The medical treatment for stroke has advanced greatly in recent years. Thrombolytic therapy with tissue plasminogen activator (t-PA) is one of the mainstream treatments, but it still has many ...problems, including short half-life, and t-PA-induced reperfusion and oxidative injuries. To broaden the therapeutic window of t-PA and reduce its associated oxidative stress after reperfusion, t-PA-installed, nitroxide radical-containing, self-assembled polyion complex nanoparticles (t-PA@iRNP) were designed. Encapsulation of t-PA in the self-assembled antioxidant nanoparticles improved its bioavailability and extended its therapeutic window. To suppress reactive oxygen species (ROS) in the ischemic penumbra area, the low-molecular-weight nitroxide antioxidant 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was covalently conjugated with the nanoparticle matrix, thus suppressing oxidative damage in the brain after reperfusion. t-PA and nitroxide radicals were confined and protected in the core of t-PA@iRNP, thereby preventing their rapid metabolism and excretion out of the body after systemic circulation for prolonged period. The nano-sized formulation prevented non-specific internalization of t-PA@iRNP in healthy cells, thereby preserving the normal function of redox reactions in the cells, especially important redox reactions such as electron transport chains. This improved pharmacological performance of t-PA@iRNP remarkably extended the in vivo half-life of t-PA in systemic circulation. Using a mouse model of photo-thrombotic middle cerebral artery occlusion, we found that t-PA@iRNP treatment, compared with naked t-PA, void iRNP, or t-PA@niRNP (non-ROS scavenging nanoparticle as a control), significantly suppressed increases in cerebral infarct volume and improved neurological deficit after brain ischemia. t-PA-induced subarachnoid hemorrhage was also suppressed by t-PA@iRNP treatment through elimination of overproduced ROS. Based on these data, t-PA@iRNP presents therapeutic potential through synergistic effect of thrombolysis and antioxidant effects for preventing and treating ischemia-reperfusion injury.
ObjectiveStatus epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam ...(LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE.MethodsWe initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000–3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug.ResultsA total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI −4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061).ConclusionThe efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT.Trial registration numberjRCTs031190160.
The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated ...co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL/6N mice. Over 84 days, myoblast engraftment and gene product expression, hemodynamic impairment, transpial collateralization, angiogenesis, pericyte recruitment and post-ischemic neuroprotection were assessed. By day 42, animals that received PDGF-BB in combination with VEGF (VIP) showed superior hemodynamic recovery, EMS collateralization and ischemic protection with improved pericyte recruitment around the parenchymal vessels and EMS collaterals. Also, supplementation of PDGF-BB resulted in a striking astrocytic activation with intrinsic VEGF mobilization in the cortex below the EMS. Our findings suggest that EMS surgery together with myoblast-mediated co-delivery of VEGF/PDGF-BB may have the potential to serve as a novel treatment strategy for augmentation of collateral flow in the chronically hypoperfused brain.
Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case ...and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.
In clinical practice, acute post-stroke paresis of the extremities fundamentally complicates timely rehabilitation of motor functions; however, recently, residual and distorted musculoskeletal ...signals have been used to initiate feedback-driven solutions for establishing motor rehabilitation. Here, we investigate the possibilities of basic hand gesture recognition in acute stroke patients with hand paresis using a novel, acute stroke, four-component multidomain feature set (ASF-4) with feature vector weight additions (ASF-14NP, ASF-24P) and supervised learning algorithms trained only by surface electromyography (sEMG). A total of 19 (65.9 ± 12.4 years old; 12 men, seven women) acute stroke survivors (12.4 ± 6.3 days since onset) with hand paresis (Brunnstrom stage 4 ± 1/4 ± 1, SIAS 3 ± 1/3 ± 2, FMA-UE 40 ± 20) performed 10 repetitive hand movements reflecting basic activities of daily living (ADLs): rest, fist, pinch, wrist flexion, wrist extension, finger spread, and thumb up. Signals were recorded using an eight-channel, portable sEMG device with electrode placement on the forearms and thenar areas of both limbs (four sensors on each extremity). Using data preprocessing, semi-automatic segmentation, and a set of extracted feature vectors, support vector machine (SVM), linear discriminant analysis (LDA), and k-nearest neighbors (k-NN) classifiers for statistical comparison and validity (paired t-tests, p-value < 0.05), we were able to discriminate myoelectrical patterns for each gesture on both paretic and non-paretic sides. Despite any post-stroke conditions, the evaluated total accuracy rate by the 10-fold cross-validation using SVM among four-, five-, six-, and seven-gesture models were 96.62%, 94.20%, 94.45%, and 95.57% for non-paretic and 90.37%, 88.48%, 88.60%, and 89.75% for paretic limbs, respectively. LDA had competitive results using PCA whereas k-NN was a less efficient classifier in gesture prediction. Thus, we demonstrate partial efficacy of the combination of sEMG and supervised learning for upper-limb rehabilitation procedures for early acute stroke motor recovery and various treatment applications.
Most asymptomatic patients with chronic subdural hematoma (CSDH) are followed conservatively but can require surgical treatment if the hematoma expands. We conducted a retrospective evaluation of the ...effect of Gorei-san on CSDH. This study included patients treated between April 2013 and March 2015. In total, 289 patients were diagnosed with CSDH and 110 patients received conservative management. Finally, 39 patients who met the requirements were registered. We retrospectively examined the age, gender, medical history, hematoma thickness, clarity of sulci below hematomas, and midline shift of the patients. The primary outcome was the median surgery-free interval, and the secondary results were the rate of CSDH shrinkage and surgery avoidance. A comparison of patient characteristics between the Gorei-san (G) and non-Gorei-san (NG) groups found no significant differences in the percentage of men, average ages, past history, thickness of CSDH (15.0 ± 3.1 mm vs. 15.3 ± 2.6 mm, p = 0.801), or midline shift (2.0 ± 2.7 mm vs. 4.0 ± 5.0 mm, p = 0.230). The median surgery-free interval was significantly different between the G and NG groups n. r. vs. 41 days (95% CI: 5-79), log-rank p = 0.047. The CSDH avoidance rate was not significantly different between the two groups (70.0% vs. 34.4%, p = 0.071). Additionally, the CSDH shrinkage rate was significantly different between the two groups (60.0% vs. 10.3%, p = 0.004). This retrospective study demonstrated that CSDH treatment with Gorei-san reduces hematoma significantly more than treatment that does not include Gorei-san.
Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective ...treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score ≥4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.
BACKGROUND AND PURPOSE—Reperfusion therapy by mechanical thrombectomy is used to treat acute ischemic stroke. However, reactive oxygen species generation after reperfusion therapy causes cerebral ...ischemia–reperfusion injury, which aggravates cerebral infarction. There is limited evidence for clinical efficacy in stroke for antioxidants. Here, we developed a novel core-shell type nanoparticle containing 4-amino-4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (nitroxide radical-containing nanoparticles RNPs) and investigated its ability to scavenge reactive oxygen species and confer neuroprotection.
METHODS—C57BL/6J mice underwent transient middle cerebral artery occlusion and then received RNPs (9 mg/kg) through the common carotid artery. Infarction size, neurological scale, and blood-brain barrier damage were visualized by Evans blue extravasation 24 hours after reperfusion. RNP distribution was detected by rhodamine labeling. Blood-brain barrier damage, neuronal apoptosis, and oxidative neuronal cell damage were evaluated in ischemic brains. Multiple free radical-scavenging capacities were analyzed by an electron paramagnetic resonance–based method.
RESULTS—RNPs were detected in endothelial cells and around neuronal cells in the ischemic lesion. Infarction size, neurological scale, and Evans blue extravasation were significantly lower after RNP treatment. RNP treatment preserved the endothelium and endothelial tight junctions in the ischemic brain; neuronal apoptosis, O2 production, and gene oxidation were significantly suppressed. Reactive oxygen species scavenging capacities against OH, ROO, and O2 improved by RNP treatment.
CONCLUSIONS—An intra-arterial RNP injection after cerebral ischemia–reperfusion injury reduced blood-brain barrier damage and infarction volume by improving multiple reactive oxygen species scavenging capacities. Therefore, RNPs can provide neurovascular unit protection.
BackgroundTransvenous embolization (TVE), such as selective shunt occlusion, is the first line treatment for cavernous sinus dural arteriovenous fistula (CSDAVF). Despite the favorable outcomes of ...TVE, some cases necessitating retreatment due to recurrence or incomplete occlusion persist. Given the physical, psychological, and financial burden of multiple treatments, understanding the predictive factors for recurrence, spontaneous occlusion, or retreatment is important. However, few reports have addressed these factors, complicating decision making regarding the need for retreatment. This study analyzed predictive factors for retreatment and spontaneous occlusion to offer new insights into CSDAVF management.MethodsThis retrospective, observational study was conducted in two acute care hospitals. Patients aged 18–100 years undergoing endovascular treatment for CSDAVF from January 2011 to December 2022 were included.ResultsOf 65 patients treated with TVE, 29 experienced immediate complete occlusion. Meanwhile, 22 of 36 patients with incomplete occlusion had spontaneous occlusion, and retreatment was performed in 20% of patients. Additional outlet occlusion was negatively associated with retreatment (P=0.046), and it tended to promote spontaneous occlusion (P=0.056). Favorable functional outcomes were observed in all patients, and approximately 94% of patients showed complete occlusion at the latest follow-up.ConclusionTVE is an effective treatment for CSDAVF. Outlet occlusion, when immediate complete occlusion is unattainable, is important to reduce retreatment and promote spontaneous occlusion. Substantially reducing shunt flow, carefully assessing dangerous drainage routes, and closely monitoring the residual shunt are crucial for preventing intracranial hemorrhage when outlet occlusion is performed.
Hemichorea-hemiballism (HCHB) due to transient ischemic attacks (TIAs) is rare. An 83-year-old woman had repeated episodes of right-sided HCHB for 3 months. Magnetic resonance (MR) angiography ...demonstrated occlusion of the left carotid and middle cerebral arteries and severe stenosis of the innominate artery, and 24-hour ambulatory blood pressure monitoring showed a blood pressure decrease of >20 mmHg after each meal. We speculated that HCHB developed as TIAs due to hemodynamic failure in the left cerebral hemisphere, caused by a combination of severe stenosis of the innominate artery concomitant with occlusion of the left carotid and middle cerebral arteries as well as postprandial hypotension.
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