Comparison of Prognosis and Cognitive Function of Holistic Neurological Disease: Tochigi Neurological Disease Cohort Study.

Background: While many studies focus on the prognosis of individual neurological diseases, very few comprehensively compare and analyze real-world data of these diseases. Objective: To address this gap in knowledge, in this study, we comprehensively analyzed the real-life data of patients with neurological diseases. Methods: We prospectively enrolled patients with neurological diseases at three hospitals from December 1, 2016 to September 30, 2020. Neurological diseases were classified into nine groups: Dementia, Cerebrovascular disease, Parkinson's and related, Functional, Spinocerebellar degeneration, Neuroimmune, Epilepsy, Muscle dystrophy disease, and Hypertension. Patients were followed up for three years, and their prognosis and evaluation of their cognitive function served as the endpoint. Results: A total of 426 patients were finally enrolled. Both mortality and cognitive function differed among the neurological disease categories. After 3 years, mortality was highest in the Dementia (25.5%), Parkinson's and related (21.6%), and Spinocerebellar degeneration (35.3%) groups while the cognitive function of patients in these three groups was significantly lowest. Conclusions: When the neurological diseases were holistically observed, both mortality and cognitive function of the Dementia, Parkinson's and related, and Spinocerebellar degeneration groups were significantly worse than the remaining diseases.

Significance of Persistent Systemic Support in the Clinical Course of Delayed Post-hypoxic Leukoencephalopathy Following Severe Coronavirus Disease 2019.

A 45-year-old woman was hospitalized with severe coronavirus disease 2019 pneumonia. Following cytokine storm-induced multiorgan failure and lethal arrhythmia, the patient developed a sustained coma with flaccid quadriplegia. A cerebrospinal fluid examination excluded infectious and immunogenic encephalopathies, and diffusion-weighted magnetic resonance imaging demonstrated high-intensity areas in the white matter with a cortex-sparing distribution, suggesting delayed post-hypoxic leukoencephalopathy. As a result of intensive cardiopulmonary support for a month, the neurological function gradually recovered. Based on the reversible clinical course noted in this patient, accurate diagnosis and persistent medical approaches are important for the management of coronavirus disease 2019-related delayed post-hypoxic leukoencephalopathy.

Impact of COVID-19 pandemic on mortality and cognitive function of dementia patients: Tochigi Dementia Cohort Study.

OBJECTIVES: The coronavirus disease 2019 pandemic significantly affected Japanese society and the health of its population. Despite this, few studies have evaluated the influence of the pandemic on patients with neurological diseases or dementia, which we assessed through the Tochigi Dementia Cohort Study. METHODS: Participants were divided into two groups. The pre-pandemic group included patients who were enrolled from December 1, 2016 to November 30, 2018, and were followed up until November 30, 2019 (i.e., before the pandemic). The post-pandemic group included patients who were enrolled from December 1, 2019 to November 30, 2021, and were followed up until November 30, 2022 (i.e., during the pandemic). We recorded their age, sex, mortality, and treatment withdrawal during the follow-up period. Furthermore, we examined their cognitive function at the baseline, and after 6 and 12 months. RESULTS: A total of 384 patients were enrolled in this study, including 199 patients in the pre-pandemic group and 185 in the post-pandemic group. The mortality of dementia patients was significantly higher in the post-pandemic group than in the pre-pandemic group" (5.3% vs. 18.5%, p < 0.05*). The cognitive function scores at 12 months were also significantly lower in the dementia patients of the post-pandemic group than in those of the pre-pandemic group (p < 0.05*). CONCLUSIONS: This longitudinal cohort study conducted in a local Japanese area revealed that mortality rate and cognitive function worsened in dementia patients during the pandemic.

Spontaneous Echo Contrast in the Left Atrium and Aortic-Arch Atheroma, Detected by Transesophageal Echocardiography, Was Negatively Correlated with Cognitive Function.

