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.

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.

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.

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.

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.

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.

Generalized myasthenia gravis patients infected with COVID-19 should continue eculizumab.

Eculizumab, a humanized monoclonal antibody, is a complement inhibitor indicated for refractory generalized myasthenia gravis (MG). However, there are limited data on the safety of eculizumab for MG during coronavirus disease 2019 (COVID-19) infection. We report a case in which eculizumab was continued for MG after contracting COVID-19, followed by a favorable outcome.

Middle Cerebral Artery Pulsatility Index Correlates with Prognosis and Diastolic Dysfunctions in Acute Ischemic Stroke.

OBJECTIVE: To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions. MATERIALS AND METHODS: Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated. RESULTS: We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI. CONCLUSIONS: High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.

Face pareidolia is associated with right striatal dysfunction in drug-naïve patients with Parkinson's disease.

BACKGROUND AND AIM: Some patients with Parkinson's disease (PD) present with pareidolia, an illusion of a meaningless stimulus as a familiar object known to the observer. Since the striatum is associated with processing of visual information, we investigated correlations of pareidolia with motor symptoms and striatal dopaminergic function. METHOD: A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naïve PD patients. A number of images in which a participant noticed an illusory face (number of illusory responses) were compared with motor assessment scores and uptake of 123I-ioflupane in the striatum. RESULTS: Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p<0.05), rigidity (p<0.05), and rigidity on the left side of the body (p<0.01) in patients with pareidolia were significantly higher than those in patients without pareidolia. Uptake of 123I-ioflupane in the right caudate nucleus (p<0.05), anterior putamen (p<0.01), and posterior putamen (p<0.01) in patients with pareidolia was significantly lower than in patients without pareidolia. In the 22 patients with pareidolia, the number of illusory responses was significantly correlated with total scores for MDS-UPDRS part III (r=0.443, p<0.05) and subscores for bradykinesia (r=0.440, p<0.05) and bradykinesia on the left side of the body (r=0.564, p<0.01). The prevalence of pareidolia in left-dominant parkinsonism (16/30 patients) was higher than that in right-dominant parkinsonism (6/28 patients) (p<0.05 by chi-square test). CONCLUSION: Pareidolia in PD patients is associated with dysfunction in the right striatum.

Differences in correlations of depression and anhedonia with cardiovascular sympathetic functions during a head-up tilt test in drug-naïve Parkinson's disease patients.

BACKGROUND: Depression is a symptom of Parkinson's disease (PD) and may be correlated with cardiovascular sympathetic function. Anhedonia is an element of depression, but these symptoms can emerge independently in PD. A correlation of anhedonia with cardiovascular sympathetic function has rarely been examined. OBJECTIVE: To compare correlations of depression and anhedonia with cardiovascular sympathetic function in drug-naive PD patients. METHODS: Assessments of depression (Self-rating Depression Scale; SDS), anhedonia (Snaith-Hamilton Pleasure Scale; SHAPS), myocardial 123I-MIBG (123I-meta-iodobenzylguanidine) scintigraphy (heart to mediastinum (H/M) ratios in early and delayed images), and head-up tilt test (HUT) up to 60° for 10 min were performed in 45 drug-naïve PD patients. During the HUT, blood pressure was measured every minute and the maximum decrease in systolic blood pressure (SBP) was determined. Plasma noradrenaline (NA) and arginine vasopressin (AVP) levels were examined at baseline and 10 min after tilt, with subsequent calculation of increases in plasma NA and AVP levels in this 10 min. Correlation coefficients were calculated among these assessment parameters. RESULTS: SDS significantly correlated with % maximum decrease in SBP (r = 0.344, p = 0.02), but not with H/M ratios in both images and increases in plasma NA and AVP levels. SHAPS did not correlate with the change in SBP, H/M ratios in both images, or plasma NA and AVP levels. CONCLUSION: Depression was correlated with the % maximum decrease in SBP during a 10-min HUT, but anhedonia did not show this relationship. This suggests that depression and anhedonia may have different pathophysiological backgrounds in drug-naïve PD patients.