Effects and safety of high-frequency rTMS in subacute ischemic stroke patients.

OBJECTIVE: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown benefits in chronic stroke, its application in subacute ischemic stroke remains underexplored. This study aims to investigate the effects and safety of lesion-side HF-rTMS in subacute ischemic stroke. METHODS: Prospective lesion-side HF-rTMS was conducted on consecutive ischemic stroke patients within 3 days of onset from February 2019 to June 2022. Inclusion criteria required persistent paralysis (NIHSS score ≥ 1 for at least 7 days). Exclusion criteria comprised cortical infarction, disturbance of consciousness, and age over 80 years. A conventional rehabilitation group meeting the same criteria from June 2015 to January 2019 served as a comparison. We compared the two groups regarding clinical background and outcome. We also evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. RESULTS: Seventy-eight patients participated, with 50% in the HF-rTMS group. Median time from onset to HF-rTMS initiation was 9 (IQR 7-12) days. A favorable outcome (modified Rankin Scale score 0-2) at 3 months was more frequent in the rTMS group (80% vs. 44%, p = 0.002). HF-rTMS was independently associated with a favorable outcome at 3 months (OR = 5.60, 95% CI = 1.53-20.50, p = 0.009). No cases of epilepsy or exacerbation of NIHSS score were observed. CONCLUSIONS: HF-rTMS demonstrates potential effectiveness and safety in subacute ischemic stroke patients.

Bathing-Related Ischemic Stroke: Association between Stroke Subtype and Cerebral Small Vessel Disease.

AIMS: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS. METHODS: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS. RESULTS: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases. CONCLUSIONS: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.

Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

Thin aortic arch plaque is associated with the development of atrial fibrillation for embolic stroke of undetermined source in patients with an insertable cardiac monitor.

BACKGROUND AND OBJECTIVE: This study's objective is to investigate whether mild aortic arch plaque is associated with the development of atrial fibrillation (AF) in stroke patients with embolic stroke of undetermined source (ESUS) during the first year following the implantation of an insertable cardiac monitor (ICM). METHODS: The participants in this cross-sectional observational study were consecutive patients with ESUS, even after transesophageal echocardiography. We assessed the relationship between the thickness of the participants' aortic arch plaque and AF detected after ICM implantation. RESULTS: Of the 50 consecutive patients with ESUS enrolled in this study, 12 (24%) developed AF. We observed that thicker aortic arch plaque was associated with undetected AF (2.3 mm vs. 1.2 mm, p < 0.001). Aortic arch plaque thickness was independent associated with undetected AF (OR 54.00, 95% CI 2.706-1077.544, p = 0.009). When the cut-off value for aortic arch plaque thickness was 1.8 mm, the sensitivity and specificity were 71.1% and 91.7%, respectively (95% CI = 0.75-0.98, p < 0.001). Also, patients having both aortic arch plaque with a thickness < 1.8 mm and a CHADS2 score ≥ 4 were more likely to have detectable AF than no AF (88% vs. 12%, p < 0.001). CONCLUSION: A thinner aortic arch plaque was associated with the development of AF. Patients with mild aortic plaques below 4 mm but ≥1.8 mm in thickness and without other high-risk features are less likely to have paroxysmal AF on ICM, and these plaques may be a possible source of embolism for their strokes.

Relation between severity of cerebral small vessel disease and pulsatility index of internal carotid artery in small vessel occlusion.

BACKGROUND AND PURPOSE: The total small vessel disease (SVD) score, calculated using magnetic resonance imaging (MRI), is used to assess the risk of cerebral infarction. Stroke patients with total SVD scores of three or higher are reported to have a significantly increased risk of recurrent stroke. Similar to the total SVD score, carotid ultrasonography findings have been reported to be indicators of atherosclerosis. Although the total SVD score effectively reflects SVD progression, its correlation with carotid ultrasonography findings remains unknown. We aimed to investigate whether there is a relationship between these two factors. METHODS: Patients with small-vessel occlusion within 24 h of onset were retrospectively selected. Atherosclerotic factors were evaluated using the left-right average Gosling pulsatility index (PI) in the internal carotid artery (ICA-PI) and cardio-ankle vascular index (CAVI). Differences in clinical backgrounds, including atherosclerotic factors, were evaluated by dividing patients into two groups: those with a total SVD score of two or less (low-score group) and those with scores of three or more (high-score group). RESULTS: A total of 122 patients were included in this study. ICA-PI was significantly higher in the high-score group than in the low-score group. A high score was independently correlated with ICA-PI after adjusting for age, CAVI, smoking, and history of secondary atherosclerosis. CONCLUSIONS: Increased ICA-PI was associated with a high total SVD score in acute small-vessel occlusion and may be an alternative method for predicting the total SVD score, enabling the administration of interventions to prevent stroke relapse without the need for MRI.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

