Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia.

OBJECTIVE: We examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia. METHODS: We prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement. RESULTS: CCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts. CONCLUSION: For the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus. SIGNIFICANCE: This intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.

Diffusion tensor imaging--arcuate fasciculus and the importance for the neurosurgeon.

OBJECTIVE: Tumors in eloquent areas of the brain like Broca or Wernicke might have disastrous consequences for patients. We intended to visualize the arcuate fasciculus (AF) and to demonstrate his relation with the corticospinal tract and the visual pathway using diffusion tensor imaging (DTI). METHODS: We depicted between 2012 and 2014 the AF in 71 patients. Men and women of all ages were included. Eleven patients had postoperative controls also. We used a 3DT1-sequence for the navigation. Furthermore T2- and DTI-sequences were performed. The FOV was 200 × 200 mm(2), slice thickness 2mm, and an acquisition matrix of 96 × 96 yielding nearly isotropic voxels of 2 × 2 × 2 mm. 3-Tesla-MRI was carried out strictly axial using 32 gradient directions and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2. b-Value was 800 s/mm(2). Additional scanning time was less than 9 min. RESULTS: AF was portrayed in 63 patients bilaterally. In one glioblastoma patient it was impossible to visualize the left AF and in seven other patients we could not portray the right one. The lesions affected AF by disrupting or displacing the fibers. CONCLUSIONS: DTI might be a useful tool to portray AF. It is time-saving and can be used to preserve morbidity in patients with lesions in eloquent brain areas. It might give deeper insights of the white matter and the reorganization of AF-fibers postoperatively.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

BACKGROUND: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). METHODS AND MATERIALS: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. RESULTS: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. CONCLUSION: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Correlation between language function and the left arcuate fasciculus detected by diffusion tensor imaging tractography after brain tumor surgery.

OBJECT: Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language-processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery. METHODS: Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB). RESULTS: After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039). CONCLUSIONS: The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.

Overview of animal models of obesity.

The focus of this overview is on the animal models of obesity most commonly utilized in research. The models include monogenic models in the leptin pathway, polygenic diet-dependent models, and, in particular for their historical perspective, surgical and chemical models of obesity. However, there are far too many models to consider all of them comprehensively, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, the generation and use of inducible transgenic animals (induced knock-out or knock-in) is not covered, even though they often carry significant advantages compared to traditional transgenic animals, e.g., influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this unit.

Integration of diffusion tensor-based arcuate fasciculus fibre navigation and intraoperative MRI into glioma surgery.

This study was designed to evaluate the feasibility and efficacy of diffusion tensor-based arcuate fasciculus (AF) fibre navigation in combination with 1.5-Tesla (1.5-T) intraoperative MRI (iMRI) for the resection of gliomas involving eloquent language fibre tracts (AF tracts). Twenty patients with AF tract-involved gliomas in the dominant hemisphere were prospectively enrolled. The patients were divided into two groups. The normal group included nine patients with preoperative intact language function, while the aphasia group consisted of 11 patients who presented with different levels of conduction aphasia. The AF tractography results were integrated into three-dimensional (3D) datasets used for neuronavigation, and their course was superimposed onto the surgical field during glioma resection. The iMRI was used to compensate for the effects of brain shift and to evaluate the extent of resection. Fibre tract visualisation provided a quick and intuitive overview of the displaced course of the AF in 3D space and the surgical field under a microscope. At a 3-month to 6-month follow-up, only two patients from the normal group suffered exacerbated language deficits due to tumour recurrence. Meanwhile, language function in all patients in the aphasia group had improved. Therefore, AF neuronavigation, combined with 1.5 T iMRI, is a feasible method of maximising resection and minimising language deficits when removing gliomas that involve the AF.

Pro-opiomelanocortin gene transfer to the nucleus of the solitary track but not arcuate nucleus ameliorates chronic diet-induced obesity.

