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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.

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 (R

The aim of the study was to evaluate the cross-sectional area of the cauda equina in amyotrophic lateral sclerosis (ALS) on routine lumbar magnetic resonance imaging and investigate the diagnostic accuracy in comparison with age- and sex-matched non-ALS controls.This retrospective study included 15 ALS patients and 15 age- and sex-matched non-ALS controls. Two independent neuroradiologists measured and compared the total cross-sectional area of the cauda equina of ALS patients and the non-ALS controls at the level of the L3 and L4 using axial T2-weighted images. The cutoff value, sensitivity, specificity, and area under the curve were measured. The interobserver reproducibility of the 2 independently obtained measurements was evaluated.The total cross-sectional area of the cauda equina in the ALS group was significantly smaller than that in the non-ALS group (L3: median, 66.73 vs 90.19 mm 2 , P0.001; L4: median, 52.9 vs 67.63 mm 2 , P0.001). The cutoff values at L3 and L4 were 76.95 and 61.04 mm 2 with a sensitivity and specificity of 1 and 0.87 and 0.8 and 0.87, respectively. The area under the curve at L3 and L4 were high at 0.96 and 0.94, respectively. The interobserver reproducibility was 0.88 at L3 and 0.89 at L4.The ALS patients showed significant atrophy of the cauda equina compared with non-ALS patients.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder that affects multiple organs, including the muscle and eye, caused by a CTG triplet expansion of the 3' untranslated region (UTR) of the DMPK gene. Cataracts and retinal degeneration are major eye complications in patients with DM1. We reported the case of a Japanese patient with DM1 who exhibited submacular hemorrhage unilaterally, rarely complicating DM1.A 56-year-old woman presented with loss of visual acuity in the left eye (LE). The patient was diagnosed with DM1, who carried expanded CTG repeats (1100) of the 3' UTR of DMPK. Her corrected visual acuities were 20/100 and 20/2000 in the right eye (RE) and LE, respectively. Cataracts were observed in both eyes. Fundoscopy and angiography revealed submacular hemorrhage in the LE due to polypoidal choroidal vasculopathy (PCV, also known as aneurysmal type 1 neovascularization). The patient underwent intravitreal injections of an anti-vascular endothelial growth factor drug and sulfur hexafluoride gas in the LE. Full-field electroretinography was performed, showing that the rod and standard-flash responses were reduced to 50% and below 10% in the RE and LE, whereas the cone and 30-Hz flicker responses were reduced to 40-50% and 15-20% in the RE and LE, respectively, compared with the controls. Multifocal electroretinography revealed that the overall responses were extinguished in the LE and considerably attenuated in the RE.This is the first patient with DM1 complicated with PCV. Widespread retinal dysfunction may be associated with expanded CTG repeats, which is significantly longer than the mean repeat number of patients with DM1.

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-2β-carbomethoxy-3β-(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, and motor severity on multiple regression analysis (left caudate; β = 0.269, p = 0.030, left anterior putamen; β = 0.315, p = 0.012). HRV was closely related to striatal dopamine depletion, especially in the left associative striatum, in patients with PD.

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.To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function.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.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.Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

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.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.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).HF-rTMS may be safe and effective in acute ICH patients.

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. A noise pareidolia test, assessment of motor symptoms using MDS-UPDRS and 123I-Ioflupane SPECT were performed in 58 drug-naive 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. Of the 58 participants, 22 had at least one illusory response. Mean scores for MDS-UPDRS part III (p

Aim Olfactory impairment as a prodromal symptom, as well as sarcopenia, frailty and dependence as geriatric syndromes, is often associated with cognitive decline in older adults with progression of Alzheimer's disease. The present study aimed to evaluate the associations of olfactory and cognitive decline with these geriatric syndromes, and with structural changes of the brain in older adults.

