Mizuya Shinoyama

Long-term Outcome of Cervical and Thoracolumbar Dural Arteriovenous Fistulas With Emphasis on Sensory Disturbance and Neuropathic Pain

BACKGROUND Clinical features and prognosis of sensory disturbance in spinal dural arteriovenous fistula (SDAVF) have not been well documented. Here we report long-term outcomes and detailed sensory evaluations of surgically treated SDAVF, including 14 patients with the craniocervical fistulas. METHODS Thirty-four consecutive patients with SDAVF treated at our institute during a period of 14 years were reviewed (mean age, 64.6 years; 67.6% men). Fistulas were located at the craniocervical junction in 14 patients (CC group) and in the thoracolumbar spine in 20 patients (TL group). In the CC group, six patients presented with subarachnoid hemorrhage. Fistulas were found incidentally in seven patients. One patient in the CC group and all patients in the TL group presented with progressive myelopathy. Most patients underwent microsurgery either alone (30 patients) or combined with embolization (3 patients). One patient was treated by embolization only. The follow-up ranged from 12 to 145 months (mean, 57 months). RESULTS All but one patient in the CC group had excellent surgical outcome. Most patients in the TL group stabilized or improved neurologically. Shorter duration before treatment indicated better gait recovery. Important, a few patients in the TL group suffered worsening or development of new pain, as well as lesser degree of improvement in gait and micturition. Spinal cord atrophy was correlated with clinical deterioration. CONCLUSIONS In craniocervical SDAVF, surgical treatment provides favorable long-term outcomes without risk of recurrence. In the thoracolumbar SDAVF, irreversible structural changes, such as spinal cord atrophy, may lead to poor recovery. Early diagnosis and treatment are thus warranted.

Spinal cord infarction demonstrated by diffusion-weighted magnetic resonance imaging.

Spinal cord infarction is a rare entity of varying etiology although most often associated with atherosclerotic aortic disease. Definitive diagnosis of (idiopathic) spinal cord infarction in the acute stage and in the absence of demonstrable predisposing factors is not always possible even with MRI. Diffusion-weighted MRI (dwMRI) may provide valuable information in the evaluation of spinal cord ischemia. A 45-year-old woman presented with idiopathic spinal cord infarction manifesting as sudden onset of paraparesis and sphincter dysfunction. Both T2-weighted and line-scan dwMRI revealed hyperintense signals in the dorsal part of the spinal conus. Apparent diffusion coefficient values were significantly low in the lesion, suggesting cytotoxic edema compatible with acute ischemia. The clinical course and other radiographic findings were also compatible with idiopathic spinal cord infarction. Diffusion-weighted MRI is an important diagnostic tool for examining patients with suspected spinal cord ischemia.

Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury

Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP), mental retardation, and epilepsy, which last throughout the individuals lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.

Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage.

OBJECTIVE Subarachnoid clots play an important role in development of delayed vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to compare clearance of subarachnoid clots using external ventricular drainage (EVD) or lumbar drainage (LD) after Guglielmi detachable coil (GDC) embolization for aneurysmal SAH. METHODS The subjects were 51 treated with GDC coil embolization for aneurysmal Fisher group 3 SAH within 72 h of ictus. Software-based volumetric quantification of the subarachnoid clots was performed on CT scans and the hemoglobin (Hb) level was measured in CSF drained from each catheter. RESULTS Clearance of subarachnoid clots was more rapid in patients treated with LD (n=34) compared to those treated with EVD (n=17). The Hb level in CSF was significantly higher in the LD group on Days 4-5 after onset of SAH (P<0.05), but was higher in the EVD group on Days 8-9. The incidence of symptomatic vasospasm did not differ between the two groups. The rate of occurrence of a new low density area on CT scans was higher in patients treated with EVD, but not significantly higher than the rate in the LD group. CONCLUSION GDC embolization followed by lumbar drainage accelerates the reduction of subarachnoid clots, but EVD may contribute to stasis of hemorrhage within subarachnoid spaces.

