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We explored changes in clinical features and neuropathological mechanisms underlying olfactory dysfunction (OD) in 60 patients with Alzheimer's disease (AD). Olfactory function was evaluated using the Sniffin' Sticks test and a threshold discrimination identification (TDI) score. Based on the TDI score, we divided patients according to the presence or absence of OD (AD-OD and AD-NOD, respectively). Cognitive and neuropsychiatric symptoms were evaluated by a series of rating scales. The volumes and cortical thickness of the thalamus, hippocampus, and amygdala were measured using structural magnetic resonance imaging. Neuropathological protein levels in cerebrospinal fluid were measured. The frequency of OD was 50%. TDI scores were lower in the AD-OD group than in the AD-NOD group (p < 0.001). Compared with the AD-NOD group, the AD-OD group showed greater cognitive function impairments (p < 0.001), and daily living activities were more severely compromised (p = 0.019). The AD-OD group had lower hippocampal and amygdala volumes (p = 0.025, p = 0.030, respectively) and a more pronounced reduction in cortical thickness (p = 0.010). The total tau level was lower in the AD-OD group than the AD-NOD group (p = 0.040). Lower Mini-Mental State Examination scores and thinner AD-signature cortices were associated with lower TDI scores (OR = 0.826, p < 0.001; OR = 1.433, p = 0.008). Overall, in AD patients, the impairments in olfactory discrimination and identification seem to be more correlated with cognitive levels. OD in AD may be an indicator of pathological cognitive decline and structural changes.

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

As a new type of antiparasitic drugs, ivermectin (IVM) has been widely applied in agriculture, stock raising and aquaculture in China because of its broad spectrum and high efficiency. In order to evaluate the IVM' s reproductive toxicity to male Crucian carp (Carassius auratus), IVM was orally given to the experimental fish with different dosages and the gonadosomatic index (GSI), sexual hormone contents (including testosterone and estradiol) in serum and testis, γ-aminobutyric acid content in serum and brain tissues, ultra-structure of spermatozoa and gonadal tissue in fish were determined in this study. The experimental fish were classified into A, B, C and D groups corresponding to the different dosages of IVM (0, 0.3, 0.9 and 1.5 mg . kg-1, respectively once a day for 3 days continuously). Several indices in fish were detected after 8 days self-purification. The results indicated that GSI gradually decreased with the increase of drug dosage, and GSI in groups C and D was significantly lower than that in group A. The contents of testosterone, estradiol and y-aminobutyric acid exhibited a trend of first increasing and then decreasing and reached the peak at group B. Sperm longevity gradually decreased and the motion time also decreased in II, III and IV level sperms with the increasing dosage of IVM, which appeared to be especially obvious in group C and D. No obvious differences were found in the ultra-structure of spermatozoa and gonadal tissues. In conclusion, this study suggested that IVM had no obvious reproductive toxicity to male Crucian carp at the normal therapeutic dosage but could cause serious potential reproductive toxicity to fish at a high concentration.

Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.

Reconstruction after intercalary excision of tibia malignancy is challenging. The combined use of a vascularized fibular flap and allograft can provide a reliable reconstructive option. Eight patients underwent reconstruction with an allograft and vascularized fibula following tibia malignancy resection. Patients were examined clinically and radiographically. The average age of patients was 16.5 years. The mean follow-up time was 38.4 months. Contralateral free fibula flap was used in three patients and ipsilateral pedicle fibula in five. The average length of defect was 11.8 cm and of fibula flap was 15.9 cm. Primary union was achieved in seven patients. The average time for bone union was 5.8 months at fibula-tibia junction and 14.1 months at allograft-tibia junction. Five patients had 10 complications. The Musculoskeletal Tumor Society average score was 90.8% at final follow-up. Intramedullary fibular flap in combination with massive allografts provide an excellent option for reconstruction of large bony defects after tibial malignancy extirpation. Ipsilateral pedicle fibula transportation had the advantages of short operation time and avoidance of donor site complications compared with the contralateral free fibula transfer.

Tumefactive demyelinating lesions (TDLs) are misdiagnosed frequently. To investigate the characteristics of TDLs, clinical and radiological data from nine cases with TDLs were analyzed after admission. All cases underwent surgery and pathological examination; some received postoperative steroid therapy. Onsets were mostly within 3 weeks and main presentation included intracranial hypertension, extremity weakness, epilepsy, and visual disturbance. Symptoms in children were acute and severe, frequently including headache, vomiting, and visual disturbance. Most intracephalic lesions were in cerebral hemispheres. All intraspinal lesions were in cervical segments. Radiological features included mass effect, perifocal edema and enhancement (of which open-ring enhancement was diagnostic), and decreased relative cerebral blood volume. Intraoperative frozen section did not confirm the diagnosis, while postoperative paraffin section did confirm it (by evidence of macrophage infiltration). The patients responded well to steroid therapy and no relapse was found during following up. Thus, intensive analysis of both clinical and radiological data may provide some clues for diagnosis. For suspected cases, it is advisable to take steroid therapy or undergo advanced radiological examinations, such as serial magnetic resonance spectroscopy. However, in difficult cases, pathological evidence is beneficial to a final diagnosis.

