Serotonergic mechanisms of the median raphe nucleus-dorsal hippocampus in conditioned fear: Output circuit involves the prefrontal cortex and amygdala

Independent studies have shown that the median raphe nucleus (MRN) and dorsal hippocampus (DH) are involved in the expression of contextual conditioned fear (CFC). However, studies that examine the integrated involvement of serotonergic mechanisms of the MRN-DH are lacking. To address this issue, a CFC paradigm was used to test whether the serotonergic projections from the MRN to DH can influence CFC. Serotoninergic drugs were infused either into the MRN or DH prior to testing sessions in which freezing and startle responses were measured in the same context where 6 h previously rats received footshocks. A reduction of serotonin (5-HT) transmission in the MRN by local infusions of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) decreased freezing in response to the context but did not reduce fear-potentiated startle. This pattern of results is consistent with the hypothesis that MRN serotonergic mechanisms selectively modulate the freezing response to the aversive context. As for the DH, a decrease in postsynaptic 5-HT receptor activity at projection areas has been proposed to be the main consequence of 5-HT(1A) receptor activation in the MIRN. Intra-DH injections of 8-OH-DPAT inhibited both the freezing and fear-potentiated startle response to the context. To reconcile these findings, an inhibitory mechanism may exist between the incoming 5-HT pathway from the MRN to DH and the neurons of the DH output to other structures. The DH-amygdala or medial prefrontal cortex projections could well be this output circuit modulating the expression of CFC as revealed by measurements of Fos immunoreactivity in these areas. (C) 2009 Elsevier B.V. All rights reserved.

Stereotactic disconnection of hypothalamic hamartoma to control seizure and behavior disturbance: case report and literature review

An 18-year-old boy with refractory epilepsy and aggressiveness associated to a hypothalamic hamartoma was submitted to a stereotactically guided lesion by thermocoagulation. The target was based on magnetic resonance (MR) images merged with computed tomography scan images taken on the day of surgery while patient was on a stereotactic frame. In order to reveal structures not discernible in MR images, the Schaltenbrand digital brain atlas was merged onto the patient`s images. Target and trajectory of the depth electrode were chosen based on three-dimensional imaging reconstructions. A surgical plan was devised to disconnect the hypothalamic hamartoma from the hypothalamus, medial forebrain bundle, fasciculus princeps, and dorsal longitudinal fasciculus. Our target was placed at the inferior portion of the posterolateral component of the hamartoma, bordering the normal hypothalamus. The patient evolved with marked lessening of aggressiveness. Seizure frequency was reduced from several seizures per day to less than one tonic-clonic seizure during sleep per month and only two episodes suggestive of partial complex seizures during daytime. These results have remained consistent over a 24-month postoperative follow-up. Functional neuroanatomy of hypothalamic connections involved in seizure propagation and aggressive behavior was reviewed.

Surgical Correction of Aesthetically Deformed Eyebrows Using Local Transposition Flaps

Eyebrow positions differ in many ways. They vary in shape, thickness, length, and distance between the eyebrows, making the face more or less harmonious. When a large distance exists between the eyebrows and the medial brow is slanting downward, the glabellar area is larger, giving the face an awkward appearance. To correct this deformity, the authors propose using two Z-plasties to allow transposition of flaps in the region of the medial brow. The Z-shaped flap is outlined at the medial third of the brow, in the glabellar region, with the eyebrow centered in the lower portion of the ""Z"" and the hairless skin in the upper portion. The flaps then are transposed and sutured. Transposition of the flaps, lifting the brow flap to the glabellar region, results in horizontal positioning of the medial and central third of the eyebrow. The proposed transpositioning of ""Z"" flaps in this region corrects this type of deformity of the medial and central portions of the eyebrows, with an aesthetically satisfactory result.