The Effect of Hypothermia Therapy on Cortical Laminar Disruption following Ischemic Injury in Neonatal Mice

Hypothermia has been proposed as a treatment for reducing neuronal damage in the brain induced by hypoxic ischemia. In the developing brain, hypoxic ischemia-induced injury may give rise to cerebral palsy (CP). However, it is unknown whether hypothermia might affect the development of CP. The purpose of this study was to investigate whether hypothermia would have a protective effect on the brains of immature, 3-day old (P3) mice after a challenge of cerebral ischemia. Cerebral ischemia was induced in P3 mice with a right common carotid artery ligation followed by hypoxia (6% O2, 37°C) for 30 min. Immediately after hypoxic ischemia, mice were exposed to hypothermia (32°C) or normothermia (37°C) for 24 h. At 4 weeks of age, mouse motor development was tested in a behavioral test. Mice were sacrificed at P4, P7, and 5 weeks to examine brain morphology. The laminar structure of the cortex was examined with immunohistochemistry (Cux1/Ctip2); the number of neurons was counted; and the expression of myelin basic protein (MBP) was determined. The hypothermia treatment was associated with improved neurological outcomes in the behavioral test. In the normothermia group, histological analyses indicated reduced numbers of neurons, reduced cortical laminar thickness in the deep, ischemic cortical layers, and significant reduction in MBP expression in the ischemic cortex compared to the contralateral cortex. In the hypothermia group, no reductions were noted in deep cortical layer thickness and in MBP expression in the ischemic cortex compared to the contralateral cortex. At 24 h after the hypothermia treatment prevented the neuronal cell death that had predominantly occurred in the ischemic cortical deep layers with normothermia treatment. Our findings may provide a preclinical basis for testing hypothermal therapies in patients with CP induced by hypoxic ischemia in the preterm period.

A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts.

Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a β-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the β-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by β-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process.

Neuroendoscopic evacuation of intraventricular hematoma associated with thalamic hemorrhage to shorten the duration of external ventricular drainage.

Background: We report neuroendoscopic evacuation of an intraventricular hematoma (IVH) in 13 patients with thalamic hemorrhage. We discuss strategies to improve the outcome and to shorten the management period by using external ventricular drainage (EVD). Methods: Patients were classified into fair (modified Rankin scale [mRS] grade 4 or less) and poor (mRS grade 5) outcome groups, and depending on the duration of EVD, into short (7 days or shorter) and long EVD (8 days or longer) groups. Results: The postoperative residual IVH, graded using the Graeb score, was better for the fair outcome group than for the poor outcome group (3.9 [1.2] vs. 5.7 [1.0], P < 0.05). The postoperative Graeb score was significantly better for the short EVD group than for the long EVD group (3.6 [0.8] vs. 6.0 [0.6], P < 0.01). The duration of EVD was not correlated with the IVH at the fourth ventricle, but it was correlated with the IVH at the foramen of Monro (P < 0.05) and the third ventricle (P < 0.01). Reduction in the volume of thalamic hemorrhage had no effect on the neurological outcome or duration of EVD. Conclusion: Neuroendoscopic evacuation of the IVH at the foramen of Monro and the third ventricle shortened the duration of EVD for hydrocephalus caused by thalamic hemorrhage with IVH involvement. Removal of the thalamic hemorrhage and IVH at the fourth ventricle was not necessary.

Real-time ultrasound-guided endoscopic surgery for putaminal hemorrhage.

OBJECT Endoscopic surgery plays a significant role in the treatment of intracerebral hemorrhage. However, the residual hematoma cannot be measured intraoperatively from the endoscopic view, and it is difficult to determine the precise location of the endoscope within the hematoma cavity. The authors attempted to develop real-time ultrasound-guided endoscopic surgery using a bur-hole-type probe. METHODS From November 2012 to March 2014, patients with hypertensive putaminal hemorrhage who underwent endoscopic hematoma removal were enrolled in this study. Real-time ultrasound guidance was performed with a bur-hole-type probe that was advanced via a second bur hole, which was placed in the temporal region. Ultrasound was used to guide insertion of the endoscope sheath as well as to provide information regarding the location of the hematoma during surgical evacuation. Finally, the cavity was irrigated with artificial cerebrospinal fluid and was observed as a low-echoic space, which facilitated detection of residual hematoma. RESULTS Ten patients with putaminal hemorrhage>30 cm3 were included in this study. Their mean age (±SD) was 60.9±8.6 years, and the mean preoperative hematoma volume was 65.2±37.1 cm3. The mean percentage of hematoma that was evacuated was 96%±3%. None of the patients exhibited rebleeding after surgery. CONCLUSIONS This navigation method was effective in demonstrating both the real-time location of the endoscope and real-time viewing of the residual hematoma. Use of ultrasound guidance minimized the occurrence of brain injury due to hematoma evacuation.