BACKGROUND: The relationship between transesophageal echocardiography findings and cognitive function. OBJECTIVE: This study aimed to establish an association between transesophageal echocardiography findings and cognitive function in stroke survivors. METHODS: A single-center study was conducted between April 1, 2017 and March 31, 2022. All subjects that were included had a past history of ischemic stroke and were admitted after >21 days from onset. The participants underwent cognitive function tests including a Mini-Mental State Examination, Revised Hasegawa Dementia Scale, Frontal Assessment Battery, and transesophageal echocardiography. RESULTS: The results of 126 participants were analyzed. The cognitive function of participants with a spontaneous echo contrast (+) in the left atrium including appendage or of those with an aorta-arch plaque with a maximum thickness ≥4 mm significantly worse while neither the patent foramen ovale nor the branch extending plaque influenced cognitive function (The median cognitive scores of the spontaneous echo contrast (-) versus (+) were 26 versus 22, p < 0.01**, 26 versus 21, p < 0.001***, and 14 versus 11, p < 0.01**. Those of the aortic-arch plaque max thickness (<4 mm) versus (≥4 mm) were 26 versus 25, p < 0.05*, 27 versus 24, p < 0.05*, and 15 versus 13, p < 0.05*). CONCLUSION: Our findings show that spontaneous echo contrast in the left atrium and aortic-arch atheroma detected by transesophageal echocardiography, were negatively associated with cognitive function.

Real-time data on the prognosis of acute ischemic stroke patients in the Tochigi Clinical ObservatioNal registry for 1-year mortality of aCute ischEmic stRoke patieNt (T-CONCERN) study.

BACKGROUND: It is important to gauge mortality in real time following an ischemic stroke. However, there is limited in-hospital and post-discharge clinical data that focuses on the real-time prognosis of acute ischemic strokes. PURPOSE: To comprehensively analyze ischemic stroke mortality during a hospital stay and 1 year after the onset of a stroke. MATERIALS AND METHODS: Initially, 1514 consecutive acute ischemic stroke patients were admitted to our facility within 7 days after the onset of a stroke. Of these, 1116 patients who were successfully surveyed 1 year after onset were finally analyzed. Baseline, physical, laboratory, and stroke clinical data were recorded and analyzed. RESULTS: The proportion of deaths within 1 year was 14.5%, 4.9% without discharge was and 9.6% after discharge within 1 year. Cardioembolic ischemic strokes were responsible for nearly 50% of the deaths within 1 year while the remaining deaths were due to non-cardioembolic ischemic strokes. After 1 year, survival rate in the hospital decreased significantly, depending on whether the stroke was recurrent or if there was bleeding without a stroke. CONCLUSIONS: Our study reveals the real-time survival data 1 year after the onset of a stroke, in-hospital and post-discharge mortality rates, and several issues associated with the treatment of acute ischemic strokes.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Higher incidence of cervical spinal cord compression in amyotrophic lateral sclerosis: a single-institute cohort study.

BACKGROUND: Although the relationship between amyotrophic lateral sclerosis (ALS) and cervical spondylotic myelopathy (CSM) is important, data relating to CSM complications in ALS remain lacking. PURPOSE: We aimed to investigate and validate the spinal cord conditions of ALS patients. MATERIALS AND METHODS: We recruited all patients diagnosed with ALS, Parkinson's disease (PD), or chronic inflammatory demyelinating polyneuropathy (CIDP) who were admitted to our department from April 1, 2017, to March 31, 2020. We analyzed the cervical or thoracolumbar magnetic resonance imaging (MRI) scans of these 128 patients. Data relating to spondylosis, cord compression, spinal canal diameter, spinal cord diameter, and the closest distance between the cervical spinal canal and cord were validated using MRI. RESULTS: Of the 128 patients, 52 had ALS, 48 had PD, and 28 had CIDP. The proportions of both cervical spondylosis and cervical cord compression were highest in the ALS group compared with the other patient groups (p < 0.05). The proportion of cervical spondylosis in ALS patients reached 38.3%, and that of cervical cord compression reached 53.2%. The closest distance between the cervical spinal canal and cord was also significantly smaller in ALS patients compared with CIDP patients (p < 0.05). In contrast to the cervical cord findings, there were no significant differences in the thoracolumbar cord between ALS patients and the other patient groups. CONCLUSIONS: Of the three disease groups, the proportion of CSM was highest in ALS patients. Furthermore, cervical cord conditions were significantly more crowded in the ALS patients than in the other patient groups.

Coexisting of aortic arch atheroma and atrial fibrillation for short-term recurrence and poor functional outcome in acute stroke.