Short-term pharmacological melanocortin activation deters diet-induced obesity (DIO) effectively in rodents. However, whether central pro-opiomelanocortin (POMC) gene transfer targeted to the hypothalamus or hindbrain nucleus of the solitary track (NTS) can combat chronic dietary obesity has not been investigated. Four-weeks-old Sprague-Dawley rats were fed a high fat diet for 5 months, and then injected with either the POMC or control vector into the hypothalamus or NTS, and body weight and food intake recorded for 68 days. Insulin sensitivity, glucose metabolism and adrenal indicators of central sympathetic activation were measured, and voluntary wheel running (WR) assessed. Whereas the NTS POMC-treatment decreased cumulative food consumption and caused a sustained weight reduction over 68 days, the hypothalamic POMC-treatment did not alter cumulative food intake and produced weight loss only in the first 25 days. At death, only the NTS-POMC rats had a significant decrease in fat mass. They also displayed enhanced glucose tolerance, lowered fasting insulin and increased QUICK value, and elevated adrenal indicators of central sympathetic activation. Moreover, the NTS-POMC animals exhibited a near 20% increase in distance ran relative to the respective controls, but the ARC-POMC rats did not. In conclusion, POMC gene transfer to the NTS caused modest anorexia, persistent weight loss, improved insulin sensitivity, and increased propensity for WR in DIO rats. These metabolic improvements may involve stimulation of energy expenditure via centrally regulated sympathetic outflow. The similar POMC treatment in the hypothalamus had minimal long-term physiological or metabolic impact. Thus, melanocortin activation in the brainstem NTS region effectively ameliorates chronic dietary obesity whilst that in the hypothalamus fails to do so.

The action of leptin on appetite-regulating cells in the ovine hypothalamus: demonstration of direct action in the absence of the arcuate nucleus.

It is widely accepted that leptin acts on first-order neurons in the arcuate nucleus (ARC) with information then relayed to other hypothalamic centers. However, the extent to which leptin mediates its central actions solely, or even primarily, via this route is unclear. We used a model of hypothalamo-pituitary disconnection (HPD) to determine whether leptin action on appetite-regulating systems requires the ARC. This surgical preparation eliminates the ARC. We measured effects of iv leptin to activate hypothalamic neurons (Fos labeling). In ARC-intact animals, leptin increased the percentage of Fos-positive melanocortin neurons and reduced percentages of Fos-positive neuropeptide Y neurons compared with saline-treated animals. HPD itself increased Fos labeling in the lateral hypothalamic area (LHA). Leptin influenced Fos labeling in the dorsomedial nucleus (DMH), ventromedial nucleus, and paraventricular nucleus (PVN) in HPD and normal animals, with effects on particular cell types varying. In the LHA and DMH, leptin decreased orexin cell activation in HPD and ARC-intact sheep. HPD abolished leptin-induced expression of Fos in melanin-concentrating hormone cells in the LHA and in CRH cells in the PVN. In contrast, HPD accentuated activation in oxytocin neurons. Our data from sheep with lesions encompassing the ARC do not suggest a primacy of action of leptin in this nucleus. We demonstrate that first order to second order signaling may not represent the predominant means by which leptin acts in the brain to generate integrated responses. We provide evidence that leptin exerts direct action on cells of the DMH, ventromedial nucleus, and PVN.

Growth patterns of craniopharyngioma in children: role of the diaphragm sellae and its surgical implication.

BACKGROUND: Most craniopharyngiomas can be classified as either "prechiasmatic" or "retrochiasmatic" according to their growth patterns. The purpose of our study was to investigate the factors determining these growth patterns. METHODS: The radiological, operative, and pathological findings of 25 consecutive cases were reviewed. RESULTS: In cases with prechiasmatic growth (n = 14), most tumors were easily separated from the undersurface of the third ventricular floor with the exception of a small area at the top of the tumor where tumor-glial interfaces occurred. Pathological examination of the tough tumor surface demonstrated well-organized collagen tissue, which is compatible with diaphragm sellae. All tumors of this type had intrasellar components, suggesting a subdiaphragmatic origin for this tumor type. On the other hand, tumors with retrochiasmatic growth (n = 11) demonstrated a prefixed chiasm, and most of the surface excluding areas exposed to ventricular cerebrospinal fluid showed tumor-glial interfaces. With the exception of three, all tumors of this type lacked intrasellar components, and the diaphragm sellae was depressed and free of tumor, suggestive of a supradiaphragmatic infundibular origin of the tumor. CONCLUSION: Growth pattern is closely correlated to the origin of the tumor, whether it is above or below the diaphragm sellae. In craniopharyngiomas with prechiasmatic growth, the major portion of the tumor could be resected by traction. These tumors are candidates for the transsphenoidal approach if the sphenoid sinus is pneumatized. Tumors with retrochiasmatic growth, which are not covered by diaphragm sellae and contact brain tissue directly, are easily torn by traction and the tumor-glial interface should be carefully dissected under direct vision.

