Negative Remodeling of Carotid Canal during Spontaneous Disease Progression in Moyamoya Disease.

OBJECTIVE: This study was designed to observe the changes in the carotid canal over time by measuring the carotid canal diameter longitudinally in adult patients with moyamoya disease in whom disease stage progressed spontaneously. METHODS: Of 70 adult patients with moyamoya disease, 10 adult patients on 15 sides with spontaneous progression of the disease stage during conservative follow-up were included in this study. Another 10 moyamoya cases on 15 sides were selected as the controls without disease progression. All patients were followed up for at least 60 months after the progression of disease stage was confirmed. In addition, 5 patients who underwent microvascular decompression were included as healthy controls. The carotid canal diameter was measured with bone window computed tomography (CT) and source images of time-of-flight magnetic resonance angiography at initial presentation, and then were serially monitored with the latter. RESULTS: There was a significant correlation between the values obtained from CT and magnetic resonance imaging (R2 = 0.992, P < 0.001). The carotid canal diameter in moyamoya disease at initial presentation was 4.29 ± 0.61 mm, being smaller than 5.20 ± 0.51 mm in healthy controls (P < 0.01). In response to disease progression, the carotid canal diameter started to decrease at 6 months after disease progression was confirmed, and reduced to about 85% of the original level during 60 months (P < 0.01). The phenomenon was not observed in patients without disease progression. CONCLUSIONS: The carotid canal diameter can decrease in response to disease progression even in adult moyamoya disease. "Negative" bone remodeling may play a key role in this unique phenomenon.

Ameliorative Effects of Combined Revascularization Surgery on Abnormal Collateral Channels in Moyamoya Disease.

OBJECT: Abnormal collateral channels, so-called moyamoya vessels, play a critical role to compensate cerebral ischemia, but carry the risk for hemorrhagic stroke in moyamoya disease (MMD). The present study was aimed to clarify if superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-myo-duro-arterio-pericranial synangiosis (EDMAPS) can efficiently regress the abnormal collateral channels in MMD patients. METHODS: This study included 92 hemispheres of 61 MMD patients who underwent STA-MCA anastomosis combined with EDMAPS between 2013 and 2019. There were 17 children and 44 adults. We retrospectively analyzed the findings on cerebral angiography before and 3 to 6 months after surgery, including Suzuki's angiographical stage, the development of surgical collaterals, and the extent of abnormal collateral channels such as lenticulostriate, thalamic, and choroidal channels. RESULTS: Following surgery, no pediatric and adult patients experienced any stroke during follow-up periods (40.2±25.5 and 54.9±19.7 months, respectively). Suzuki's stage significantly advanced in both adult and pediatric patients after surgery (P=0.042 and P<0.001). In adult patients, all of the lenticulostriate, thalamic, and choroidal channels significantly regressed after surgery (P<0.001, P=0.012, and P=0.004, respectively). In pediatric patients, however, lenticulostriate and choroidal channels significantly regressed (P=0.005 and P=0.034, respectively). Correlation analysis revealed that the development of surgical collaterals determined the postoperative regression of choroidal channels (P<0.001). CONCLUSION: STA-MCA anastomosis and EDMAPS may be one of the most effective procedures to widely provide surgical collaterals to the operated hemispheres and prevent not only ischemic but also hemorrhagic stroke by regressing the hemorrhage-prone abnormal collateral channels in MMD.

Specific clinical features and one-stage revascularization surgery for moyamoya disease with severe cerebral ischemia in the territory of posterior cerebral artery.

BACKGROUND: There are no reports describing the surgical procedure for moyamoya disease (MMD) patients with severe cerebral ischemia in the territory of the posterior cerebral artery (PCA) at initial presentation. In this study, therefore, we describe their clinical and radiological features and clinical results of one-stage revascularization surgery for both anterior and posterior circulation. METHODS: This study included 6 MMD patients who had severe cerebral ischemia in the PCA territory and underwent one-stage revascularization surgery for both anterior and posterior circulation. Of these, one patient underwent it on both sides. Their clinical and radiological data were precisely analyzed. Compared with usual procedure, craniotomy was extended towards the temporo-parietal area more widely. The parietal branch of superficial temporal artery (STA) was anastomosed to the angular or posterior temporal artery, while the frontal branch was anastomosed to the frontal branch of MCA. Ultimate indirect bypass was added. Their clinical and radiological outcomes were evaluated. RESULTS: Their neurological symptoms included visual and speech disturbance as well as numbness of the extremities. Cerebral infarct was distributed in the posterior temporal, parietal, and/or occipital lobe. Cerebral hemodynamics and metabolism were also impaired in the same regions. These findings were completely different from those in MMD patients without PCA lesion. Postoperative course was uneventful, and none of them recurred stroke during a mean follow-up period of 10.5 years. Surgical collaterals widely provided blood flow to the entire hemispheres, including the occipital lobe. Cerebral hemodynamics and metabolism markedly improved after surgery. CONCLUSION: One-stage revascularization surgery for both anterior and posterior circulation is feasible and effective to prevent future stroke in MMD patients with severe cerebral ischemia in the PCA territory at initial presentation.