BACKGROUND AND PURPOSE: Multiple embolic sources are sometimes observed simultaneously in patients with embolic stroke. The present study investigated the effects of coexisting aortic arch atheroma ≥ 4 mm thick and atrial fibrillation (AF) on short-term stroke recurrence and functional outcome. METHODS: Transesophageal echocardiography (TEE) was performed in consecutive embolic stroke patients, and 395 patients were classified into 4 groups according to the presence of aortic arch atheroma ≥ 4 mm thick and AF: AF - /ARCH - group, AF + /ARCH - group, AF - /ARCH + group, and AF + /ARCH + group. In accordance with these 4 groups, we evaluated stroke recurrence and all-cause death for 3 months after stroke onset, and also evaluated the 3-month functional outcome using the modified Rankin scale (mRS). RESULTS: Among the 128 AF patients, 39.1% also had aortic arch atheroma ≥ 4 mm thick. Of the 395 enrolled cases, the AF + /ARCH + group showed the highest frequencies of stroke recurrence and all-cause death during 3 months after onset. On multivariate analysis, stroke recurrence or all-cause death during 3 months after onset was relatively more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.34; 95% CI, 0.82-6.69; p = 0.11), but that was not statistically significant, and poor functional outcome (mRS score 3-6) at 3 months was significantly more frequent in the AF + /ARCH + group than in the AF + /ARCH - group (OR, 2.59; 95% CI, 1.08-6.24; p = 0.0339). CONCLUSIONS: Aortic arch atheroma concomitant with AF is not rare and appears associated with increased risks of stroke recurrence and poor functional outcome.

IgG4-Related Hypertrophic Pachymeningitis with Skull Base Involvement Presenting with Isolated Glossopharyngeal and Vagus Nerve Palsy.

We herein report a 70-year-old man diagnosed with IgG4-related hypertrophic pachymeningitis with skull base involvement, who presented with isolated glossopharyngeal and vagus nerve palsy. Contrast-enhanced magnetic resonance imaging (MRI) showed enhanced dural thickening of the posterior clivus and skull base involvement. When a patient with hypertrophic pachymeningitis presents with isolated cranial neuropathy without systemic manifestations or definite MRI abnormalities, it is difficult to make a diagnosis, and the patient may be misdiagnosed. This case suggests that a detailed radiological evaluation including contrast enhancement of the skull base is very important in patients with isolated glossopharyngeal and vagus nerve palsy.

Successful endovascular coiling of infectious cerebral aneurysm following Staphylococcus haemolyticus endocarditis.

Recent reports suggest that Staphylococcus haemolyticus can cause infective endocarditis (IE). However, no data are available regarding infectious intracranial aneurysm (IIA) following S. haemolyticus endocarditis. Endovascular coiling is a challenging approach for the treatment of IIA. We describe the case of a 63-year-old woman who suddenly developed aphasia and dysarthria following an acute cerebral infarction in her left insular and temporal cortex. After a total hysterectomy at the age of 39, the patient had suffered from recurrent bacterial pyomyositis in her legs. At admission, there was no evidence of cerebral aneurysm, as assessed by magnetic resonance angiography, and no vegetation, as assessed by transesophageal echocardiography (TEE), resulting in an incorrect diagnosis. However, subarachnoid hemorrhage and development of cerebral aneurysm in the left middle cerebral artery occurred within 1 week of hospitalization. Continuous positive blood culture results and a second TEE finally revealed that IE was caused by S. haemolyticus. Coil embolization of the IIA was successful on day 26 after symptom onset; after this procedure, the patient began to recover. This case demonstrates that S. haemolyticus-induced endocarditis can cause IIA. Endovascular coiling is a potentially effective approach to treat IIA.

Internal Jugular Vein Velocity and Spontaneous Echo Contrast Correlate with Alzheimer's Disease and Cognitive Function.

BACKGROUND: Many issues persist in the today's Alzheimer's disease (AD) screening and the breakthrough method is desired. OBJECTIVE: We aim to validate the association between venous reflux and AD, and to develop a new method for AD screening. METHODS: We examined spontaneous echo contrast, area, diameter, retrograde velocity, and anterograde velocity of the bilateral cervical internal jugular vein (IJV) using carotid ultrasonography. RESULTS: A total of 112 patients participated in this study, with 26 diagnosed as AD. The proportion of both or either IJV spontaneous echo contrast (+) occupied 25 of total 26 AD patients, which showed 96.2%of sensitivity and 98.5%negative predictive value. The IJV velocities also showed significant correlation with AD diagnosis, although the IJV area or diameter did not. CONCLUSION: Our results indicate that the validation of the spontaneous echo contrast or velocities of the IJV are convenient AD diagnosis screening methods and that the venous reflux disturbance correlates with AD development.

