[Transcranial motor evoked potentials monitoring for cerebral aneurysm surgery].

OBJECTIVE: To evaluate the usefulness of transcranial motor evoked potential(MEP)monitoring for aneurysm surgery. METHODS: Sixty-four patients undergoing aneurysm surgery were included in the study. We recorded MEP responses at craniotomy, when dissecting the aneurysm and surrounding tissue, after clipping, and during temporary clipping of the parent artery. We examined the relations between MEP wave pattern change and postoperative motor function. RESULTS: In all of the patients MEPs were recordable for continuous neurophysiological monitoring of the vascular territory of interest throughout the surgery. In 16 patients, significant intraoperative MEP changes occurred. Of these patients, three patients presented with postoperative transient motor deficit. From the changes in MEP wave recording after aneurismal clipping and temporary occlusion of the parent artery. We speculated that the maximal time allowed for occlusion of the perforating arteries without ischemic damage is five minutes. Intraoperative MEP changes had a sensitivity of 100%(3/3)and specificity of 78.7%(48/61). The positive predictive value of postoperative motor deficit was 18.8%(3/16), and the negative predictive value was 100%(48/48). It was important to carry out MEP monitoring, so as not to produce false-negatives. CONCLUSIONS: Intraoperative transcranial MEP monitoring is useful for predicting motor function after aneurysm surgery.

Study on the Umbilical Cord-Mesenchymal Stem Cell Manufacturing Using Clinical-Grade Culture Medium.

Mesenchymal stem/stromal cell (MSC)-based therapies have been gaining increasing attention owing to their application in various diseases and conditions. In this study, we aimed to identify the optimal condition for industrial-scale MSC manufacturing. MSCs were isolated from umbilical cord (UC) tissues by implementing the explant method (Exp) or a collagenase based-enzymatic digestion method (Col), using a good manufacturing practice-compatible serum-free medium developed in-house. Microarray analysis demonstrated that the gene expression profiles of Exp-MSCs and Col-MSCs did not significantly differ according to the method of isolation or the culture conditions used. The isolated UC-MSCs were then subjected to expansion using conventional static culture (ST) or microcarrier-based culture in stirred-tank bioreactors (MC). Metabolomic and cytokine array analyses were conducted to evaluate the biochemical status of the MSCs. However, no remarkable differences in the metabolic profile and cytokine secretome between ST-MSCs and MC-MSCs were observed. On the contrary, we observed for the first time that the hydrophobic components of ST-MSCs and MC-MSCs were different, which suggested that the cell membrane distribution of fatty acids and lipids was altered in the process of adaptation to shear stress in MC-MSCs. These results establish the flexibility of the isolation and expansion method for UC-MSCs during the manufacturing processes and provide new insights into the minor differences between expansion methods that may exert remarkable effects on MSCs. In conclusion, we demonstrated the feasibility of both Exp-MSCs and Col-MSCs and MC and ST culture methods for scale-up and scale-out of MSC production, as well as the equivalence of these cells. As for the industrialized mass production of MSCs, enzyme-based methods for isolation and cell expansion in a bioreactor were considered to be more suitable. The methods developed, which underwent comprehensive evaluation in this study, may contribute toward the provision of sufficient MSC sources and the establishment of cost-effective MSC therapies. Impact statement Our in-house-developed good manufacturing practice-grade serum-free medium could be used for both isolation (Exp and Col) and expansion (ST and MC) of umbilical cord (UC)-mesenchymal stem/stromal cells (MSCs). Characteristics of the obtained UC-MSCs were widely assessed with regard to gene expression, metabolome, and secretome. Cellular characteristics and efficacy were observed to be equivalently maintained among whichever technique was applied. In addition, our research presents the first evidence that bioreactor and microcarrier-based MSC cultures alter the fatty acid and phospholipid composition of MSCs. These results provide new insights into the differences between expansion methods that may exert remarkable effects on MSCs.

Routine aspiration method during filter-protected carotid stenting: histological evaluation of captured debris and predictors for debris amount.

