Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts. METHODS: hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a tenfold higher dose of human adipose-derived stem cells (ADSCs) were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment. RESULTS: The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages/microglia. In detail, the hAMSC treatment decreased the number of CD11b+CD45+ and Ly6G+ cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα. CONCLUSIONS: Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage/microglia cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.

Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

Utility of relative ADC ratio in patient selection for endovascular revascularization of large vessel occlusion.

PURPOSE: The relative apparent diffusion coefficient (ADC) ratio on magnetic resonance imaging (MRI) can be used to evaluate the degree of ischemia. Here, we assessed the predictability of ischemic reversibility and the risk of hemorrhagic transformation using the relative ADC ratio. METHODS: This single-center retrospective study analyzed 56 patients with acute occlusion of the internal carotid artery (ICA) or the middle cerebral artery (M1) with endovascular revascularization. Diffusion-weighted imaging (DWI) lesions were classified as reversible lesions, final infarct lesions, and hemorrhagic or non-hemorrhagic regions. The relative ADC ratio was calculated in each DWI lesion and was defined as the ratio of ADC pixel values within affected territory to ADC pixel values in contralateral normal brain regions. RESULTS: The average relative ADC ratio was 0.890±0.045 in reversible DWI lesion and 0.640±0.041 in final infarct DWI lesion (P<0.001). In 4 cases with hemorrhagic transformation, hemorrhagic transformation regions were 0.557±0.049 and non-hemorrhagic transformation regions were 0.762±0.042 (P<0.001). In addition, percentage DWI improvement was inversely correlated with DWI lesion volume at the time of hospitalization (r=-0.840) and onset-to-reperfusion time (r=-0.765), but no correlation was noted with patient age (r=-0.043) or the first NIHSS score (r=-0.277). CONCLUSIONS: The relative ADC ratio may be useful for predicting DWI reversibility and post-reperfusion hemorrhagic transformation, even in patients with an unknown time of onset.

Neonatal Brains Exhibit Higher Neural Reparative Activities than Adult Brains in a Mouse Model of Ischemic Stroke.

The neonatal brain is substantially more resistant to various forms of injury than the mature brain. For instance, the prognosis following ischemic stroke is generally poor in the elderly but favorable in neonates. Identifying the cellular and molecular mechanisms underlying reparative activities in the neonatal brain after ischemic injury may provide feasible targets for therapeutic interventions in adults. To this end, we compared the reparative activities in postnatal day 13 and adult (8-12-week-old) mouse brain following middle cerebral artery occlusion. Immunohistochemistry revealed considerably greater generation of ischemia-induced neural stem/progenitor cells (iNSPCs) expressing nestin or Sox2 in ischemic areas of the neonatal brain. The iNSPCs isolated from the neonatal brain also demonstrated greater proliferative activity than those isolated from adult mice. In addition, genes associated with neuronal differentiation were enriched in iNSPCs isolated from the neonatal brain according to microarray and gene ontogeny analyses. Immunohistochemistry further revealed considerably greater production of newborn doublecortin+ neurons at the sites of ischemic injury in the neonatal brain compared to the adult brain. These findings suggest that greater iNSPC generation and neurogenic differentiation capacities contribute to the superior regeneration of the neonatal brain following ischemia. Together, our findings may help identify therapeutic targets for enhancing the reparative potential of the adult brain following stroke.

[Cluster-like headache cause by cavernous sinus dural arteriovenous fistula, cured by transvenous embolization: a case report].

We report a unique case of cavernous sinus(CS)-dural arteriovenous fistula(dAVF)with cluster headache-like ophthalmalgia without chemosis and exophthalmos, that was successfully treated by transvenous embolization. A 25-year-old man presented with severe right cluster headache-like ophthalmalgia and could not get complete relief of symptoms by medical treatment. MRI showed a hyper-intensity signal in the right cavernous sinus and cerebral angiography revealed Barrow type D cavernous sinus dural arteriovenous fistula, which is thought to be the cause of ophthalmalgia. Percutaneous transvenous embolization of the anterior part of the right CS and superior ophthalmic vein was performed and complete obliteration of dAVF was obtained followed by complete cure of cluster headache-like ophthalmalgia. We can detect neither the recurrence of dAVF on MRI nor any clinical symptom after 23 months of the treatment. This is the first clinical presentation of cluster headache-like ophthalmalgia caused by CS dAVF and it emphasizes the unique and important potential relationship between them.

Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke.

