A quantitative MRI index for assessing the severity of hippocampal sclerosis in temporal lobe epilepsy.

BACKGROUND: Hippocampal sclerosis (HS) is associated with post-surgery outcome in patients with temporal lobe epilepsy (TLE), and an automated method that quantifies HS severity is still lacking. Here, we aim to propose an MRI-based HS index (HSI) that integrates hippocampal volume and FLAIR signal to measure the severity of HS. METHODS: Forty-two pre-surgery TLE patients were included retrospectively, with T1-weighted (T1W) and FLAIR images acquired from each subject. Two experienced neurosurgeons (W.D. and C.S.) and one neurologist (Q.L.) rated HS severity with a four-class grading scale (normal, mild, moderate and severe) based on both hippocampal volume loss and increased FLAIR signal. A consensus of HS severity for each subject was made by voting among the three visual rating results. Regarding the automatic quantification, the hippocampal volume was quantified by AccuBrain on T1W image, and the FLAIR signal of hippocampus was calculated as the mean intensity of hippocampal region on the FLAIR image (normalized by the mean intensity of gray matter). To fit the HSI from visual rating, we applied ordinal regression with the voted visual rating as the dependent variable, and hippocampal volume and FLAIR signal as the independent variables. The HSI was calculated by weighting the predicted probabilities of the four-class grading scales from ordinal regression. RESULTS: The intra-class correlation coefficient (single measure) of the three raters was 0.806. The generated HSI was significantly correlated with the visual rating scales of the three raters (W.D.: 0.823, Q.L.: 0.817, C.S.: 0.717). HSI scores well differentiated the different HS categories as defined by the agreed HS visual rating (normal vs. mild: p < 0.001, mild vs. moderate: p < 0.001, moderate vs. severe: p = 0.001). CONCLUSIONS: The proposed HSI was consistent with visual rating scales from epileptologists and sensitive to HS severity. This MRI-based index may help to evaluate HS severity in clinical practice. Further validations are needed to associate HSI with post-surgery outcomes.

Comparison of seizure outcomes and safety between anterior temporal lobotomy and lobectomy in patients with temporal lobe epilepsy.

Objectives: To compare the efficacy and safety of anterior temporal lobotomy (ATLo) and anterior temporal lobectomy (ATLe) in drug-resistant temporal lobe epilepsy.Methods: Patients diagnosed with pharmacoresistant temporal lobe epilepsy who underwent anterior temporal lobotomy (ATLo) or anterior temporal lobectomy (ATLe) performed by a single surgeon were retrospectively included. Every patient was followed up annually after surgery. The postoperative seizure outcome evaluation was based on the Engel and ILAE classifications. We compared postoperative complications and 2-year follow-up seizure outcomes between the ATLo group and the ATL group.Results: A total of 42 individuals (21 ATLo and 20 ATLe) were included. At the two-year follow-up, more patients in the ATLo group than the ATLe group had reached Engel class I (20 versus 14) and ILAE I (19 versus 13). However, these differences were not significant. One patient in the ATLo group had intraparenchymal hematoma and fully recovered. The two groups had similar incidences of other short-term complications, and no patients died or had any permanent complications.Discussion: ATLo is not inferior to ATLe for patients with drug-resistant temporal epilepsy. There was no significant difference in seizure outcomes or the rate of postoperative complications between the two groups. A large sample randomized control study is needed.

Type IIB focal cortical dysplasia with balloon cells in medial temporal lobe epilepsy: Clinical, neuroimaging, and histopathological findings.