Clinical and Radiological Features of Childhood Onset Adult Moyamoya Disease: Implication for Hemorrhagic Stroke.

Some of the pediatric moyamoya patients spend their childhood without diagnosed as moyamoya disease (MMD) because of their mild ischemic attacks and emerge again with ischemic or hemorrhagic stroke in their adulthood. This study was aimed to clarify the clinical characteristics of adult moyamoya patients with childhood onset and elucidate the impact of long disease period on their clinical features. Present study included 116 untreated hemispheres of 69 adult patients with MMD. They were divided into two groups: childhood onset group (26 hemispheres of 14 patients) and adult onset group (90 hemispheres of 55 patients). Clinical features were compared between the two groups. The incidence of hemorrhagic stroke was significantly higher in childhood onset group (P = 0.0091). Lenticulostriate and choroidal channels were more developed in childhood onset group (P = 0.044 and P <0.001, respectively). Vault moyamoya was more frequently observed in childhood onset group (P <0.001). The development of surgical collaterals through indirect bypass was more marked in childhood onset group (P = 0.0019). Multivariate analysis revealed that childhood onset and developed choroidal channels were significantly associated with the occurrence of hemorrhagic stroke (OR 4.31 [95% CI 1.21-15.4], P = 0.025 and OR 6.78 [95% CI 1.78-25.8], P = 0.0050, respectively). This study clearly shows that adult moyamoya patients with childhood onset have more developed spontaneous collaterals, which may, in turn, highly causes hemorrhagic stroke. Adult moyamoya patients with "childhood onset" should be recognized as a novel and important concept when elucidating the underlying mechanisms of hemorrhagic stroke in MMD.

Intracranial, Intra-parenchymal Capillary Hemangioma - Case Report.

We report a very rare case of intracranial capillary hemangioma. This 15-year-old girl complained of pulsating headache in the temple area that aggravated with change of body positions. This headache usually lasted for 5 min and resolved without any treatment. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) strongly suggested cavernous hemangioma in the right deep parietal lobe. She underwent complete resection of the tumor through right parietal craniotomy. Postoperative course was uneventful. Histologic examinations demonstrated a densely grown numerous capillary-like vascular structure with endothelial cells, hemosiderin deposition, and hemorrhage. Intracranial, intra-parenchymal capillary hemangioma is a very rare vascular tumor or tumor like lesions. Only four cases with intracranial, intra-parenchymal capillary hemangioma were reported previously. Differential diagnosis includes other vascular tumors such as cavernous hemangioma, but it is not so easy to differentiate capillary hemangioma from other lesions. Therefore, surgical excision and histologic diagnosis would be important to diagnose it if possible.

Late (5-20 years) outcomes after STA-MCA anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis in patients with moyamoya disease.