We recently demonstrated that injury/ischemia-induced multipotent stem cells (iSCs) develop within post-stroke human brains. Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.

Prognostic Factors in Patients with Unruptured Vertebral and Basilar Fusiform Aneurysms Treated with Endovascular Procedures : A Single Center Retrospective Analysis.

PURPOSE: Large vertebral and basilar fusiform aneurysms (VFA) are sometimes difficult to cure by endovascular treatment (EVT). We aimed to elucidate indicators of poor outcomes of EVT in patients with VFAs. METHODS: Clinical data from 48 patients with 48 unruptured VFAs in the Hyogo Medical University were retrospectively analyzed. The primary outcome was defined as satisfactory aneurysm occlusion (SAO) according to Raymond-Roy grading scale. The secondary and safety outcomes were a modified Rankin scale (mRS) score of 0-2 at 90 days, retreatment, major stroke, and aneurysm-related death after EVT. RESULTS: The EVT included stent-assisted coiling (n = 24; 50%), flow diverter (n = 19; 40%), and parent artery occlusion (n = 5; 10%). The SAO was less frequently observed in large or thrombosed VFAs at 12 months (64%, p = 0.021 and 62%, p = 0.014, respectively), especially when the aneurysms were both large and thrombosed (50%, p = 0.0030). Retreatment was more common in large aneurysms (29%, p = 0.034), thrombosed (32%, p = 0.011), and large thrombosed aneurysms (38%, p = 0.0036). Although the proportion of mRS 0-2 at 90 days and major stroke showed no significant differences, that of post-treatment rupture was significantly larger in large thrombosed VFAs (19%, p = 0.032). Aneurysm-related death occurred by aneurysm rupture and was more frequent in large thrombosed VFA (19%, p = 0.032). Multivariate analysis showed SAO at 12 months was less common (adjusted odds ratio, OR: 0.036, 95% confidence interval, CI 0.00091-0.57; p = 0.018), and retreatment was more common (adjusted OR 43, 95% CI 4.0-1381; p = 0.0012) in large thrombosed VFA. CONCLUSION: The large thrombosed VFAs were associated with poor outcomes after EVT including flow diverter.

Enhanced angiogenic properties of umbilical cord blood primed by OP9 stromal cells ameliorates neurological deficits in cerebral infarction mouse model.

Umbilical cord blood (UCB) transplantation shows proangiogenic effects and contributes to symptom amelioration in animal models of cerebral infarction. However, the effect of specific cell types within a heterogeneous UCB population are still controversial. OP9 is a stromal cell line used as feeder cells to promote the hematoendothelial differentiation of embryonic stem cells. Hence, we investigated the changes in angiogenic properties, underlying mechanisms, and impact on behavioral deficiencies caused by cerebral infarction in UCB co-cultured with OP9 for up to 24 h. In the network formation assay, only OP9 pre-conditioned UCB formed network structures. Single-cell RNA sequencing and flow cytometry analysis showed a prominent phenotypic shift toward M2 in the monocytic fraction of OP9 pre-conditioned UCB. Further, OP9 pre-conditioned UCB transplantation in mice models of cerebral infarction facilitated angiogenesis in the peri-infarct lesions and ameliorated the associated symptoms. In this study, we developed a strong, fast, and feasible method to augment the M2, tissue-protecting, pro-angiogenic features of UCB using OP9. The ameliorative effect of OP9-pre-conditioned UCB in vivo could be partly due to promotion of innate angiogenesis in peri-infarct lesions.

Localized kinking during deployment of a flow redirection lumen device (FRED) could be due to excessive pushing.

BACKGROUND: The safety and efficacy analysis of flow redirection lumen device (FRED) demonstrated the excellent safety profile of FREDs for aneurysm treatment. We describe the first case in which FRED deployment for a paraclinoid aneurysm resulted in in-stent stenosis, necessitating balloon angioplasty, and an additional stent. CASE DESCRIPTION: A 50-year-old woman had a left paraclinoid aneurysm with a maximum diameter of 6.1 mm. We planned FRED deployment. We experienced in-stent stenosis just after the deployment of a FRED. Devices such as guidewires and catheters could not cross the lesion through the FRED because of an obstruction in the FRED. Balloon angioplasty and subsequent stenting resolved thrombosis and kinking. FRED has potential for kinking locally. CONCLUSION: Surgeons should consider this possibility when treating cerebral aneurysm using FRED. Cone-beam computed tomography after deployment of FRED may be useful for evaluating the stent shape.