OBJECTIVE: The purpose of this study was to investigate the pathological alterations and the stress responses around deep brain stimulation (DBS) electrodes after magnetic resonance imaging (MRI) scans at 7.0T, 3.0T and 1.5T. MATERIALS AND METHODS: DBS devices were stereotactically implanted into the brains of New Zealand rabbits, targeting the left nucleus ventralis posterior thalami, while on the right side, a puncture passage pointing to the same target was made. MRI scans at 7.0T, 3.0T and 1.5T were performed using transmit/receive head coils. The pathological alterations of the surrounding tissue were evaluated by hematoxylin and eosin staining (H&E staining) and transmission electron microscopy (TEM). The levels of the 70 kDa heat shock protein (HSP-70), Neuronal Nuclei (NeuN) and Caspase-3 were determined by western-blotting and quantitative polymerase chain reaction (QPCR) to assess the stress responses near the DBS electrodes. RESULTS: H&E staining and TEM showed that the injury around the DBS electrodes was featured by a central puncture passage with gradually weakened injurious alterations. Comparisons of the injury across the groups manifested similar pathological alterations near the DBS electrodes in each group. Moreover, western-blotting and QPCR assay showed that the level of HSP-70 was not elevated by MRI scans (p>0.05), and the levels of NeuN and Caspase-3 were equal in each group, regardless of the field strengths applied (p>0.05). CONCLUSIONS: Based on these findings, it is reasonable to conclude that in this study the MRI scans at multiple levels failed to induce additional tissue injury around the DBS electrodes. These preliminary data furthered our understanding of MRI-related DBS heating and encouraged revisions of the current MRI guidelines for patients with DBS devices.

Magnetic resonance imaging (MRI) is commonly utilized as part of the diagnostic workup for the clinical diagnosis of glioblastoma multiforme (GBM), further guiding the clinical treatment of this aggressive cancer. Recent research has shown that microRNAs (miRNAs) may act as oncogenes, or in some cases, tumor suppressor genes that in turn may reflect the genotypic features of GBM. This study aimed to investigate the relationship between MRI features and miRNA gene expression in patients with glioblastoma multiforme.In order to identify the relationship between the radiographic findings of MRI and those identified changes in miRNA gene expression of GBM, we reviewed the MRI images of GBM patients and compared them with the identified miRNA expression profiles utilizing microarray analysis of paired GBM tumor samples. We chose five MRI imaging features: (1) contrast tumor enhanced/necrosis ratio, (2) contrast tumor enhanced/T2 ratio, (3) multiple lesions, (4) hemorrhage, and (5) necrotic volume. The relationship between these five imaging features and miRNA expression was studied using significance analysis of microarrays analysis.We found that the expression of miRNAs such as hsa-miR-892b, hsa-miR-892a, and hsa-miR-888 was inversely correlated with an enhanced/necrosis ratio ≥ 1. The miRNAs such as hsa-miR-95, hsa-miR-498, and hsa-miR-1300 were associated with a contrast tumor enhanced/T2 ratio ≥1. The miRNAs such as hsa-miR-612, hsa-miR-524-3, and hsamiR-1282 were associated with multiple lesions identified on MRI and the expression of miR-221 was associated with hemorrhage by GBM. The expression of miR-let-7, including miR-let-7f, miR-let-7i, and miR-let-7f-1*, was downregulated in the hemorrhage group. The gene expression of miRNAs such as hsa-miR-140-5p, hsa-miR-30e, and hsa-miR-301a was relatively low when compared with the larger necrotic volume group as identified by MRI.The miRNA gene expression profiles correlate with several selected MRI features of patients with GBM. Further analysis of key imaging features of MRI with correlation with miRNA gene expression patterns may help to guide treatment decisions based on these unique correlative profiles of GBM.