OBJECTIVE: Surgical revascularization is known to reduce the incidence of further ischemic and hemorrhagic events in patients with moyamoya disease, but the majority of previous studies report only short-term (< 5 years) outcomes. Therefore, in this study the authors aimed to evaluate late (5-20 years) outcomes of moyamoya patients after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect bypass (encephalo-duro-myo-arterio-pericranial synangiosis [EDMAPS]). METHODS: Cumulative incidences of late morbidity/mortality and disease progression were evaluated among 93 patients who underwent STA-MCA anastomosis and EDMAPS. All of the patients were prospectively followed up for longer than 5 years postsurgery (10.5 ± 4.4 years). There were 35 pediatric and 58 adult patients. Initial presentation included transient ischemic attack/ischemic stroke in 80 patients and hemorrhagic stroke in 10 patients, and 3 patients were asymptomatic. Surgery was performed in a total of 141 hemispheres. Follow-up MRI/MRA was performed within a 6- or 12-month interval during the follow-up periods. RESULTS: During the follow-up periods, 92/93 patients were free from any stroke or death, but 1 patient had a recurrence of hemorrhagic stroke (0.10% per patient-year). Disease progression occurred in the territory of the contralateral carotid or posterior cerebral artery (PCA) in 19 hemispheres of 15 patients (1.5% per patient-year). The interval between initial surgery and disease progression varied widely, from 0.5 to 15 years. Repeat bypass surgery for the anterior and posterior circulation resolved ischemic attacks in all 10 patients. CONCLUSIONS: The study results indicate that STA-MCA anastomosis and EDMAPS would be the best choice to prevent further ischemic and hemorrhagic stroke for longer than 10 years on the basis of the demonstrated widespread improvement in cerebral hemodynamics in both the MCA and ACA territories in the study patients. However, after 10 years postsurgery regular follow-up is essential to detect disease progression in the territory of the contralateral carotid artery and PCA and prevent late cerebrovascular events.

Unstable Carotid Plaque as a Phenotype of Chronic Systemic Inflammation Enhances Renal Insufficiency.

PURPOSE: Chronic systemic inflammation is prevalent in patients with chronic kidney disease (CKD) and is linked to the development of cerebrovascular disease. In this study, we explored the association between the unstable plaques and preoperative CKD in patients who underwent carotid endarterectomy (CEA)/carotid artery stenting (CAS). Furthermore, this study also aimed to explore whether there is a difference in the aggravation of renal function with the presence of stable or unstable plaques. PATIENTS AND METHODS: The study included 90 patients who underwent CEA/CAS for carotid artery stenosis. Multivariate analysis was performed to determine the risk factors for CKD. Kaplan-Meier estimation was employed to evaluate the aggravation of renal function following CEA/CAS. RESULTS: Multivariate analysis revealed that contralateral carotid occlusive disease (odds ratio [OR], 4.45; 95% confidence interval [CI], 1.36-14.6), and T1 high-intensity carotid plaque (OR, 3.26; 95% CI, 1.2-8.86) were independent factors of CKD. Kaplan-Meier estimation demonstrated a higher aggravation of renal function in the T1 high-intensity group compared to those in the iso-intensity (P =.03). Following CEA/CAS, the time until aggravation of renal insufficiency was 12.0 ± 9.4 months in the T1 high-intensity group and 24.5 ± 9.6 months in the iso-intensity group (P =.03). CONCLUSIONS: This study demonstrated that contralateral carotid artery stenosis and T1 high-intensity plaques are more frequently observed in patients with CKD. T1 high-intensity carotid plaque is well linked to CKD development in future.

Morbidity and Mortality Conference Can Reduce Avoidable Morbidity in Neurosurgery: Its Educational Effect on Residents and Surgical Safety Outcomes.

BACKGROUND: Morbidity and mortality conferences (MMCs) are now widely implemented in clinical hospitals, but their impact on the education for neurosurgeons remains limited. This prospective study was aimed to assess the efficacy and benefit of MMCs on the education for neurosurgeon. METHODS: All morbidity and mortality events were prospectively recorded and were categorized on the basis of 2 viewpoints. First, they were classified into "avoidable" and "unavoidable" events, based on the quality of each event. Simultaneously, they were classified into 3 groups, including the residents, attendant members, or unclassifiable, based on the experience of the neurosurgeon who were most closely related to each event. The information was compared between early (2013-2014) and late (2015-2017) study periods to evaluate the education value of MMCs. RESULTS: During a 5-year study period, 44 mortality (2.1% per patient) and 201 morbidity events (9.7% per patient) were recorded. There were no significant differences in the incidence of mortality between 2 periods (P = 0.52). The incidence of morbidity significantly decreased from 11.5% (83/723) to 8.4% (118/1403; P < 0.04). Of these, "avoidable" events, but not "unavoidable" events significantly decreased from 7.5% (54/723) to 4.2% (59/1403; P = 0.001). The decrease in the incidence of "avoidable" morbidity was more pronounced in the residents than in the attendant members (P = 0.007 and P = 0.04, respectively). CONCLUSIONS: Knowledge acquisition from MMCs can significantly reduce "avoidable" morbidity events in both residents and experienced neurosurgeons. The educational effect was more distinct in the residents.

Stenosis Severity-Dependent Shrinkage of Posterior Cerebral Artery in Moyamoya Disease.