AIMS: Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). METHODS: Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores ＞10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. RESULTS: Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). CONCLUSION: In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.

Deep and infratentorial cerebral microbleeds are related to wake-up stroke by large-artery atherosclerosis and cardioembolism.

BACKGROUND AND AIMS: Circadian variability of blood pressure (BP) and hypercoagulation in the morning have been proposed as underlying mechanisms of wake-up stroke (WUS). The aim was to determine the impact of cerebral microbleeds (CMBs), showing BP fluctuation and background hypercoagulability, on WUS. METHODS: Consecutive patients with acute ischemic stroke onset-to-door time within one week were screened. WUS was defined as an ischemic stroke that occurred during sleep at night. CMBs were categorized into three: "strictly Lobar", "strictly Deep (D) and/or Infratentorial (I)", and "Mixed". Moderate to severe CMBs were defined as having more than three in total. First, whether CMBs are associated with WUS was examined. Second, the same analysis was performed according to the stroke subtype classified as large-artery atherosclerosis (LAA), cardioembolism (CE), and small-vessel occlusion (SVO). RESULTS: A total of 1477 patients (1059 [72%] male, median age 69 years) were included, and WUS was observed in 363 (25%) patients. On Poisson regression analysis with a robust variance estimator in the total cohort, moderate to severe strictly D and/or I CMBs (PR 1.505, 95% CI 1.154-1.962, p = 0.003) were associated with WUS. From the perspective of stroke subtype, the same result was confirmed in LAA (PR 2.223, 95% CI 1.036-4.768, p = 0.040) and CE (PR 1.668, 95% CI 1.027-2.709, p = 0.039), not SVO. CONCLUSIONS: The presence of moderate to severe strictly D and/or I CMBs might be associated with the development of WUS. By stroke subtype, the same result was confirmed in LAA and CE.

Follow-Up Diffusion-Weighted Image Reveals Delayed Appearance of Ischemic Lesions in Suspected Transient Ischemic Attack.

INTRODUCTION: In patients suspected of transient ischemic attack (TIA), it is not uncommon to find no lesion on the diffusion-weighted image (DWI) on admission but a delayed appearance on the follow-up DWI. METHODS: Enrolled patients met the following criteria: (1) MRI performed within 24 hours of onset and seven days after admission; (2) National Institutes of Health Stroke Scale (NIHSS) score ≦4 on admission; (3) pre-stroke modified Rankin scale (mRS) score of 0-1. Patients were divided as follows: no lesion on the first DWI and a new lesion on the second DWI (delayed-specified ischemic stroke; DSIS); and no lesion on either the first or second DWI (well-screened TIA; WSTIA). We compared both groups regarding the clinical background and the outcome at three months. RESULTS: We identified 144 cases (male 70%; median age 64 years; DSIS, n=34) between October 2012 and March 2019. DSIS was older (71 vs. 60 years, p=0.006) and had a higher NIHSS score on admission (1 vs. 0, p=0.041), a higher rate of large vessel occlusion (LVO) (17% vs. 2%, p=0.008), and symptom duration over one hour (82% vs. 64%, p=0.041). A favorable outcome mRS score of 0-1 at three months was less frequent in DSIS (85% vs. 96%, p=0.004). Age/10 (OR 1.62, 95%CI 1.17-2.24; p=0.004) and LVO (OR 10.84, 95%CI 1.87-63.06; p=0.008) were independent factors for DSIS. CONCLUSIONS: In suspected TIA with age or LVO but no lesion in the initial DWI, the second DWI should be considered to identify the delayed appearance of an ischemic stroke.