Limb Salvage Using Bypass to the Perigeniculate Arteries

Objective: To describe bypass to perigeniculate vessels for limb salvage. Design: Retrospective cohort study. Material and methods: Between 1995 and 2009, 47 bypass procedures to perigeniculate collateral arteries were performed in 46 patients (15 women, 31 men; median age, 68 years). All patients presented with critical ischaemia (tissue loss in 87.5%, rest pain in 12.5%). Mean ankle brachial index was 0.27 +/- 0.17. The site of distal anastomosis was the descending genicular artery (DGA) in 23 bypasses (1 bilateral) and the medial sural artery (MSA) in 24. Proximal anastomosis was to the external iliac artery in 2 cases, common femoral artery in 23 cases, superficial femoral artery in 8 cases, deep femoral artery in 8 cases, above-knee poplitaeal artery in 2 cases, and previous graft in 4 cases. Results: There were four deaths during the immediate postoperative period. Mean follow-up duration was 27 months. Ten patients required major amputation. Mean ankle brachial index post-operatively was 0.60 +/- 0.21. At 3 years, primary patency was 74.7 +/- 7%, secondary patency was 83.4 +/- 8%, and the limb salvage and survival rates were 73.5 +/- 7% and 77.4 +/- 7%, respectively. Conclusion: Bypass to perigeniculate arteries is a viable treatment option for critical limb ischaemia in selected patients. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Oral-Nasal-Ocular Cleft: The Greatest Challenge Among the Rare Clefts

Introduction: Number 3 cleft or oral-nasal-ocular cleft is a well-known entity that was described by Morian over a century ago. This malformation is a paranasal-medial orbitomaxillary cleft running across the lacrimal segment of the lower eyelid and over the lacrimal groove. The Tessier number 3 naso-ocular cleft represents one of the most difficult and challenging malformations to correct for the reconstructive surgeon. We have conducted a retrospective analysis of our series consisting of 21 cases. Objective: The objective was to review the functional outcome and aesthetic results of the different techniques applied for each case. Materials and Methods: From 1997 to 2007, 21 patients with a Tessier number 3 cleft were treated in our craniofacial units. The clinical findings, tomographic studies, and surgical procedures were reviewed and analyzed. We have discussed our protocol of the treatment. Results: We have treated facial malformation in 2 craniofacial centers. Fourteen patients were evaluated in the first year of their life, with an average age at presentation of 3 years. Twelve patients were female, and 9 were male; 6 patients had amniotic bands in limbs, 5 patients had an association with Tessier number 11 cleft, 3 patients with number 9 cleft, and 1 with number 7 cleft. Related to cleft lip, 10 patients had bilateral cleft lip, and 8 patients had unilateral cleft lip. Three patients did not have any involvement of the upper lip. The alar base was deviated upward in 19 patients, 11 cases had severe anatomic alteration with the lateral border of the ala above the medial canthus, and 8 cases had a mild dislocation. Nine cases of lacrimal duct obstruction and 8 cases of lacrimal duct extrophy were identified. Twelve patients had a lower eyelid coloboma of varying grades, and there were 2 cases of microblepharia. Aiming the soft tissue reconstruction, eyelid, nose, and upper lip were evaluated regarding their position, absence of tissue, and position of medial canthus and ala. Twelve of our patients underwent correction in the same moment, their medial canthus rotated upward and the ala downward, using the contralateral side as the reference. The lip was treated using a Millard-like technique. Neo-conjunctivorhinostomy was performed in the same moment in 2 patients or later in 1 case. Four patients had plagiocephaly due to the cranial involvement, and they were submitted to cranioplasty. Three had neurosurgical approach and advancement of the frontal bandeau. One adult patient received an acrylic plate to reshape the frontal area. Conclusions: Tessier number 3 cleft is one of the most difficult and challenging malformations to correct for the reconstructive surgeon. Besides the difficulties of its treatment, patients with Tessier number 3 cleft may achieve good results when the team has good skills.

The Tessier Number 5 Facial Cleft: Surgical Strategies and Outcomes in Six Patients

The Tessier no. 5 facial cleft is an extremely rare congenital malformation. Only 26 cases have been described In the English-language literature. The cleft begins In the upper lip just medial to the oral commissure, extending across the cheek as a groove ending at the junction of the middle and lateral thirds of the lower eyelid. The bone Involvement usually Includes an alveolar cleft in the premolar region, extends across the maxilla lateral to the Infraorbital nerve, up to the infraorbital rim and orbital floor. The goals of the surgical procedure Include reconstructing the lower eyelid, repositioning the lateral canthus, closure of the labiomaxillary cleft, and restoration of the skeletal continuity (including the orbital floor defect) with bone grafts. We present six patients with the Tessier no. 5 facial cleft who have been treated in our combined centers and discuss the surgical options and difficulties faced in the reconstruction of this rare and challenging craniofacial malformation. To date, we have treated six patients (two with bilateral and four with unilateral clefts). Three of the patients with unilateral clefting had an associated no. 4 cleft and one patient with a bilateral cleft had an associated no. 3 cleft. This paper represents the largest series to date documenting surgery for patients with the Tessier no. 5 facial cleft.