Parkinson's disease (PD) is a neurodegenerative disease manifesting with motor and non-motor symptoms. Current treatment mainly relies on medication as a symptomatic therapy modulating neurotransmitters. Dopamine replacement therapy has been established, and levodopa is the gold standard for treatment of PD. However, the emergence of motor complications, such as a wearing-off phenomenon, is a clinical problem. Both primary symptoms and motor complications have been targets for the development of treatments for PD. Recent progression in the management of motor complications is supported by newly developed agents and advances in device and formulation technology to deliver drugs continuously. Elucidation of the pathophysiology of PD and the development of disease-modifying therapy that affects the underlying fundamental pathophysiology of the disease are also progressing. In this review, we introduce current knowledge on developments concerning medications for patients with PD.

Objective The presence of deep venous thrombosis (DVT) in a cryptogenic stroke (CS) patient with a right-to-left shunt (RLS) may lead to the development of paradoxical embolism. The aim of the present was to investigate the prevalence of DVT and pulmonary embolism (PE) in CS patients and the clinical features of CS in relation to DVT location and the presence of PE. Methods The medical records of 903 patients with cerebral infarction were retrospectively reviewed. For patients with a diagnosis of CS, contrast saline transcranial color-coded sonography was performed to identify an RLS. DVT and PE were assessed by duplex ultrasonography and/or contrast-enhanced computed tomography. Proximal DVT (P-DVT) was defined as DVT in the popliteal, femoral, or iliac veins, and distal DVT (D-DVT) was defined as DVT at other locations. The patients were divided into three groups: CS with P-DVT and/or PE (P-DVT/PE) group; CS with D-DVT (D-DVT) group; and CS without DVT (no DVT) group. Results Seventy-two (37%) of 194 patients with CS had an RLS. The median time to first DVT examination from stroke onset was three days. Twenty-nine percent of CS patients with an RLS had DVT. The P-DVT/PE group comprised 8.3% of the CS patients with an RLS and included a larger number of patients with multi-territory infarction than the D-DVT group. The D-DVT and P-DVT/PE groups tended to be female and older, while the P-DVT/PE group tended to have pre-stroke disability. Conclusion CS patients, especially those with multi-territory lesions, should be immediately examined for DVT and PE.

Introduction and Objectives: The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. Methods: Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, p = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, p = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0–1 at 3 months from onset). Conclusions: Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.

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.

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.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.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.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.

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

Background and Purpose: Recent several studies demonstrated that percutaneous patent foramen ovale (PFO) closure reduced the risk of stroke recurrence for patients with cryptogenic stroke (CS) and PFO. Our aim of this retrospective study is to survey the frequency of CS, which can be an indication of PFO closure. Methods: Subjects were consecutive stroke patients with symptomatic ischemic lesion detected by magnetic resonance imaging. Of them, CS were extracted according to exclusion of small-vessel collusion, large-artery atherosclerosis, cardioembolism, definite case of aortogenic embolism, and distinctive causeof ischemic stroke such as arterial dissection, hypercoagulable state and so on. After that, we selected patients in accordance with clinical guideline of PFO closure recommended by the Japanese Stroke Association (Figure). We analyzed the prevalence of CS with right-to-left shunt (RLS) as a good and recommended candidates for PFO closure. Results: Among 1,374 ischemic stroke patients from October 2012 to September 2019 , CS were 240 patients (83 females, mean age of 66 years, 17% of subjects). Of them, 100 patients (42%) had RLS (PFO; 65, atrial septal defect; 1, pulmonary arteriovenous fistula; 1, positive on transcranial Doppler (not performed in TEE) including 21 cases of definite of paradoxical embolism. In 65 patients of CS with PFO, 30 patients younger than 60 years (13% of CS) were good candidates for PFO closure. Moreover, 22 of 1,374 (1.6%) patients who were recommended candidates had one or more high risk factors of PFO, for example large shunt, atrial septal aneurysm, and the presence of shunt at rest (Figure). Conclusions: In our preliminary survey, 2% of acute ischemic stroke should be PFO closure candidates.

