent foramen ovale (PFO). METHODS: Three hundred three patients (mean age, 53 ± 9 years; 199 [66%] men) admitted with acute stroke or suspicion of stroke were included. Patients were classified into those with and without right-to-left shunt (RLS) according to the ASE results (positive ASE [n = 92] vs. negative ASE [n = 211]). Fifty-one out of ninety-two patients with positive ASE and twenty-one out of two hundred eleven patients with negative ASE underwent TEE with ASE to confirm PFO. RESULTS: Ninety-two were positive for ASE and thirty-six of the fifty-one patients who underwent TEE were confirmed as having PFO. Of the patients with RLS grade 1, 50% were diagnosed with PFO and all patients with RLS grade ≥ 2 were diagnosed with PFO. All patients with negative ASE had no PFO (sensitivity of 100% and specificity of 58%). Patients with positive ASE were younger, had a lower body mass, and a lower prevalence of hypertension. The positive ASE patients had a higher mean S' velocity and better diastolic function. Four of ninety-one patients with positive ASE and thirteen of one hundred seventy-seven showed recurrence of stroke and suspicion of stroke. CONCLUSION: Transthoracic ASE is a good method to screen for PFO. Patients with suggestive of PFO had lower risk factors, less atherosclerosis, and better cardiac performance.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Rapid diagnosis of bacterial meningitis by nanopore 16S amplicon sequencing: A pilot study.

Early administration of antibiotics is crucial in the management of bacterial meningitis. Rapid pathogen identification helps to make a definite diagnosis of bacterial meningitis and enables tailored antibiotic treatment. We investigated if the 16S amplicon sequencing performed by MinION, a nanopore sequencer, was capable of rapid pathogen identification in bacterial meningitis. Six retrospective cases of confirmed bacterial meningitis and two prospective cases were included. The initial cerebrospinal fluid (CSF) samples of these patients were used for the experiments. DNA was extracted from the CSF, and PCR was performed on the 16S ribosomal DNA (16S rDNA). Sequencing libraries were prepared using the PCR products, and MinION sequencing was performed for up to 3 h. The reads were aligned to the bacterial database, and the results were compared to the conventional culture studies. Pathogenic bacteria were successfully detected from the CSF by 16S sequencing in all retrospective cases. 16S amplicon sequencing was more sensitive than conventional diagnostic tests and worked properly even in antibiotics-treated samples. MinION sequencing significantly reduced the turnaround time, and even 10 min of sequencing was sufficient for pathogen detection in certain cases. Protocol adjustment could further increase the sensitivity and reduce the turnaround time for MinION sequencing. Finally, the prospective application of MinION 16S sequencing was successful. Nanopore 16S amplicon sequencing is capable of rapid bacterial identification from the CSF of the bacterial meningitis patients. It may have many advantages over conventional diagnostic tests and should therefore be applied in a larger number of patients in the future.

Tocilizumab treatment for new onset refractory status epilepticus.

We investigated the therapeutic potential of the interleukin-6 receptor inhibitor tocilizumab in 7 patients with new onset refractory status epilepticus (NORSE) who remained refractory to conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of SE during the observation. However, 2 patients experienced severe adverse events related to infection during the tocilizumab therapy. Further prospective controlled studies are warranted to validate the efficacy and safety of tocilizumab in patients with NORSE. Ann Neurol 2018;84:940-945.

Peripheral Blood Inflammatory Cytokines in Idiopathic REM Sleep Behavior Disorder.

BACKGROUND: Although previous research provides insight into the role of neuroinflammation in idiopathic REM sleep behavior disorder, the association of this disorder with peripheral blood inflammatory markers remains unclear. OBJECTIVE: To investigate inflammatory cytokines in plasma samples in patients with idiopathic rapid eye movement sleep behavior disorder and to explore whether these markers are associated with prodromal symptoms of α-synucleinopathies. METHODS: We collected plasma from patients with polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder without parkinsonism or dementia (n = 54) and from healthy controls (n = 56). The following cytokines were measured: interleukin-1ß, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor-α. The idiopathic REM sleep behavior disorder patients underwent sleep, motor, cognitive, olfactory, and autonomic testing. RESULTS: The anti-inflammatory cytokine, interleukin-10, levels in the idiopathic rapid eye movement sleep behavior disorder group were significantly upregulated compared to the control group (P = 0.022), but this difference did not withstand Bonferroni correction. The other proinflammatory cytokine levels did not differ between the groups. No correlation was found between the cytokine levels and any clinical variable. CONCLUSIONS: Our data do not provide evidence supporting the role of peripheral inflammation in idiopathic rapid eye movement sleep behavior disorder. However, considering the limited statistical power because of the small sample size, further large-scale longitudinal studies with a broader spectrum of cytokines are needed to clarify this issue. © 2019 International Parkinson and Movement Disorder Society.

