The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement.

Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving young Mt, but not aged Mt improved cognitive function and hippocampal integrity. Using a CCL11-induced aging-like model in vitro, we found that astrocytic Mt protect hippocampal neurons and enhance a regenerative environment through upregulating synaptogenesis-related gene expression and anti-oxidants that were suppressed by CCL11. Moreover, the inhibition of CCL11-specific receptor C-C chemokine receptor 3 (CCR3) boosted the expression of synaptogenesis-related genes in the cultured hippocampal neurons and restored the neurite outgrowth. This study suggests that young astrocytic Mt can preserve cognitive function in the CCL11-mediated aging brain by promoting neuronal survival and neuroplasticity in the hippocampus.

Transplantation of astrocytic mitochondria modulates neuronal antioxidant defense and neuroplasticity and promotes functional recovery after intracerebral hemorrhage.

Astrocytes release functional mitochondria (Mt) that play regulatory and pro-survival functions upon entering adjacent cells. We recently demonstrated that these released Mt could enter microglia to promote their reparative/pro-phagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, a relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt that upon entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH. Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt upon entering neurons prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels, while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. Furthermore, we found that Mt genome-encoded small peptide humanin (HN) that is normally abundant in Mt, could simulate Mt-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under ICH-like injury. This study demonstrates that adoptive astrocytic Mt transfer enhances neuronal Mn-SOD-mediated anti-oxidative defense and neuroplasticity in the brain, which potentiate functional recovery following ICH.SIGNIFICANCE STATEMENTMitochondrial dysfunction and antioxidant defense play essential role in brain damage after intracerebral hemorrhage (ICH). Astrocytes release functional mitochondria (Mt) that enter adjacent cells to help brain homeostatic function. Here, we show that systemic transplantation of astrocytic Mt restores ICH-impaired neuronal anti-oxidative defense, enhances neurite outgrowth, and improves stroke recovery after ICH. Our study suggests that systemic transplantation of astrocytic Mt could be considered as a novel and potentially promising strategy for ICH treatment.

Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study.

INTRODUCTION: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. METHODS: This study included 16 consecutive pediatric MMD patients (age, 6-16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110-130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. RESULTS: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as "immediate redistribution pattern." In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as "transient hypoperfusion pattern." Although 8 patients, including 4 with "transient hypoperfusion pattern" (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. DISCUSSION/CONCLUSIONS: This study revealed that the "transient hypoperfusion pattern" after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.

Association between RNF213 c.14576G>A Variant (rs112735431) and Peripheral Pulmonary Artery Stenosis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) and peripheral pulmonary artery stenosis (PPAS) are relatively rare and demonstrate steno-occlusive vascular lesions in different organs. Genetic studies identified RNF213 polymorphism c.14576G>A (rs112735431) as a susceptibility variant for East Asian MMD. RNF213 polymorphism c.14576G>A is further associated with various vascular lesions of other organs. In this study, we aimed to clarify the incidence and clinical manifestations of PPAS in MMD patients and analyze the correlation between RNF213 genotype and PPAS. METHODS: This retrospective case-control study investigated the association between RNF213 polymorphism and PPAS in 306 MMD/quasi-MMD patients, reviewing the medical charts and imaging records of consecutive patients with MMD admitted from January 2015 to December 2020. RESULTS: PPAS was observed in 3 MMD/quasi-MMD patients (0.98%, 3/306). RNF213 polymorphism c.14576G>A was determined for all 306 MMD/quasi-MMD patients. The incidence of PPAS in RNF213-wildtype, RNF213-heterozygote, and RNF213-homozygote MMD/quasi-MMD patients was 0% (0/101), 0.5% (1/200), and 40% (2/5), respectively. The association between PPAS and homozygote polymorphism of RNF213 c.14576G>A was statistically significant in MMD/quasi-MMD patients (p = 0.0018). In all cases, pulmonary artery hypertension due to PPAS was evident during their childhood and young adolescent stages. Surgical indications for MMD were discouraged in 1 case due to her severe cardiopulmonary dysfunction. CONCLUSIONS: The homozygote variant of RNF213 polymorphism c.14576G>A can be a potential predisposing factor for PPAS in MMD/quasi-MMD patients. Despite the relatively rare entity, PPAS should be noted to determine surgical indications for MMD/quasi-MMD patients.