PURPOSE: Type IIB focal cortical dysplasia (FCD) is an important cause of drug-resistant epilepsy. However, balloon cells located in the medial temporal lobe have been seldom reported. We aimed to discuss the clinical and pathological features of Type IIB FCD with balloon cells in the medial temporal lobe (MTLE-FCDIIB) and the differential diagnosis with other types of mesial temporal lobe epilepsy. METHODS: Three MTLE-FCDIIB cases were enrolled from Peking Union Medical College Hospital. Clinical and neuroimaging data were analyzed and histology features observed on hematoxylin-eosin (H&E) staining and immunochemical staining, including vimentin, nestin, S-100, CD34, neuronal nuclei antigen (Neun), glial fibrillary acidic protein (GFAP), neurofilament heavy chain (SMI32), were discussed. RESULTS: All cases involved drug-resistant epilepsy patients with childhood onset. The semiology of the epileptic seizure was a highly frequent partial seizure with or without generalized tonic-clonic seizures. Magnetic resonance imaging showed hyper-intensity in the medial temporal lobe without atrophy, different from mesial temporal sclerosis. Histological examination indicated the presence of balloon cells in the white matter of the para-hippocampal gyrus, subiculum, and cornu ammonis with cortical disorganization, and SMI32 positive dysmorphic neurons in the gray matter. Balloon cells were immunohistochemically stained with vimentin and nestin. Granular cell dispersion and pyramidal cell loss were not found. CONCLUSIONS: The presence of balloon cells in the medial temporal lobe is observed in a rare subgroup of FCD, named MTLE-FCDIIB. It has distinct clinical manifestations, neuroimaging features, pathological changes, and prognosis, which should be differentiated from mesial temporal lobe sclerosis and mesial temporal lobe tumors. Our findings enable more accurate diagnosis of mesial temporal lobe epilepsy.

The interactome and proteomic responses of ALKBH7 in cell lines by in-depth proteomics analysis.

BACKGROUND: ALKBH7 is a mitochondrial protein, involved in programmed necrosis, fatty acid metabolism, cell cycle regulation, and prostate cancer disease. However, the exact roles of ALKBH7 and the underlying molecular mechanisms remain mysterious. Thus, investigations of the interactome and proteomic responses of ALKBH7 in cell lines using proteomics strategies are urgently required. METHODS: In the present study, we investigated the interactome of ALKBH7 in mitochondria through immunoprecipitation-mass spectrometry/mass spectrometry (IP-MS/MS). Additionally, we established the ALKBH7 knockdown and overexpression cell lines and further identified the differentially expressed proteins (DEPs) in these cell lines by TMT-based MS/MS. Two DEPs (UQCRH and HMGN1) were validated by western blotting analysis. RESULTS: Through bioinformatic analysis the proteomics data, we found that ALKBH7 was involved in protein homeostasis and cellular immunity, as well as cell proliferation, lipid metabolism, and programmed necrosis by regulating the expression of PTMA, PTMS, UQCRH, HMGN1, and HMGN2. Knockdown of ALKBH7 resulted in upregulation of UQCRH and HMGN1 expression, and the opposite pattern of expression was detected in ALKBH7 overexpression cell lines; these results were consistent with our proteomics data. CONCLUSION: Our findings indicate that the expression of UQCRH and HMGN1 is regulated by ALKBH7, which provides potential directions for future studies of ALKBH7. Furthermore, our results also provide comprehensive insights into the molecular mechanisms and pathways associated with ALKBH7.

Pallidal Deep Brain Stimulation in Patients With Chorea-Acanthocytosis.

INTRODUCTION: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center. METHODS: We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months. RESULTS: All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 µsec to 98 µsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes.

Subthalamic Nuclei Stimulation in Patients With Pantothenate Kinase-Associated Neurodegeneration (PKAN).

INTRODUCTION: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disease that leads to extrapyramidal symptoms, such as dystonia, ataxia, dysarthria, and involuntary movements. Treatment of PKAN with deep brain stimulation (DBS) has been reported, but mainly focuses on targeting the globus pallidus internus (GPi). Subthalamic nuclei (STN) may also be a potential target for treatment of PKAN. METHODS: In this study, we reviewed three patients with PKAN (two with typical PKAN and one with atypical PKAN) treated by bilateral STN stimulation and present a review of the literature. All patients received neurological evaluation using the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS) scoring system before and after surgery. Patients were then subject to regular clinical follow-ups (ranging from 22 to 44 months). RESULTS: The mean stimulation amplitude, pulse width and frequency was 2.65 ± 0.45 V, 91.7 ± 21.9 µs, and 146.7 ± 12.5 Hz, respectively. BFMDRS scores were improved in all patients after surgery, ranging from 41.6 to 73.1%. Improvements of appendicular symptoms ranged from 46.2 to 94.1%, and improvements of axial symptoms ranged from 27.3 to 33.3%. No side effects were reported in patients 1 and 2; whereas patient 3 exhibited a mild decline in verbal fluency one year after surgery. CONCLUSION: STN stimulation could serve as a candidate DBS target in the treatment of PKAN, especially for patients with prominent appendicular symptoms.