OBJECTIVE: The involved carotid forks in moyamoya disease (MMD) will show decreases in both luminal caliber and outer diameter. The present study aimed to clarify the changes in the outer diameter associated with luminal stenosis/occlusion of the posterior cerebral artery (PCA) in patients with MMD. METHODS: The present study included 24 pediatric and 48 adult patients with MMD and 17 healthy adult controls. Using magnetic resonance angiography, the degree of PCA involvement was classified into 3 grades: grade 0, normal; grade 1, stenotic; and grade 2, occluded. Using 3-dimensional constructive interference in steady state, the outer diameters were quantified in the P2 segment. All the patients were followed up to identify the disease progression in the PCA. RESULTS: The outer diameter of the P2 segment significantly decreased in a stepwise fashion in parallel with the severity of the luminal stenosis. In pediatric patients, the outer diameters of the P2 segments were 2.0 ± 0.26 mm, 1.5 ± 0.42 mm, and 0.87 ± 0.15 mm in those with grade 0, 1, and 2, respectively (P < 0.001). In adult patients, the outer diameters of the P2 segments were 2.0 ± 0.34 mm, 1.5 ± 0.34 mm, and 1.1 ± 0.17 mm in those with grade 0, 1, and 2, respectively (P < 0.001). We found no significant difference between grade 0 PCA of the adult patients and the PCA of the healthy controls (P = 0.92). Disease progression led to further arterial shrinkage of the P2 segment (n = 4). CONCLUSIONS: The results of our study have shown that the involved PCA demonstrates, not only luminal stenosis, but also arterial shrinkage in MMD. This finding strongly suggests that the underlying mechanism in the development of MMD is common in both the carotid fork and PCA.

Persistent Primitive Olfactory Artery as Novel Collateral Channel to the Anterior Cerebral Artery in Moyamoya Disease.

BACKGROUND: There are a variety of collateral routes to compensate persistent cerebral ischemia in moyamoya disease. However, there is no report presenting the persistent primitive olfactory artery (POA) as a spontaneous collateral route to the anterior cerebral artery (ACA) in moyamoya disease. METHODS: We precisely examined cerebral angiography in 84 patients with moyamoya disease to identify the collateral channel through the persistent POA. Its anatomy was evaluated on pre- and postoperative angiography. RESULTS: Of 84 patients, four (4.8%) had spontaneous collateral channel through the persistent POA. All of these four hemispheres were categorized into Stage 5. In all four patients, the collateral blood flow arose from the ophthalmic artery and run to the persistent POA through the ethmoidal moyamoya. The persistent POA provided collateral blood flow from the ophthalmic artery to the ACA in all four patients. Superficial temporal artery to middle cerebral artery anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis was performed in three of four patients. After surgery, the collateral channel through the persistent POA completely disappeared or markedly regressed, suggesting a significant improvement of cerebral hemodynamics in the territory of not only the MCA but also the ACA. CONCLUSION: The persistent POA can potentially provide collateral blood flow to the ACA in about 5% of patients with moyamoya disease, and should be recognized as a novel collateral channel in moyamoya disease. The persistent POA may be useful to evaluate therapeutic effects of surgical revascularization on the ACA territory.

Efficacy of Carotid Endarterectomy for Mild (<50%) Symptomatic Carotid Stenosis with Unstable Plaque.

BACKGROUND: Carotid endarterectomy (CEA) is known to reduce stroke risk in patients with symptomatic, moderate to severe carotid stenosis but has no apparent impact in patients with symptomatic, mild (less than 50%) carotid stenosis. However, recent development of noninvasive imaging modalities has shown that a certain subgroup of patients are at high risk for further ischemic events despite antiplatelet therapy. This study, therefore, aimed to clarify the patients' clinical features and explore the impact of CEA for them. METHODS: This prospective cohort study included 74 patients who underwent CEA for symptomatic carotid stenosis between April 2012 and December 2016. Of these, 16 (22%) had mild (less than 50%) carotid stenosis. Their demographic, radiologic, intraoperative, and pathologic findings were precisely analyzed, and their outcome after CEA was examined for 38.5 ± 13.3 months. RESULTS: Of these 16 patients, 12 had already been treated with antiplatelets against previous ischemic cerebrovascular or coronary artery diseases. Plaque magnetic resonance imaging revealed that all patients had vulnerable plaque, including lipid-rich plaque (n = 6) and intraplaque hemorrhage (n = 10). Intraoperative observations confirmed this. Histologic analysis revealed that inflammatory cells and fragile angiogenesis were widely found in the specimens. Only 1 patient experienced transient (less than 30 days) neurologic deficit after CEA, and none of them repeated cerebrovascular events during the follow-up period. CONCLUSIONS: It is not rare the patients who are at high risk for subsequent ischemic events because of vulnerable plaque despite mild (less than 50%) carotid stenosis. Magnetic resonance imaging is quite useful to noninvasively detect such vulnerable plaque. CEA is a promising procedure to treat these patients.

Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke.

Bone marrow stromal cell (BMSC) transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP) sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo). A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.

Direct Anastomosis Using Occipital Artery for Additional Revascularization in Moyamoya Disease After Combined Superficial Temporal Artery-Middle Cerebral Artery and Indirect Bypass.

BACKGROUND: The posterior cerebral artery (PCA) is involved in approximately 30% of moyamoya disease (MMD) cases. However, there have been insufficient reports describing revascularization techniques in the posterior portion of the brain, particularly of direct anastomosis. OBJECTIVE: To perform a technical assessment in patients with MMD who underwent either occipital artery (OA)-PCA bypass or OA-middle cerebral artery (MCA) bypass. METHODS: A total of 428 revascularization procedures in 368 patients were retrospectively assessed by reviewing clinical charts and radiological data. RESULTS: Ten patients (3.5%) were treated with direct bypass after the anterior revascularization with a median interval of 30 months (range, 5 months-16 years). Seven patients were < 18 years of age (average age, 17.5 ± 15.6 years). Preoperative symptoms included transient motor deficits involving the lower extremities (n = 5), visual disturbances (n = 6), and cerebral infarctions (n = 6). A favorable outcome (modified Rankin Scale score < 3) was achieved in 9 of these 10 patients. Direct anastomosis was performed in 3 hemispheres with an OA-MCA bypass and in 8 hemispheres with an OA-PCA bypass. Patency of the direct bypass was confirmed on angiogram in 7 of 7 patients who underwent conventional angiogram performed within 1 year after the surgery. None of the 10 patients demonstrated cerebral infarctions after the posterior revascularization. CONCLUSION: In MMD, symptomatic PCA regression after anterior revascularization was found predominantly in children and young adults. Direct anastomosis in the posterior portion of the brain can be successfully achieved and is effective in preventing ischemic events.

Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic change toward neural cells.

Background. Transplantation of bone marrow stromal cells (BMSCs) may contribute to functional recovery after stroke. This study was designed to clarify their mechanisms, trophic effects of neurotrophic factors, and neural differentiation. Methods. Mouse neurons exposed to glutamate were cocultured with mouse BMSCs. Either neutralizing antibodies against brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) or Trk inhibitor K252a was added to explore the mechanism of their protective effects. Fluorescence in situ hybridization (FISH) was used to assess BDNF or NGF mRNA expression in BMSCs. The mice were subjected to permanent focal ischemia, and 7 days later, either BMSCs or the vehicle was stereotactically transplanted into the ipsilateral striatum. The mouse brains were processed for FISH and immunostaining 2 or 4 weeks after transplantation. Results. BMSCs significantly ameliorated glutamate-induced neuronal death. Treatment with anti-BDNF antibody significantly reduced their protective effects. FISH analysis showed that the majority of BMSCs expressed BDNF and NGF mRNA in vitro. BMSC transplantation significantly improved the survival of neurons in peri-infarct areas. FISH analysis revealed that approximately half of BMSCs expressed BDNF and NGF mRNA 2 weeks after transplantation; however, the percentage of BDNF and NGF mRNA-positive cells decreased thereafter. Instead, the percentage of microtubule-associated protein 2-positive BMSCs gradually increased during 4 weeks after transplantation. Conclusions. These findings strongly suggest that BDNF may be a key factor underlying the trophic effects of BMSCs. BMSCs might exhibit the trophic effect in the early stage of cell therapy and the phenotypic change toward neural cells thereafter.

Platelet lysate and granulocyte-colony stimulating factor serve safe and accelerated expansion of human bone marrow stromal cells for stroke therapy.

