Tatsushi Mutoh

Background/Objectives: Dietary supplementation with medium-chain triglycerides (MCTs) improves walking balance and cognitive function in healthy older adults. This study aimed to determine the biological effects of MCTs on gait-related skeletal muscles in healthy older adults by analyzing muscle density and glucose metabolism. Methods: ¹⁸F-FDG-PET/CT imaging data from 63 participants (18 g/day of MCTs and matching placebo in the form of a jelly stick [6 g each, ingested 3 times/day]) in a randomized clinical trial were analyzed. The three-dimensional regions of interest were set as muscles associated with walking balance (bilateral triceps, psoas, and vastus medialis). Each muscle’s mean standardized uptake value (SUV_mean) and Hounsfield units (HU) were calculated for relative quantitative measurements. Results: MCT supplementation for 3 months decreased the SUV_mean (p < 0.001) and increased the HU of the psoas (r = −0.61) and vastus medialis muscles (r = −0.59) (p < 0.001); no changes were apparent in participants supplemented with long-chain triglycerides. The changes in the SUV_mean for each muscle were correlated negatively with those of plasma β-hydroxybutyrate in MCT-supplemented participants (r = −0.57 [psoas] and −0.59 [vastus medialis]; p < 0.001). Conclusion: A 3-month MCT supplementation suppressed glucose metabolism and increased the muscle density in gait-related skeletal muscles, consistent with previous findings that MCT supplementation stabilizes balance functions during walking in healthy older adults.

Delayed cerebral ischemia (DCI) which is mainly attributable to cerebral vasospasm, is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (SAH). Hemodynamic augmentation with vasopressors or inotropes is traditionally used in the clinical management of post-SAH DCI. Although the rationale for such treatment is to improve the regional cerebral blood flow (rCBF) to prevent secondary ischemia, brain-perfusion data underlying such systemic hemodynamic manipulation are limited. Here, we present two cases of SAH with symptomatic DCI caused by focal or multiple-vessel vasospasm to demonstrate the effects of dobutamine on serial rCBF measurements using ¹⁵O-labelled water positron-emission tomography. In the patient with localized proximal vasospasm, immediate rCBF uptake was observed in affected brain areas, yielding neurological improvement soon after dobutamine infusion and increasing cardiac output above normal levels. In the other patient, no rCBF responses were observed in multiple and diffuse vasospasm-affected regions, resulting in severe cerebral infarction and functional impairments. We speculate that dobutamine may act via the relief of microcirculatory disturbance attributable to vasospasm, as demonstrated by the increased velocities of circulating blood in cortical microvessels distal to the vasospasm early after infusion rather than in the spastic vessels themselves. This is the first report to present the effectiveness and limitations of the acute rCBF response to hyperdynamic therapy with dobutamine for DCI, depending on the extent and severity of the vasospasm.

Murine subarachnoid hemorrhage (SAH) induced using the filament perforation method is a useful in vivo experimental model to investigate the pathophysiological mechanisms in the brain underlying SAH. However, identifying mice with comorbid acute neurogenic pulmonary edema (NPE), a life‐threatening systemic consequence often induced by SAH, in this model is difficult without histopathological investigations. Herein, we present an imaging procedure involving dual‐energy X‐ray absorptiometry (DXA) to identify NPE in a murine model of SAH. We quantified the lung lean mass (LM) and compared the relationship between micro‐computed tomography (CT) evidence of Hounsfield unit (HU) values and histopathological findings of PE. Of the 85 mice with successful induction of SAH by filament perforation, 16 (19%) had NPE, as verified by postmortem histology. The DXA‐LM values correlate well with CT‐HU levels ( r = 0.63, p < 0.0001). Regarding the relationship between LM and HU in mice with post‐SAH NPE, the LM was positively associated with HU values ( r ² = 0.43; p = 0.0056). A receiver operating characteristics curve of LM revealed a sensitivity of 87% and specificity of 57% for detecting PE, with a similar area under the curve as the HU (0.79 ± 0.06 vs. 0.84 ± 0.07; p = 0.21). These data suggest that confirming acute NPE using DXA‐LM is a valuable method for selecting a clinically relevant murine NPE model that could be used in future experimental SAH studies.

Clazosentan prevents vasospasms after aneurysmal subarachnoid hemorrhage (SAH). However, clinical data on patients with SAH with ruptured vertebral artery dissecting aneurysms (VADAs) are limited. We report the case of a 49-year-old male patient with mild-grade (WFNS grade 1) thick and diffuse (modified Fisher grade 3) SAH who underwent endovascular trapping of a ruptured VADA, resulting in a poor functional outcome with a modified Rankin Scale score of 4 due to severe symptomatic vasospasm refractory to clazosentan, requiring repeated rescue endovascular therapies and chronic communicating hydrocephalus. A retrospective analysis of the clot density in the basal and Sylvian cisterns, assessed by the Hounsfield unit (HU) values of serial CT scans, in this patient showed persistent higher values, distinct from another VADA case that showed a decline in HU values with a good clinical course. These results imply the limited effectiveness of clazosentan in cases of thick and diffuse SAH after a ruptured VADA, even in good-clinical-grade patients treated with less invasive modalities. The HU values may become a simple quantitative marker for predicting symptomatic vasospasms and chronic hydrocephalus.