A 60-year-old man developed aphasia and transient right upper limb paresis in the presence of chronic subdural hematoma and was transferred to our hospital at an early stage. Cranial MRI within an hour after onset showed diffusion-weighted image (DWI) hyperintensity in the left parietal, temporal, and insular cortex and the pulvinar, and decreased apparent diffusion coefficient (ADC) in the left parietal cortex and pulvinar, suggesting a differential diagnosis of hyper-acute ischemic stroke. However, the distribution and timing of the MRI abnormalities were considered to be atypical for hyper-acute ischemic stroke. The area with both DWI hyperintensity and decreased ADC included the cerebral cortex adjacent to the hematoma and the ipsilateral pulvinar, and fluid-attenuated inversion recovery (FLAIR) hyperintensity co-existed with DWI hyperintensity within only an hour from onset. Furthermore, FLAIR images showed infiltration of the hematoma content into the subarachnoid space, which might have triggered the attack. These findings collectively led us to diagnose an epileptic seizure. The present case suggests that the distribution and timing of MRI abnormalities are essential to differentiate epileptic seizures from hyper-acute ischemic stroke.

Background: Orthostatic hypotension (OH) at an early stage of Parkinson’s disease (PD) predicts poor prognosis, which may suggest degeneration of dopaminergic neurons affects sympathetic function, causing OH. Objective: We tested the hypothesis that striatal dopaminergic depletion is associated with OH in PD. Methods: Out of 99 patients with newly diagnosed untreated PD, 81 patients were enrolled according to our selection criteria. All patients underwent head-up tilt-table testing and striatal 123I-2β-carbomethoxy-3β-(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. The association between hemodynamic changes and 123I-FP-CIT uptake was examined. Results: 123I-FP-CIT uptake in the putamen, especially the anterior part and left side, was related not only to motor severity but also to OH. Change in systolic blood pressure correlated negatively with 123I-FP-CIT uptake in bilateral anterior putamen (left: p

Objectives To investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome. Materials and methods Symptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes. Results We screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome. Conclusions Patients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.

OBJECTIVES Minor hallucinations (MHs), including sense of presence, passage hallucinations, and visual illusions, have been reported in Parkinson's disease (PD). Here, we investigated the prevalence and associated risk factors for MHs according to appearance time. METHODS Data on the clinical characteristics and the appearance time of MHs for 100 PD patients were collected using a questionnaire and analyzed. MHs were classified into two groups according to the time when MHs appeared: MHs appearing while awake during the daytime (dMHs) and MHs appearing at arousal from sleep during the night or early morning (aMHs). RESULTS Thirty-eight patients (38%) experienced MHs. dMHs and aMHs were present in 21 (21%) and 28 patients (28%), respectively. Compared to patients without MHs, patients with dMHs had more severe motor symptoms, longer disease duration, higher levodopa equivalent daily dose (LEDD), and higher rates of cognitive impairment and visual hallucinations during the daytime, whereas patients with aMHs had a higher rate of rapid eye movement sleep behavior disorder (RBD), longer disease duration, higher LEDD, and higher dopamine agonist dosage. Logistic regression analysis showed that cognitive impairment was significantly associated with dMHs (odds ratio (OR) 7.292, p = .001), and that RBD (OR 8.306, p

Delayed orthostatic hypotension (DOH), a fall in blood pressure after a 3-min cutoff, is clinically meaningful. The aim of this study was to elucidate the clinical and neuroendocrinological characteristics of DOH in patients with Parkinson’s disease (PD). A total of 132 patients with newly diagnosed PD were enrolled. Baseline clinical characteristics, including olfactory function, and changes in norepinephrine (NE) and vasopressin (ADH) concentrations during the head-up tilt test (HUT), were examined. Fifty-five patients (42%) had classical orthostatic hypotension (COH), and 19 patients (14%) had DOH. Patients with COH and DOH tended to have more severe hyposmia than patients without OH. A multivariate linear regression model showed that hyposmia was associated with DOH and COH. The increase of heart rate against the fall in blood pressure was significantly lower in patients with COH and DOH than those without OH. The NE levels at supine rest and after upright tilting were lower in the COH group than in the PD without OH and DOH groups. The levels of ADH were higher in the DOH group than in the COH group at supine rest and higher than in the PD without OH group after upright tilting. There was no significant difference in the cardiac 123I-MIBG scintigraphy between the COH and DOH groups. Compared with patients without OH, patients with DOH had severe hyposmia. Relatively preserved peripheral sympathetic nervous system function in patients with DOH suggests that DOH might be an early and milder form of OH in PD.

