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.

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.

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.

Relapsing polychondritis coupling with cerebral amyloid deposit inducing cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Almost no abnormality including intracranial microbleeding was detected by cranial magnetic resonance image (MRI) at diagnosis. However, he developed a headache and hallucination after five months. Seven-month cranial MRI showed novel, multiple, intracranial microbleeding, especially in the bilateral but asymmetry posterior, temporal, and parietal lobes. 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow in the bilateral posterior lobes. After treatment, both of his neurological symptoms and increased cerebral blood flow improved to mild. Photon emission computed tomography using Pittsburgh compound B (PiB) for evaluation of brain amyloidosis at 12 months after onset showed an amyloid deposit in the bilateral frontal lobes, but a lack of uptake corresponded to the RP lesions. Our case suggests that inflammation coupled with an amyloid deposit, induced the multiple intracranial bleeding, and resulted in the lack of PiB uptake. Findings from our case show that inflammation including excess blood flow coupled with an amyloid deposit synergistically facilitate intracranial bleeding.

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.

Catastrophic Secondary Infarctions with Onset Seizure Following Tissue Plasminogen Activator Therapy.

Fatalities following intravenous recombinant tissue-type plasminogen activator therapy have been reported. Major fatal complications following intravenous recombinant tissue-type plasminogen activator therapy include intracranial hemorrhage, aortic dissection, and extracranial bleeding. However, the possibility that intravenous recombinant tissue-type plasminogen activator therapy itself paradoxically induces synchronized multiple cerebral novel infarctions has never been considered. We herein report the first case of bilateral internal carotid artery infarction with onset seizure following intravenous recombinant tissue-type plasminogen activator therapy for a vertebral-basilar artery infarction. A 75-year-old man was transferred to our hospital and diagnosed with acute ischemic stroke in the basilar artery. His National Institute of Health Stroke Scale score was 4. The intravenous recombinant tissue-type plasminogen activator therapy was initiated 234 minutes after stroke onset because no contraindications were present. Almost 2 hours after the intravenous recombinant tissue-type plasminogen activator therapy, the patient suddenly fell into a deep coma with generalized convulsions. A huge secondary infarction was found in the bilateral anterior circulation territories, and he died 7 days after stroke onset. This case alerts clinicians to the possibility of synchronized multiple cerebral infarctions following intravenous recombinant tissue-type plasminogen activator therapy as a dangerous complication in patients with multiple severe stenoses in the cerebral arteries.

Repetitive Episodic Isolated Vertigo in a Patient with Cerebellar Infarction.

Isolated vertigo is an important symptom of posterior circulation stroke. It has been reported that 11.3% of patients with isolated vertigo have a stroke and that most lesions are located in the cerebellum, particularly in the posterior inferior cerebellar artery. We report the case of a 63-year-old man with multiple atherosclerotic risk factors and atrial fibrillation who showed repeated episodes of isolated vertigo. His repeated vertigo was short-lasting and was often triggered by body position, mimicking benign paroxysmal positional vertigo. Cranial computed tomography on the third hospital day showed left cerebellar infarction within the territory of the posterior inferior cerebellar artery. The vertigo was ameliorated on the fifth hospital day and warfarin was prescribed for secondary prevention. Clinicians should pay special attention to cases in which a patient presents isolated vertigo, even if it shows transient recurrence or is triggered by a positional change, especially in patients with multiple cerebrovascular risk factors.

Successful Tissue Plasminogen Activator for a Patient with Stroke After Stanford Type A Aortic Dissection Treatment.