Identification of Novel Multipotent Stem Cells in Mouse Spinal Cord Following Traumatic Injury.

We showed that injury-induced multipotent stem cells (iSCs) emerge in the brain after stroke. These brain-derived iSCs (B-iSCs) can differentiate into various lineages, including neurons. This study aimed to determine whether similar stem cells can be induced even after nonischemic injuries, such as trauma to the spinal cord. We characterized these cells, mainly focusing on their stemness, multipotency, and neuronal differentiation activities. Spinal cord injury (SCI) was produced using forceps in adult mice. On day 3 after SCI, samples were obtained from the injured areas. Spinal cord sections were subjected to histological analyses. Cells were isolated and assessed for proliferative activities, immunohistochemistry, reverse transcriptase-polymerase chain reaction, fluorescence-activated cell sorter, and microarray analysis. Although nerve cell morphology was disrupted within the injured spinal cord, our histological observations revealed the presence of cells expressing stem cells, such as nestin and Sox2 in these areas. In addition, cells extracted from injured areas exhibited high proliferative abilities. These cells also expressed markers of both neural stem cells (eg, nestin, Sox2) and multipotent stem cells (eg, Sox2, c-myc, Klf4). They differentiated into adipocytes, osteocytes, and chondrocytes, as well as neuronal cells. Microarray analysis further identified similar properties between spinal cord (SC)-derived iSCs and B-iSCs. However, SC-iSCs revealed specific genes related to the regulation of stemness and neurogenesis. We identified similar features related to multipotency in SC-iSCs compared with B-iSCs, including neuronal differentiation potential. Although the differences between SC-iSCs and B-iSCs remain largely undetermined, this study shows that iSCs can develop even after nonischemic injuries such as trauma. This phenomenon can occur outside the brain within the central nervous system.

Mechanical Thrombectomy via the Transfemoral Approach for Acute Middle Cerebral Artery M1 Occlusion That Occurred during Intra-Aortic Balloon Pumping Application.

Objective: We report a case of cardioembolic stroke treated by mechanical thrombectomy (MT) via the transfemoral approach under the assistance of intra-aortic balloon pumping (IABP). Case Presentation: A 64-year-old man suddenly developed consciousness disturbance, aphasia, and left hemiparesis during intensive care for acute myocardial infarction (AMI) with IABP. The patient was transferred to our hospital and diagnosed with acute right middle cerebral artery (MCA) occlusion. We performed MT using a balloon-guiding catheter via the transfemoral approach and achieved complete recanalization. Conclusion: Endovascular therapy for acute MCA M1 occlusion via the transfemoral route was safe even when the patient was treated using IABP.

Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation.

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

Intentional Herniation Technique with the Neuroform EZ Stent System for Preservation of Aneurysmal Neck Branch: A Case Report.

Endovascular treatment of bifurcation aneurysms is difficult and complicated because arterial branches may arise from the aneurysmal neck. We treat these cases with complex techniques such as Y or T stenting. In this report, we deployed one Neuroform EZ stent using the intentional herniation technique for the preservation of arterial branches. A 78-year-old female presented with two unruptured aneurysms. One was an 8 mm aneurysm located at the bifurcation of the internal carotid artery and the posterior communicating artery (PcomA). The other was an 11 mm aneurysm located at the cavernous segment of the internal carotid artery. A 4.5x20 mm Neuroform EZ stent was placed across the aneurysm neck. The delivery wire and microcatheter were pushed during deployment, similar to braided stents. High resolution cone beam computed tomography (CT) after stenting revealed the stent strut to be vertically aligned near the aneurysmal sac, and the PcomA orifice was preserved. We performed coil embolization easily and achieved acceptable obliteration. Our intentional herniation technique may be useful in some cases. Open cell stents have some advantages depending on the method of deployment.

Intravenous administration of human adipose-derived stem cells ameliorates motor and cognitive function for intracerebral hemorrhage mouse model.