Deep Learning-Based Functional Independence Measure Score Prediction After Stroke in Kaifukuki (Convalescent) Rehabilitation Ward Annexed to Acute Care Hospital.

Introduction Prediction models of functional independent measure (FIM) score after kaifukuki (convalescent) rehabilitation ward (KRW) are needed to decide the treatment strategies and save medical resources. Statistical models were reported, but their accuracies were not satisfactory. We made such prediction models using the deep learning (DL) framework, Prediction One (Sony Network Communications Inc., Tokyo, Japan). Methods Of the 559 consecutive stroke patients, 122 patients were transferred to our KRW. We divided our 122 patients' data randomly into halves of training and validation datasets. Prediction One made three prediction models from the training dataset using (1) variables at the acute care ward admission, (2) those at the KRW admission, and (3) those combined (1) and (2). The models' determination coefficients (R2), correlation coefficients (rs), and residuals were calculated using the validation dataset. Results Of the 122 patients, the median age was 71, length of stay (LOS) in acute care ward 23 (17-30) days, LOS in KRW 53 days, total FIM scores at the admission of KRW 85, those at discharge 108. The mean FIM gain and FIM efficiency were 19 and 0.417. All patients were discharged home. Model (1), (2), and (3)'s R2 were 0.794, 0.970, and 0.972. Their mean residuals between the predicted and actual total FIM scores were -1.56±24.6, -4.49±17.1, and -2.69±15.7. Conclusion Our FIM gain and efficiency were better than national averages of FIM gain 17.1 and FIM efficiency 0.187. We made DL-based total FIM score prediction models, and their accuracies were superior to those of previous statistically calculated ones. The DL-based FIM score prediction models would save medical costs and perform efficient stroke and rehabilitation medicine.

Chronic subdural hematoma in patients over 65 years old: Results of using a postoperative cognitive evaluation to determine whether to permit return to driving.

BACKGROUND: Chronic subdural hematoma (CSDH) is usually associated with good recovery with burr hole irrigation and postoperative drainage under local anesthesia. In Japan, traffic accidents by the elderly drivers over 65 years old are severely increasing, and there is no consensus on whether or not to return to driving after CSDH treatment. We perform a postoperative cognitive assessment. We retrospectively investigated the return-to-driving rate and associated factors. METHODS: Of the 45 patients over 65 y.o. and who had usually driven, 30 patients wished to drive again. We performed tests composed of Mini-Mental State Examination (MMSE), line cancellation and line bisection task, Kohs block design test, trail making test (TMT)-A and B, Kana-hiroi test, Rey-Osterrieth complex figure test, and behavioral assessment of the dysexecutive syndrome, in order. When all tests' scores were better than the cutoff values, we let patients drive again. When some of the scores were worse than the cutoff values, we reevaluated the patients at the outpatient every month. If the patients' scores could not improve at the outpatient, we recommended them to stop driving. RESULTS: Nineteen of 30 patients could return to driving. Worse MMSE, Kohs block design test, TMT-A, TMT-B scores, higher age, dementia, or consciousness disturbance as chief complaints were associated with driving disability. CONCLUSION: CSDH is known as treatable dementia. However, we should perform an objective cognitive assessment before discharge because only 63% of the patients over 65 y.o. who wished to drive could return to driving.

A Rare Case of Intracerebral Pneumocephalus Caused by Preexisting Multiple Bone Defects and Encephalocele after Resection of Meningioma.