Neuroendocrine regulation of seasonal gonadotrophin and prolactin rhythms: lessons from the Soay ram model.

Marked seasonality, responsiveness to photoperiod, diurnal behaviour, large body size, long lifespan and adaptability in captivity are characteristics that make the Soay ram a useful model for neuroendocrine research. Adult rams are routinely housed indoors under artificial lighting of alternating 16 week periods of long and short days to entrain the seasonal cycles in reproduction, growth and metabolism. The long-term cycles in individuals are monitored directly (measurements of testis diameter, androgen-dependent skin coloration, food intake, pelage moult, locomotor activity) and retrospectively (measurements of reproductive and metabolic hormone concentrations in peripheral blood). A wide spectrum of experimental procedures, including serial blood and cerebrospinal fluid (CSF) sampling with hormone or drug treatments, tissue biopsy, stereotaxic cerebral implantation and surgical lesions, not feasible in smaller species, are used to investigate the multiple interactive neuroendocrine systems regulating seasonality. The results from a recent experiment in which rams received a lesion of the caudal arcuate nucleus (caudal ARCX) or hypothalamo-pituitary disconnection (HPD) are presented to demonstrate the fidelity of long-term data derived from the Soay ram model. The results support the view that the melatonin signal that encodes photoperiod acts within the mediobasal hypothalamus to time the gonadotrophin/gonadal cycle, but acts directly within the pituitary gland to time the prolactin/pelage cycle.

Arcuate nucleus ablation prevents fasting-induced suppression of ProTRH mRNA in the hypothalamic paraventricular nucleus.

Fasting results in reduced thyroid hormone levels and inappropriately low or normal thyroid-stimulating hormone (TSH), partly attributed to central hypothyroidism due to suppression of pro TRH gene expression in the hypothalamic paraventricular nucleus. Recently, we demonstrated that the systemic administration of leptin to fasting animals restores plasma thyroxine (T4) and proTRH mRNA in the paraventricular nucleus to normal, suggesting that the fall in circulating leptin levels during fasting acts as a signal to hypophysiotropic neurons in the paraventricular nucleus to reset the set point for feedback regulation of pro TRH mRNA by thyroid hormone. To determine whether the effect of fasting on the hypothalamic-pituitary-thyroid axis is mediated through the hypothalamic arcuate nucleus where leptin receptors are highly concentrated, we studied the effect of fasting and exogenous leptin administration on plasma thyroid hormone levels and proTRH mRNA concentration in the paraventricular nucleus in adult animals with arcuate nucleus lesions induced pharmacologically by the neonatal administration of monosodium L-glutamate (MSG). In normal animals, fasting reduced plasma T4 and TSH levels and the concentration of proTRH mRNA in the hypothalamic paraventricular nucleus. In contrast, neither fasting nor leptin administration to fasting MSG-treated animals had any significant effects on plasma thyroid hormone and TSH levels and proTRH mRNA in the paraventricular nucleus. These studies suggest that during fasting, the arcuate nucleus is essential for the normal homeostatic response of the hypothalamic-pituitary-thyroid axis and may serve as a critical locus to mediate the central actions of leptin on proTRH gene expression in the paraventricular nucleus.

Correction of tetralogy of Fallot with combined transatrial and pulmonary approach: experience with 184 consecutive cases.

The authors present their technique and results for complete correction of Fallot's tetralogy by closure of the ventricular septal defect by the transatrial approach, and resection of the infundibular hypertrophy by a combined approach through the tricuspid and pulmonary valve orifices. Right ventricular pressures were often high at the end of operation due to a residual muscular gradient but the outcome of these postoperative gradients was similar to that of valvular pulmonary stenosis with an intact ventricular septum.