Case report of an elderly woman with atypical imaging for primary central nervous system lymphoma who needed a brain biopsy for diagnosis.

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma, but its diagnosis is challenging in some cases. A brain biopsy is the gold standard for diagnosing PCNSL, but its invasiveness can be problematic. Thus, noninvasive imaging examinations have been developed for the pre-surgical diagnosis of PCNSL, including gadolinium-enhanced magnetic resonance imaging (MRI), 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT), and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET). Here, we report the case of a 71-year-old woman with negative imaging findings for PCNSL, but who was diagnosed with PCNSL by a brain biopsy and histological analysis. Her imaging results were negative for gadolinium-enhanced cranial MRI, with low uptake in 123I-IMP SPECT and hypometabolism in 18F-FDG PET. However, a stereotactic brain biopsy from an abnormal lesion revealed that many round cells had infiltrated into the brain. Moreover, many infiltrating cells were positive for cluster of differentiation (CD)20 and CD79a, and proliferation marker protein Ki-67-positive cells accounted for nearly 80% of all cells. Based on these results, our final pathological diagnosis was PCNSL. The present case highlights the possibility of a PCNSL diagnosis even when all imaging-related examinations display negative results.

Noteworthy Cardiovascular Involvement with Sporadic Late-onset Nemaline Myopathy.

Cardiac involvement has recently been the focus of sporadic late-onset nemaline myopathy (SLONM). However, right ventricular failure and pulmonary hypertension, in addition to repetitive cardiac arrest, are noteworthy characteristics of SLONM. We herein report a 66-year-old woman with SLONM whose main symptoms were cardiac arrest, right ventricular failure, and pulmonary hypertension. Despite permanent pacemaker replacement, cardiac arrest occurred repetitively, and even with continuous positive airway pressure, right ventricular failure and pulmonary hypertension persisted. The patient was finally diagnosed with SLONM by a muscle biopsy. Our case suggests the possibility of cardiovascular involvement in SLONM, especially right ventricular failure and pulmonary hypertension.

Complex Aortic Arch Atherosclerosis in Acute Ischemic Stroke Patients with Non-Valvular Atrial Fibrillation.

AIM: Aortic arch atherosclerosis, particularly complex aortic arch plaques (CAPs), is an important source of cerebral emboli. CAPs and atrial fibrillation (AF) often co-exist; however, the prevalence and risk of CAPs in acute ischemic stroke patients with AF is unclear. METHODS: In patients with acute ischemic stroke with non-valvular AF admitted to Jichi Medical University Hospital during April 2016 to September 2019, we retrospectively evaluated the presence of CAPs on transesophageal echocardiography (TEE). RESULTS: CAPs were observed in 41 (38.7 %) of 106 patients with non-valvular AF. Older age, diabetes mellitus, chronic kidney disease, low high-density lipoprotein cholesterol (HDL-C) levels, higher levels of glycohemoglobin A1c (HbA1c), higher CHADS2 and CHA2DS2-VASc scores, and intracranial or carotid artery stenosis were more frequently observed in CAPs-positive than in CAPs-negative patients. In multivariable analyses, older age (odds ratio [OR]: 1.2 per year increase; 95% confidence interval [CI]: 1.07-1.24; P＜0.0001), diabetes mellitus (OR: 4.7; 95%CI: 1.27-17.35; P＜0.05), and low HDL-C (OR: 0.95 per 1 mg/dl increase; 95%CI: 0.92-0.99; P＜0.01) were independent risk factors for CAPs. The prevalence of CAPs was age-dependent, and there was a significantly higher risk in patients aged either 75-84 years or ＞84 years than in those aged ＜65 (OR: 7.6; 95%CI: 1.50-38.62, and OR: 32.1; 95%CI: 5.14-200.11, respectively). CONCLUSIONS: Even in patients with ischemic stroke with non-valvular AF, concomitant CAPs should be considered in older individuals and those who have diabetes or low HDL-C.