Pneumocephalus is generally secondary to direct damage to the skull base. Spontaneous intracerebral pneumatocele without head injury was extremely rare, but previously reported as a serious complication of shunt procedures. We describe a 40-year-old man with intracerebral pneumocephalus who previously underwent craniotomy for large frontal convexity meningioma and lumbo-peritoneal shunting. He presented with gait disturbance 14 months after tumor resection. Computed tomography and magnetic resonance imaging showed intracerebral pneumocephalus in the right temporal lobe, which continued into the mastoid air cells through a bone defect of the right petrous bone. We performed urgent right temporal craniotomy to reduce the mass effect and to repair the fistula. Intraoperatively, bone defects were identified at the roof petrous bone, into which the encephalocele had penetrated. The herniated cerebral parenchyma was removed, and the pneumocephalus opened. The dura was closed with sutures and covered with fascia. To elucidate the underlying mechanism for the development of intracranial pneumocephalus, the previous images obtained before or immediately after resection of meningioma were reviewed. We founded that multiple preexisting bone defects and encephaloceles, one of which was considered to be the cause of the intracerebral pneumocephalus. This case demonstrates that intracerebral pneumocephalus can be caused by preexisting bone defect and encephalocele, and this finding may be useful for prediction of pneumocephalus after shunt procedures.

Preliminary development of a prediction model for daily stroke occurrences based on meteorological and calendar information using deep learning framework (Prediction One; Sony Network Communications Inc., Japan).

BACKGROUND: Chronologically meteorological and calendar factors were risks of stroke occurrence. However, the prediction of stroke occurrences is difficult depending on only meteorological and calendar factors. We tried to make prediction models for stroke occurrences using deep learning (DL) software, Prediction One (Sony Network Communications Inc., Tokyo, Japan), with those variables. METHODS: We retrospectively investigated the daily stroke occurrences between 2017 and 2019. We used Prediction One software to make the prediction models for daily stroke occurrences (present or absent) using 221 chronologically meteorological and calendar factors. We made a prediction models from the 3-year dataset and evaluated their accuracies using the internal cross-validation. Areas under the curves (AUCs) of receiver operating characteristic curves were used as accuracies. RESULTS: The 371 cerebral infarction (CI), 184 intracerebral hemorrhage (ICH), and 53 subarachnoid hemorrhage patients were included in the study. The AUCs of the several DL-based prediction models for all stroke occurrences were 0.532-0.757. Those for CI were 0.600-0.782. Those for ICH were 0.714-0.988. CONCLUSION: Our preliminary results suggested a probability of the DL-based prediction models for stroke occurrence only by meteorological and calendar factors. In the future, by synchronizing a variety of medical information among the electronic medical records and personal smartphones as well as integrating the physical activities or meteorological conditions in real time, the prediction of stroke occurrence could be performed with high accuracy, to save medical resources, to have patients care for themselves, and to perform efficient medicine.

Usefulness of 3 Tesla Ultrashort Echo Time Magnetic Resonance Angiography (UTE-MRA, SILENT-MRA) for Evaluation of the Mother Vessel after Cerebral Aneurysm Clipping: Case Series of 19 Patients.

It is important to assess the cerebral arteries near the clip after cerebral aneurysm clipping. Contrast-enhanced computed tomography angiography has side effects of contrast medium and radiation exposure. Time-of-flight magnetic resonance angiography (TOF-MRA) is a fast and non-invasive method, but clip-induced artifact limits the assessment around the clip. Recently, 3 tesla MRA with ultrashort echo time called SILENT MRA (GE Healthcare Life Sciences, UK) has been reported to have the potential to overcome these disadvantages. We herein present consecutive 19 cerebral aneurysm patients treated by clipping and evaluated using SILENT MRA. The 19 patients (15 women and 4 men) underwent TOF-MRA and SILENT MRA during the same scan session. Two neurosurgeons independently assessed the visibility of the mother vessel at the clipping site in TOF-MRA and SILENT MRA. We also investigated the factors related to visibility in SILENT MRA. All patients' mother vessels were not described in TOF-MRA, and that of 16 patients (84%) were described in SILENT MRA. Overall agreement was 100% in the two neurosurgeons, and the fixed marginal kappa = 1.00 (95% CI: 0.36-1.00). Univariate analysis revealed that larger aneurysm dome and long clip blade length contributed to the visibility of the mother vessel in SILENT MRA. (p = 0.023, 0.007, each). In conclusion, SILENT MRA can be applied for the assessment of the arteries and aneurysm neck remnants near the clip. Using clips with long blade and ligation with its tip would be related to the visibility of the mother vessels in SILENT MRA.