Some stroke patients with the acute aortic dissection receiving thrombolysis treatment resulted in fatalities. Thus, the concurrent acute aortic dissection is the contraindication for the intravenous recombinant tissue-type plasminogen activator. However, the safety and the effectiveness of the intravenous recombinant tissue-type plasminogen activator therapy are not known in patients with stroke some days after acute aortic dissection treatment. Here, we first report a case of a man with a cardioembolism due to the nonvalvular atrial fibrillation, who received the intravenous recombinant tissue-type plasminogen activator therapy 117 days after the traumatic Stanford type A acute aortic dissection operation. Without the intravenous recombinant tissue-type plasminogen activator therapy, the prognosis was expected to be miserable. However, the outcome was good with no complication owing to the intravenous recombinant tissue-type plasminogen activator therapy. Our case suggests the effectiveness and the safety of the intravenous recombinant tissue-type plasminogen activator therapy to the ischemic stroke some days after acute aortic dissection treatment.

Tissue Plasminogen Activator to Treat a Stroke after Foam Sclerotherapy in a Woman with a Patent Foramen Ovale.

Although foam sclerotherapy to varicose veins is now a popular treatment because of its high efficacy and safety, some neurologic complications have recently been reported. Presently, the effectiveness and safety of intravenous recombinant tissue-type plasminogen activator therapy to stroke following foam sclerotherapy remain unclear. Here, we report the case of a 68-year-old woman whose ischemic symptoms following foam sclerotherapy were treated by intravenous recombinant tissue-type plasminogen activator. After she was admitted, the venous thrombosis in her right soleus vein and a patent foramen ovale causing the right-to-left shunt were revealed. Thus, we diagnosed the ischemic symptoms were due to paradoxical embolism following foam sclerotherapy. After intravenous recombinant tissue-type plasminogen activator therapy, there was no complication and the outcome was good. Our case suggests the effectiveness and the safety of intravenous recombinant tissue-type plasminogen activator therapy to paradoxical embolism following foam sclerotherapy.

Vertical Gaze Palsy Caused by Selective Unilateral Rostral Midbrain Infarction.

Vertical gaze palsy is rarely a neurological symptom, although it has been observed in some cases. Here, we report the case of a patient presenting with complete upward and downward gaze palsy. In this case, a small lesion in the left rostral midbrain was observed on diffusion-weighted magnetic resonance (MR) images, and the lesion was considered to cause the ocular symptom. We consider that vertical gaze palsy is an important clue to an accurate topical diagnosis of a brain lesion.

Developmentally Regulated RNA-binding Protein 1 (Drb1)/RNA-binding Motif Protein 45 (RBM45), a Nuclear-Cytoplasmic Trafficking Protein, Forms TAR DNA-binding Protein 43 (TDP-43)-mediated Cytoplasmic Aggregates.

Cytoplasmic protein aggregates are one of the pathological hallmarks of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Several RNA-binding proteins have been identified as components of inclusion bodies. Developmentally regulated RNA-binding protein 1 (Drb1)/RNA-binding motif protein 45 is an RNA-binding protein that was recently described as a component in ALS- and FTLD-related inclusion bodies. However, the molecular mechanism underlying cytoplasmic Drb1 aggregation remains unclear. Here, using an in vitro cellular model, we demonstrated that Drb1 co-localizes with cytoplasmic aggregates mediated by TAR DNA-binding protein 43, a major component of ALS and FTLD-related inclusion bodies. We also defined the domains involved in the subcellular localization of Drb1 to clarify the role of Drb1 in the formation of cytoplasmic aggregates in ALS and FTLD. Drb1 predominantly localized in the nucleus via a classical nuclear localization signal in its carboxyl terminus and is a shuttling protein between the nucleus and cytoplasm. Furthermore, we identify a double leucine motif serving as a nuclear export signal. The Drb1 mutant, presenting mutations in both nuclear localization signal and nuclear export signal, is prone to aggregate in the cytoplasm. The mutant Drb1-induced cytoplasmic aggregates not only recruit TAR DNA-binding protein 43 but also decrease the mitochondrial membrane potential. Taken together, these results indicate that perturbation of Drb1 nuclear-cytoplasmic trafficking induces toxic cytoplasmic aggregates, suggesting that mislocalization of Drb1 is involved in the cause of cytotoxicity in neuronal cells.

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.

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.

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.

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.