The REMIT scale: A novel prediction scale for embolism in hyperacute stroke with large vessel occlusion.

BACKGROUND AND PURPOSE: Large vessel occlusion (LVO) in hyperacute ischemic stroke occurs mainly by one of two mechanisms, embolism or atherosclerosis. However, the mechanism is difficult to identify prior to treatment. We aimed to investigate the factors associated with embolic LVO in hyperacute ischemic stroke, and to develop a preoperative predictive scale for the event. MATERIALS AND METHODS: This retrospective multicenter study was conducted with consecutive ischemic stroke patients with LVO who underwent thrombectomy, thrombolysis, or both. The embolic LVO was defined as an occlusion that underwent recanalization with no residual stenosis. Multivariate logistic regression analysis for embolic LVO was performed to identity the independent risk factors. With this approach, a novel prediction scale (Rating of Embolic Occlusion for Mechanical Thrombectomy [REMIT] scale) was developed. RESULTS: A total of 162 patients (104 men; median age 76 years; interquartile range 68-83) were included in this study. Embolic LVO was observed in 121 patients (75%). Multivariate logistic regression analysis showed that embolic LVO was independently associated with high brain natriuretic peptide (BNP), high National Institutes of Health Stroke Scale (NIHSS) on admission, and absence of non-culprit stenosis (NoCS). The REMIT scale comprises high BNP (>100 pg/dL), high NIHSS (>14) and absence of NoCS, with one point for each risk factor. The frequencies of embolic LVO for the REMIT scale scores were as follows: score 0, 25%; score 1, 60%; score 2, 87%; score 3, 97% (C-statistic 0.80, P < 0.001). CONCLUSION: The novel REMIT scale has predictive value for embolic LVO.

A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber.

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3-8 min). Mean infarct volume was 388 mm3 (IQR, 354-420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke.

Urinary Immunoglobulin G Is Associated with Deep and Infratentorial Cerebral Microbleeds in Stroke Patients.

BACKGROUND: Cerebral microbleeds (CMBs) detected on susceptibility-weighted imaging (SWI) are associated with cerebral small vessel disease. Chronic kidney disease and microalbuminuria have been associated with the presence of CMBs in stroke patients. Urinary immunoglobulin G (IgG) is measured to document glomerular injury; however, the relationship between urinary IgG and CMBs is unknown. METHODS: We retrospectively enrolled consecutive patients who had been admitted with transient ischemic attack (TIA) or ischemic stroke and identified those who had undergone SWI and a spot urine test. The location of CMBs was classified on magnetic resonance imaging as strictly lobar, deep/infratentorial (D/I), or mixed areas. We analyzed the association between urinary IgG and the presence and location of CMBs. RESULTS: We included 298 patients (86 female, median age 70 years, median eGFR 65.8 mL/min/1.73 m2). Positive urinary IgG and CMB results were found in 58 (19%) and 160 patients (54%), respectively. Urinary IgG positivity was significantly associated with CMBs compared with non-CMBs (28% vs. 9%, p < 0.001), and with D/I or mixed CMBs compared with non-D/I or mixed CMBs (34% vs. 10%, p < 0.001). Multivariate analysis revealed that urinary IgG and hypertension positivity were strongly associated with D/I or mixed CMBs (OR 3.479, 95% CI: 1.776-6.818, p < 0.001; OR 3.415, 95% CI: 1.863-6.258, p < 0.001). CONCLUSIONS: Urinary IgG was associated with the prevalence of D/I or mixed location CMBs in TIA or ischemic stroke patients. Our findings provide new insights into the association between urinary IgG and the distribution of CMBs.

Old thalamic lacunes contralateral to a supratentorial intracerebral hemorrhage are associated with an unfavorable outcome.