Tessier No. 4 Facial Cleft: Evolution of Surgical Treatment in a Large Series of Patients

Background: Tessier no. 4 facial cleft is a rare, complex, and challenging craniofacial malformation. The present article aims to describe different clinical features evidenced in 21 cases of this malformation, discussing a 20-year experience with and evolution of its surgical treatment. Methods: Some demographic data, clinical features, and reconstructive results were evaluated retrospectively. These patients have been evaluated and treated in three specialized Brazilian craniofacial centers. Nineteen were already operated on, with a mean follow-up of 3.5 years (range, 1 to 20 years). Results: Sex distribution showed a male prevalence (2: 1). The average age of initial treatment was 5.4 years. Four cases were affected on the right side of the face, seven on the left, and 10 bilaterally. Six patients had other rare associated facial clefts, including nos. 5 (three patients), 7, 9, and 10. Cleft upper lip was evidenced in all patients, and maxillary hypoplasia was present in five and maxilla cleft in eight. Lower eyelid coloboma was seen in almost every case (19 patients); 10 of these had medial canthus dystopia. Four patients had amniotic bands in the limbs. Surgical repair was individualized to each patient. Surgical experience gained with these patients allowed the authors to develop some technical modifications, which have improved aesthetic results, camouflaging scars into natural folds and anatomical units, without compromising functional outcomes. Conclusions: The great majority of Tessier no. 4 facial clefts can be appropriately treated using local flaps. Classic techniques are extremely useful, but long-term results could be improved if the technical modifications described were adopted. (Plast. Reconstr. Surg. 122: 1505, 2008.)

Auto-antibodies do not influence development of atherosclerotic plaques in rheumatoid arthritis

Background: Many questions remain unanswered about premature atherosclerosis in rheumatoid arthritis (RA). Besides inflammation, some studies have suggested the role of autoantibodies on its pathogenesis. Objective: The aim of this study was to investigate the presence of antibodies against phospholipids, beta2-glycoproteinl (beta2-gpl), lipoprotein lipase, and heat shock proteins (Hsp) in RA patients and to evaluate their possible association with subclinical carotid atherosclerosis. Methods: Seventy-one RA patients and 53 age- and sex-matched controls were selected to perform anticardiolipin antibodies (aCL) (IgG and IgM), anti-beta2-gpl (IgG, IgM, and IgA), anti-lipoprotein lipase (anti-LPL), anti-Hsp 60, and anti-Hsp 65 by ELISA tests. Intima-medial thickness (IMT) of common carotid and presence of plaques were assessed by high-resolution B-mode ultrasonography. Exclusion criteria were smoking, diabetes, and arterial hypertension. Lipoproteins, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen levels, as well as health assessment questionnaire (HAQ) and disease activity score (DAS) 28 were also evaluated. Results: Age (48.93 +/- 12.31 vs. 45.37 +/- 9.37 years; p = 0.20) and body mass index (BMI) (p = 0.69) were similar in RA and controls, as well as female gender (p = 0.56). The mean IMT was similar between RA and controls (0. 721 +/- 0.16 vs. 0.667 +/- 0.14 turn, p = 0.07) but the frequency of plaques was higher in RA (14.1% vs. 1.9%; p = 0.02). In RA patients, IMT measurements did not differ according to the presence or absence of these antibodies: IgG aCL (0.62 +/- 0.64 vs. 0.72 +/- 0.17 mm, p = 0.24), IgM aCL (0.65 +/- 0.79 vs. 0.73 +/- 0.17 mm, p = 0.33), anti-Hsp 60 (0.78 +/- 0.20 vs. 0.71 +/- 0.16 mm, p = 0.27), anti-Hsp 65 (0.73 +/- 0.16 vs. 0.72 +/- 0.17 mm, p = 0.77), IgG anti-beta2-gpl (0.73 +/- 0.16 vs. 0.71 +/- 0.17 mm, p = 0.72), and anti-CCP (0.71 +/- 0.16 vs. 0.76 +/- 0.20 mm, p = 0.36). In addition, IMT did not correlate with antibodies titers: IgG aCL (r = -0.09, p = 0.47), IgM aCL (r = - 0.15, p = 0.21), anti-Hsp 60 (r = 0.10, p = 0.42), anti-Hsp 65 (r = 0.05, p = 0.69), IgG anti-beta2-gpl (r = - 0.07, p = 0.57), IgM anti-beta2-gpl (r = - 0.05, p = 0.69), IgA anti-beta2-gpl (r = 0.03, p = 0.79), and anti-CCP (r = - 0.07, p = 0.57). RA patients with plaques had a significantly higher age compared to those without plaques (p = 0.001), as well as higher mean IMT (p < 0.001), total cholesterol (p = 0.001), and LDL (p = 0.003). Conclusions: In RA a clear association between all autoantibodies studied herein and increased IMT or presence of plaques was not observed. The great prevalence of carotid atherosclerosis in RA was related to age, total and LDL cholesterol, as identified in normal population. (c) 2008 Elsevier Masson SAS. All rights reserved.