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

Introduction: No lesion on admission DWI but delayed appearance in the follow-up DWI are not uncommon in acute stroke. Our aim is to investigate clinical features of patients with delayed-high intensity area (DHIA) on follow-up DWI. Methods: We enrolled 1) TIA patients and 2) clinically suspected stroke patients sustaining a neurological deficit over 24 hours without ischemic lesion on initial DWI. Follow-up DWI was performed in 7 days after admission. We divided into two groups as follows; DHIA group and no hyper-intense lesion on initial and second DWI (NHIA group). Univariate and multivariate logistic regression analysis were conducted on backgrounds, clinical courses including time from onset to MRI, symptom duration, and favorable outcome (mRS 0-1) in 3 months in both groups. Results: One hundred seventy-two cases were identified (male 68%, median age 66 yo, median NIHSS score 1, delayed-HIA group; 48 patients) between October 2012 and March 2019. DHIA group was older (72 yo vs 64 yo, p Conclusion: Follow-up DWI may play an important role of outcome biomarker in TIA and initially suspected stroke. Repeated MRI should be performed for elder and severe neurological deficits.

Background and Purpose: We aimed to investigate the differences in weekly variations of stroke occurrence between hyper-acute ischemic stroke patients with and without regular employments (RE), and the impact of RE on outcome. Methods: Consecutive symptomatic ischemic stroke patients with < 4.5 h from onset to door between October 2012 and May 2018 were enrolled. All the situations of employment on admission were obtained from interviews with the participant or substitute guardians. First, we divided the patients into with and without RE to evaluate the differences in weekly variations of stroke occurrence. Second, we divided the same patients into with and without favorable outcome (mRS score of 0 to 2 at 3 months from the onset) to evaluate the impact of RE on outcome. Results: We screened 1,249 consecutive symptomatic ischemic stroke patients, including 385 patients (292 (76%) male, median age 67 years) with hyper-acute ischemic stroke. Of all, 251 patients (65%) were included in RE group. In the multivariate analysis, patients with RE were more likely to develop strokes on Monday compared to that on Sunday and public holiday (OR 2.841, 95% CI 1.145-7,049, p = 0.024, Figure A). In the multivariate analysis, the factors associated with favorable outcome were low NIHSS score on admission (OR 0.909, 95% CI 0.857-0.964, p = 0.001), not receiving endovascular therapy (OR 0.175 95% CI 0.069-0.444, p p = 0.039, Figure B). Conclusions: There were dramatic differences in weekly variations of hyper-acute ischemic stroke occurrence between patients with and without RE. Monday seems to be “a black day” for ischemic stroke patients with RE. RE had a positive impact on outcome in hyper-acute ischemic stroke.

Background and Purpose: Hyperintense vessel sign on FLAIR (HVS) has been described in hyperacute stroke patients with arterial occlusion. It’s a surrogate marker for stroke severity in patients with acute ischemic stroke of the anterior circulation. We aimed to reveal the clinical significance of HVS in patients with acute posterior circulation infarction. Methods: This observational study is based on a single-center prospective registry study. Inclusion criteria were: symptomatic ischemic stroke patients who have lesions only in posterior circulation; and taken initial MRI within 14 days from onset.An unfavorable outcome was defined as mRS score of 2 to 6 at 3 months from the onset. First investigation is to estimate whether HVS could be related to the subtype of acute ischemic stroke (cohort A). Second, the correlation between HVS and mRS at 3 months was evaluated (cohort B). Results: From October 2012 to May 2019, consecutive 1,079 ischemic stroke subjects were screened, including 277 in cohort A (191 male, median age 64 years) and 240 in cohort B (165 male, median age 66 years, Figure A). In cohort A, HVS was independently associated with intracranial artery dissection (OR 5.228; 95% CI 2.270-12.039; p = 0.001) and large-artery atherosclerosis (OR 3.582; 95% CI 1.244-10.317; p = 0.018, Figure B). In cohort B, HVS was not a factor independently associated with unfavorable outcome (OR 2.925; 95% CI 0.881-9.714; p = 0.080). Conclusions: HVS in patients with posterior circulation infarct suggests intracranial artery dissection or large-artery atherosclerosis, but does not have impact on their clinical courses.