BACKGROUND: A routine aspiration method in filter-protected carotid artery stenting (CAS) has been reported recently in which the proximal internal carotid artery (ICA) blood column was aspirated using an aspiration catheter after postdilatation regardless of flow state on digital subtraction angiography. We examined the debris particles captured by this method. METHODS: The routine aspiration method was used in 71 CAS procedures. In two procedures, captured debris particles were examined histologically. In the remaining 69 procedures, the size and number of debris particles were measured under a stereoscopic microscope, and then relationships between the amount of debris particles and clinical variables were evaluated using multivariate regression analysis. RESULTS: Histologically, the captured debris contained platelet-precipitating, thrombotic, lipid-rich fibrous and calcified material. The number of debris particles ≥1 mm was 19.6 ± 12.1 (mean ± SD) in 60 procedures with normal flow and 25.9 ± 17.2 (mean ± SD) in 9 procedures with slow/stop flow. Multivariate regression analysis demonstrated that extension of a proximal ICA angulation was an independent predictor of the amount of debris particles with a maximum diameter of either ≥1 mm or <1 mm but ≥0.5 mm (p < 0.05). CONCLUSIONS: The captured debris appeared to originate from atheromatous plaques. If the routine aspiration method had not been used in the present series, the debris might have migrated into intracerebral arteries. Restriction of the extension of a proximal ICA angulation might reduce the amount of debris associated with CAS, especially when the proximal ICA angulation is pronounced.

Umbilical cord derived mesenchymal stromal cells in microcarrier based industrial scale culture sustain the immune regulatory functions.

Mesenchymal stromal cells (MSCs) have been isolated from numerous sources and are potentially therapeutic against various diseases. Umbilical cord-derived MSCs (UC-MSCs) are considered superior to other tissue-derived MSCs since they have a higher proliferation rate and can be procured using less invasive surgical procedures. However, it has been recently reported that 2D culture systems, using conventional cell culture flasks, limit the mass production of MSCs for cell therapy. Therefore, the development of alternative technologies, including microcarrier-based cell culture in bioreactors, is required for the large-scale production and industrialization of MSC therapy. In this study, we aimed to optimize the culture conditions for UC-MSCs by using a good manufacturing practice (GMP)-compatible serum-free medium, developed in-house, and a small-scale (30 mL) bioreactor, which was later scaled up to 500 mL. UC-MSCs cultured in microcarrier-based bioreactors (MC-UC-MSCs) showed characteristics equivalent to those cultured statically in conventional cell culture flasks (ST-UC-MSCs), fulfilling the minimum International Society for Cellular Therapy criteria for MSCs. Additionally, we report, for the first time, the equivalent therapeutic effect of MC-UC-MSCs and ST-UC-MSCs in immunodeficient mice (graft-versus-host disease model). Lastly, we developed a semi-automated cell dispensing system, without bag-to-bag variation in the filled volume or cell concentration. In summary, our results show that the combination of our GMP-compatible serum-free and microcarrier-based culture systems is suitable for the mass production of MSCs at an industrial scale. Further improvements in this microcarrier-based cell culture system can contribute to lowering the cost of therapy and satisfying several unmet medical needs.

Obstruction of pores in distal protection filters and angiographically-documented flow impairment during carotid artery stenting.

