A Case of Multiple Cerebral Infarcts Due to Severe Anemia Preceded by Migraine-like Headache with Aura.

We herein report a 47-year-old woman who developed migraine-like headache with aura and subsequent multiple cerebral infarcts, likely due to severe iron deficiency anemia (IDA) from menorrhagia. The progression from IDA to ischemic stroke involves several pathophysiological mechanisms, including reduction of erythrocyte deformability, reactive thrombocytosis, and anemic hypoxia. We speculate that a microembolus first caused cortical spreading depression without infarcts and that a larger thromboembolus then caused multiple infarcts. This case highlights the transition from migraine-like headache to ischemic stroke. New-onset migraine-like headache is a warning of impending ischemic stroke, and IDA may be a potential underlying cause.

Thyrolinguofacial trunk arising from the common carotid artery and diagnosed by computed tomography angiography.

PURPOSE: Various variations in the head and neck vasculature have been reported. The purpose of this report is to describe an extremely rare case of thyrolinguofacial trunk (TLFT) arising from the common carotid artery (CCA). METHODS: A 66-year-old woman with vertigo, dizziness, and heaviness in the head underwent computed tomography (CT) angiography of the neck and head region for evaluation of cerebrovascular diseases. RESULTS: The TLFT originated from the anterior wall of the right CCA and was divided into the superior thyroid artery and linguofacial trunk (LFT). The LFT was divided into lingual and facial arteries. In addition, we observed fusiform dilatation of the intracranial right vertebral artery, which might have caused these symptoms. CONCLUSION: The presence of a common trunk of the external carotid artery (ECA) branches increases the risk of complications such as bleeding and ischemia during treatment of the head and neck region, including chemoradiotherapy for oral bleeding and tongue cancer. Therefore, this is an area of significant interest across various medical specialties, including surgery, otolaryngology, and radiology. Understanding the diverse variations in the neck vasculature is expected to lead to a reduction in complications associated with various procedures.

COVID-19 and Listeria Meningitis Treated by Ampicillin, Sulfamethoxazole/Trimethoprim and Meropenem.

Background: Secondary bacterial infection was initially rare in SARS-CoV-2 infectious disease (COVID-19) patients, but COVID-19-associated bacterial infectious diseases have recently been increasing. Furthermore, it might be difficult to distinguish COVID-19 from bacterial meningitis by the symptoms, and one might be uncertain about antibiotic therapy for Listeria meningitis infection-typically caused by eating contaminated food-in elderly persons and pregnant women. Case Report: A 96-year-old woman who had been living alone was found to have SARS-CoV-2 infection in February 2023. She was admitted to our hospital with high fever and disturbance of consciousness and was started on treatment with remdesivir. Two days later, her consciousness was still disturbed, and she was found to have a stiff neck. In addition, increased white blood cell counts and C-reactive protein suggested bacterial infection. Therefore, a lumbar puncture was done, and Listeria monocytogenes was ultimately isolated from blood cultures and its genetic material was detected in cerebrospinal fluid. She had previously eaten refrigerated food and cheese products. Intravenous ampicillin 1.0 g 6×/day was started, but one week later, loss of consciousness continued, and the cerebrospinal findings were not improved, although nasal swab became negative for SARS-CoV-2. Intravenous sulfamethoxazole/trimethoprim (ST) 80/400 mg 3×/day was added, and her consciousness and fever improved by one week later. A drug rash appeared after ST was started, and she was switched to meropenem. Her condition finally improved. Conclusion: COVID-19-associated secondary listeria infection was found in an elderly woman. She was treated with not only ampicillin, but also ST and meropenem. Meningitis caused by Listeria monocytogenes should be considered as a secondary complication and carefully treated with antibiotics during the period of the COVID-19 pandemic.

Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required. METHODS: We applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients. RESULTS: We found significant hypomethylation of contracted 4q-D4Z4 repeats in FSHD1, and both 4q- and 10q-D4Z4 repeats in FSHD2. We also found that the hypomethylation in the contracted D4Z4 in FSHD1 is moderately correlated with patient phenotypes. CONCLUSIONS: Our method contributes to the development for the diagnosis of FSHD using Nanopore long-read sequencing. This finding might give insight into the mechanisms by which repeat contraction causes disease pathogenesis.