Characteristics of obstructive sleep apnea in myasthenia gravis patients: a single center study.

BACKGROUND: Recent studies have shown a high prevalence of obstructive sleep apnea in myasthenia gravis compared to the normal population. The aim of this study was to elucidate clinical and polysomnographic differences between clinically stable Korean MG patients with and without OSA. METHODS: A total of 18 consecutively stable MG patients were included in this prospective study. We compared MG patients with OSA (n = 7) and without OSA (n = 11) with respect to the baseline characteristics and overnight polysomnography (PSG) parameters. Demographic parameters, prescribed medication status, thymectomy status, myasthenia gravis foundation of America score, and antibody status were obtained from their medical records. We performed the Korean version of Pittsburg sleep quality index to assess the subjective quality of sleep. Statistical analyses were performed using SPSS version 18.0 with Wilcoxon rank sum test, chi-square test, Fisher's exact test, and Spearman correlation test. RESULTS: Among the clinical parameters, MG patients with OSA showed a higher proportion of male sex (p = 0.016) and increased body mass index (p = 0.033). The PSG showed an 11-fold higher supine apnea-hyponea index (AHI) in MG patients with OSA. AHI was further analyzed with supine and non-supine position. MG patients with OSA had a higher supine AHI (19.5 ± 15.8) compared to those without OSA (1.9 ± 1.2, P = 0.008). Most of MG patients with OSA (85.7%) showed more than two times higher supine AHI than non-supine AHI. CONCLUSIONS: This study showed that the occurrence of OSA in patients with MG is associated with male sex and obesity, which is in accordance with the normal population. Moreover, PSG data showed a high prevalence of supine dominant OSA in MG patients with OSA.

LGI1 expression and human brain asymmetry: insights from patients with LGI1-antibody encephalitis.

BACKGROUND: While brain asymmetry has been a fascinating issue in neuroscience, the critical mechanism remains to be elucidated. Based on some index cases with asymmetric 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) uptake in leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis, we hypothesized LGI1 expression could be asymmetrically distributed in the human brain. METHODS: We enrolled 13 patients who were diagnosed with LGI1-antibody encephalitis between June 2012 and January 2018 at Seoul National University Hospital. Their pretreatment 18F-FDG-PET images were analyzed to find asymmetry between the left and right hemispheres. Guided by these observations, expression of LGI1 in the human hippocampus and the globus pallidus of both cerebral hemispheres was studied in nine post-mortem human brains. RESULTS: Eleven of the 13 LGI1-antibody encephalitis patients (84.6%) showed asymmetrical FDG high uptake in the hippocampus: nine (81.8%) on the left hippocampus and two (18.2%) on the right. In the basal ganglia, seven patients (53.8%) showed asymmetry: four (57.1%) on the left and three (42.9%) on the right. The asymmetry was not evident in the laterality of faciobrachial dystonic seizures, brain MRI, and EEG. When the expression of LGI1 protein was analyzed in nine post-mortem human brains by western blotting, LGI1 expression was higher on eight left globus pallidus samples (88.89%, P = 0.019) and on four left hippocampal samples (44.44%, P = 0.652), compared to their right hemisphere samples. CONCLUSIONS: Imaging parameters from patients with LGI1-antibody encephalitis and studies of LGI1 protein expression suggest that LGI1 is asymmetrically distributed in the human brain. These observations have implications for our understanding of human brain development.

Anti-LGI1 encephalitis is associated with unique HLA subtypes.

OBJECTIVE: Autoimmune encephalitis (AE), represented by anti-leucine-rich glioma-inactivated 1 (anti-LGI1) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes. METHODS: We compared the HLA genotypes of 11 anti-LGI1 and 17 anti-NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans. RESULTS: Anti-LGI1 encephalitis was associated with the DRB1*07:01-DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti-LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti-NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA-peptide binding prediction algorithms and computational docking underpinned the close relationship. INTERPRETATION: This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.

Increased adverse events associated with antiepileptic drugs in anti-leucine-rich glioma-inactivated protein 1 encephalitis.

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis.

Clinical manifestations and treatment outcomes of parvovirus B19 encephalitis in immunocompetent adults.