PURPOSE: To determine any relationship between angiographically documented flow impairment associated with the Angioguard XP cerebral protection filter during carotid artery stenting (CAS) and the condition of the pores in the retrieved filter. METHODS: To obtain baseline characteristics of the Angioguard XP, an unused filter was fully expanded and examined photographically from the cephalad end of the device to determine the structure of the pores in the filter basket. Ten pores assembled in a hexagonal pattern made up a pore group, several of which were arranged in 4 concentric rings surround a central hub that did not have any pores. For each ring of pore groups, the ring diameter, number of pore groups, and the mean minimum pore diameter were measured on a plane perpendicular to the long axis of the device. From these, the area of the ring membrane, the area of the pores, and the ratio of pore area to membrane area were calculated for each ring. Filters retrieved from 56 CAS procedures were retrospectively analyzed along with the operative records and intraprocedural angiograms performed after filter placement, predilation, stent placement, postdilation, aspiration of blood, and filter retrieval. The operators classified blood flow immediately before filter retrieval as normal, slow, or stopped. After retrieval, the filter was cut, rinsed with saline, fixed in 10% neutral buffer formalin, and macroscopically and microscopically inspected. The number of the open pores without any obstruction was counted for each ring. RESULTS: Retrieved filters from flow-impaired cases showed a significantly lower percentage of open pores in comparison to normal-flow cases (p<0.05). In some normal-flow cases, however, the obstruction rates were higher than mean obstruction rates of the slow-flow cases. In normal-flow cases, <5% of pores from the center to the second ring of the filter were open; this constituted more than two thirds of the entire filter diameter. CONCLUSION: The flow state on DSA was related to, but did not completely depend on, filter patency. The low patency rate of the filter in normal-flow cases suggested that flow impairment was occurring but could not be detected by the qualitative evaluation of flow on angiography.

Low birth weight as a risk factor for seizure following acute subdural hematoma.

PURPOSE: The purpose of this study is to determine the factors associated with posttraumatic seizure in patients under 2 years old with acute subdural hematoma (ASDH). METHODS: Twenty-one patients under 2 years old (15 males and six females) with ASDH, who were admitted to our hospital between January 2002 and September 2008, were studied retrospectively. Clinical findings including birth weight and gestational age were defined. A head computed tomography scan was conducted at admission. Outcome at time of discharge was assessed using the score. RESULTS: Seizures occurred in eight patients (38%). Recurrent seizures occurred in three of eight patients (38%). In patients with seizures, birth weight, gestational age, and birth weight ratio were significantly lower than for those without seizure (p < 0.05). CONCLUSIONS: Special attention should be paid to infants with ASDH who have a history of low birth weight, low gestational age, and low birth weight ratio because risk for posttraumatic seizure is considered higher in these infants than in other infants.

Myxoid chondrosarcoma in the pineal region.

The authors report a case of a myxoid chondrosarcoma of the pineal region in a 37-year-old woman who presented with an intratumoral hemorrhage. Partial removal of the tumor in an initial surgery resulted in failure to establish a definitive diagnosis. The residual tumor enlarged after a second intratumoral hemorrhage 14 months after the onset of the first symptoms, and gross-total resection of the tumor was achieved in a second surgery. Histological and immunohistochemical findings after the second surgery were consistent with a diagnosis of myxoid chondrosarcoma. Radical excision of a tumor was considered to play an important role in the management of intracranial myxoid chondrosarcoma.

Unusual giant cerebral venous varix associated with brain abscess: variant of hereditary hemorrhagic telangiectasia--case report.

A 35-year-old man suffered secondary generalized tonic-clonic convulsions due to a large brain abscess. Neuroimaging incidentally revealed another tumor-like lesion. Cerebral angiography confirmed that the lesion was an unusual giant venous varix associated with a high-flow pial arteriovenous fistula (AVF) and showed one more small arteriovenous malformation (AVM). Pulmonary AVF, which can cause brain abscess, was also detected. Surgical ligation of the AVF and removal of the small AVM via individual craniotomies resulted in successful extirpation of the cerebrovascular malformations. Although the typical mucocutaneous symptoms were absent in this patient, the combination of arteriovenous anomalies was highly suggestive of hereditary hemorrhagic telangiectasia.

Evaluation of the stability of aneurysms after embolization using detachable coils: correlation between stability of aneurysms and embolized volume of aneurysms.

BACKGROUND AND PURPOSE: The long-term outcome of aneurysmal coil embolization has not been determined. We retrospectively analyzed the results of our cases treated with detachable coils and evaluated the long-term stability of embolized aneurysms. METHODS: This study involved 100 aneurysms in 93 patients who underwent follow-up angiography > or = 3 months after initial treatment between December 1993 and December 1999. The percentage of the coil volume occupying the aneurysm lumen (embolized volume) was used as an index to evaluate the stability of embolized aneurysms. The reliability of the embolized volume was also evaluated by comparing angiographic percentage occlusion. RESULTS: Follow-up angiographic assessment was conducted 12 +/- 8.5 months after initial treatment. Angiographic evaluation of percentage occlusion at initial treatment did not always predict long-term stability of embolized aneurysms. Of 49 aneurysms judged as being totally occluded at initial treatment, 44 remained unchanged and five showed recanalization. The embolized volume of unchanged aneurysms was 30.8 +/- 10.2%, and that of recanalized aneurysms was 19.9 +/- 10.6%. There was a significant difference between these two groups (P=.03). Of 29 subtotally occluded aneurysms, nine had further thrombosis (embolized volume = 31.8 +/- 12.7%), nine remained unchanged (embolized volume = 23.2 +/- 10.3%), and 11 had recanalization (embolized volume = 14.1 +/- 6.1%). The mean embolized volume of 11 recanalized aneurysms was significantly lower than in the thrombosed group and the unchanged group (P=.002 and P <.001, respectively). Large aneurysms tended to have recanalization more frequently (59%) than did small aneurysms (15%). CONCLUSION: There is a significant correlation between embolized volume and stability of embolized aneurysms. Embolized volume is a more objective index than is subjectively angiographic percentage occlusion. In addition to angiographic assessment, measurement of embolized volume could be useful to predict angiographic changes of aneurysms.

Long-term follow-up of intra-aneurysmal coil embolization for unruptured paraclinoid aneurysms.

OBJECTIVES: The selection of therapeutic modalities, including endovascular coil embolization and surgical clipping, for management of unruptured paraclinoid aneurysms, remains controversial. Detailed long-term outcome data for endovascular coil embolization of unruptured paraclinoid aneurysms are still lacking. Thus, we evaluated the safety and efficacy of coil embolization of unruptured paraclinoid aneurysms. METHODS: From January 1998 to July 2010, 138 patients underwent endovascular coiling for 140 unruptured paraclinoid aneurysms. Their medical records and radiologic images were reviewed retrospectively. RESULTS: Complications occurred in 5·7% of 140 procedures and the morbidity rate was 0·7%. Of the 140 unruptured paraclinoid aneurysms, a total of 111 aneurysms underwent follow-up imaging evaluation at 2 years or more, or showing reopening on imaging studies within 2 years (65·6±37·2 months). Multivariate analysis revealed two predictors for reopening of the aneurysms: a maximum diameter of aneurysms and a dome/neck ratio of aneurysms (P<0·05). Reopening rates of aneurysms with maximum sizes of <8, 8-10, and >10 mm were 1%, 25%, and 75%, respectively. Reopening rates were significantly different among the three groups (P<0·05). In aneurysms with a maximum diameter of 8-10 mm, there was a significant difference of dome/neck ratios between the presence and absence of reopened aneurysms (P<0·05). DISCUSSION: The results indicate that endovascular coil embolization is a safe and effective treatment modality in selected patients with unruptured paraclinoid aneurysms. Consideration of the aneurysm size and the dome/neck ratio could assist in the selection of therapeutic modalities for these aneurysms.

Change in cortical vein appearance on susceptibility-weighted MR imaging before and after carotid artery stenting.

OBJECTIVES: Susceptibility-weighted (SW) magnetic resonance (MR) imaging is a sensitive test to detect intravenous deoxygenated blood. On SW images, dilated appearing draining veins in tissue with perfusion impairment occur due to an increase in intravenous deoxyhemoglobin levels, and could indicate poor perfusion areas in which there is an elevated oxygen extraction fraction. In this study, patients with possible chronic ischemia caused by internal carotid artery stenosis underwent carotid artery stenting (CAS). Changes in cortical vein diameters were evaluated before and after CAS using SW imaging. METHODS: Twenty-two patients with 25 lesions underwent 3 T SW imaging before and after CAS. The diameters of cortical veins were measured on SW images. Blood flow reduction and cerebrovascular reserve were examined before CAS using a single-photon emission computed tomography (SPECT) study, including an acetazolamide stress test. RESULTS: Two of six patients with both decreased blood flow and reduced cerebrovascular reserve on SPECT showed significantly increased cortical vein diameters on pre-CAS SW images (P<0.05). After CAS, these same two patients demonstrated a significant decrease in their cortical vein diameters (P<0.05). DISCUSSION: The present study demonstrates that dilated cortical veins as seen on SW imaging may reflect areas of altered oxygen extraction fraction due to chronic ischemia in patients with carotid artery stenosis, and that cortical venous dilatation is reversed after successful CAS. In the future, estimations of the cortical vein diameters on SW imaging may help to qualitatively evaluate areas of poor perfusion in chronic ischemia.

Flow impairment during filter-protected carotid artery stent placement: frame-by-frame evaluation of digital subtraction angiography images.

OBJECTIVE: To evaluate quantitatively flow impairment of contrast medium on digital subtraction angiography (DSA) performed before and after filter retrieval following carotid artery stent (CAS) placement with distal filter protection. METHODS: Retrospective analysis was performed of 55 CAS placement procedures with distal filter protection in 51 patients. From a qualitative analysis, the operators determined if there was flow reduction of contrast medium on digital subtraction angiography (DSA) before filter retrieval. A quantitative analysis was performed of frame-by-frame images before and after filter retrieval to compare the flow state of contrast medium. RESULTS: Stop-flow or slow-flow classified by the operators during CAS placement was found in 10 (18%) of 55 procedures. However, the frame-by-frame analysis of DSA images showed flow reduction of contrast medium in 46 (84%) of 55 procedures. Among 45 procedures with normal-flow as classified by the operators, 36 (80%) procedures showed ≥1 frames with delay of contrast medium based on quantitative analysis. CONCLUSIONS: The frame-by-frame comparison of angiographic images revealed a much higher incidence of blood flow impairment on DSA before filter retrieval compared with the operators' classification during CAS placement procedures. Considering the high incidence of blood flow impairment, the possibility of stagnation of blood flow in the internal carotid artery (ICA) column should be expected during every CAS placement procedure.

Hematoma in the splenium of the corpus callosum in the subacute stage of subarachnoid hemorrhage--three case reports.

Three patients developed hemorrhage in the splenium of the corpus callosum 2 weeks after the onset of subarachnoid hemorrhage (SAH) associated with acute hydrocephalus. Computed tomography performed a few days after the onset showed a low density area in the splenium of corpus callosum in all three patients, and preventive measures against symptomatic vasospasm were begun, including vasodilator administration. Computed tomography showed hemorrhage in the splenium of the corpus callosum 17 to 22 days after onset of SAH, manifesting as mental deterioration or headache. Antivasospasm agents were immediately discontinued, and strict blood control measures were instituted. Splenial hematoma is another potential cause of neurological deterioration after surgery for SAH, in addition to vasospasm, hydrocephalus, and rebleeding.

Three-dimensional digital subtraction angiography in evaluation of vertebro-basilar artery dissections: comparison with 2D DSA.

BACKGROUND AND PURPOSE: The purpose of this study was to clarify characteristic findings on three-dimensional (3D) digital subtraction angiography (DSA), and to investigate diagnostic usefulness of 3D DSA in vertebro-basilar dissections (VBD). METHODS: In 25 consecutive patients with VBD, two-dimensional (2D) DSA, and 3D DSA findings were evaluated by a scoring system. The effects of 3D DSA results on diagnosis were scored in comparison with 2D DSA results. RESULTS: A proximal stenosis, a distal stenosis, a bleb, and a relationship between the posterior inferior cerebellar artery and the dissection were significantly better visualized in 3D DSA than those in 2D DSA (P < .05). A characteristic finding of VBD on 3D DSA was a combination of an aneurysmal bulging and its proximal and distal stenoses, which was observed in 92% of the 25 patients. CONCLUSIONS: Three-dimensional DSA was more useful for diagnosis in patients with VBD in comparison with 2D DSA.