OBJECTIVE: To determine the impact of old lacunes and their sites on the prognosis of one-sided supratentorial intracerebral hemorrhage (ICH) by classifying lacunes sites in relation to anatomical structures using MRI. METHODS: Consecutive patients with one-sided supratentorial ICH ≤72 h from onset to door who underwent MRI were retrospectively included. The sites of old lacunes were categorized as follows: deep subcortical white matter, caudate head, lentiform, posterior limb and genu of the internal capsule, thalamus, and brainstem. We also evaluated all other cerebral small vessel disease markers. An unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 months after onset. We investigated whether old lacunes in particular locations were related to unfavorable outcomes. RESULTS: We included 186 patients with one-sided supratentorial ICH (126 [68%] males, median age 62 years). Of 186 patients, 65 (35%) patients had unfavorable outcomes. Factors associated with unfavorable outcomes were age (OR 2.261, 95% CI 1.332-3.839, p = 0.003), National Institutes of Health Stroke Scale [NIHSS] score at admission (OR 1.175, 95% CI 1.090-1.267, p < 0.001), and old thalamic lacunes contralateral to the hematoma (OR 3.805, 95% CI 1.009-14.340, p = 0.048). Patients with old thalamic lacunes contralateral to the hematoma tended to have arm (p = 0.006) and leg (p = 0.011) motor impairment on the paralyzed side at discharge as estimated by the NIHSS score. CONCLUSIONS: Old thalamic lacunes contralateral to the hematoma may be related to unfavorable outcomes in ICH.

Effects of monotherapy with a monoamine oxidase B inhibitor on motor symptoms in Parkinson's disease are dependent on frontal function.

BACKGROUND: Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity. AIM: To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function. PATIENTS AND METHODS: Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1 mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19 weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis. RESULTS: In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p < 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group. CONCLUSION: Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

Effects and safety of high-frequency rTMS in acute intracerebral hemorrhage patients: A pilot study.

OBJECTIVE: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) in chronic intracerebral hemorrhage (ICH) is beneficial, it has been poorly investigated in rTMS for acute ICH. Our aim is to investigate the effects and safety of rTMS in acute spontaneous ICH. METHODS: We prospectively performed HF-rTMS on consecutive patients with ICH within 24 h from onset between April 2019 and August 2021. The inclusion criterion was (1) persistent paralysis, with an NIHSS scale of 1 or higher for at least 3 days after onset. The exclusion criteria were (1) cortical, subcortical, and cerebellar ICH, (2) disturbance of consciousness, and (3) over 80 years of age. For the purpose of comparison, we used a conventional rehabilitation group whose patients met the same criteria between April 2016 and March 2019. We evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. We also compared the two groups regarding clinical background and outcome. RESULTS: Enrolled in the study were a total of 44 patients. Of the patients, 22 (50%) were in the rTMS group. The median (IQR) time from onset to the start of rTMS was 9 (6-12) days. There were no cases of epilepsy or exacerbation of NIHSS after the start of rTMS. Favorable outcome (modified Rankin Scale score of between 0 and 2) at 3 months was frequently observed in the rTMS group (73% vs 27%, p = 0.006). HF-rTMS was independently associated with favorable outcome at 3 months (OR = 11.5, 95% CI = 2.194-60.447, p = 0.004). CONCLUSIONS: HF-rTMS may be safe and effective in acute ICH patients.

The association between urinary pentosidine levels and cognition in drug-naïve patients with Parkinson's disease.

Advanced glycation end products (AGEs) are suggested to play a potential role in the progression of Parkinson's disease (PD). The association between urinary levels of pentosidine, one of the best-characterized AGEs, and clinical conditions such as motor severity and cognition were investigated in patients with PD. Data on the clinical characteristics and urinary levels of pentosidine for 44 drug-naïve patients aged 60 years or older with PD were collected. The association between urinary pentosidine levels and severity of motor symptoms and cognition was analyzed using the Montreal Cognitive Assessment Scale (MoCA). Urinary pentosidine values increased with age (R2 = 0.286, p < 0.001) and were negatively correlated with the MoCA score (R2 = 0.255, p = 0.001). Urinary pentosidine levels were significantly correlated with age (r = 0.535, p < 0.001), Hoehn-Yahr stage (r = 0.340, p < 0.05), and total MoCA score (r = - 0.505, p < 0.001). Multiple linear regression analysis showed that older age (ß = 0.543; 95% confidence interval [CI] 0.300, 1.307; p = 0.003) was significantly associated with severity of motor symptoms, and that older age (ß = - 0.456; 95% CI - 0.287, - 0.054; p = 0.005) and urinary pentosidine levels (ß = - 0.311; 95% CI - 0.428, - 0.004; p = 0.046) were significantly associated with a lower MoCA score. Urinary pentosidine levels were significantly associated with lower cognition in drug-naïve PD patients. These findings have important clinical implications and suggest that pentosidine may be a potential marker for cognitive impairment in early PD.