Quantitative protein profiling of hippocampus during human aging.

The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions.

Schwannoma in Sellar Region Mimics Invasive Pituitary Macroadenoma: Literature Review With One Case Report.

In central nervous system, schwannomas, as ubiquitous tumors, mostly originate from sensory nerves like auditory and trigeminal nerves. However, intrasellar schwannomas are extremely rare. They are often misdiagnosed as pituitary adenomas. We report a rare case of schwannoma in the sellar region--a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test. We represent a 65-year-old woman who had suffered from headaches, hypothyroidism, and visual disturbance. Her MRI revealed an abnormal sellar region mixed-signal mass lesion with suprasellar, left parasellar, and sellar floor invasiveness. We present detailed analysis of the patient's disease course and review relevant literatures. Written informed consent was obtained from the patient for publication of this article. A copy of the written consent is available for review by the editors of MEDICINE. Because this article does not involve any human or animal trials, there is no need to conduct special ethic review and the ethical approval is not necessary. When surgically treated, her specimen revealed a typical histopathology pattern of schwannoma. The patient's symptoms improved a lot after surgery and he continues to be under observation. Despite its rarity, intrasellar schwannoma should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas.

CD34 Over-Expression is Associated With Gliomas' Higher WHO Grade.

CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta-analysis is the best choice for drawing a convincing conclusion. Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas' WHO grades, patients' ages and gender. We used the Galbraith figure, the I test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results' stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments. There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot. Our results suggested that CD34 overexpression is associated with higher WHO grades of gliomas. CD34 may serve as a potential diagnostic and prognostic marker, or it could be a useful therapy target.

Does Tenascin have Clinical Implications in Pathological Grade of Glioma Patients?: A Systematic Meta-Analysis.

Tenascin (TN) is an extracellular oligomeric glycoprotein that participates in the adhesion of cells to extracellular matrixc (ECM). Studies have shown that the expression levels of TN are upregulated in a variety of cancers, including colon cancer, lung cancer, brain tumor, and breast cancer. However, the implications and utilities of TN in clinical grading and prognosis of glioma patients were seldom reported and the effects of its pathway are still unclear and controversial. Thus, it is essential to carry out a meta-analysis to draw a convincing conclusion.A literature search was carried out up to April 2015. Data was collected using a purpose-designed form including glioma's WHO grade, etc. Differences were expressed as odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (CIs). Galbr figure, Cochran's Q test, and I test were all performed to judge the heterogeneity between included studies. To examine the stability of the pooled results, a sensitivity analysis was performed. Potential publication bias was assessed by visual inspection of funnel plot. As this meta-analysis, as a systematic review, does not involve animal experiments or direct human trials, there is no need to conduct special ethic review and the ethical approval is not necessary.In this meta-analysis, 8 eligible studies involving 456 patients were incorporated. Six studies with dichotomous data revealed TN overexpression in glioma tissues and/or surrounding neoplastic vessels was closely associated with high WHO grade (III + IV) (odds ratio 3.398, 95% confidence interval 1.933, 5.974; P = 0.000); three continuous data studies showed there were close statistical associations between TN and WHO grade (SMD -2.114, 95% CI -2.580, -1.649; P = 0.000) too. Sensitivity analysis indicated a statistically robust result. No publication bias was revealed.Our meta-analysis suggests that TN expression is potentially associated with higher WHO grade of gliomas. More evidences on the basis of the evidence-based medicine are needed to prove it.

[Significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery].

OBJECTIVE: To explore the significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery. METHODS: For 22 patients with pituitary adenomas over a period of 2 years at Peking Union Medical College Hospital, resection of pseudocapsule was applied for complete tumor removal. Pituitary function test and radiological imaging were performed at pre-operation, 3 months post-operation and at subsequent 6-12 months intervals postoperatively. RESULTS: All pituitary adenomas were totally removed under microscope. The symptoms of headache, disorder of sight and visual field disappeared postoperatively in nonfunctional pituitary adenomas. The GH levels of 2/5 growth hormone secreting adenoma patients were 4.2 and 7.7 µg/L while it was under 1 µg/L for another 3. The postoperative level of prolactin was 4.3 µg/L in prolactin secreting adenoma. The level of adrenocorticotropic hormone decreased under 5 ng/L except one was 15.7 ng/L. Leakage of cerebrospinal fluid occurred intraoperatively in 3 patients and postoperatively in 1. No leakage was found after repair. Diabetes insipidus occurred in one patient and was controlled with Minirin. Pseudocapsule was confirmed by pathological examination. Special staining revealed reticulum fibers in pseudocapsule. CONCLUSION: Resection of pseudocapsule may achieve a higher remission rate without deteriorating pituitary function.