Subinsular stroke (subIS) can occur between the penetrating middle cerebral artery (MCA) branches, which clinical and radiological findings sometimes encounter in patients after the recanalization of left proximal MCA occlusion. However, no supportive data are available to clarify this relationship. This study investigated whether the involvement of subIS can impact outcomes after successful reperfusion therapy. Data from 152 consecutive patients who underwent endovascular thrombectomy between 2019 and 2023 were collected. A 3-month functional independence defined as a modified Rankin Scale 0–2 (primary outcome) and influencing factors were analyzed retrospectively. Recanalization was achieved in 35 patients, of whom 11 (31%) developed subIS. Patients with subIS were older in age (81 vs. 75; p < 0.05), had lower apparent diffusion coefficient (ADC) values on admission (0.52 vs. 0.62; p < 0.001), and higher modified Rankin Scale (mRS) scores (4 vs. 2; p < 0.001) than those without subIS. In a multivariate analysis, subIS was independently associated with a worse functional outcome (odds ratio: 10.5, p = 0.02). The cut-off value of the ADCs was 0.52 with a sensitivity and specificity of 70% and 64%, respectively. Subinsular ischemic lesions contribute to poor functional independence in patients after the successful recanalization of left MCA occlusion. The attenuation of the ADC value in these territories could be a valuable predictor of the outcome.

Background: Intravenous thrombolysis and mechanical thrombectomy are the first-line reperfusion therapies for acute ischemic stroke. Here, we describe the utility of diffusion magnetic resonance imaging (MRI) fiber tractography and ¹²³I-iomazenil benzodiazepine receptor single-photon emission computed tomography to estimate the prognosis of post-stroke aphasia after successful reperfusion therapy. Case report: An 81-year-old man was admitted to the hospital approximately 3.5 h after the onset of symptoms, including decreased consciousness, right hemiparesis, and aphasia. An MRI revealed acute cerebral infarction due to M1 segment occlusion. Intravenous alteplase thrombolysis followed by endovascular thrombectomy resulted in recanalization of the left middle cerebral artery territory. A subsequent MRI showed no new ischemic or hemorrhagic lesions. Although the patient’s motor hemiparesis gradually recovered, motor aphasia persisted. Diffusion MRI fiber tractography performed 2 weeks after admission revealed partial injury to the left arcuate fasciculus, indicated by lower fractional anisotropy values than on the contralateral side. A decreased benzodiazepine receptor density was also detected in the left perisylvian and temporoparietal cortices. The patient showed no clear signs of further improvement in the chronic stage post-stroke and was discharged to a nursing home after 3 months. Conclusions: The application of functional neuroimaging techniques to assess neuronal damage to the primary brain regions 2 weeks after reperfusion therapy for large-vessel occlusion may allow for an accurate prognosis of post-stroke aphasia. This may have a direct clinical implication for navigating subacute-to-chronic phases of rehabilitative care.

Clazosentan has been shown to prevent vasospasm and reduce mortality in patients after aneurysmal subarachnoid hemorrhage (SAH) and has been approved for clinical use in Japan; however, its systemic events in the elderly (aged ≥ 75 years) have not been well-documented. Here, we report serious/intolerable cardiopulmonary complications requiring discontinuation of drug therapy in elderly SAH patients. In this single-center case series study, medical records of consecutive SAH patients treated postoperatively with clazosentan (10 mg/h) between June 2022 and May 2023 were reviewed retrospectively. Thirty-three patients received clazosentan therapy, of whom six were elderly with a mean age of 80.3 ± 5.2 (range 75–89) years. Among them, despite no obvious medical history of systemic abnormalities, clazosentan was discontinued in three (50%) patients due to pleural effusion and hypoxemia with or without hypotension at 5 ± 3 days after therapy initiation, which was higher than the incidence for younger patients (15%). The elderly patients had significantly lower urine output (1935 ± 265 vs. 1123 ± 371 mL/day, p = 0.03) and greater weight gain (2.1 ± 1.1 vs. 4.2 ± 1.9 kg from baseline, p = 0.04) than patients who completed the therapy. One 89-year-old female developed congestive heart failure and hydrostatic pulmonary edema associated with increased intravascular and lung volumes even after therapy was discontinued, while the remaining two cases recovered within 2 days after drug cessation. These results suggest that elderly patients are more vulnerable to fluid retention and have a higher risk of cardiopulmonary complications during clazosentan therapy than younger patients. Careful monitoring of urine volume and weight gain and caution regarding age- and therapy-related hemodynamic insufficiencies are required.

BACKGROUND Clazosentan is an endothelin receptor antagonist approved in Japan for preventing cerebral vasospasm and vasospasm-associated cerebral ischemia and infarction. This study included elderly patients aged ≥75 years with aneurysmal subarachnoid hemorrhage (SAH) and aimed to evaluate the factors associated with discontinuing anti-vasospasm therapy with clazosentan. MATERIAL AND METHODS In this single-center retrospective observational study, we extracted diagnostic and therapeutic work-up data of consecutive 40 patients with SAH treated with clazosentan infusion (10 mg/h) as first-line anti-vasospasm therapy between May 2022 and August 2023. Patient data were compared between the discontinued and completed groups, and related factors for the discontinuation were further analyzed. RESULTS Clazosentan was discontinued in 22% (n=9) of patients due to intolerable dyspnea accompanied by hypoxemia at 5±3 days after therapy initiation, in which 44% (n=4) were elderly (≥75 years). Patients who discontinued clazosentan therapy showed significantly lower urine volumes compared with those who completed the therapy (P<0.05). Multivariate regression analysis revealed that day-to-day urine volume variance and older age were independent risk factors for drug cessation (P<0.05). The cut-off value for predicting clazosentan discontinuation was -0.7 mL/kg/h with sensitivity of 86% and specificity of 75% (area under the curve: 0.76±0.10; 95% confidence interval: 0.56-0.96; P=0.035). CONCLUSIONS Our results suggest that approximately 20% of SAH patients suffered from intolerable respiratory symptoms attributable to hypoxemia. We found that both reduced day-to-day urine volume variation and older age are independent risk factors for drug discontinuation.