Ultrasonic cleaning is effective in removing carbonized clots and tissue from the insulation-tipped diathermic knife-2.

Objectives: Since carbonized clots and tissue (debris) tend to adhere firmly to the tip of the endoscopic submucosal dissection (ESD) knife as the procedure proceeds, manual removing the firm debris is often challenging and time-consuming. Recently, effective ultrasonic cleaning for other medical devices has been reported. The aim of the present study was to clarify whether ultrasonic cleaning is effective in removing the debris on the insulation-tipped diathermic (IT) knife-2. Methods: This study was an ex-vivo experimental randomized study. A total of 40 IT knife-2 knives with debris on their tip surfaces were prepared and randomly assigned to two groups (Group A and Group B). The knives in Group A were cleaned using the conventional scrubbing method for 30 s (conventional cleaning method), while those in Group B were cleaned using a combined method of scrubbing for 20 s and ultrasonic cleaning for 10 s (combined ultrasonic cleaning method). The tip electrode of the knife after cleaning was photographed under a microscope (40x). The 40 images of the knives were evaluated by independent three endoscopists and two clinical engineers using the five-step evaluation criteria ranging from cleaning score 1 (dirty) to 5 (clean). Results: The mean cleaning score of 3.78 (range: 2.33-4.67) in Group B was significantly higher than that of 1.68 (range: 1.00-2.83) in Group A. Conclusions: The combined ultrasonic cleaning method could remove debris adhering to the IT knife-2 more effectively than the conventional cleaning method. Ultrasonic cleaning may be applied for real-world ESD.

Differences in oral anticoagulant prescriptions between specialists and non-specialists in patients with cardioembolic stroke caused by non-valvular atrial fibrillation.

Atrial fibrillation (AF) is a common disease encountered in daily practice; however, few patients with AF received oral anticoagulant (OAC) therapy. This study focused on differences in OAC prescriptions and influencing factors between specialists (neurological and cardiovascular) and non-specialists. A retrospective comparative analysis was conducted on 480 patients with acute cardioembolic stroke caused by non-valvular AF who were admitted to our hospital between January 1, 2015, and December 31, 2020. All patients had visited our hospital or other hospitals for their underlying diseases. Overall, 232 (specialist group SG) and 248 patients (non-specialist group NSG) were examined by specialists and non-specialists, respectively. The NSG had a significantly lower percentage of OAC prescriptions on admission than the SG (P < 0.01), even after propensity score matching. Factors influencing OAC prescription in the SG were age, hypertension, paroxysmal AF, dementia, CHADS2 score, and antiplatelet drug use, while those in the NSG were a history of cerebral infarction, paroxysmal AF, dementia, and antiplatelet drug use [SG: age, odds ratio (OR) 0.919, 95% confidence interval (CI) 0.865-0.976; hypertension, OR 0.266, 95% CI 0.099-0.713; paroxysmal AF, OR 0.189, 95% CI 0.055-0.658; dementia, OR 0.253, 95% CI 0.085-0.758; CHADS2 score, OR 2.833, 95% CI 1.682-4.942; and antiplatelet drug use, OR 0.072, 95% CI 0.025-0.206; NSG: cerebral infarction, OR 5.940, 95% CI 1.581-22.309; paroxysmal AF, OR 0.077, 95% CI 0.010-0.623; dementia, OR 0.077, 95% CI 0.014-0.438; and antiplatelet drug use, OR 0.024, 95% CI 0.004-0.152]. In conclusion, the OAC prescription rate was higher in patients with non-valvular AF whose family physicians were specialists at the time of cerebral infarction onset. In addition, in the SG, advanced age and hypertension were associated with not prescribing OAC, whereas a higher CHADS2 score was associated with the prescription of OACs. In the NSG, a history of cerebral infarction was associated with the prescription of OACs. Further, paroxysmal AF, antiplatelet drug use, and dementia were associated with non-OAC therapy in both the groups.