Background and Purpose: To determine the parameters of transcranial color-coded duplex sonography (TCCS) related to unfavorable outcomes, and further to clarify the correlation between those parameters and heart functions in acute ischemic stroke without vessel stenosis. Methods: Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: acute ischemic stroke or TIA; able to measure blood flow of either the left or right middle cerebral artery (M1) by TCCS with ≤7 days from onset; and have no vessel stenoses or occlusions assessed by MRA and carotid artery ultrasonography. An unfavorable outcome was defined as mRS score of 2 to 6 at 3 months from the onset. First, we investigated the parameters of TCCS related to unfavorable outcomes (cohort A). Second, the correlation between those parameters and heart functions assessed by transthoracic echocardiography was evaluated (cohort B). Results: We screened 1,529 consecutive ischemic stroke patients, including 173 in cohort A (146 (84%) male, median age 59 years) and 192 in cohort B (162 (84%) male, median age 60 years) (Figure A). In cohort A, high M1 pulsatility index (PI) (OR 0.043; 95% CI 0.005-0.407; p = 0.006) was independently associated with an unfavorable outcome (Figure B). In cohort B, higher age (OR 1.532; 95% CI 1.118-2.009; p = 0.008), higher E/e' (OR 1.143; 95% CI 1.011-1.292; p = 0.033), and aortic valve regurgitation (AR > mild) (OR 4.780; 95% CI 1.261-18.114; p = 0.021) were factors independently associated with high M1 PI (Figure C). Conclusions: High M1 PI predicts an unfavorable outcome and correlates with high E/e' suggesting diastolic heart dysfunction and aortic valve regurgitation in acute ischemic stroke without vessel lesion.

A 69-year-old man was admitted to our hospital because of dysesthesia in right palm and left upper limb, gait disturbance, and muscle weakness in both lower limbs. At the same time of neurological impairment appeared, he developed pemphigoid. Lumber MRI showed swelling of cauda equina nerve root. We diagnosed as chronic inflammatory demyelinating polyneuropathy based on an electrophysiological examination, and 2 courses of intravenous immunoglobulin therapy (IVIG) were initiated. After the treatments, symptoms improved immediately. However, thrombocytopenia was seen after each treatment which began on the second day of treatment start, reaching the lowest point from about 10 to 14 days, and improved naturally from 10 to 15 days after the end of IVIG. Difficulty in hemostasis was seen during dialysis due to thrombocytopenia. As a cause of thrombocytopenia, formation of IgG-platelet complexes could be considered, and the presence of multiple inflammatory diseases which activated Fcγ receptors play key roles could be a risk for IVIG related thrombocytopenia.

Selective plasma exchange could preserve fibrinogen and is a useful treatment for multiple sclerosis.

We report the case of a 74-year-old woman with treatment-naive chronic inflammatory demyelinating polyneuropathy evaluated by both nerve conduction studies and nerve ultrasound (NUS) before and after initial treatment. Performing both nerve conduction study and NUS before and after initial treatment seems rare for treatment-naive chronic inflammatory demyelinating polyneuropathy. This case yielded two major findings. First, improvement of nerve swelling as evaluated by NUS correlated well with the improvement of neurological symptoms. Second, NUS improvements were seen right after treatment, whereas electrophysiological improvements were not. Nerve ultrasound might thus allow for judgment of curative effects much more immediately and sensitively than nerve conduction study in treatment-naive chronic inflammatory demyelinating polyneuropathy.

In general, involuntary movements after stroke are due to a disturbance in the unilateral cortico-basal ganglia loop and appear contralateral to stroke lesions. Crossed involuntary movements after unilateral stroke are very rare. We observed a case of crossed involuntary movements in the left upper limb and right lower limb after a right thalamic hemorrhage expanded to the right subthalamic nucleus. We considered a possible three-step theory as the basis of crossed choreoathetosis. This case informs our better understanding of the cortico-basal ganglia loop and involuntary movements after stroke.

Sympathetic nervous denervation may be associated with the development of anemia. We aimed to investigate the association between sympathetic nervous denervation and hemoglobin levels in patients with Parkinson’s disease (PD). As indices of sympathetic nervous denervation, we investigated resting norepinephrine levels, increased norepinephrine levels after tilt-up, cardiac uptake of 123I-metaiodobenzylguanidine, supine blood pressure, and the degree of orthostatic hypotension in 132 patients with de novo PD. Older age, female sex, severe motor dysfunction, and lower body mass index were associated with decreased hemoglobin levels. After adjustment for these covariables, resting norepinephrine levels were negatively associated with hemoglobin levels. Hemoglobin levels were not associated with cardiac sympathetic denervation or orthostatic intolerance. Hemoglobin levels in PD seem to be closely related to noradrenergic nervous activity and nigrostriatal dopaminergic degeneration. In contrast to expectations, decreased hemoglobin levels were associated with increased whole-body sympathetic nervous activity in PD.

The precise mechanisms underlying the expansion of lacunar and giant lacunar infarction remain unclear. We aimed to determine risk factors for lacunar and giant lacunar infarction and to clarify differences in pathophysiological mechanisms for these two groups.Patients were selected from a comprehensive stroke center with ≤24 h from onset to initial magnetic resonance imaging with lacunar and giant lacunar infarction. All patients underwent a second magnetic resonance imaging during hospitalization. Infarct size was calculated and compared by the positive region on diffusion-weighted imaging. Factors related to infarct expansion were evaluated separately in the two groups.We screened 1558 consecutive ischemic stroke patients, including 154 patients with small vessel disease (lacunar infarction, 81 patients; giant lacunar infarction, 73 patients). Age (odds ratio (OR), 0.899; 95% confidence interval (CI), 0.824-0.981, p = 0.016), higher cardio-ankle vascular index (OR, 6.011; 95%CI, 2.319-15.581, p 0.001), higher uric acid (OR, 2.584; 95%CI, 1.091-6.121, p = 0.031), and lower/normal low-density lipoprotein (LDL)-cholesterol (OR, 0.718; 95%CI, 0.557-0.926, p = 0.011) were independently associated with infarct expansion in lacunar infarction patients. Concerning giant lacunar infarction, higher LDL-cholesterol (OR 1.509, 95%CI 1.083-2.103; p = 0.015) and lower/normal body mass index (OR 0.725, 95%CI 0.567-0.926; p = 0.010) were factors independently associated with infarct expansion.Risk factors for infarct expansion differed between lacunar and giant lacunar infarction. The underlying pathophysiological mechanisms for infarct expansion in these two groups should be recognized individually.

Background and Purpose: The purpose of this study was to determine risk factors for lacunar and giant lacunar infarction and to clarify differences in pathophysiological mechanisms for these two groups. Methods: Patients were selected from a comprehensive stroke center with ≤24 h from onset to initial magnetic resonance imaging (MRI) with lacunar and giant lacunar infarction. All patients underwent second MRI during hospitalization. Infarct expansion was defined as present when the area of the diffusion-weighted imaging (DWI)-positive region on second MRI exceeded that on the initial MRI. To calculate the area of the DWI-positive region, we manually traced each region of interest and calculated the DWI-positive region area in each slice. Infarct size was calculated and compared by the positive region on DWI. Factors related to infarct expansion were evaluated separately in the two groups. Results: We screened 950 consecutive ischemic stroke patients, including 106 patients with small vessel disease (lacunar infarction, 54 patients; giant lacunar infarction, 52 patients). High cardio-ankle vascular index (odds ratio, 6.255; 95% confidence interval, 1.791-21.846; p = 0.004) was independently associated with infarct expansion in lacunar infarction patients (Figure 1A). Concerning giant lacunar infarction, high concentration of low-density lipoprotein-cholesterol (odds ratio, 1.923; 95% confidence interval, 1.158-3.194; p = 0.012) and low/normal body mass index (odds ratio, 0.714; 95% confidence interval, 0.515-0.989; p = 0.042) were factors independently associated with infarct expansion (Figure 1B). Conclusions: Risk factors for infarct expansion differed between lacunar and giant lacunar infarction. The underlying pathophysiological mechanisms for infarct expansion in these two groups should be recognized individually.