Transsphenoidal approach for pituitary adenomas in patients with McCune-Albright syndrome.

The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.

[Clinical application of neuronavigation in transsphenoidal microsurgery of pituitary adenomas].

OBJECTIVES: To summarize the experiences in clinical application of neuronavigation in transsphenoidal microsurgery of specific pituitary adenomas, and to discuss its indications. METHODS: From January 2006 to December 2010, 138 cases of transsphenoidal microsurgery for specific pituitary adenomas under neuronavigation were reviewed. The indications for neuronavigation in transsphenoidal microsurgery includes: recurrent or regrowth of residual pituitary adenomas after former transsphenoidal surgery in 36 cases, invasive pituitary adenomas in 45 cases, extremely laterally or deeply situated microadenomas in 45 cases, poor pneumatization of the sphenoid in 4 cases, skull base anomalies due to osteodysplasia fibrosa in 3 cases, narrow space between bilateral internal carotid arteries in 4 cases, distortion of nasal septum in 1 case. RESULTS: In the recurrence group, 12 were totally removed, 9 subtotally removed; postoperative complications included hematoma within the tumor cavity in 2 cases, cerebrospinal fluid (CSF) leakage in 4 cases among which 3 developed intracranial infection and 2 communicating hydrocephalus, oculomotor paralysis in 1 case and hypopituitarism in 3 cases; 9 were cured and 8 remission. In the invasive group, 5 were totally removed, 27 subtotally removed; postoperative complications included hematoma within the tumor cavity in 1 case, CSF leakage and intracranial infection in 1 case; 2 were cured and 22 remission. None of the 30 invasive hormone-secreting adenomas were cured or remission. The 45 cases of hormone-secreting microadenomas were all totally removed, among which 38 were cured. Among the poor sphenoid pneumatization group, total and subtotal tumor removal were achieved in 2 cases respectively with only one cured. In the skull base anomaly group, 2 were totally removed and 1 subtotally removed, with only one cured. For the cases with narrow space between bilateral internal carotid arteries and distortion of nasal septum, all were totally removed and cured. CONCLUSIONS: Transsphenoidal microsurgery under neuronavigation can be applied for pituitary adenomas in above specific indications. It is an accurate, safe and effective approach for specific pituitary adenomas, which can not only expand the indication of transsphenoidal microsurgery for pituitary adenomas, but also reduce the harmful exposure of X-rays for the operating staff.

A case of McCune-Albright syndrome associated with pituitary GH adenoma: therapeutic process and autopsy.

BACKGROUND: McCune-Albright syndrome (MAS) is a clinical syndrome with low incidence, and its concurrence with pituitary GH adenoma is rare. Little of the history, treatment and outcome has been studied. METHOD: Follow-up of a 37-year-old male patient of MAS associated with pituitary GH adenoma was performed continuously recording the disease development and the treatment process until death, after which an autopsy was performed. RESULTS: Radiation therapy (RT) efficaciously controlled GH hypersecretion, however, it may have been the cause of the malignant transformation of the dysplastic bone tissue, which eventually caused brain hernia and death; autopsy demonstrated that the cranium had significant thickening (as much as 10 cm), the pathological diagnosis was fibrous dysplasia of bone associated with chondrosarcoma; and undifferentiated chondrosarcoma with malignant fibrous histocytoma subtype in the sellar region; nodular goiter with the thyroid gland, one nodus was pathologically demonstrated as papillary carcinoma. CONCLUSION: GH adenoma, present in a patient with MAS, might be cured by RT; but the risk of malignant transformation of the dysplastic bone tissue in the field of irradiation make it controversial. Lessons from the case reported here told us that we should take great caution when recommending RT for patients like this.

Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats.