Unilateral posterior reversible encephalopathy syndrome characterized with a long and gradually exacerbating course over 3 years and that presented propofol infusion syndrome - A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by acute neurological symptoms and vasogenic edema, and most patients wholly recover. We report a unilateral PRES patient characterized by a gradual onset followed by propofol infusion syndrome (PRIS) due to general anesthesia therapy. CASE DESCRIPTION: A 32-year-old woman had ovarian dysfunction treated by Kaufmann's treatment for 17 years. Three years ago, she developed seizures, and photophobia and myoclonus sometimes occurred. This time, she had strong photophobia and nausea for 3 months and then developed tonic-clonic seizures for 3 min. Her blood pressure and laboratory test on admission were all within normal limits. She presented no neurological deficits at admission, but the T2-weighted image (T2WI) showed a high-intensity area (HIA), and arterial spin labeling (ASL) image described cerebral blood flow (CBF) increase in the left parieto-occipital region. We diagnosed PRES and started anticonvulsants, antihypertensive, and steroid pulse therapy. However, her aphasia and neuroimaging findings worsened, so we started general anesthesia treatment with propofol on day 29. On day 32, she suddenly developed multiple organ dysfunctions due to PRIS. After intensive care with other sedatives over 2 months, the systemic status and neurological symptoms gradually improved almost as before the onset. On day 90, HIA in the T2WI in the lesion became small, and CBF was severely downregulated in the ASL image. CONCLUSION: Unilateral PRES's pathophysiology and the association with the female hormone remain unknown. Some patients undergo gradual onset and long-term courses, and we should care for PRIS during PRES treatment.

Three tesla magnetic resonance angiography with ultrashort echo time describes the arteries near the cerebral aneurysm with clip and the peripheral cerebral arteries.

BACKGROUND: The assessment of the clipped cerebral aneurysm and the cerebral arteries after the treatment of subarachnoid hemorrhage (SAH) is important to find aneurysm regrowth or postoperative cerebral vasospasm. Usually, contrast-enhanced computed tomography angiography is performed for the evaluation of the arteries, but it has side effects of contrast medium. Time-of-flight magnetic resonance angiography (MRA) is a fast and non-invasive method, but clip-induced artifact limits assessment of the artery in the vicinity of the clip. 1.5T MRA with ultrashort echo time (UTE) reduces metal artifact, but the obtained image is too rough to evaluate the aneurysm remnant, and the description range is too narrow to assess the cerebral vasospasm. We routinely use SIGNA Pioneer 3.0T (GE Healthcare Life Sciences, Buckinghamshire, England) and perform SILENT SCAN with UTE-MRA for the postoperative assessment of the clipped aneurysm and cerebral arteries for SAH patients treated by clipping. It has better image quality and describes arteries with a wide description range, so it possesses the potential to overcome the disadvantages of 1.5T UTE-MRA. CASE DESCRIPTION: We presented a representative SAH patient who postoperatively underwent 3.0T UTE- MRA after clipping. The artery near the clipped aneurysm was evaluated in detail, and the cerebral arteries were described from the main trunk to the peripheral parts with a wide description range, which enabled the assessment of cerebral vasospasm. CONCLUSION: 3.0T UTE-MRA may be helpful for the usual assessment of the arteries after clipping and cerebral vasospasm in the future.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.