Background and Purpose: Nontraumatic convexal subarachnoid hemorrhage (cSAH) rarely occurs concomitant with acute ischemic stroke. The purpose of this study was to investigate the incidence, imaging findings, clinical backgrounds, and outcomes of hyperacute ischemic stroke with cSAH. Methods: Patients were selected from a comprehensive stroke center with ≤4.5 h from onset to door with symptomatic ischemic stroke between October 2012 and May 2018. All patients underwent CT and/or MRI on admission and we reviewed them to identify cSAH. Follow-up CT and/or MRI were also reviewed. cSAH caused by trauma, detected after thrombolysis or endovascular treatment, and accompanied with intracerebral hemorrhage was excluded. Retrospective review of cSAH incidence, imaging findings, clinical backgrounds, and outcomes was performed. Results: We screened 1249 consecutive symptomatic ischemic stroke patients, including 466 patients with ≤4.5 h from onset to door (342 (73%) male, median age 68 years). Of 466 hyperacute ischemic stroke patients, cSAH was observed in 5 (1.1%) patients (5 male, median age 49 years): 3 were detected on admission and the other was detected at follow-up. None had any meningeal irritation signs, and all were detected incidentally. Four patients (case 1-4) were diagnosed as arterial infarction, and 1 as venous infarction. Of the 4 arterial infarction patients, arterial stenosis or occlusion was observed ipsilaterally to the cSAH (Figure). In addition, of the 4 arterial infarction patients, hyperintense vessel signs were observed on FLAIR imaging on admission suggesting retrograde flow via collateral vessels, or slow flow (Figure). In all, cSAH disappeared gradually, and outcomes were favorable (modified Rankin Scale 0-1 at 3 months from the onset). Conclusions: cSAH was accompanied with approximately 1% of hyperacute ischemic stroke. Patients with arterial infarction and cSAH had arterial stenosis or occlusion ipsilaterally to cSAH.

A 75-year-old man was admitted to our hospital because of repeated transient visual obscurations of greying vision. The transient visual obscurations were caused by rotating his neck or the Valsalva manoeuver, and they recovered in about 30 seconds. A few weeks later, pulsatile tinnitus of the right ear and a dull headache developed. Both ocular fundi showed papilledema, and there was significant intracranial hypertension on cerebrospinal fluid examination. He was diagnosed as having right sigmoid sinus thrombosis and a dural arteriovenous fistula with a rapid arteriovenous shunt from the right ascending pharyngeal artery and the right occipital artery to the right transverse sinus. Anticoagulant therapy was started, and coil embolization was performed. The transient visual obscurations, headache, and tinnitus improved dramatically after the procedure. We hypothesized that the transient visual obscurations were triggered by rotating the neck or performing the Valsalva manoeuver as they both increase the pressure of cerebrospinal fluid, inducing transient optic nerve ischemia and visual obscurations under mild intracranial hypertension. Transient visual obscurations are an important initial symptom of intracranial hypertension.