Characteristics of aged ischemic stroke patients indicative of cardioembolism.

The treatment of ischemic stroke has recently witnessed dramatic developments. However, there are limited data on ischemic stroke characteristics in aged patients. As part of the South Tochigi Acute Ischemic Stroke Registry, we prospectively enrolled 636 consecutive acute ischemic stroke patients (within 7 days after the onset) who were ≥ 60 years of age and who were admitted to two independent institutes from April 1, 2016 to February 28, 2019. We analyzed three groups divided by age: early-aged (60-69 years), middle-aged (70-79 years), and oldest-aged (≥ 80 years). From the 636 subjects, 194 were early-aged, 215 were middle-aged, and 227 were oldest-aged. There were significant differences in the ischemic stroke subtypes in each aging group (p < 0.01). The proportion of cardioembolism was 22.2% in early-aged, 27.4% in middle-aged, and 41.4% in the oldest-aged patients. The proportion of patients with a modified Rankin Scale of 0-2 at 1 year after onset decreased to 42.2% in middle-aged and 17.8% in oldest-aged with cardioembolic ischemic stroke. The proportion of patients receiving anticoagulation therapy before admission was 25.6% (36.7% of atrial fibrillation [AF]) in early-aged, 39.0% (52.3% of AF) in middle-aged, and 18.1% (21.0% of AF) in oldest-aged patients (p < 0.001). Our study reports characteristics of clinical ischemic stroke in an aging population. The assessment of cardiogenic embolism is important for an aging population.

Clinical Characteristics and Clinical Course of Body Lateropulsion in 47 Patients with Brainstem Infarctions.

BACKGROUND: In patients with lower lateral medullary infarction (LMI) located under the vestibular nucleus, proprioceptive impairment due to dorsal spinocerebellar tract (DSCT) is considered a pathological condition for body lateropulsion. In patients with brainstem infarction located at or above the level of the vestibular nucleus, other pathways, such as the crossed vestibulothalamic tract (CVTT), are considered responsible. RESEARCH QUESTION: The clinical course of body lateropulsion between each anatomical level of infarction remains unclear. Further, whether body lateropulsion refers to a static or a dynamic symptom also remains unclear. METHODS: We examined 47 patients who exhibited body lateropulsion and categorized them into four groups: lower LMI under the vestibular nucleus, LMI at the level of the vestibular nucleus, pontine infarction, and midbrain infarction. The patients' time to acquire static upright standing position and gait in a straight line were statistically analyzed by a log-rank test using the Kaplan-Meier method. RESULTS: Body lateropulsion in the static upright position was less frequent in the lower LMI group than in the other groups. SIGNIFICANCE: Lower LMI primarily affected body lateropulsion in gait. DSCT damage could affect ipsilateral hip joint or leg coordination, causing body lateropulsion in dynamic situation.

A new simple method using carotid duplex ultrasonography to assess intracranial vertebrobasilar arterial stenosis.

OBJECTIVES: Magnetic resonance angiography (MRA), three-dimensional computed tomography angiography, and cerebral angiography may be used to assess intracranial vertebrobasilar stenosis. However, these examinations cannot be performed at patients' bedsides. Our purpose was to develop a new bedside method to assess intracranial vertebrobasilar arterial stenosis. METHODS: We developed the new method using carotid duplex ultrasonography combined with the head-up test. A total of 141 subjects admitted between June 1, 2017 and March 31, 2019 were enrolled in this study. We calculated vertebral arterial peak systolic velocities (PSVs), end-diastolic velocities (EDVs), and mean velocities (MVs) at 0°, 16°, and 30° head-up angles. Vertebrobasilar arterial stenosis was confirmed using MRA. RESULTS: We excluded 28 subjects and included data for 113 subjects and 226 vessels in the final analysis. Cervical vertebral arterial PSV, EDV, and MV gradually decreased from 0° to 30° only in stenotic intracranial vertebral arteries. Sensitivity (probability of detection) was 75.5% and specificity (true negative rate) was 79.7% when EDV at the 30° head-up angle decreased ≥19.5% from the initial 0° head-up angle. Specificity was better (86.4%; sensitivity: 69.4%) when EDV was <9.1 cm/s at the 30° head-up angle. CONCLUSION: This new method easily detects intracranial vertebrobasilar arterial stenosis.