Collagen is reduced and disrupted in human aneurysms and dissections of ascending aorta

In ascending aorta aneurysms, there is an enlargement of the whole vessel, whereas aortic dissections (ADs) are characterized by the cleavage of the wall into 2 sheets at the external half. We searched if alterations in collagen could be related to these diseases. Sections of aortas from 14 case patients with acute dissections, 10 case patients with aneurysms, and 9 control subjects were stained with picrosirius. Slides were analyzed under polarized microscopy to evaluate the structure of collagen fibers. The proportion of collagen was calculated in each half of the medial layer by color detection in a computerized image analysis system. Collagen appearance under polarized light was consistent with collagenolysis. The mean collagen proportions at the inner and outer halves, respectively, were 0.50 +/- 0.13 and 0.40 +/- 0.08 in the control group, 0.20 +/- 0.10 and 0.18 +/- 0.12 in the AD group, and 0.33 +/- 0.12 and 0.19 +/- 0.12 in the aneurysm group. The AD (P < .01) and control (P = .04) groups had less collagen at the external half, no difference was found in the aneurysm group (P = .71). In both halves, there was less collagen in the case patients than in the control subjects (all P < .01), but at the internal half, the decrease was significantly greater in the case patients with aneurysms than in those with dissections (P = .03; at the external half, P = .99). Aortic dissections and aneurysms show a decrease in collagen content that could be related to a weakness of the wall underlying the diseases, but the locations of the decrease differ: in dissections, it is situated mostly at the external portion of the media (site of cleavage), whereas in aneurysms, it is more diffuse, consistent with the global enlargement. (c) 2008 Elsevier Inc. All rights reserved.

Severe Periodontitis Is Associated With Diastolic Blood Pressure Elevation in Individuals With Heterozygous Familial Hypercholesterolemia: A Pilot Study

Background: This pilot study evaluates the association of severe periodontitis with pulse wave velocity (PWV), carotid artery intima-medial thickness (IMT), and clinical, metabolic, and atherogenic inflammatory markers in 79 subjects with heterozygous familial hypercholesterolemia (hFH). All subjects were free of previous vascular disease manifestations. Methods: The body mass index (in kilograms per square meter), plasma lipids, glucose, C-reactive protein, and white blood cell counts were evaluated. After full-mouth periodontal examinations, patients were categorized into the severe periodontitis group (SPG) or non-severe periodontitis group (NSPG). Results: The SPG showed significantly higher values of cholesterol-year scores, triglycerides, glucose, PWV, IMT, and diastolic blood pressure (DBP) (P <= 0.05) than the NSPG. After adjustment for traditional risk factors for atherosclerosis, only the association between severe periodontitis and DBP (odds ratio: 3.1; 95% CI: 1.1 to 8.5; P = 0.03) was confirmed. Conclusion: In individuals with hFH, severe periodontitis was associated with a higher DBP, which suggests that severe periodontitis, itself, may contribute to the increased cardiovascular risk profile in this population. J Periodontol 2011;82:683-688.

rTMS treatment for depression in Parkinson`s disease increases BOLD responses in the left prefrontal cortex

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson`s disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic Stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Age-related gray matter volume changes in the brain during non-elderly adulthood

Previous magnetic resonance imaging (MRI) studies described consistent age-related gray matter (GM) reductions in the fronto-parietal neocortex, insula and cerebellum in elderly subjects, but not as frequently in limbic/paralimbic structures. However, it is unclear whether such features are already present during earlier stages of adulthood, and if age-related GM changes may follow non-linear patterns at such age range. This voxel-based morphometry study investigated the relationship between GM volumes and age specifically during non-elderly life (18-50 years) in 89 healthy individuals (48 males and 41 females). Voxelwise analyses showed significant (p < 0.05, corrected) negative correlations in the right prefrontal cortex and left cerebellum, and positive correlations (indicating lack of GM loss) in the medial temporal region, cingulate gyrus, insula and temporal neocortex. Analyses using ROI masks showed that age-related dorsolateral prefrontal volume decrements followed non-linear patterns, and were less prominent in females compared to males at this age range. These findings further support for the notion of a heterogeneous and asynchronous pattern of age-related brain morphometric changes, with region-specific non-linear features. (C) 2009 Elsevier Inc. All rights reserved.

White matter microstructure underlying default mode network connectivity in the human brain

Resting state functional magnetic resonance imaging (fMRI) reveals a distinct network of correlated brain function representing a default mode state of the human brain The underlying structural basis of this functional connectivity pattern is still widely unexplored We combined fractional anisotropy measures of fiber tract integrity derived from diffusion tensor imaging (DTI) and resting state fMRI data obtained at 3 Tesla from 20 healthy elderly subjects (56 to 83 years of age) to determine white matter microstructure e 7 underlying default mode connectivity We hypothesized that the functional connectivity between the posterior cingulate and hippocampus from resting state fMRI data Would be associated with the white matter microstructure in the cingulate bundle and fiber tracts connecting posterior cingulate gyrus With lateral temporal lobes, medial temporal lobes, and precuneus This was demonstrated at the p<0001 level using a voxel-based multivariate analysis of covariance (MANCOVA) approach In addition, we used a data-driven technique of joint independent component analysis (ICA) that uncovers spatial pattern that are linked across modalities. It revealed a pattern of white matter tracts including cingulate bundle and associated fiber tracts resembling the findings from the hypothesis-driven analysis and was linked to the pattern of default mode network (DMN) connectivity in the resting state fMRI data Out findings support the notion that the functional connectivity between the posterior cingulate and hippocampus and the functional connectivity across the entire DMN is based oil distinct pattern of anatomical connectivity within the cerebral white matter (C) 2009 Elsevier Inc All rights reserved

Depression in Parkinson`s disease: Convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus

Depression is the most frequent psychiatric disorder in Parkinson`s disease (PD). Although evidence Suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontall cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation. (C) 2009 Elsevier Inc. All rights reserved.

Ligaments of the Posterior and Lateral Talar Processes: MRI and MR Arthrography of the Ankle and Posterior Subtalar Joint with Anatomic and Histologic Correlation

OBJECTIVE. MRI and combined ankle and posterior subtalar MR arthrography in cadavers were used to evaluate the ligaments of the posterior and lateral talar processes. Subsequent anatomic and histologic correlation was performed. MATERIALS AND METHODS. Ten cadaveric ankles were used. Routine radiography and MRI were initially performed. Ankle and posterior subtalar MR arthrography, followed by anatomic and histologic analysis, was then performed to allow better assessment of the ligaments of the lateral and posterior talar process. RESULTS. In all subjects, MR arthrography provided superior delineation of the articular and periarticular structures, as well as the ligaments. The lateral talocalcaneal and medial talocalcaneal ligaments were best seen in the axial and coronal planes, respectively. The axial plane was best for visualizing the fibulotalocalcaneal ligament, and the sagittal plane was best for evaluating the posterior talocalcaneal ligament. The anterior and posterior talofibular ligaments and the posterior tibiotalar ligament (superficial and deep portions) were best seen in the axial plane. Histologic analysis was correlated to anatomic sectioning and showed the attachment sites of these ligaments. CONCLUSION. Combined ankle and posterior subtalar MR arthrography enhances visualization of the ligaments attaching to the posterior and lateral talar processes, including the posterior, lateral, and medial talocalcaneal and fibulotalocalcaneal ligaments.