Mesenchymal stem cells (MSCs) have been successfully used for the treatment of experimental stroke. However, the neurorestorative mechanisms by which MSCs improve neurological functional recovery are not fully understood. Endogenous cell proliferation in the subventricular zone (SVZ) after stroke is well known, but most of newly formed cells underwent apoptosis. In the present study, we tested the hypothesis that neurotrophic factors secreted by human bone marrow-derived MSCs (hBMSCs) promote endogenous neurogenesis, reduce apoptosis, and improve functional recovery. Adult rats subjected to 2-h middle cerebral artery occlusion (MCAO) were transplanted with hBMSCs or saline into the ipsilateral brain parenchyma at 3days after ischemia. There was a significant recovery of behavior in the hBMSCs-treated rats beginning at 14days after MCAO compared with the control animals. Higher levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and vascular endothelial growth factor (VEGF) were detected in the hBMSCs-treated rat brain than the control. Human BMSCs treatment also enhanced endogenous cell proliferation both in the SVZ and in the subgranular zone (SGZ) of the hippocampus. In addition, more neuronal progenitor cells migrated from the SVZ to the ischemic boundary zone (IBZ) and differentiated into mature neurons with less apoptosis in rats treated with hBMSCs. Overall, these data suggest an essential role for hBMSCs in promoting endogenous neurogenesis, protecting newly formed cells, and improving functional recovery after ischemia in rats.

[Clinical efficacy of microvascular decompression plus intraoperative monitoring of abnormal muscle response in the treatment of hemifacial spasm].

OBJECTIVE: To explore the clinical efficacy of microvascular decompression plus intraoperative monitoring of abnormal muscle response in the treatment of hemifacial spasm. METHODS: Between 2009 and 2010, a total of 47 patients underwent microvascular decompression for hemifacial spasm. There were 15 males and 32 females with an age range 23 - 70 years old. During operations, intermittent electrical pulses were applied to stimulate the zygomatic branch of facial nerve at the spasm side. And evoked potentials were monitored in orbicularis oris. All patients were followed up for 5 - 22 months. RESULTS: The abnormal muscle responses were recorded pre-operatively in all 47 patients at the spasm side. In 42 patients, the abnormal muscle responses disappeared at the different stages of operations (4 while opening dura, 9 while dissecting arachnoid membrane and 29 while separating responsible vessels). All 42 patients were cured during the follow-up period. In the remaining 5 patients, the abnormal muscle response were still recorded even at the end of operations. Two of 5 patients were free from spasm during the follow-up period while the symptoms of other 3 patients became obviously relieved. CONCLUSION: The combined approaches of microvascular decompression and intraoperative monitoring of abnormal muscle response may assist the identification of responsible vessels and improve the outcomes of hemifacial spasm.

Intraventricular pre-treatment with rAAV-VEGF induces intracranial hypertension and aggravates ischemic injury at the early stage of transient focal cerebral ischemia in rats.

OBJECTIVE: To examine the effects of intraventricular pre-treatment with recombinant adeno-associated virus vectors encoding VEGF (rAAV-VEGF) on early stroke in a rat model of transient middle cerebral artery occlusion (tMCAO). METHODS: rAAV-VEGF, rAAV-null or physiologic saline was delivered into the lateral ventricle of 93 Wistar rats, respectively. Eight weeks later, the rats were subjected to tMCAO for 2 hours. During the early stage following ischemic reperfusion, intracranial pressure (ICP) and brain water content were measured to make a correlation analysis, T2-weighted MRI was performed to observe cerebral edema volume, and TTC-derived cerebral infarct volume and modified neurological severity scores (NSS) were determined to evaluate the therapeutic efficacy of rAAV-VEGF in tMCAO. RESULTS: Twenty-four hours following tMCAO, the rAAV-VEGF group, with VEGF overexpression in the rats brain, showed a significantly increase in ICP, brain water content and cerebral edema volume compared with two control groups (p<0.05). The ICP significantly correlated with the brain water content in the infarct hemisphere in all three groups during 24 hours following tMCAO (r=0.93, p<0.05). Forty-eight hours following tMCAO, a 1.3-fold larger infarct volume and 1.3-fold higher NSS were observed in the rAAV-VEGF group than both control groups (p<0.05). CONCLUSION: Our results indicate that intraventricular rAAV-VEGF pre-treatment can result in deleterious intracranial hypertension and augment secondary ischemic insults at the early stage of tMCAO, and pre-ischemic VEGF gene transfer via intraventricular approach may not be a favorable therapeutic strategy for tMCAO which should be adopted with caution or avoided in experimental stroke.