Parvovirus B19 (PVB19) has rarely been identified as a cause of encephalitis in immunocompetent adults, in whom clinical information regarding PVB19 encephalitis has remained unclear. Herein, we report the clinical presentations, laboratory and imaging findings, and treatment outcomes of five immunocompetent adults with PVB19 encephalitis. Although none of the patients showed any distinctive features of PVB19 infection, they showed various clinical manifestations, including one instance of brainstem involvement. Additionally, immunotherapy can be considered an effective approach, especially in immunocompetent adults with PVB19 encephalitis who are resistant to the initial management.

Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome.

BACKGROUND: Patients with postural tachycardia syndrome often appear depressive and report diminished quality of life (QOL). In the current study, we first evaluated if the maximal heart rate (HR) increment after standing is associated with the clinical symptoms in patients with excessive orthostatic tachycardia (OT). Next, we investigated the correlations among the symptoms of orthostatic intolerance (OI), depression, and health-related QOL in these patients. Finally we assessed if patients with minimal OI symptoms suffer from depression or diminished QOL. METHODS: We performed a comprehensive questionnaire-based assessment of symptoms in 107 patients with excessive OT with a ≥ 30 beats/min heart rate increment (or ≥ 40 beats/min in individuals aged between 12 and 19) within 10 min after standing up. An existing orthostatic intolerance questionnaire (OIQ), the Beck depression inventory-II (BDI-II), and the 36 Item Short-Form Health Survey were completed prior to any treatment. Correlation analyses among the items of the questionnaires and other parameters were performed. Additionally, patients with minimal OI symptoms were analysed separately. RESULTS: The maximal orthostatic HR increment was not associated with the clinical symptoms. The OI symptoms were significantly correlated with depression and diminished QOL. The BDI-II score demonstrated a positive linear relationship with total OIQ score (r = 0.516), and both physical and mental component summary scales of SF-36 showed a negative linear relationship with total OIQ score (r = -0.542 and r = -0.440, respectively; all p <0.001). Some OI symptoms were more strongly associated with depression, and others were more strongly related to QOL. Chest discomfort and concentration difficulties were the most influential OI symptoms for depression, while nausea and concentration difficulties were the most influential symptoms for physical and mental QOL, respectively. Dizziness and headache were the two most common complaints in patients with mild to moderate OI symptoms. In addition, subjects with minimal OI symptoms also had considerable deterioration in QOL. CONCLUSION: The OI symptoms, but not the maximal HR increment, are significantly correlated with depression and diminished QOL in patients with excessive OT. Therefore, pervasive history taking is important when encountering patients with excessive OT.

Peripheral blood inflammatory cytokines in prodromal and overt α-synucleinopathies: a review of current evidence.

While the pathomechanisms of α-synucleinopathies are not completely understood, accumulating evidence suggests a role of neuroinflammation in the development and progression of the diseases. In addition, emerging data provide insights into the potential role of central neuroinflammation in prodromal α-synucleinopathies. Given the considerable bidirectional crosstalk between peripheral and central inflammation, peripheral blood inflammatory cytokines may be a useful tool to understand immune responses in association with α-synucleinopathies. Indeed, the accessibility and practicality of using blood samples have facilitated multiple investigations evaluating peripheral blood inflammatory cytokines in overt α-synucleinopathies, whereas the associations between these biomarkers and prodromal α-synucleinopathies remain unclear. In this review, we provide an overview of the current evidence available for the role of peripheral blood inflammatory cytokines in prodromal and overt α-synucleinopathies.

Trends in sleep duration in Korea: The Korean time use survey.

OBJECTIVES: An accurate assessment of sleep duration is important in that it can be one of the indicators of a country's overall health and well-being. The global trend in sleep duration is controversial according to study types. We investigated trends in sleep duration in South Korea with a time diary method. METHODS: Data from the Korean Time Use Survey (KTUS) in 2004, 2009, 2014, and 2019, were analyzed. The KTUS is a nationwide, cross-sectional survey that measures daily time use patterns of individuals and has been performed every five years by Statistics Korea. For this survey, all participants were asked to record their activities for 2 continuous days in 10-min intervals. RESULTS: Among the 168,682 people who completed the survey in 2004 through 2019, the final analytical sample consisted of 91,998 individuals. Over 15 years, the sleep duration of the Korean population increased from 411.1 min (SD 22.5) in 2004 to 434.5 min (SD 26.1) in 2019 (p for trend <0.001). This increase was observed for all age groups. Over the study period, while bedtime showed no significant change, wake time was generally delayed for all age groups. The increase in sleep duration in the Korean population was largely due to catch-up sleep on Saturdays, which was substantially prolonged with belated wake times. CONCLUSION: Our nationwide time use survey data showed that sleep duration in South Korea has increased over the past 15 years but still has room for improvement in terms of weekday sleep duration.