Low dihomo-γ-linolenic acid is associated with susceptibility vessel sign in cardioembolism.

BACKGROUND AND AIMS: The susceptibility vessel sign (SVS) on susceptibility-weighted image, a magnetic resonance imaging technique, reveals thrombi as hypointense signals. We aimed to examine the association between polyunsaturated fatty acid (PUFA) levels and the presence of the SVS and its length in cardioembolism due to atrial fibrillation (AF). METHODS: Consecutive ischemic stroke patients who met the following inclusion criteria were screened: 1) patients with cardioembolism, defined by Trial of ORG 10172 in Acute Stroke Treatment, secondary to AF; 2) onset to door time within 24 h; 3) availability of magnetic resonance images, including susceptibility-weighted images, obtained at our hospital before performing recanalizing therapy; and 4) availability of PUFA measurements on the day of or the day after the hospital visit. We evaluated whether PUFA levels might be associated with the presence of the SVS and its length. RESULTS: We retrospectively screened 1720 consecutive ischemic stroke patients, and included 137 patients (95 (69%) male, median age 73 years) who met the inclusion criteria in the analyses. In binomial logistic regression analysis, lower dihomo-γ-linolenic acid (DGLA) level was associated with the presence of SVS (odds ratio 0.545, 95% confidence interval 0.374 to 0.794, p = 0.002). Multiple linear regression analysis revealed a significant negative association between DGLA levels and SVS length (unstandardized coefficient -7.430, 95% confidence interval -13.256 to -1.603, p = 0.013). CONCLUSION: Low DGLA level is associated with the presence of SVS and its length in patients with cardioembolism secondary to AF.

A case of idiopathic hypertrophic pachymeningitis with high adenosine deaminase in cerebrospinal fluid.

Adenosine deaminase (ADA) in cerebrospinal fluid (CSF) has been reported as useful to diagnose tuberculous meningitis and hypertrophic pachymeningitis (HP). The case of a 59-year-old woman with impaired vision and an auditory disturbance due to massive intracranial HP is presented. Although acid-fast bacillus cultures and polymerase chain reaction tests for Mycobacterium tuberculosis in the CSF were negative, tuberculous HP was diagnosed clinically because of the high ADA in CSF, and anti-tuberculosis drugs were administered with prednisolone because idiopathic HP (IHP) could not be ruled out. Since the impaired vision worsened with prednisolone reduction despite the continuation of anti-tuberculosis drugs, a dural biopsy was performed, and the patient was diagnosed with IHP. ADA is associated with lymphocyte proliferation and differentiation and increased by activation of cell-mediated immunity. Elevated CSF-ADA might be caused by lymphocyte infiltration in the thickened dura mater.

Association between heart rate variability and striatal dopamine depletion in Parkinson's disease.

Striatal dopamine depletion is associated with not only motor symptom but also non-motor symptoms in patients with Parkinson's disease (PD). The purpose is to elucidate the relation between heart rate variability (HRV) and dopaminergic depletion in specific striatal subregions. The subjects were 84 patients with newly diagnosed untreated PD. All patients underwent striatal 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single-photon emission computed tomography (DAT-SPECT). DaTQUANT software (GE Healthcare) was used as a semi-quantitative tool to analyze DAT-SPECT data. Association of HRV with dopaminergic depletion in specific striatal subregions was examined. HRV was related to dopamine depletion in the caudate and anterior putamen, especially the left side, after controlling for age, hemoglobin A1c level, disease duration, motor severity and global cognition on multiple regression analysis (left caudate p = 0.012). HRV was closely related to striatal dopamine depletion, especially in the left associative striatum, in patients with PD.