Autologous human bone marrow stromal cells (hBMSCs) should be expanded in the animal serum-free condition within clinically relevant periods in order to secure safe and effective cell therapy for ischemic stroke. This study was aimed to assess whether the hBMSCs enhance their proliferation capacity and provide beneficial effect in the infarct brain when cultured with platelet lysate (PL) and granulocyte-colony stimulating factor (G-CSF). The hBMSCs were cultured in the fetal calf serum (FCS)-, PL-, or PL/G-CSF-containing medium. Cell growth kinetics was analyzed. The hBMSCs-PL, hBMSC-PL/G-CSF, or vehicle was stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion 7 days after the insult. Motor function was assessed for 8 weeks, and the fate of transplanted hBMSCs was examined using immunohistochemistry. As the results, the hBMSCs-PL/G-CSF showed more enhanced proliferation than the hBMSCs-FCS and hBMSCs-PL. Transplantation of hBMSCs expanded with the PL- or PL/G-CSF-containing medium equally promoted functional recovery compared with the vehicle group. Histological analysis revealed that there were no significant differences in their migration, survival, and neural differentiation in the infarct brain between the hBMSCs-PL and hBMSCs-PL/G-CSF. These findings strongly suggest that the combination of PL and G-CSF may accelerate hBMSC expansion and serve safe cell therapy for patients with ischemic stroke at clinically relevant timing.

Bone marrow stromal cell transplantation enhances recovery of motor function after lacunar stroke in rats.

This study was aimed to clarify if the bone marrow stromal cells (BMSCs) significantly improve functional outcome after lacunar stroke when stereotactically transplanted into the brain. Ouabain, a Na/K ATPase pump inhibitor, was stereotactically injected into the right striatum of Wistar rats. One week later, the superparamagnetic iron oxide (SPIO)-labeled rat BMSCs (n=7) or vehicle (n=8) were stereotactically transplanted into the left striatum. Using rotarod test, motor function was serially evaluated through the experiment. A 7.0-T MR apparatus was employed to serially monitor the migration of BMSCs in the host brain. Histological analysis was performed at 7 weeks after ouabain injection, i.e., 6 weeks after BMSC transplantation. Ouabain injection yielded the reproducible, focal lesion in the right striatum, causing continuous motor dysfunction throughout the experiment. BMSC transplantation significantly enhanced the recovery of motor function after ouabain injection. MR imaging demonstrated that the BMSCs aggressively migrated towards the lesion through the corpus callosum. Histological analysis supported the findings on MRI. The BMSCs significantly enhanced the neurogenesis in the subventricular zone (SVZ) on both sides. Some of them also expressed neuronal or astrocytic phenotypes in the neocortex, SVZ, corpus callosum, and peri-lesion area. These findings strongly suggest that the BMSCs may serve therapeutic impacts on lacunar stroke when stereotactically transplanted at clinically relevant timing.

Reversible Isolated Accessory Nerve Palsy due to a Large Thrombosed Vertebral Aneurysm.

OBJECTIVE: Isolated accessory nerve palsy due to intracranial disorders is uncommon because intracranial accessory nerve injury usually occurs in case of a skull base tumor or trauma, resulting in one of multiple cranial nerve palsies. We report a very rare case of isolated accessory nerve palsy due to a large thrombosed aneurysm of the intracranial vertebral artery. Full recovery was achieved after surgery. CASE REPORT: A patient complaining of transient numbness in the right side was referred to our hospital. An MRI indicated a large thrombosed aneurysm of the right vertebral artery. The aneurysm severely compressed the medulla oblongata. First, the proximal vertebral artery (VA) was clipped with an aneurysm clip to reduce the pressure inside the aneurysm. However, cerebral angiography revealed a partial recanalization of the right VA. The patient then underwent coil embolization of the right VA just proximal to the aneurysm clip. Subsequently, the right VA was completely obliterated. The patient was discharged without any neurological deficit. Two weeks later, however, she complained of right shoulder pain. Physical and neurological examinations demonstrated atrophy of the right trapezius and sternocleidomastoid muscle, leading to a deepening of the right supraclavicular fossa. The symptoms were considered to result from the right isolated accessory nerve palsy. Follow-up MRI showed that the VA aneurysm gradually decreased in size over a period of several months. At the same time, her symptoms disappeared completely. CONCLUSION: We should keep in mind that isolated accessory nerve palsy can be caused by a large or giant vertebral aneurysm.

123I-iomazenil single photon emission computed tomography visualizes recovery of neuronal integrity by bone marrow stromal cell therapy in rat infarct brain.