Association of Early Weight Change With Cognitive Decline in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVE: To examine whether early weight change is associated with subsequent deterioration in cognitive function, including overall performance and specific domains, in Parkinson disease (PD). METHODS: This observational study used data from the Parkinson Progression Markers Initiative cohort. The patients underwent annual nonmotor assessments covering neuropsychiatric, sleep-related, and autonomic symptoms for up to 8 years of follow-up. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and detailed neuropsychological testing. Linear mixed-effects models were applied to investigate the association of early weight change with longitudinal evolution of cognitive and other nonmotor symptoms. RESULTS: A total of 358 patients with early PD were classified into weight loss (decrease of >3% body weight during the first year; n = 98), weight maintenance (within ±3%; n = 201), and weight gain (increase of >3%; n = 59) groups. The weight loss group showed a significantly faster decline in MoCA scores than the weight maintenance group (ß = -0.19, 95% CI -0.28 to -0.10). With respect to specific cognitive domains, the weight loss group showed a steeper decline in sematic fluency test scores (ß = -0.37, 95% CI -0.66 to -0.08) and MoCA phonemic fluency scores (ß = -0.18, 95% CI -0.31 to -0.05) and, to a lesser extent, Letter-Number Sequencing scores (ß = -0.07, 95% CI -0.14 to 0.01) compared with the weight maintenance group. Conversely, the weight gain group showed a slower decline in the Symbol Digit Modalities Test scores (ß = 0.34, 95% CI 0.05 to 0.63), although no association was found with longitudinal changes in MoCA scores. We did not find any significant effects of weight change on the progression of other nonmotor symptoms. DISCUSSION: Early weight loss was associated with a faster progression of decline in global cognitive function and executive function in patients with PD, whereas early weight gain was associated with a slower progression of decline in processing speed and attention. The impact of early weight change on nonmotor symptoms seemed to be specific to cognition.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up.

OBJECTIVE: Although orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DESIGN: An 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. SETTING AND PARTICIPANTS: A total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. METHODS: The patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. RESULTS: The prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (ß = -0.11, 95% CI -0.20 to -0.02, t = -2.44, P = .015) and Semantic Fluency Test (SFT) (ß = -0.44, 95% CI -0.81 to -0.08, t = -2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (ß = -0.08, 95% CI -0.14 to -0.01, t = -2.20, P = .028) and SFT (ß = -0.36, 95% CI -0.63 to -0.08, t = -2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. CONCLUSIONS AND IMPLICATIONS: Both OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

Effects of high-intensity interval training and moderate-intensity continuous training on sarcopenia-related parameters in participants with Parkinson's disease: A 24-week randomized pilot trial substudy.

OBJECTIVE: To evaluate the potential efficacy of two different supervised exercise regimens, namely high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on sarcopenia-related parameters in participants with Parkinson's disease (PD). METHODS: We analyzed data from a randomized controlled pilot trial (CRIS identifier: KCT0007130). An aerobic exercise intervention using a cycle ergometer (40-60 min) in combination with calisthenics (5 min) was performed in three sessions/week for 24 weeks for HIIT (60% maximum aerobic power for 30-50 s with 1-min rest intervals) and MICT (50% peak oxygen consumption) groups. Changes in sarcopenia-related parameters, including appendicular skeletal muscle mass (ASM), ASM index (ASM/height2), handgrip strength, 6-min walking distance, and 30-s chair-stand test (30CST) score, were compared among the HIIT (n = 9), MICT (n = 10), and usual care (n = 11) groups. RESULTS: The HIIT group showed greater increases in leg lean mass (p = 0.011), ASM (p = 0.035), and ASM index (p = 0.025), and greater improvements in 6-min walking distance (p = 0.024) and 30CST scores (p = 0.026) compared with the usual care group. However, among these parameters, only the 30CST score significantly improved in the MICT group compared to the usual care group (p = 0.002). Three of the four (75%) sarcopenic patients who underwent HIIT showed improved sarcopenia after the 24-week exercise intervention, whereas it did not improve in the sarcopenic patients included in the MICT (n = 2) and usual care (n = 2) groups. CONCLUSION: This study suggests that HIIT may be superior to MICT in improving sarcopenia in patients with PD. Further large-scale investigations are required to confirm our findings.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

STUDY OBJECTIVES: The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). METHODS: We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RESULTS: RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). CONCLUSIONS: Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.