Even today, intracerebral hemorrhage (ICH) is a major cause of death and disabilities. Rehabilitation is preferentially applied for functional recovery although its effect is limited. Recent studies have suggested that intravenous administration of mesenchymal stem cells would improve the post-ICH neurological deficits. Human adipose-derived stem cells (hADSCs) have been established in our laboratory. We aimed to evaluate the therapeutic efficacy of the hADSCs on the post-ICH neurological deficits using a clinical-relevant ICH mouse model. We also evaluated immune responses to clarify the underlying mechanisms. The hADSCs expressed MSC markers at high levels. The hADSCs administration into the ICH-bearing mice improved the neurological deficits during the subacute phases, which was shown by neurobehavioral experiments. Besides, the hADSC administration decreased the number of CD11+CD45+ cells and increased the proportion of CD86+ and Ly6C+ cells in the ICH lesions. In summary, intravenous administration of hADSCs during the acute phase improved ICH-induced neurological deficits during the subacute phase because of the suppression of acute inflammation mediated by CD11+CD45+ subpopulations. Our data suggest that hADSCs can be served as a novel strategy for ICH treatment.

Isolation and Characterization of Cerebellum-Derived Stem Cells in Poststroke Human Brain.

There is compelling evidence that the mature central nervous system (CNS) harbors stem cell populations outside conventional neurogenic regions. We previously demonstrated that brain pericytes (PCs) in both mouse and human exhibit multipotency to differentiate into various neural lineages following cerebral ischemia. PCs are found throughout the CNS, including cerebellum, but it remains unclear whether cerebellar PCs also form ischemia-induced multipotent stem cells (iSCs). In this study, we demonstrate that putative iSCs can be isolated from poststroke human cerebellum (cerebellar iSCs [cl-iSCs]). These cl-iSCs exhibited multipotency and differentiated into electrophysiologically active neurons. Neurogenic potential was also confirmed in single-cell suspensions. DNA microarray analysis revealed highly similar gene expression patterns between PCs and cl-iSCs, suggesting PC origin. Global gene expression comparison with cerebral iSCs revealed general similarity, but cl-iSCs differentially expressed certain cerebellum-specific genes. Thus, putative iSCs are present in poststroke cerebellum and possess region-specific traits, suggesting potential capacity to regenerate functional cerebellar neurons following ischemic stroke.

Therapeutic strategy for pineal parenchymal tumor of intermediate differentiation (PPTID): case report of PPTID with malignant transformation to pineocytoma with leptomeningeal dissemination 6 years after surgery.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is rare. The WHO first classified PPTID in 2000 as a pineal parenchymal tumor (PPT) with an intermediate prognosis between pineocytoma (PC) and pineoblastoma (PB). It is considered an intermediate-grade tumor and divided into WHO grade II or III.The number of available reports about PPTID is presently limited, and the appropriate management for this tumor has not yet been determined.The authors report a rare case of PC in a 63-year-old woman who presented with lower-extremity weakness and gait disturbance. A pineal mass lesion was detected on MRI. A diagnosis of PC was established after microsurgical gross-total tumor resection, and the patient received no adjuvant therapy after surgery. Two years after surgery, a partial recurrence was recognized and Gamma Knife radiosurgery was performed. Fours years later, the patient developed diffuse leptomeningeal dissemination. She was successfully treated with craniospinal irradiation. Leptomeningeal dissemination may develop 6 years after the initial diagnosis of PC. A histopathological study of the recurrent tumor revealed a malignant change from PC to PPTID.The present case shows the importance of long-term follow-up of patients with PPTs following resection and the efficacy of craniospinal irradiation in the treatment of leptomeningeal dissemination.

Utility of MRI-based disproportionately enlarged subarachnoid space hydrocephalus scoring for predicting prognosis after surgery for idiopathic normal pressure hydrocephalus: clinical research.