Transsphenoidal surgery in a patient with acromegaly and McCune-Albright syndrome: application of neuronavigation.

The McCune-Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.

[Treatment of stroke in rats with bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effects of treatment of stroke in rats with bone marrow mesenchymal stem cells (BMSCs) and mechanism thereof. METHODS: Bone marrow of a healthy volunteer was collected and the BMSCs were separated with density gradient centrifugation. The hBMSC were cultivated and harvested until the third passage. A number of adult male Sprague-Dawley rats received corresponding behavioral training before surgery and underwent transient middle cerebral arterial occlusion (MCAO) for 2 hours. Sixty of them showing the scores of 6 approximately 12 according to the modified neurological severity score system were randomly divided into 2 groups: treatment group (n = 48, injected into the cortex around the ischemic areas with hBMSCs 3x10(5)/15 microl) and control group (n = 12, injected with D-Hanks solution 15 microl 24 hours after the establishment of MCAO models. Morris water maze test, Rotarod test and adhesive-removal test were performed since the 4th day to the 32 day after transplantation once every 3 days. 1, 2, 3, and 4 weeks after the transplantation 12 rats from each group were killed randomly to take out their brains. Immunofluorescence was used to identify the migration, survival and differentiation of the hBMSC. RESULTS: A large number of hBMSC could be seen within 2 weeks after transplantation. The number of hBMSC decreased since the 21st day after transplantation and few cells could be found at the end of 1 month after. No definite evidence supported the differentiation of neural cells derived from the hBMSCs during the whole process. Morris water maze test showed that the mean escape time 1 week after transplantation of the treatment group was (69 +/- 10) s, significantly shorter than that of the control group [(120 +/- 0) s, P < 0.05] The significant difference persisted until the 4(th) week (P > 0.05). Rotarod test with the speed of 10 r/min showed that the mean latency period 10 days after transplantation of the treatment group was (167 +/- 18) s, significantly longer than that of the control group [(37 +/- 19) s, P < 0.05]. The significant difference persisted until the experimental terminal. The adhesive-removal test showed that the mean latency period 13 days after transplantation of the treatment group was (33 +/- 8) s, significant shorter than that of the control group [(84 +/- 13) s, P < 0.05]. The significant difference persisted until the experimental terminal. CONCLUSION: Injection of hBMSCs into brain cortex improves neurological functional recovery after stroke. The transplanted cells can migrate and survive for a certain period, but no hBMSC express proteins phenotype of neural cells.

[In vivo tracking of bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide after cerebral ischemia in rats by magnetic resonance imaging].

OBJECTIVE: To explore the feasibility of in vivo tracking of bone marrow mesenchymal stem cells (BMSCs) labeled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) in rats after cerebral ischemia, and to analyze the influence of stem cell therapy on the volume of cerebral infarction. METHODS: The samples of rat bone marrow were collected. BMSCs separated by density gradient centrifugation were cultivated and harvested until the third passage. BMSCs were labeled with SPIO, which was mixed with poly-L-lysine. The labeling efficiency was evaluated by Prussian blue staining. Transient middle cerebral arterial occlusion (MCAO) was performed successfully in 18 adult Sprague-Dawley rats that scored from 6 to 12 by the modified neurological severity test. The 18 rats were then randomly divided into group A, B, and C, with 6 rats in each group and Group C was regarded as control group. BMSCs were injected into the contralateral cortex of ischemia in group A, ipsilateral corpora striata in group B, while D-Hank's solution was injected into ipsilateral corpora striata (group C) 24 hours after MCAO. MRI was performed 1 day after MCAO, 1 day and 14 days after transplantation. The volume of infarcted brain tissue was measured and analyzed. Prussian blue staining of brain tissues was performed to identify the migration of BMSCs. RESULTS: The labeling efficiency of BMSCs with SPIO was 96%. The transplanted BMSCs migrated to the ischemic hemisphere along the corpus callosum and to the border of the infarction, which was confirmed by MRI and Prussian blue staining. The changes of infarction volume were not significantly different among these three groups. CONCLUSIONS: MRI is feasible for in vivo tracking of BMSCs labeled with SPIO in rats. The stem cell therapy may not be able to affect the volume of cerebral infarction.