Dietary supplement with fermented soybeans, natto, improved the neurobehavioral deficits after sciatic nerve injury in rats.

Clearance of fibrin and associated inflammatory cytokines by tissue-type plasminogen activator (t-PA) is related to improved regeneration in neurological disorder. The biological activity of fermented soybean (natto) is very similar to that of t-PA. We investigated the effect of the dietary supplement of natto on peripheral nerve regeneration. The peripheral nerve injury was produced by crushing the left sciatic nerve with a vessel clamp in Sprague-Dawley rats. The injured animals were fed orally either with saline or natto (16 mg/day) for seven consecutive days after injury. Increased functional outcome such as sciatic nerve functional index, angle of ankle, compound muscle action potential and conduction latency were observed in natto-treated group. Histological examination demonstrated that natto treatment improved injury-induced vacuole formation, S-100 and vessel immunoreactivities and axon loss. Oral intake of natto prolonged prothrombin time and reduced fibrinogen but did not change activated partial thromboplastin time and bleeding time. Furthermore, natto decreased injury-induced fibrin deposition, indicating a tolerant fibrinolytic activity. The treatment of natto significantly improved injury-induced disruption of blood-nerve barrier and loss of matrix component such as laminin and fibronectin. Sciatic nerve crush injury induced elevation of tumor necrosis factor alpha (TNF-alpha) production and caused apoptosis. The increased production of TNF-alpha and apoptosis were attenuated by natto treatment. These findings indicate that oral intake of natto has the potential to augment regeneration in peripheral nerve injury, possibly mediated by the clearance of fibrin and decreased production of TNF-alpha.

Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration.

Amniotic fluid mesenchymal stem cells (AFS) harbor the potential to improve peripheral nerve injury by inherited neurotrophic factor secretion, but present the drawback of the short-term survival after transplantation. Granulocyte-colony stimulating factor (G-CSF) has a diversity of functions, including anti-inflammatory and anti-apoptotic effects. This study was conducted to evaluate whether G-CSF could augment the neuroprotective effect of transplanted AFS against peripheral nerve injury. The potential involvement of anti-inflammation/anti-apoptosis effect was also investigated. Peripheral nerve injury was produced in Sprauge-Dawley rats by crushing left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. G-CSF (50 microg/kg) was administrated by intra-peritoneal injection for 7 consecutive days. Cell apoptosis, inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. Crush injury induced inflammatory response, disrupted nerve integrity, and impaired nerve function in sciatic nerve. Crush injury-provoked inflammation was attenuated in groups receiving G-CSF but not in AFS only group. In transplanted AFS, marked apoptosis was detected and this event was reduced by G-CSF treatment. Increased nerve myelination and improved motor function were observed in AFS transplanted, G-CSF administrated, and AFS/G-CSF combined treatment groups. Significantly, the combined treatment showed the most beneficial effect. In conclusion, the concomitant treatment of AFS with G-CSF augments peripheral nerve regeneration which may involve the suppression of apoptotic death in implanted AFS and the attenuation of inflammatory response.

Enhanced regeneration in spinal cord injury by concomitant treatment with granulocyte colony-stimulating factor and neuronal stem cells.

Granulocyte colony-stimulating factor (G-CSF) inhibits programmed cell death and stimulates neuronal progenitor differentiation. Neuronal stem cells transplanted into injured spinal cord can survive, differentiating into astroglia and oligodendroglia, and supporting axon growth and myelination. Herein, we evaluate the combined effects of G-CSF and neuronal stem cells on spinal cord injury. For 40 Sprague-Dawley rats (n=10 in each group) transverse spinal cord resections at the T8-9 level were carried out, leaving an approximately 2-mm gap between the distal and proximal ends of the cord. Neuronal stem cells embedded in fibrin glue treated with or without G-CSF (50 microg/kg x 5 days) (groups III and IV) or fibrin glue with or without G-CSF (50 microg/kg x 5 days) (groups I and II) were transplanted into the gap in the injured spinal cord. Spinal cord regeneration was assessed using a clinical locomotor rating scale scores and electrophysiological, histological and immunohistochemical analysis 3 months after injury. Regeneration was more advanced in group IV than in groups III or II according to the clinical motor score, motor evoked potential, and conduction latency. Most advanced cord regeneration across the gap was observed in group IV rats. Higher densities of bromodeoxyuridine in the injured area and higher expression levels of Neu-N and MAP-2 over the distal end of the injured spinal cord were observed in group IV compared with groups II or III, but there was no significant difference in expression of glial fibrillary acid protein. This synergy between G-CSF and neuronal stem cells may be due to increased proliferation of progenitor cells in the injured area and increased expression of neuronal stem cell markers extrinsically or intrinsically in the distal end of injured cord.

Effects of tissue plasminogen activator on cerebral microvessels of rats during focal cerebral ischemia and reperfusion.

The time window in the treatment of ischemic stroke with tissue plasminogen activator (tPA) is narrow, arbitrarily within 3 hours after the onset of symptom. Hemorrhagic transformation resulting from cerebral ischemia may be related to damage of the microvascular basal lamina of the brain, which may in turn cause microvascular fibrin deposition and aggravate cerebral ischemia. Here, we investigated the effect of tPA on the microvascular tissue changes during cerebral ischemia/reperfusion. Sprague-Dawley rats were subjected to focal cerebral ischemia by ligation of the right middle cerebral artery and bilateral common carotid arteries for 90 minutes. Sixty minutes after the onset of ischemia, escalated dosages of tPA from 2.5 to 10 mg/kg or saline were intravenously infused for 60 minutes. Twenty-four hours after reperfusion, the animals were allowed to be killed for examination. Low dosage of tPA (2.5-7.5 mg/kg) reduced post-ischemic brain infarction, suppressed metalloproteinase 2 (MMP-2) activity and restored blood-brain barrier (BBB) integrity. In contrast, high dose of tPA (10 mg/kg) aggravated brain infarction, increased MMP-2 activity and exacerbated BBB disruption. Cerebral ischemia/reperfusion decreased the immunoreactivity of both collagen type IV- and laminin-positive microvessels, whereas the low dosage of tPA (2.5-7.5 mg/kg) attenuated the reduction. When these molecules in whole cortical tissues were analysed, tPA dosage-dependently decreased the total content of collagen type IV, laminin and fibronectin. Although the detailed mechanisms regarding the action of tPA are yet to be investigated, our findings demonstrate that the detrimental effect of tPA was mediated, at least in part, through the destruction of the basal lamina in the cerebral microvessels by activating MMP-2.

Hollow bone cement filled with impacted cancellous bone as a substitute for bone grafts in cervical spine fusion.

Autogenous iliac crest bone is the gold standard for graft material in cervical spinal fusion, but a high incidence of donor site morbidity has been reported. Therefore, to achieve a better fusion rate and decrease the rate of donor site morbidity, we used a novel method whereby hollow bone cement filled with impacted cancellous bone is used as a substitute for bone graft in cervical interbody fusion. From 2003 to 2004, 21 patients with cervical spinal disorders who were treated using this method were included in this study. Fourteen patients underwent single-level grafts and seven underwent two-level grafts. Evaluation included a monthly clinical and X-ray examination for the first 3 months, and then follow-up every 3 months thereafter. Multiple-slice computed tomography (CT) scan with reconstruction to evaluate the viability of the bone graft was performed when evidence of bone fusion was found on X-ray. The mean age of the patients was 59 years (range 27-79). The mean follow-up period was 19 months (13-24 months). Evidence of impacted cancellous bone bridging the adjacent vertebral body was observed in all patients at the 6-month follow-up based on X-rays and reconstructive CT scans. No severe donor site morbidity occurred. One patient experienced hardware failure due to screw fracture, but a reconstructive CT scan revealed well-bridged cancellous bone between the vertebral bodies. Hollow bone cement filled with impacted cancellous bone could be an alternative material for cervical spine interbody fusion. Using this method, we found not only satisfactory growth of cancellous bone in the holes of the bone cement, but also low morbidity in the donor site. However, for this method, the long-term stability, potential complications, and the necessity of instrumentation all require further investigation.

An online evaluation of problem-based learning (PBL) in Chung Shan Medical University, Taiwan - a pilot study.

INTRODUCTION: Problem-based learning (PBL) embraces principles of good learning and teaching. It is student-directed, fosters intrinsic motivation, promotes active learning, encourages peer teaching, involves timely feedback, and can support student self and peer assessment. The most important function of the assessment process is to enhance student learning, to improve the curriculum and to improve teaching. MATERIALS AND METHODS: To improve the PBL tutorial in Chung Shan Medical University, we developed an online evaluation system containing the evaluation forms for students, tutor, self and peer. The Cronbach alpha reliability coefficients were 0.9480, 0.9103, and 0.9198 for the Student, Tutor and Self and Peer Evaluation Form, respectively. The online evaluations were mandatory to both students and tutors, and the information was completely anonymous. RESULTS AND CONCLUSIONS: The survey response rates of the online evaluations ranged from 95.6% to 100%. The online evaluations provided a documented feedback to the students on their knowledge, skills and attitudes. Correspondingly, tutors too received feedback from students in evaluating their performance on the appropriateness and effectiveness of tutoring the group. Although there was an initial lack of coordination regarding responsibilities and how to use the online system for both students and the Faculty, the system enabled us to look into how effective our PBL course had been, and it provided both process and outcome evaluations. Our strategy for evaluating the success of PBL is only at its initial stage; we are in an ongoing process of collecting outcome data for further analysis which will hopefully provide more constructive information to the PBL curricula.

Enhanced regeneration in injured sciatic nerve by human amniotic mesenchymal stem cell.

OBJECTIVE: Amniotic fluid mesenchymal stem cells (MSCs) have the potential to differentiate into neuronal stem cells in vitro. We evaluated using amniotic fluid MSCs to support or enhance the ability of the injured sciatic nerve to cross a nerve gap. MATERIALS AND METHODS: We created a 5 mm nerve defect in Sprague Dawley rats. One group received therapy with MSCs embedded into woven oxidised regenerated cellulose gauze (Surgical; Ethicon, Somerville, NJ) and fibrin glue, while a control group received woven Surgicel and fibrin glue only. Evaluation methods included behavioural, electrophysiological and immunohistochemical studies. RESULTS: In gait analysis, the angle of the ankles in the treatment and control group were 46.4 degrees (standard deviation [SD]=15 degrees) and 36 degrees (SD=8.2 degrees), respectively, which was statistically significant (p=0.045). Five of 10 treated rats (50%) demonstrated partial foot movement, while none of the control group had any movement. The percentage amplitude of muscle compound action potential in the experimental group was 43% (SD=12.5%) compared to 29% (SD=8.8%) in the control group (p=0.038). The conduction latencies in the control and experimental groups was 2.5 ms (SD=0.45) and 1.7 ms (SD=0.47), respectively (p=0.005). Histological examination demonstrated that 70% of the treatment group achieved a maximum axon diameter percentage across the nerve gap of greater than 50%, compared with 0% in the control group. There were no differences in direction of fibre growth and fibrotic reaction between the two groups. CONCLUSION: Amniotic fluid MSC can augment growth of injured nerve across a nerve gap. This effect may be due to neurotrophic or induction effects of the MSC interacting with Schwann cells. Further study is required to determine the underlying mechanism of this effect.

Multidisciplinary treatment of cavernous sinus dural arteriovenous fistulae with radiosurgery and embolization.

OBJECTIVE: With the advent of interventional neuroradiology and stereotactic radiosurgery, dural arteriovenous fistulae are less often managed with open surgery. We evaluated the outcome of dural arteriovenous fistulae of the cavernous sinus treated with a combination of radiosurgery and embolization. MATERIAL AND METHODS: Twenty dural arteriovenous fistulae located in the cavernous sinus were enrolled in our study. Fifteen patients received X-knife radiosurgery alone and 5 also required embolization, one before radiosurgery and 4 after radiosurgery. The mean volume of the lesions was 2.8 ml (range 0.2-12.6), the corresponding radiation volume was 6.5 ml (range 0.6-24.6), and the conformity index was 2.9 (range 1.8-5.3). The mean peripheral and maximum radiation dose was 17.8 Gy (range 17-20) and 28.3 Gy (range 19-37) Gy, respectively. The clinical and imaging data were analyzed. RESULTS: The mean follow up period was 29 months (23-39). Seventy-five percent (15/20) of patients receiving radiosurgery alone achieved a symptomatic cure and with additional embolization 90% (18/20) were cured. All patients achieved cure on imaging after radiosurgery alone or in combination with embolization. Abnormal imaging findings were observed in two patients after treatment, one had an intracerebral hemorrhage and the other radiation edema, but both were asymptomatic. CONCLUSION: With multidisciplinary treatment with combined radiosurgery and embolization, satisfactory results can be achieved for dural arteriovenous fistulae with a low complication rate. In patients with mild symptoms, radiosurgery is the initial treatment option. Embolization should be performed in patients with severe symptoms or who have failed radiosurgery.

Upper thoracic sympathectomy for axillary osmidrosis or bromidrosis.

The difference between axillary osmidrosis (AO) and axillary bromidrosis (AB) is the degree of odor and quantity of sweat, which is associated with selection of therapeutic modality theoretically. Upper thoracic sympathectomy has been used for both diseases but its effect needs to be further evaluated with more clinical data. We collected 108 patients with AO or AB treated by upper thoracic sympathectomy from July 1995 to July 2002. Of these patients, 42 suffered AO alone, 17 had AB (AO with axillary hyperhidrosis [AH]), and 49 had AO with palmar hyperhidrosis (PH). Ninety-two patients (183 sides) received anterior subaxillary transthoracic endoscopic sympathectomy (TES) and 17 patients (33 sides) received posterior percutaneous thoracic phenol sympathicolysis (PTPS). The levels of sympathectomy or sympathicolysis were T3-4 for AO and AB, and T2-4 for AO with PH. Mean follow-up period was 45.2 months (13-97 months). The satisfaction rates of patients were 52.4%, 70.6% and 61.2% for AO, AB and AO with PH, respectively. The rates of patients with improvement and satisfaction were 78.6%, 88.2% and 85.7% for AO, AB, and AO with PH, respectively. These results suggest that upper thoracic sympathectomy may be an acceptable treatment for AB or AO with PH rather than AO only.

Calcification and ossification of chronic encapsulated intracerebral haematoma: case report.

We report a case of calcified chronic encapsulated intracerebral haematoma (ICH) in a 29-year-old female who presented with progressive left sided weakness and intermittent seizures since childhood. The preoperative magnetic resonance (MR) imaging of the head initially suggested that a partially thrombosed aneurysm or vascular malformation was present. However, no vascular stain was found on the digital subtraction angiography (DSA) of both the carotid and vertebral arteries. The excised mass was histologically diagnosed as a chronic ICH. We traced the patient's medical history and found that at the age of one she sustained a head injury after a fall. So far, to our knowledge, no case of epilepsy secondary to a calcified chronic encapsulated ICH occurring 28 years after head injury has been reported. Calcified chronic encapsulated ICH concomitant with new bone formation within is even rarer. The possible pathogenesis of this case is discussed.

Treatment of neuroblastoma with intraspinal extensions.

Neuroblastoma is the most common malignant cause of spinal compression in the paediatric population. Chemotherapy is commonly considered as the first-line treatment for these patients. The role of neurosurgical decompression and radiotherapy are still controversial. Thirteen children diagnosed as having neuroblastoma with intraspinal extension were included in this report. All patients presented with neurological deficits and were treated with chemotherapy initially, after which 3 patients recovered, 4 improved and 6 were aggravated into paraplegia. Two of the 6 aggravated patients received emergent laminectomy with removal of intraspinal tumour and recovered satisfactorily. Although spread of tumour into the spinal canal indicates an advanced disease, aggressive treatments such as chemotherapy and surgical resection can often improve neurological symptoms and life quality. Neurological decompression is recommended for patients with intraspinal neuroblastoma and rapid neurological deterioration during chemotherapy.

A modified method to perform the frameless biopsy.

Neuronavigation is increasingly being used to assist in stereotactic neurosurgery due to its frameless property. In this study, we developed and assessed a modified method of performing stereotactic brain biopsies by combining the use of the Fisher stereotactic biopsy instrument, that was fixed on universal quick-lock holder, under infrared guidance of the BrainLab VectorVision Neuronavigation system. Eighteen patients received a frameless stereotactic procedure in this study, including 5 cases of brain biopsy, 2 cases of abscess aspiration, 10 cases of hematoma aspiration and one case of Ommaya reservoir implantation. All cases were on target and successful. In this paper, we present our technique, discuss the advantage and disadvantages of the method and review the literature.

Intraventricular malignant meningioma: one case report.

We report a case of primary intraventricular malignant meningioma in a 74-year-old man who presented with progressive weakness of the left limbs and dizziness, The preoperative magnetic resonance (MR) imaging of the head initially suggested that a glioblastoma multiforme or a metastatic lesion might be present. But later, the excised tumor was histologically diagnosed as a primary malignant meningioma. So far, only a few cases of intraventricular malignant meningioma have been reported. The MR imaging of this tumor has rarely been described in the literature. In the present case, the mass lesion showed hyperintensity on the T1-weighted image (T1WI) and hypointensity on the T2-weighted image (T2WI) which was not commonly seen in meningioma. The unusual MR imaging of this case may be attributed to the intratumoral hemorrhage. Although intraventricular malignant meningioma is difficult to diagnose based on MR or computed tomographic images alone, the characteristics of the MR images in the present case may offer an option for preoperative differential diagnosis of intraventricular tumors.

Intra-extracranial hemangiopericytoma: clinical manifestations, histopathological features, diagnosis, treatment, and outcomes.

BACKGROUND: Intra-extracranial hemangiopericytomas (HPCs) are rare vascular neoplasms. This paper reports the clinical manifestations, histopathological features, diagnosis, treatment, and outcomes of HPCs. METHODS: We reviewed three patients with intracranial HPC and one patient with HPC of the scalp who were surgically treated at Taichung Veterans General Hospital between 1989 and 1999. RESULTS: All four patients underwent surgery and postoperative radiotherapy. After surgery, three patients showed improvement compared with their preoperative neurological function. Two patients had recurrent tumors, one patient was well and free from tumor recurrence, and one patient was lost during follow-up. CONCLUSIONS: Clinical presentation and radiographic appearance of intracranial HPC can be indistinguishable from meningioma. Intracranial HPC is an aggressive neoplasm with malignant potential. Both benign and malignant variations of HPC of the scalp exist. The principal treatment is surgical excision. Survival is influenced by more aggressive primary resection and by postoperative radiotherapy. Recurrences are common. Metastases may be multiple and can develop in many organs and systems.

Tissue plasminogen activator for the treatment of intraventricular hematoma: the dose-effect relationship.

In this study, we investigated the dose-effect relationship and safety of tissue plasminogen activator (tPA) for the treatment of intraventricular hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected with autologous blood into the left lateral ventricle to establish IVH. Two hours later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the IVH over 3 h. The regional cerebral blood flow (rCBF) on the surface of the left parietal cortex was measured with laser Doppler flowmetry. Twenty-four hours after the build-up of IVH, the brains were removed for morphometrical and histological studies. A dose of 0.5-2 microg tPA significantly diminished the IVH in a dose-dependent manner (p < 0.001). However, only the dose of 0.5 microg tPA significantly ameliorated the reduction of rCBF 24 h after IVH (p < 0.01). TPA did not improve the ventricular dilatation on the side with IVH. Instead, 1-2 microg of tPA caused additional injuries, including intraventricular leukocytosis and edema of periventricular tissues and choroid plexus on both hemispheres. These results indicate that higher doses of tPA may have detrimental effects on the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the satisfactory fibrinolysis and less damage to the brain.