OBJECTIVE The presence of disproportionately enlarged subarachnoid space hydrocephalus (DESH) on brain imaging is a recognized finding of idiopathic normal pressure hydrocephalus (iNPH), but the features of DESH can vary across patients. The aim of this study was to evaluate the utility of MRI-based DESH scoring for predicting prognosis after surgery. METHODS In this single-center, retrospective cohort study, the DESH score was determined by consensus between a group of neurosurgeons, neurologists, and a neuroradiologist based on the preoperative MRI findings of the patients with suspected iNPH. The DESH score was composed of the following 5 items, each scored from 0 to 2 (maximum score 10 points): ventriculomegaly, dilated sylvian fissures, tight high convexity, acute callosal angle, and focal sulcal dilation. The association between the DESH score and improvement of the scores on the modified Rankin Scale (mRS), iNPH Grading Scale (iNPHGS), Mini-Mental State Examination (MMSE), Trail Making Test-A (TMT-A), and Timed 3-Meter Up and Go Test (TUG-t) was examined. The primary end point was improvement in the mRS score at 1 year after surgery, and the secondary outcome measures were the iNPHGS, MMSE, TMT-A, and TUG-t scores at 1 year after surgery. Improvement was determined as improvement of 1 or more levels on mRS, ≥ 1 point on iNPHGS, ≥ 3 points on MMSE, a decrease of > 30% on TMT-A, and a decrease of > 10% on TUG-t. RESULTS The mean DESH score for the 50 patients (mean age 77.6 ± 5.9 years) reviewed in this study was 5.58 ± 2.01. The mean rate of change in the mRS score was -0.50 ± 0.93, indicating an inverse correlation between the DESH score and rate of change in the mRS score (r = -0.749). Patients who showed no improvement in mRS score tended to have a low DESH score as well as low preoperative MMSE and TMT-A scores. There were no differences in the areas of deep white matter hyperintensity and periventricular hyperintensity on the images between patients with and without an improved mRS score (15.6% vs 16.7%, respectively; p = 1.000). The DESH score did differ significantly between patients with and without improved scores on the iNPHGS (6.39 ± 1.76 vs 4.26 ± 1.69, respectively; p < 0.001), MMSE (6.63 ± 1.82 vs 5.09 ± 1.93; p = 0.010), TMT-A (6.32 ± 1.97 seconds vs 5.13 ± 1.93 seconds; p = 0.042), and TUG-t (6.48 ± 1.81 seconds vs 4.33 ± 1.59 seconds; p < 0.001). CONCLUSIONS MRI-based DESH scoring is useful for the prediction of neurological improvement and prognosis after surgery for iNPH.

Segmental Arterial Mediolysis Involving Both Vertebral and Middle Colic Arteries Leading to Subarachnoid and Intraperitoneal Hemorrhage.

BACKGROUND: Segmental arterial mediolysis (SAM) is not yet well known in the neurosurgical field, even though it has become an increasingly recognized pathology in arterial dissection. CASE DESCRIPTION: A case of SAM presented as subarachnoid hemorrhage (SAH) due to a dissecting aneurysm of the left intracranial vertebral artery (VA), which extended from the proximal VA union to the distal portion of the left posterior inferior cerebellar artery. The lesion was successfully embolized by an endovascular technique. However, subsequent intraperitoneal hemorrhage due to rupture of a fusiform aneurysm of the middle colic artery prompted surgical treatments. The features of the extirpated visceral vascular lesion were compatible with the diagnosis of SAM based on histopathologic examinations. CONCLUSIONS: It is very important that SAM is recognized as a systemic disease that affects the central nervous system, visceral arteries, and coronary arteries. The possibility of SAM should always be considered, particularly in patients with ruptured VA dissection-which is nowadays treated by endovascular techniques-since concomitantly involved visceral arteries may cause unexpected hemorrhagic complications other than SAH.

Correlation of middle cerebral artery tortuosity with successful recanalization using the Merci retrieval system with or without adjunctive treatments.

The Merci retrieval system is a useful modality for the recanalization of acute cerebral artery occlusion. However, it remains unclear whether the tortuosity of the middle cerebral artery (MCA) plays a role in successful recanalization. In this study, we investigated the association between the shape of the horizontal MCA segment (M1) and successful recanalization using the Merci retrieval system with or without adjunctive treatments. Twenty-three patients with M1 occlusion underwent thrombectomy using the Merci retrieval system with or without adjunctive treatments between July 2010 and July 2012. The anteroposterior view of final angiograms was used to measure the M1 curve angles. M1 with a curve angle measuring < 100° was defined as arch-type M1, whereas that with a curve angle measuring ≥ 100° was defined as straight-type M1. Angiographic findings were evaluated on the basis of the thrombolysis in cerebral infarction grade; grade 2B or 3 corresponds to successful recanalization. Eight patients had arch-type M1 and 15 patients had straight-type M1. Successful recanalization was achieved in 2 patients (25%) with arch-type M1 and 12 patients (80%) with straight-type M1 (p = 0.023). The mean M1 curve angle was significantly greater in the 14 patients in whom successful recanalization was achieved than in the 9 patients in whom it was not achieved (129 ± 21° vs. 93 ± 29°, p = 0.002). Arch-type M1 was an independent predictive factor of unsuccessful recanalization (odds ratio, 0.045; 95% confidence interval, 0.03-0.696). A tortuous M1 was associated with unsuccessful recanalization by the Merci retrieval system, even when adjunctive treatments were used.