The mechanism of acupuncture analgesia in craniotomy has been widely studied. However, the theoretical basis for selection of acupoints has not been examined. In this study, we used the regional homogeneity method blood oxygen level-dependent (BOLD) signals to determine changes in brain activity in response to transcutaneous electrical stimulation on acupoints and non-acupoints in resting state functional magnetic resonance imaging (fMRI).Twelve healthy volunteers were enrolled in this study. BOLD fMRI scanning of the brain was performed for 306 seconds before and 30 minutes after transcutaneous electrical stimulation on acupoints UB63 (Jinmen), LV3 (Tai chong), ST36 (Zusanli), and GB40 (Qiuxu). The procedure was repeated after one week with stimulation on non-acupoints (one was 9 above BL67, the second was 12 above BL67 (Kunlun), the third was 7 above KI3, and the fourth was 10 above KI3 (Taixi)).The regional homogeneity in the acupoint group was increased in the left thalamus, caudate, putamen, lentiform nucleus (BA19, 30, 39), postcentral gyrus, precentral gyrus (BA3, 4, 30, 32), calcarine fissure, middle temporal gyrus (BA30), right superior temporal gyrus, inferior temporal gyrus (BA38), cuneus, and precuneus (BA7, 19) when compared to the non-acupoint group. The regional homogeneity of the acupoint group was decreased in the left cerebellum posterior lobe, middle frontal gyrus (BA10), double-side precuneus (BA7), and the postcentral gyrus (BA40).The brain region activated following acupoint stimulation is the ipsilateral pain-related brain region, which may relate to the therapeutic effect of acupuncture on pain relief. Further acupoint stimulation causes different central nervous responses compared to non-acupoint stimulation.

Localization of sensory cortical areas during the operation is essential to preserve the sensory function. Intraoperative direct electrostimulation under awake anesthesia is the golden standard but time-consuming. We applied 3T high field blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to identify the relationship between glioma and cortical sensory areas preoperatively and to guide intraoperative direct electrostimulation for quick and precise localization.Five glioma patients with sensory cortex involvement by or next to the lesion had preoperative BOLD fMRI to determine the spatial relationship of cortical sensory areas to the tumours. Bilateral hand opposite movement was performed by these patients for fMRI. Precentral and postcentral gyri were identified by electrical stimulation during the operation. Karnofsky Performance Status scores of the patients' pre- and postoperative and the role of BOLD fMRI were evaluated.The cortical sensory areas were all activated in five glioma patients involving postcentral gyrus areas by BOLD fMRI with bilateral hand opposite movement. The detected activation areas corresponded with the results from cortical electrical stimulation.The relationship between cortical sensory areas and tumour can be accurately shown by BOLD fMRI before operation. And the information used to make the tumour resection could obtain good clinical results.

To locate motor functional area of patients who undergone modified anatomical hemispherectomy in order to analysis the plasticity of upper limbs motor.The patients who undergone modified anatomical hemispherectomy were performed BOLD sequences, to locate functional cortical areas in their residual brain.6 patients have performed examination of BOLD sequences by 3.0-T MRI.5 of them obtained contralateral upper limb motor areas in their residual brain, and 3 of them obtained ipsilateral and contralateral upper limb motor area map in cortex. The ipsilateral upper limb motor areas in the M1, SMA and posterior parietal cortex.The patients who undergone modified anatomical hemispherectomy is an excellent model to investigate mechanism of plasticity in the developing brain. Functional magnetic resonance (fMRI) provided fine spatial detail of brain responses, would describe the motor functional area of cortical maps. These patients exist ipsilateral motor areas in their residual mono hemisphere. The study indicated there maybe have somewhat extent of correlation between the surgical procedure and the outcome of neuroplasticity.

To explore the role of preoperative blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) to identify the relationship between motor cortical area, pyramidal tracts with brain gliomas in neurosurgical treatment of intraoperative electrical stimulation for gliomas involving motor areas at 3T.Twenty-eight patients with brain gliomas involving motor areas were included. They underwent MRI examination, which included conventional T1WI, T2WI, BOLD-fMRI of bilateral hands movement paradigm and diffusion tensor imaging (DTI). The data of BOLD-fMRI and DTI were transferred to the workstation (Leonardo syngo 2003A, Siemens) and analyzed. Activation mapping of hands movement, fractional Anisotropy (FA) Color and three dimensional pyramidal tracts were produced. The relationship between motor cortical area, pyramidal tracts and brain gliomas was demonstrated, which was used to optimize the pre-surgical planning. With guidance of the result of BOLD-fMRI and DTT, all patients received microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations. The brain lesions were removed as far as possible in the case of eloquent areas and sub-cortical important white matters preservation. The preoperative and postoperative KPS of all patients were operated to evaluate the state of patients.BOLD-fMRI, DTI were performed successfully in 28 patients. The relationship between the primary motor cortex, premotor area, supplementary motor area, pyramidal tracts and brain gliomas localized by preoperative fMRI and DTI. Under anaesthesia retaining consciousness, the primary motor area was monitored by the method of direct electrical stimulations with the guidance of preoperative BOLD-fMRI. There was good correlation between preoperative fMRI and intraoperative cortical stimulation. Furthermore, the preoperative mappings and DTT could make up for the un-monitored motor areas and pyramidal tracts during operative cortical stimulation. Comparing the preoperative KPS, the postoperative KPS was advanced.BOLD-fMRI and DTT could non-invasively localize the relationship between brain motor cortex, pyramidal tracts and brain gliomas in vivo to optimize the surgical planning, guide the microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations and remove brain tumors as far as possible in the case of eloquent areas and sub-cortical important white matters preservation.