A case of cerebral infarction due to pleomorphic carcinoma of the lung.

BACKGROUND: With the increase in endovascular treatment, reports of embolism other than thrombus are scattered, but intracranial tumorigenic embolism is rare and difficult to diagnose. Here, we describe a case of a tumorigenic embolism in a patient with lung cancer whose invasion into the vascular system was not detected on preoperative whole-body imaging. CASE DESCRIPTION: A 66-year-old man who was hospitalized to undergo radiotherapy for pulmonary carcinoma suddenly developed left hemiplegia. He exhibited atrial fibrillation, and emergent radiographic examination revealed a right middle cerebral artery occlusion. Urgent mechanical embolectomy was performed, with successful revascularization. The excised embolus had a unique morphology and was pathologically diagnosed as a cerebral embolism caused by pleomorphic pulmonary carcinoma. CONCLUSION: Tumor-derived cerebral embolism is extremely rare, but it is necessary to consider it as a potential source of embolism during differential diagnosis in patients with malignant tumors.

Spontaneous Intracranial Hypotension Associated with Postural Tachycardia Syndrome.

Postural tachycardia syndrome (POTS) can cause orthostatic headache. However, it is difficult to differentiate POTS from spontaneous intracranial hypotension (SIH) caused by cerebrospinal fluid (CSF) leaks. We herein report a 53-year-old woman who presented with SIH associated with POTS. A cervicothoracic and lumbar epidural blood patch rapidly improved not only the headache but also the orthostatic tachycardia, suggesting POTS secondary to SIH. This case suggests that a CSF leak can cause secondary POTS. Therefore, POTS should be considered in patients with orthostatic headaches, even in the presence of a CSF leak.

[Recombinant tissue plasminogen activator therapy for acute ischemic stroke in older patients].

AIM: As the number of aged stroke patients increases in Japan, the proportion of older patients who receive recombinant tissue plasminogen activator (rt-PA, 0.6 mg/kg) is also rising. However, the Japanese stroke guideline indicates that rt-PA therapy must be administered very carefully in older patients (i.e. ≥81 years of age) because of serious complications after the therapy. We retrospectively assessed the clinical outcomes of rt-PA therapy in older patients. METHODS: This study included 321 patients who received rt-PA therapy for acute cerebral infarction at our hospital between April 2007 and April 2017. The outcomes (modified Rankin Scale [mRS] score at 3 months after treatment) and symptomatic intracerebral hemorrhaging (sICH) were compared and analyzed between patients ≥81 years of age (group A) and those <81 years of age (group B). In addition, propensity score matching was performed for the factors shown to have significant differences by a univariate analysis in order to adjust for confounding factors, and the outcomes were compared. RESULTS: There were 58 patients in group A (18.1%) and 263 patients in group B (81.9%). The rate of favorable outcomes (mRS 0-1) was lower in group A (12.1%) than in group B (44.1%) (P<0.01). The mortality rate was higher in group A (17.2%) than in group B (4.6%) (P=0.002). No marked differences were observed between the 2 groups regarding the rate of sICH (group A, 3.4%; group B, 3.0%; P=1.00). After propensity score matching, the proportion of patients with favorable outcomes was significantly lower in group A (13.2%) than in group B (36.8%) (P=0.032). There were no marked differences in the mortality rates between the groups (group A, 17.2%; group B, 4.6%) (P=0.200), and no patients in either group had sICH. CONCLUSION: No marked differences in the incidence of ICH were observed between the older and younger groups receiving intravenous rt-PA therapy. However, in terms of efficacy, the proportion of patients with favorable outcomes was significantly lower in the older group than in the younger group.

Verticilide, a new ryanodine-binding inhibitor, produced by Verticillium sp. FKI-1033.

A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N-methyl- L-alanyl](4). Verticilide inhibited ryanodine binding to ryanodine receptors in the cockroach at an IC(50) value of 4.2 microM, whereas inhibition against mouse ryanodine receptors was weak (IC(50)=53.9 microM).

High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate.

Over the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry.