Relevance of the Foramen of Vesalius for Preoperative Tumor Embolization in Skull Base Meningioma.

OBJECTIVE: The objective of this study was to investigate the role of the foramen of Vesalius (FV) in the pathogenesis of skull base meningioma by analyzing data from various multi-image modalities. METHODS: For this single-center retrospective study, 39 consecutive patients with skull base meningioma who underwent tumor resection between January 2020 and March 2023 were enrolled. The anatomical and pathological characteristics of the FV were evaluated using computed tomography and 3-dimensional digital subtraction angiography. The clinical significance of the FV in tumor hemodynamics and treatment, such as preoperative tumor embolization, was investigated using the 3-dimensional digital subtraction angiography/computed tomography fusion images. RESULTS: We identified FV in 52% (17/27) of the finally included patients. In 10 (30%) patients, the FV was found bilaterally with no significant variation in appearance between the healthy and tumor-affected sides (P = 0.786). The mean FV diameter was significantly larger on the tumor-affected side (P = 0.010). No significant anatomical differences, like duplication and partial assimilation with the foramen ovale, were observed between the 2 sides. The FV was involved in venous skull base perfusion around the tumor in 9 cases. In 4 cases where it was the pathway for tumor feeders, preoperative tumor embolization via the FV resulted in disappearance of the tumor stain. No complications associated with endovascular treatment were observed. CONCLUSIONS: This study elucidated the anatomical asymmetry of the FV and its role in the hemodynamics of skull base meningioma. Our findings highlight the significance of performing anatomical and pathological evaluations of the FV in determining treatment strategies, including preoperative embolization, for skull base lesions.

Characteristics of MicroRNA Expression Depending on the Presence or Absence of Meningioma in Patients with Neurofibromatosis Type 2: A Secondary Analysis.

Meningioma is the second most frequent tumor in patients with neurofibromatosis type 2 (NF2). The presence of meningioma is believed to be a negative prognostic marker in these patients. However, the molecular mechanisms involved in the tumorigenesis of NF2-associated meningioma are not well characterized. Epigenetic regulation, including microRNAs (miRNAs), may be involved in the development of different tumor types in patients with NF2. The objective of this study is to explore the different characteristics of serum miRNA expression depending on the presence or absence of meningioma in patients with NF2. Nine patients with NF2 who were treated at the Department of Neurosurgery, Hiroshima University Hospital, were included. Total RNA (including small RNAs) was extracted from serum samples for the preparation of a small RNA library for next-generation sequencing analysis. Differentially expressed miRNAs (DEMs) were analyzed using the DESeq2 package to compare the characteristic miRNA expression profiles of patients with and without meningioma. In small RNA sequencing analysis, out of a total of 1,879 miRNAs registered in the database, the expressions of 657 miRNAs were observed. In DEM analysis, the expressions of four miRNAs, namely, hsa-miR-664b, hsa-miR-7706, hsa-miR-590, and hsa-miR-6513, were downregulated in patients with NF2 with meningioma compared with patients with NF2 without meningioma. Hsa-miR-193a was identified as the only upregulated miRNA in patients with NF2 with meningioma. In conclusion, we identified different circulating miRNA expression characteristics depending on the presence or absence of meningioma in patients with NF2.

Shorter survival time of adolescents and young adult patients than older adults with spinal cord glioblastoma: a multicenter study.

OBJECTIVE: Cancers in adolescents and young adults (AYAs) (age 15-39 years) often present with unique characteristics and poor outcomes. To date, spinal cord glioblastoma, a rare tumor, remains poorly understood across all age groups, including AYAs. This comparative study aimed to investigate the clinical characteristics and outcomes of spinal cord glioblastoma in AYAs and older adults (age 40-74 years), given the limited availability of studies focusing on AYAs. METHODS: Data from the Neurospinal Society of Japan's retrospective intramedullary tumor registry (2009-2020) were analyzed. Patients were dichotomized on the basis of age into AYAs and older adults. Univariate and multivariate Cox proportional hazards regression models were utilized to explore risk factors for overall survival (OS). RESULTS: A total of 32 patients were included in the study, with a median (range) age of 43 (15-74) years. Of these, 14 (43.8%) were AYAs and 18 (56.2%) were older adults. The median OS was 11.0 months in AYAs and 32.0 months in older adults, and the 1-year OS rates were 42.9% and 66.7%, respectively, with AYAs having a significantly worse prognosis (p = 0.017). AYAs had worse preoperative Karnofsky Performance Status (KPS) than older patients (p = 0.037). Furthermore, AYAs had larger intramedullary tumors on admission (p = 0.027) and a significantly higher frequency of intracranial dissemination during the clinical course (p = 0.048). However, there were no significant differences in the degrees of surgical removal or postoperative radiochemotherapy between groups. The Cox proportional hazards regression model showed that AYAs (HR 3.53, 95% CI 1.17-10.64), intracranial dissemination (HR 4.30, 95% CI 1.29-14.36), and no radiation therapy (HR 57.34, 95% CI 6.73-488.39) were risk factors for mortality for patients of all ages. Worse preoperative KPS did not predict mortality in AYAs but did in older adults. The high incidence of intracranial dissemination may play an important role in the poor prognosis of AYAs, but further studies are needed. CONCLUSIONS: The clinical characteristics of AYAs with spinal cord glioblastoma differ from those of older adults. The prognosis of AYAs was clearly worse than that of older adults. The devastating clinical course of spinal glioblastoma in AYAs was in line with those of other cancers in this age group.

The Impact of Adjuvant Radiotherapy on Clinical Performance Status in Patients With Grade II Spinal Cord Astrocytoma - A Nationwide Analysis by the Neurospinal Society of Japan.

OBJECTIVE: The impact of adjuvant radiotherapy on overall survival (OS) and progression-free survival (PFS) of patients with grade II spinal cord astrocytomas remains controversial. Additionally, the relationship between progression and clinical deterioration after radiotherapy has not been well investigated. METHODS: This study included 53 patients with grade II intramedullary spinal cord astrocytomas treated by either subtotal, partial resection or open biopsy. Their clinical performance status was assessed immediately before operation and 1, 6, 12, 24, and 60 months after surgery by Karnofsky Performance Scale (KPS). Patients with and without adjuvant radiotherapy were compared. RESULTS: The groups with and without radiation comprised 23 and 30 patients with a mean age of 50.3 ± 22.6 years (range, 2-88 years). The mean overall disease progression rate was 47.1% during a mean follow-up period of 48.4 ± 39.8 months (range, 2.5-144.5 months). In the radiation group, 11 patients (47.8%) presented with progressive disease, whereas 14 patients (46.7%) presented with progressive disease in the group without radiation. There were no significant differences in OS or PFS among patients with or without adjuvant radiotherapy. KPS in both groups, especially radiation group, gradually decreased after operation and deteriorated before the confirmation of disease progression. CONCLUSION: Adjuvant radiotherapy did not show effectiveness regarding PFS or OS in patients with grade II spinal cord astrocytoma according to classical classification based on pathohistological findings.

Clinical Characteristics and Long-term Outcomes of Spinal Pilocytic Astrocytomas: A Multicenter Retrospective Study by the Neurospinal Society of Japan.

OBJECTIVE: The characteristics, imaging features, long-term surgical outcomes, and recurrence rates of primary spinal pilocytic astrocytomas (PAs) have not been clarified owing to their rarity and limited reports. Thus, this study aimed to analyze the clinical presentation, radiological features, pathological findings, and long-term outcomes of spinal PAs. METHODS: Eighteen patients with spinal PAs who were surgically treated between 2009 and 2020 at 58 institutions were included in this retrospective multicenter study. Patient data, including demographics, radiographic features, treatment modalities, and long-term outcomes, were evaluated. RESULTS: Among the 18 consecutive patients identified, 11 were women and 7 were men; the mean age at presentation was 31 years (3-73 years). Most PAs were located eccentrically, were solid or heterogeneous in appearance (cystic and solid), and had unclear margins. Gross total resection (GTR), subtotal resection (STR), partial resection (PR), and biopsy were performed in 28%, 33%, 33%, and 5% of cases, respectively. During a follow-up period of 65 ± 49 months, 4 patients developed a recurrence; however, the recurrence-free survival did not differ significantly between the GTR and non-GTR (STR, PR, and biopsy) groups. CONCLUSION: Primary spinal PAs are rare and present as eccentric and intermixed cystic and solid intramedullary cervical tumors. The imaging features of spinal PAs are nonspecific, and a definitive diagnosis requires pathological support. Surgical resection with prevention of neurological deterioration can serve as the first-line treatment; however, the resection rate does not affect recurrence-free survival. Investigation of relevant molecular biomarkers is required to elucidate the regrowth risk and prognostic factors.

Orbital fibrous capsule formation with abscess found 3 years after penetrating injury from a wooden chopstick.

Intraorbital wooden foreign bodies are sometimes difficult to diagnose because of nonspecific clinical manifestations and diversity of imaging characteristics. We herein report a case involving a 72-year-old woman with a history of trauma induced by a coated wooden chopstick 3 years prior. Two years after the incident, computed tomography (CT) scan revealed an intraorbital mass that was initially diagnosed as an intraorbital hemangioma. The patient presented with hyperemia, impairment of ocular movement, and optic neuropathy in her right eye. Magnetic resonance imaging (MRI) showed granulation tissue and an abscess around a foreign body, which was compressing the eyeball. Surgical extraction of the foreign body was performed, leading to resolution of symptoms. The depiction of wooden foreign bodies by imaging is complicated and affected by several factors, increasing the risk of delayed diagnosis. To avoid permanent sequelae, MRI might be helpful because its imaging capabilities are superior to those of CT.

Impact of intravenously administered cranial bone-derived mesenchymal stem cells on functional recovery in experimental spinal cord injury.

Impairments of the central nervous system, such as stroke, brain trauma, and spinal cord injury (SCI), cannot be reversed using current treatment options. Herein, we compared the characteristics of rat cranial bone-derived mesenchymal stem cells (rcMSCs) and rat bone marrow-derived mesenchymal stem cells (rbMSCs). We also investigated the therapeutic effects of intravenously administered rcMSCs and rbMSCs in a rat model of cervical SCI (cSCI) and elucidated its undrelying mechanism. Comprehensive comparative bioinformatics analysis of rcMSCs and rbMSCs RNA sequencing revealed that genes associated with leukocyte transendothelial migration and chemokine signaling were significantly downregulated in rcMSCs. Rats were divided into three groups that received intrtravenous administration of rcMSC, rbMSC, or phosphate-buffered saline (control) 24 h after cSCI. The rcMSC-treated group showed improved functional recovery over the rbMSC-treated and control groups, and reduced lesion volume compared with the control group. The mRNA expression of nitric oxide synthase 2 at the spinal cord lesion site was significantly higher in the rcMSC-treated group than in the control and rbMSCs-treated groups, whereas that of transforming growth factor-ß was significantly higher in the rcMSC-treated group compared to that in the control group. The transcriptome data indicated that rcMSCs and rbMSCs differentially affect inflammation. The intravenous administration of rcMSCs contributed to functional recovery and lesion reduction in cSCI. The rcMSCs have the potential to induce an anti-inflammatory environment in cSCI.

A novel rat model for longitudinal electrophysiological evaluation after cold-induced brain injury.

OBJECTIVE: Cerebral contusion models of cold-induced injury are widely used in animal studies. However, owing to the difficulty of longitudinal recording of electrical stimulation transcranial motor evoked potential (tcMEP) in brain injury models of incomplete paralysis, to the authors' knowledge there have been no multimodal evaluations of cold-induced brain injury models that have included motor function and electrophysiological and histological evaluations. Therefore, in this study the authors aimed to perform a multimodal evaluation of a rat model of brain injury. METHODS: A brain injury model in female rats and a tcMEP recording technique based on the authors' previous study were established to enable multifaceted analysis, including longitudinal electrophysiological evaluation. RESULTS: The model showed incomplete paralysis of the right forelimb. Motor function showed recovery over time, and histological evaluation showed tissue changes associated with cerebral contusion. In addition, stable tcMEP waveforms were recorded before and after surgery and up to 4 weeks after injury. The tcMEP amplitude decreased significantly after injury and recovered over time. Furthermore, the amplitudes at 1, 7, and 14 days after injury were significantly lower than those at preinjury (p < 0.0006, p < 0.0007, and p < 0.0067, respectively). CONCLUSIONS: In the present study, the authors established a novel cold-induced brain injury rat model and technique that allowed for the evaluation of longitudinal tcMEP recording and demonstrated that multimodal evaluation for brain injury can be performed. This model can potentially be applied in future investigations of various therapies for brain injury.

Assessment of Intraoperative Spinal Angiography via the Popliteal Artery for Spinal Vascular Diseases.

OBJECTIVE: Intraoperative spinal angiography via the popliteal artery for patients in the prone position has been reported only twice in 4 patients. This study aimed to clarify the safety precautions to be taken with this technique in a larger patient cohort. METHODS: Seven patients with spinal vascular disorders underwent intraoperative spinal angiography in the prone position via the popliteal artery. Ultrasound was used to evaluate the neurovascular anatomy in the popliteal fossa and guide the arterial puncture. Patient characteristics, features of angiography devices, puncture attempts, and angiography-related complications, such as hematoma formation and injury to the neurovascular bundle, were analyzed. RESULTS: The average number of arterial puncture attempts was 1.3 times (range: 1-2). Sheaths (4 and 4.5 Fr) with different ineffective lengths were used. In 1 case, a 4.5-Fr sheath was replaced with a 4-Fr sheath with a shorter noneffective length as the length of the catheter limited access to the target. Catheters with Type-JB2 tip shapes were used for craniocervical junction lesions, and those with Type-KAGAWA tip shapes were used for thoracic and lumbar spinal lesions. No puncture site complications were observed in any patient. CONCLUSIONS: Intraoperative spinal angiography via the popliteal artery was an effective tool in surgeries for spinal vascular diseases. The introduction of the ultrasound enabled atraumatic puncture of the popliteal artery. Spinal targets above T5 to T6 may be inaccessible from the popliteal fossa when using a 100-cm-long catheter.

Establishment of longitudinal transcranial stimulation motor evoked potentials monitoring of the forelimbs and hindlimbs in an ischemic stroke rat model.

Evaluation of motor function ischemic stroke rat models includes qualitative assessments such as the modified neurological severity score (mNSS). However, mNSS cannot evaluate the function of forelimbs and hindlimbs separately. We quantitatively assessed motor function in a middle cerebral artery occlusion (MCAO) rat model of ischemic stroke. We recorded transcranial stimulation motor evoked potentials (tcMEPs) from MCAO rats and measured the changes in onset latency and amplitude at the forelimbs and hindlimbs up to 28 days after stroke. All MCAO subjects showed hemiparesis. The amplitudes of tcMEPs in both fore- and hindlimbs were inversely correlated with mNSS scores, but the amplitudes in the forelimbs improved later than those in the hindlimbs. The onset latency of tcMEPs in the forelimbs and hindlimbs remained almost unchanged during the follow-up period. Our results showed the differences in tcMEPs amplitude recovery times between the forelimbs and hindlimbs after MCAO, which emphasizes the importance of separately evaluating forelimbs and hindlimbs in post-ischemic stroke models. This minimally invasive and longitudinal quantitative method could be useful for further research on diseases and neurogenesis.

Natural history of acute unruptured vertebral basilar artery dissection: Temporal changes in imaging findings and contributory factors.

OBJECTIVES: To investigate temporal changes in imaging findings of conservatively treated acute unruptured vertebral basilar artery dissection (VBAD) and its contributing factors. METHODS: Fifty-three patients who underwent conservative treatment for 64 cases of acute VBAD diagnosed between January 2006 and March 2019 with follow-up of at least 12 months after onset were retrospectively investigated. Statistical analyses of age, sex, medical history, pattern of onset, lesion site, imaging findings and changes over time, regular medication, and outcomes were performed. RESULTS: Changes in the vascular morphology of the lesion site during the follow-up period were observed in only 23 (43 %) patients (median time until change: 19 days). Univariate analysis of factors contributing to morphological changes at the dissection site showed that changes were significantly more likely in younger patients (p = 0.011). Patients taking antiplatelet drugs had a significantly greater rate of deterioration at the dissection site (p = 0.028) than others. On multivariate analysis, age was an independent factor contributing to changes at the dissection site, and taking antiplatelet drugs, particularly clopidogrel, was an independent factor contributing to deterioration. No patient developed intracranial hemorrhage, cerebral infarction, or worsening of neurological symptoms during follow-up. CONCLUSIONS: Morphological changes at the dissection site are more likely in younger patients with acute unruptured VBAD and those taking antiplatelet drugs. However, chances of intracranial hemorrhage, cerebral infarction, or worsening of neurological symptoms during conservative therapy are low; therefore, acute unruptured VBAD may be considered a benign condition.

Longitudinal electrophysiological changes after mesenchymal stem cell transplantation in a spinal cord injury rat model.

Transcranial electrically stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans and animals. However, the relationship between tcMEPs and the recovery of paralysis remains unclear. We previously reported that transplantation of mesenchymal stem cells to a spinal cord injury (SCI) rat model resulted in various degrees of recovery from paraplegia. As a continuation of this work, in the present study, we aimed to establish the longitudinal electrophysiological changes in this SCI rat model after mesenchymal stem cell transplantation. SCI rats were established using the weight-drop method. The model rats were transvenously transplanted with two types of mesenchymal stem cells (MSCs), one derived from rat cranial bones and the other from the bone marrow of the femur and tibia bone, 24 h after SCI. A phosphate-buffered saline (PBS) group that received only PBS was also created for comparison. The degree of paralysis was evaluated over 28 days using the Basso-Beattie-Bresnahan (BBB) scale and inclined plane task score. Extended tcMEPs were recorded using a previously reported bone-thinning technique, and the longitudinal electrophysiological changes in tcMEPs were investigated. In addition, the relationship between the time course of recovery from paralysis and reappearance of tcMEPs was revealed. The appearance of the tcMEP waveform was earlier in MSC-transplanted rats than in PBS-administered rats (earliest date was 7 days after SCI). The MEP waveforms also appeared at approximately the same level on the BBB scale (average score, 11 points). Ultimately, this study can help enhance our understanding of the relationship between neural regeneration and tcMEP recording. Further application of tcMEP in regenerative medicine research is expected.

Ischemic complications in the neurosurgical and endovascular treatments of craniocervical junction arteriovenous fistulas: a multicenter study.

OBJECTIVE: A recent comparative analysis between neurosurgical and endovascular treatments for craniocervical junction (CCJ) arteriovenous fistulas (AVFs) revealed better treatment outcomes in the neurosurgery group than in the endovascular group. This finding was attributed to the higher than expected rate of ischemic complications in the endovascular group than in the neurosurgery group (26% vs 7.7%, p = 0.037). The aim of the present study was to describe ischemic complications associated with treatments for CCJ AVFs. METHODS: This descriptive study was authorized by the Neurospinal Society of Japan. Data from 97 consecutive patients with CCJ AVFs who underwent neurosurgical (n = 78) or endovascular (n = 19) treatment between 2009 and 2019 were collected from 29 centers. The primary endpoints were details on ischemic complications and their risk factors. Secondary endpoints were details on other complications. RESULTS: Among all major complications, ischemic complications were the most common (11% of 97 patients), followed by hemorrhagic complications (7.2%), hydrocephalus (2.1%), and CSF leakage (2.1%). Ischemic complications included 8 spinal, 2 brainstem, and 1 cerebellar infarctions. Iatrogenic occlusion of the anterior or posterior spinal artery from the radiculomedullary or radiculopial arteries caused these complications. Ischemic complications resulted in neurological deficits, including motor paresis, sensory disturbances, and brainstem dysfunction. The modified Rankin Scale score was 3 or higher in 36% of patients with ischemic complications at the final follow-up of 23 months. Risk factors associated with ischemic complications were endovascular treatment (OR 4.3, 95% CI 1.1-16) and spinal feeding arteries (OR 3.8, 95% CI 1.03-14). Most of the other complications were addressed by additional treatment without permanent neurological deficits. CONCLUSIONS: Among ischemic complications associated with treatments for CCJ AVFs, spinal infarctions were the most common and were mostly attributed to endovascular procedures for CCJ AVFs fed by spinal arteries. These results support the use of neurosurgery as the first-line treatment for CCJ AVFs.

Healing process of Type II odontoid fractures after C1-C2 posterior screw fixation: Predictive factors for pseudoarthrosis.

Background: The healing process after C1-C2 posterior screw fixation (C1-C2 PSF) for odontoid fractures is not well understood. Here, we evaluated such processes and identified factors potentially contributing to pseudoarthroses following fusions for Type II odontoid fractures. Methods: Pre- and post-operative cervical radiographs and computed tomography (CT) images from 15 patients with preoperative Type II odontoid fractures who underwent C1-C2 PSF were retrospectively reviewed. Results: CT images identified three areas of bone fusion: The primary fracture site in the dens (9/15 patients, 60%), the atlanto-dental interspace (ADI) (10/15, 67%), and C1-C2 interlaminar space after onlay bone grafting (4/15, 27%). All patients showed bone fusion in at least one of three areas, while only one patient (6.7%) achieved bone fusion in all three areas. With these overall criteria, nine of 15 patients (60%) were considered fused, while six patients (40%) were determined to exhibit pseudoarthroses. Univariate analyzes showed that the preoperative C2-C7 SVA for the nonunion group was significantly larger versus the union group, and bone fusion at the level of the ADI was significantly more common in the nonunion versus the union group. Conclusion: CT studies identified three anatomical areas where bone fusion likely occurs after C1-C2 PSF. Increased sagittal balance in the cervical spine may negatively impact the fusion of odontoid fractures. Further, bone fusion occurring at other sites, not the primary fracture location, through stress shielding may contribute to delayed or failed fusions.

Distinctive MicroRNA Profiles in Serum of Patients with Neurofibromatosis Type 2: A Bioinformatic Exploratory Study.

OBJECTIVE: The objective of this study was to explore serum microRNA (miRNA) profile characteristic of patients with neurofibromatosis type 2 (NF2), including both sporadic and familial cases, by comprehensive analysis of miRNA expression using next-generation sequencing. METHODS: Nine patients with NF2 were included in this study. In addition, 7 patients with unilateral acoustic neuroma without a family history of NF2 were invited to participate as the control cohort in the study. Total RNA including the small RNAs was extracted from serum. We comprehensively analyzed the expression of miRNAs using next-generation sequencing, and differentially expressed miRNAs (DEMs) were analyzed. Biological implications of DEMs were analyzed by Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis. RESULTS: Distinctive miRNA profiles (16 miRNAs were significantly downregulated, and 4 miRNAs were significantly upregulated) were observed in the comparison between all patients with NF2 and controls. In the NF2 subgroup analysis, 23 miRNAs (including hsa-miR-let7b, hsa-miR-let7c, and hsa-miR-200a) and 7 miRNAs (including hsa-miR-193b) were identified as specifically downregulated miRNAs in sporadic NF2 and familial NF2, respectively. Moreover, hsa-miR-193a and hsa-miR-504 were identified as specifically upregulated miRNAs in sporadic NF2 and familial NF2, respectively. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that identified DEMs were mainly enriched in gene silencing by miRNA, miRNAs in cancer, and regulation of angiogenesis. CONCLUSIONS: We were able to identify distinctive miRNA profiles in the serum of patients with NF2, including both sporadic and familial cases, by comprehensive miRNA expression analysis using miRNA sequencing.

Intramuscular Coherence of the Lower Flexor Muscles during Robotic Ankle-Assisted Gait.

A close-fitting assisted walking device (RE-Gait) designed to assist ankle movements might be a novel approach for acquiring the forefoot rocker function in the gait cycle. The purpose of the present study was to investigate the effects of using RE-Gait by evaluating the intramuscular coherence (IMC) of the two parts of the tibialis anterior muscles (TA), which could indicate whether a common synaptic drive is present. Seventeen healthy volunteers walked on a treadmill at a comfortable speed before, during, and immediately after 15-minute RE-Gait intervention. After RE-Gait intervention, IMC of the two parts of the TA muscles in the beta frequency band in the initial swing phase was significantly enhanced during RE-Gait intervention. In addition, IMCs in the beta and low-gamma frequency bands were significantly correlated with the enhancement ratio of the step length. These results suggest that robotic ankle plantar flexion and dorsiflexion assistance in the initial swing phase may be effective for improving gait function with enhancement of the functioning of the sensorimotor loop.

Neurosurgical versus endovascular treatment of craniocervical junction arteriovenous fistulas: a multicenter cohort study of 97 patients.

OBJECTIVE: Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are treated using neurosurgical or endovascular options; however, there is still no consensus on the safest and most effective treatment. The present study compared the treatment results of neurosurgical and endovascular procedures for CCJ AVFs, specifically regarding retreatment, complications, and outcomes. METHODS: This was a multicenter cohort study authorized by the Neurospinal Society of Japan. Data on consecutive patients with CCJ AVFs who underwent neurosurgical or endovascular treatment between 2009 and 2019 at 29 centers were analyzed. The primary endpoint was the retreatment rate by procedure. Secondary endpoints were the overall complication rate, the ischemic complication rate, the mortality rate, posttreatment changes in the neurological status, independent risk factors for retreatment, and poor outcomes. RESULTS: Ninety-seven patients underwent neurosurgical (78 patients) or endovascular (19 patients) treatment. Retreatment rates were 2.6% (2/78 patients) in the neurosurgery group and 63% (12/19 patients) in the endovascular group (p < 0.001). Overall complication rates were 22% and 42% in the neurosurgery and endovascular groups, respectively (p = 0.084). Ischemic complication rates were 7.7% and 26% in the neurosurgery and endovascular groups, respectively (p = 0.037). Ischemic complications included 8 spinal infarctions, 2 brainstem infarctions, and 1 cerebellar infarction, which resulted in permanent neurological deficits. Mortality rates were 2.6% and 0% in the neurosurgery and endovascular groups, respectively (p > 0.99). Two patients died of systemic complications. The percentages of patients with improved modified Rankin Scale (mRS) scores were 60% and 37% in the neurosurgery and endovascular groups, respectively, with a median follow-up of 23 months (p = 0.043). Multivariate analysis identified endovascular treatment as an independent risk factor associated with retreatment (OR 54, 95% CI 9.9-300; p < 0.001). Independent risk factors associated with poor outcomes (a postoperative mRS score of 3 or greater) were a pretreatment mRS score of 3 or greater (OR 13, 95% CI 2.7-62; p = 0.001) and complications (OR 5.8; 95% CI 1.3-26; p = 0.020). CONCLUSIONS: Neurosurgical treatment was more effective and safer than endovascular treatment for patients with CCJ AVFs because of lower retreatment and ischemic complication rates and better outcomes.

Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury.

Cell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for SCI.

A novel bone-thinning technique for transcranial stimulation motor-evoked potentials in rats.

Transcranial electrical stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans, and even in animal studies, tcMEPs are used to evaluate neurological dysfunction. However, there is a dearth of reports on extended tcMEP recordings in both animal models and humans. Therefore, this study examined a new technique for stably recording tcMEPs over several weeks in six healthy female Sprague-Dawley rats. We thinned the skull bone using the skull base and spinal surgery technique to reduce electrical resistance for electrical stimulation. tcMEPs were recorded on days 1, 7, 14, 21, and 28 after surgery. The onset latency and amplitude of tcMEPs from the hindlimbs were recorded and evaluated, and histological analysis was performed. Stable amplitude and onset latency could be recorded over several weeks, and histological analysis indicated no complications attributable to the procedure. Thus, our novel technique allows for less invasive, safer, easier, and more stable extended tcMEP recordings than previously reported techniques. The presently reported technique may be applied to the study of various nerve injury models in rats: specifically, to evaluate the degree of nerve dysfunction and recovery in spinal cord injury, cerebral infarction, and brain contusion models.

Comparisons of Neurotrophic Effects of Mesenchymal Stem Cells Derived from Different Tissues on Chronic Spinal Cord Injury Rats.

Cell-based therapies with mesenchymal stem cells (MSCs) are considered as promising strategies for spinal cord injury (SCI). MSCs have unique characteristics due to differences in the derived tissues. However, relatively few studies have focused on differences in the therapeutic effects of MSCs derived from different tissues. In this study, the therapeutic effects of adipose tissue-derived MSCs, bone marrow-derived MSCs, and cranial bone-derived MSCs (cMSCs) on chronic SCI model rats were compared. MSCs were established from the collected adipose tissue, bone marrow, and cranial bone. Neurotrophic factor expression of each MSC type was analyzed by real-time PCR. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 4 weeks after SCI. Hindlimb motor function was evaluated from before injury to 4 weeks after transplantation. Endogenous neurotrophic factor and neural repair factor expression in spinal cord (SC) tissue were examined by real-time PCR and western blot analyses. Although there were no differences in the expression levels of cell surface markers and multipotency, expression of Bdnf, Ngf, and Sort1 (Nt-3) was relatively higher in cMSCs. Transplantation of cMSCs improved motor function of chronic SCI model rats. Although there was no difference in the degree of engraftment of transplanted cells in the injured SC tissue, transplantation of cMSCs enhanced Bdnf, TrkB, and Gap-43 messenger RNA expression and synaptophysin protein expression in injured SC tissue. As compared with MSCs derived other tissues, cMSCs highly express many neurotrophic factors, which improved motor function in chronic SCI model rats by promoting endogenous neurotrophic and neural plasticity factors. These results demonstrate the efficacy of cMSCs in cell-based therapy for chronic SCI.