BACKGROUND AND PURPOSE: This study was aimed to assess whether (123)I-iomazenil (IMZ) single photon emission computed tomography can serially monitor the effects of bone marrow stromal cell (BMSC) transplantation on neuronal integrity in infarct brain of rats. METHODS: The BMSCs were harvested from green fluorescent protein-transgenic rats and were cultured. The rats were subjected to permanent middle cerebral artery occlusion. Their motor function was serially quantified throughout the experiments. The BMSCs or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 days after the insult. Using small-animal single photon emission computed tomography/computed tomography apparatus, the (123)I-IMZ uptake was serially measured at 6 and 35 days after the insult. Finally, fluorescence immunohistochemistry was performed to evaluate the distribution of engrafted cells and their phenotypes. RESULTS: The distribution of (123)I-IMZ was markedly decreased in the ipsilateral neocortex at 6 days postischemia. The vehicle-transplanted animals did not show a significant change at 35 days postischemia. However, BMSC transplantation significantly improved the distribution of (123)I-IMZ in the peri-infarct neocortex as well as motor function. The engrafted BMSCs were densely distributed around cerebral infarct, and some of them expressed neuronal nuclear antigen and γ-aminobutyric acid type-A receptor. CONCLUSIONS: The present findings strongly suggest that the BMSCs may enhance functional recovery by improving the neuronal integrity in the peri-infarct area, when directly transplanted into the infarct brain at clinically relevant timing. (123)I-IMZ single photon emission computed tomography may be a promising modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situation.

Validity of dual MRI and F-FDG PET imaging in predicting vulnerable and inflamed carotid plaque.

BACKGROUND: Vulnerable and inflamed plaques in the carotid artery are at high risk of ischemic stroke, suggesting the importance of diagnostic modalities to detect them in patients with carotid stenosis with high sensitivity and specificity. Although many investigators have reported that magnetic resonance imaging (MRI) is a useful tool to predict the vulnerable components of carotid plaque, its validity is not established. On the other hand, (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis. Therefore, this study aimed at evaluating the validity of MRI and FDG-PET to predict vulnerable and inflamed carotid plaque. METHODS: This prospective study totally included 25 patients who underwent carotid endarterectomy (CEA) for carotid artery stenosis at our institute between January 2009 and January 2012. Prior to CEA, FDG-PET, black-blood T1-weighted imaging (BB-T1WI), and 3-dimensional time-of-flight (TOF) imaging were performed. The specimens were stained with hematoxylin-eosin to assess the different plaque components (lipid, hemorrhage, calcification, and fibrous tissue). In addition, they were stained with primary antibodies against CD68 (activated macrophages) and matrix metalloproteinase (MMP)-9. RESULTS: High FDG uptake was detected in 13 (52.0%) of 25 patients. All of them had lipid-rich plaque. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to identify the lipid-rich plaques were all 100% for FDG-PET. More importantly, all of the FDG-positive plaques had strong immunoreactivity against both CD68 and MMP-9. There was a significant correlation between the findings on FDG-PET and those on immunohistochemistry against CD68 and MMP-9 (p = 0.006 and 0.004, respectively). On the other hand, 16 (64.0%) of 25 patients had high signal intensity plaque on BB-T1WI. In 7 of these 16 patients, the lesions also showed high signal intensity on TOF imaging. All of them had a large intraplaque hemorrhage. The sensitivity, specificity, PPV, and NPV to identify a large intraplaque hemorrhage were 70, 100, 100, and 83%, respectively, for MRI. CONCLUSIONS: These findings suggest that FDG-PET and MRI are complementary to predict high-risk carotid plaque, such as lipid-rich or hemorrhagic plaque. FDG-PET can accurately predict the lipid-rich and inflamed plaque. MRI is valuable to identify unstable plaque with a large intraplaque hemorrhage. The combination of these two modalities may play an important role in predicting carotid plaque at high risk of ischemic stroke.

[Cerebrospinal fluid shunts for hydrocephalus and related disorders].

Cerebrospinal fluid (CSF) shunts are commonly employed to treat patients with hydrocephalus. A large number of papers have been published focusing on complications and failures of CSF shunts. However, there appears to be a paucity of knowledge comprehensively covering both common complications and rare ones. In this systematic review, we surveyed articles about surgical complications of CSF shunts as comprehensively as possible. Quantitative analysis was performed to determine the frequency of well-known complications, mortality and revision rates of CSF shunts. Furthermore, rare complications of CSF shunts have also been reviewed.