Initial ‘TTP Map-Defect’ of Computed Tomography Perfusion as a Predictor of Hemorrhagic Transformation of Acute Ischemic Stroke

Background: Hemorrhagic transformation (HT) following acute ischemic stroke is a major problem, especially for the indication of reperfusion therapy including intravenous administration of recombinant tissue plasminogen activator (IV rt-PA). The specific predictive factors of HT have not yet been established. The present study evaluated the findings of computed tomography perfusion (CTP) images as predictors of subsequent HT to identify patients with low HT risk for reperfusion therapy such as IV rt-PA. Methods: We retrospectively reviewed 68 consecutive stroke patients (41 males; mean age 72.9 years) with steno-occlusive lesions in the major trunk, including 10 patients who underwent IV rt-PA. Each HT was detected on a follow-up T2*-weighted magnetic resonance image until 2 weeks after stroke onset and categorized into four groups [hemorrhagic infarction (HI) type 1 and 2, and parenchymal hematoma (PH) type 1 and 2] according to the European Cooperative Acute Stroke Study (ECASS) classification. We assessed clinical features and radiological findings between the HT and non-HT groups or the PH2 and non-PH2 groups. The efficacy of initial time to peak (TTP) mapping of CTP for predicting HT or PH2 was evaluated. Results: Thirty-four patients (50%) developed subsequent HT: 18 (52.9%) had HI and 16 (47.1%) had PH, including 9 PH2 patients (13.2%). IV rt-PA was not significantly associated with HT or PH2 occurrence. Forty of the 68 patients (59%) revealed defect areas on the initial TTP mapping (TTP map-defect), and 34 of these 40 patients (85%) developed secondary HT and 9 patients (22.5%) developed PH2. Initial ‘TTP map-defect’ was significantly associated with the occurrence of HT (p < 0.0001) and PH2 (p = 0.0070). Thirty of the 34 patients (88.2%) in the HT group experienced delayed recanalization of the occluded vessels, in contrast to only 8 of the 34 patients (23.6%) in the non-HT group. All patients of the PH2 group showed recanalization (p = 0.0042). In 40 ‘TTP map-defect’-positive patients, delayed recanalization was associated with the occurrence of HT (p < 0.0001) and PH2 (p = 0.0491). All 28 patients without ‘TTP map-defect’ did not develop HT, including 8 patients (28.6%) with delayed recanalization. Conclusions: Initial ‘TTP map-defect’ of CTP could accurately predict HT risk including PH2 risk and identify low-risk patients even in the delayed period.

Idiopathic basal ganglia calcification associated with cerebral micro-infarcts: a case report

BackgroundIdiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by symmetric intracranial calcium deposition. We report a patient with IBGC associated with cerebral infarction due to impairment of cerebrovascular reactivity based on single-photon emission computed tomography (SPECT) with acetazolamide challenge.Case presentationA 66-year-old male presented with right conjugate deviation, right hemiparesis and total aphasia due to a convulsive seizure. Brain computed tomography showed symmetric calcifications in the bilateral basal ganglia, thalamus, cerebellar dentate nuclei, which were consistent with IBGC. Diffusion-weighted brain magnetic resonance imaging showed multiple small infarctions in the bilateral cerebral subcortical area. In the search for the cause of cerebral infarction, SPECT with acetazolamide challenge revealed heterogeneous impairment of cerebrovascular reactivity in the whole brain, despite the absence of evidence for steno-occlusive changes in proximal arteries.ConclusionCerebrovascular insufficiency due to the lack of elasticity caused by microvascular calcification might have been one of the pathophysiological features of IBGC in this case. Thus, vascular calcification may cause cerebrovascular disturbance and could lead to ischemic stroke in patients with IBGC.