Surgical improvement of brain edema related to hypertensive intracerebral hemorrhage.

BACKGROUND: Patients with hypertensive intracerebral hemorrhage (ICH) are at risk for delayed neurological deterioration, especially during the second week after onset. Mass effect due to vasogenic edema caused by ICH has been shown to cause later deterioration. Control of brain edema and increased intracranial pressure (ICP) are related events that determine outcome. In this study, we compared the effects of three different treatments on brain edema caused by ICH. METHODS: Thirty-nine patients with ICH were involved in this study. Of these patients, 11 had medical therapy (group A), 15 were treated with stereotactic aspiration plus local administration of urokinase (group B), and 13 underwent conventional craniotomy and hematoma removal (group C). The intracerebral hematoma volume on admission was measured on the the brain computed tomographs (CTs), and the cerebral edema volumes surrounding the hematoma were assessed with CT scans every 5 to 7 days after symptom onset. RESULTS: The median intracerebral hematoma volumes were 23, 50 and 51 ml in groups A, B and C, respectively. Peak edema volume surrounding the hematoma was observed 5 to 15 days after symptom onset. A significant correlation (p < 0.05) was noted between peak edema and hematoma volumes in all groups. The ratio of median peak edema volume to median hematoma volume was 3.280 in group A, which was significantly higher than those in group B (0.745) and group C (0.863) (p < 0.05). CONCLUSIONS: The study revealed that brain edema induced by hypertensive ICH could be significantly ameliorated by surgical management. Stereotactic aspiration with local administration of urokinase was as effective as conventional craniotomy in reduction of brain edema volume caused by ICH and was characterized by its minimal invasiveness, easy performance, and safety.

Anatomical location of T2-3 sympathetic trunk and Kuntz nerve determined by transthoracic endoscopy.

OBJECT: Bilateral subaxillary transthoracic endoscopic sympathectomy (TES) is a popular procedure of upper thoracic sympathectomy. The anatomical locations of the T-2 and T-3 sympathetic trunks, as viewed under the endoscope, are varied in the rib head areas. In this study, the authors investigated the more visible anatomical locations of the T-2 and T-3 sympathetic trunks, the so-called nerves of Kuntz, and intercostal rami by performing transthoracic endoscopy. METHODS: Seventy patients with palmar hyperhidrosis undergoing bilateral TES (140 sides) via the anterior subaxillary approach were included in this study. The operative findings and video images of the T-2 and T-3 sympathetic trunks and ganglia were recorded and analyzed. The anatomical locations of the T-2 and T-3 sympathetic trunks along the horizontal axes of the rib heads were determined using a three-region system constructed by the authors. The area between the rib neck and the medial border of the rib head was equally divided into Region E (external half) and Region M (medial half). The area between the medial border of the rib head and the paravertebral ligament was defined as Region I. The incidence of the T-2 and T-3 sympathetic trunks found in Regions E, M, and I were 31.4 to 42.9%, 50 to 57.1%, and 7.1 to 11.4%, respectively, on the left side, and 24.3 to 34.3%, 57.1 to 65.7%, and 8.6 to 10%, respectively, on the right side. One right (1.4%) and six left (8.6%) Kuntz nerves originating from the T-3 sympathetic trunk were found in seven patients (10%). The intercostal ramus was found around the T-2 rib neck in 24 patients (34.3%), with 18 cases (25.7%) for each side. The intercostal ramus around the T-3 rib neck was found in 17 patients (24.3%): 12 (17.1%) on the right and nine (12.9%) on the left. CONCLUSIONS: These results indicate that approximately 90% of the T-2 or T-3 sympathetic trunks are located on the rib head. These findings may also be used to assist the surgeon in fluoroscopic guidance for locating the T-2 and T-3 sympathetic trunks during posterior percutaneous sympathectomy.