Background: Although subcortical infarction patients sometimes show larger infarction size than the definition of small vessel occlusion (SVO), there are no specific predictors of larger size. The aim of this study was to identify the factors, including magnetic resonance imaging (MRI) and ultrasonographic parameters, to predict larger subcortical infarction. Methods: Consecutive patients with acute supratentorial subcortical infarction were studied. Patients were classified into 2 groups (L: larger group, ≥15 mm and ≥3 slices; S: smaller group, SVO based on the TOAST classification). Clinical information, MRI findings including the presence of microbleeds, and ultrasonography findings were evaluated and compared between the 2 groups. Results: A total of 120 patients (81 male, mean 67 years old) were enrolled. The L group included 22 patients (18%), and the S group had 98 patients (82%). On neuroimaging, microbleeds were seen less frequently in the L group than in the S group (23 vs. 53%, p = 0.017), and peak systolic velocity (PSV) by transcranial color-coded sonography was faster in the L group than in the S group (121 ± 39.8 vs. 83.4 ± 25.4 cm/s, p = 0.002). On multivariate logistic regression analysis, no evidence of microbleeds (OR 4.4, 95% CI 1.41–13.68, p = 0.011) and PSV over 92 cm/s (OR 3.1, 95% CI 1.007–9.719, p = 0.049) were found to be independently associated with larger size. Conclusion: Microbleeds is related to smaller size and middle cerebral artery PSV > 92 cm/s indicate larger size in supratentorial subcortical infarcts.

Thrombotic microangiopathies (TMAs) are systemic microvascular occlusive disorders. The present report describes a patient with relapsing-remitting multiple sclerosis who had been treated with interferon (IFN)-β1b therapy for eight years and developed TMA. The patient presented with headache, thrombocytopenia, renal dysfunction, severe hypertension, posterior reversible encephalopathy syndrome, and gastrointestinal involvement. After discontinuation of the medication and initiation of antihypertensive treatment, the patient rapidly improved. This is the first report of TMA with gastrointestinal involvement (intestinal TMA) induced by IFN-β. The new onset of hypertension or headache requires careful attention in cases of long-term administration of IFN-β1b.

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Carotid stump syndrome is a cause of recurrent embolic stroke following occlusion of the ipsilateral internal carotid artery. The present report describes a case of recurrent cerebral embolism ipsilateral to a chronically occluded left common carotid artery (CCA), i.e., "CCA stump syndrome." Doppler color flow imaging showed anterograde flow in the left internal and external carotid arteries, which were supplied by collateral flow from the superior thyroid artery inflowing just proximal to the left carotid bifurcation. According to carotid duplex ultrasonography (CDU), a low-echoic mobile thrombus was noted at the distal stump of the occluded CCA, which presumably caused distal embolism. The low-echoic mobile thrombus dramatically changed to a homogenously high-echoic thrombus, and there was no recurrence of stroke after antiplatelet and anticoagulant therapy. This is the first report to demonstrate a CDU-verified temporal change in the thrombus at the stump in CCA stump syndrome. CDU is a noninvasive and useful technique to characterize hemodynamics, thrombus morphology, and the response to therapy.

Background Precise associations between clinical characteristics of transient ischemic attack (TIA) patients and diffusion-weighted imaging (DWI) positivity are still controversial. Thus, the purposes of this were to investigate the clinical characteristics associated with DWI positivity in patients with TIA and to develop a risk score for the prediction of DWI positivity in TIA. Methods Between April 2008 and June 2011, we retrospectively enrolled consecutive patients, who were admitted to our hospital with TIA and underwent DWI within 24 hours of admission. Patients were divided into a DWI-positive or DWI-negative group. The clinical characteristics of the 2 groups were compared, and a DWI positivity score was determined for each patient. We calculated the DWI positivity score by assigning a point value of 1 to the following factors: blood urea nitrogen to serum creatinine (BUN/Cr) ratio greater than 17.5, glucose greater than 161 mg/dL, and brain natriuretic peptide (BNP) greater than 55.4 pg/dL. Values below these cutoffs were given a value of 0, and the 3 point values were summed to obtain the final DWI positivity score (from 0 to 3). Results A total of 41 patients (median age = 62 years; 8 women) were enrolled in this study. There were 14 (35%) patients with DWI positivity. The median of the BUN/Cr ratio, blood glucose, and BNP were significantly higher in the DWI-positive than that in the DWI-negative group. As the DWI positivity score increased, there was an increased rate of DWI positivity. Conclusions Our data indicate that seminal scores that included BUN/Cr ratio, glucose, and BNP contributed to DWI positivity in TIA patients.