When Playing Is a Problem: An Atypical Case of Alien Hand Syndrome in a Professional Pianist.

Alien hand syndrome (AHS) is a neurological illness characterized by limb movements which are carried out without being aware of it. Many patients describe these movements as aggressive and some perceive a strong feeling of estrangement and go so far as to deny ownership. The sense of body ownership is the perception that parts of one's body pertain to oneself, despite it is moving or not and if movement is intentional or unintentional. These anomalous self-experiences may arise in patients with focal brain lesions and provide unique opportunities to disclose the neural components underlying self-body perception. The feeling of foreignness described in AHS is often observed in post-central cortical lesions in the non-dominant hemisphere and is typical of the "posterior alien hand variant". We used Diffusion-Tensor magnetic resonance imaging (DT-MRI) in an unusual case of posterior AHS of the dominant hand in a professional pianist with corticobasal syndrome (CBS). The patient showed uncontrolled levitation with the right arm while playing the piano and perceived as if her hand had a "mind of its own" which prevented her from playing. MRI-scans show asymmetric brain atrophy, mainly involving left post-central regions and SPECT-Tc99m-ECD patterns of hypometabolism over the left parietal-occipital cortices. DT-MRI revealed extensive damage which comprised left fronto-temporal cortex and extends into the ipsilateral parietal cortex causing a disruption of corpus callosum (CC) projections from the rostrum to the splenium. Our case illustrates that posterior AHS may occur in the dominant hemisphere due to widespread damage, which exceed parietal cortex. The parietal lobe has been recognized as a multimodal association region that gets input from several networks and organizes motor output. We suggest that the disturbance to this pathway could result in disruption of motor output and associate an abnormal motor control and anomalous self-body perception.

Efficient Variational Approach to Multimodal Registration of Anatomical and Functional Intra-Patient Tumorous Brain Data.

This paper addresses the functional localization of intra-patient images of the brain. Functional images of the brain (fMRI and PET) provide information about brain function and metabolism whereas anatomical images (MRI and CT) supply the localization of structures with high spatial resolution. The goal is to find the geometric correspondence between functional and anatomical images in order to complement and fuse the information provided by each imaging modality. The proposed approach is based on a variational formulation of the image registration problem in the frequency domain. It has been implemented as a C/C[Formula: see text] library which is invoked from a GUI. This interface is routinely used in the clinical setting by physicians for research purposes (Inscanner, Alicante, Spain), and may be used as well for diagnosis and surgical planning. The registration of anatomic and functional intra-patient images of the brain makes it possible to obtain a geometric correspondence which allows for the localization of the functional processes that occur in the brain. Through 18 clinical experiments, it has been demonstrated how the proposed approach outperforms popular state-of-the-art registration methods in terms of efficiency, information theory-based measures (such as mutual information) and actual registration error (distance in space of corresponding landmarks).

Evolution of Liver Steatosis Quantified by MR Imaging and MR Spectroscopy, in Morbidly Obese Patients Undergoing Sleeve Gastrectomy: Short-Term Outcomes.

BACKGROUND: Currently, the standard procedure used to evaluate hepatic steatosis is the liver biopsy. This is an invasive practice that presents inherent risks. Increasing evidence suggests that magnetic resonance imaging (MRI) and MR spectroscopy (MRS) may represent an accurate method to determine the hepatic lipid content. The aim of this study was to evaluate the effect of sleeve gastrectomy on liver steatosis, quantified by MRI and MRS. PATIENTS AND METHODS: A prospective observational study of patients undergoing laparoscopic sleeve gastrectomy was performed. All patients underwent a MRI and a MRS study 2 weeks before the intervention and 6 months after the surgery. Anthropometric, biochemical, and radiological parameters were analyzed. RESULTS: Twenty-three patients were included, 21 females and 2 males, with a mean age of 47.6 ± 10.6 years and mean pre-op BMI 47.6 ± 6.7 Kg/m2. Six months after surgery, mean BMI was 32.2 ± 5.1 Kg/m2, with a mean excess weight loss of 68.2 ± 18.6%. Mean preoperative hepatic volume was 1999.9 ± 436.2 ml and 6 months after surgery it decreased to 1568 ± 170.3 ml (p = 0.005). Mean preoperative percentage of lipid content was 14.2 ± 15.4% and 6 months after surgery, it decreased to 4.3 ± 3.2% (p = 0.007). A significant reduction of steatosis grade was observed, with disappearance of preoperative steatosis in 54.9% of the patients. CONCLUSION: Six months after sleeve gastrectomy, a significant reduction of liver steatosis is observed, as demonstrated by reduction in the percentage of intrahepatocitary lipids and liver volume, determined by MRS and MRI. These imaging techniques can be considered as noninvasive, accurate methods for monitoring liver steatosis in morbidly obese patients undergoing bariatric surgery.

Is diffusion tensor imaging useful in the assessment of the sciatic nerve and its pathologies? Our clinical experience.

OBJECTIVE: To evaluate the usefulness of diffusion tensor imaging (DTI) in the clinical setting as a complementary tool to conventional MRI in the study and assessment of the sciatic nerve and its pathologies. METHODS: 17 patients diagnosed with different types of sciatic neuropathy and 10 healthy controls underwent a conventional MRI and a DTI study in a 3-T MR scanner (Achieva(®) 3-T X-Series; Philips Healthcare, Netherlands). RESULTS: In the control group, we were able to track and visualize the common sciatic nerve and its main branches from hip to foot. In the patient group, the affected sciatic nerves presented statistically significant lower fractional anisotropy values and higher apparent diffusion coefficient values when compared with controls, suggesting nerve damage. In all cases, DTI offered complementary information for diagnosis and/or confirmation of the suspected pathology. When compared with conventional MRI, DTI showed higher sensitivity for nerve damage detection. CONCLUSION: DTI offers a significant improvement and an important complement to visualize the sciatic nerve and its main branches. In patients with sciatic nerve pathology DTI allows to a better detection and characterization of the nerve damage. ADVANCES IN KNOWLEDGE: DTI enables in vivo dissection of the sciatic nerve white matter fibres; its use offers a significant improvement and complement to conventional MRI.

Gd-Si Oxide Nanoparticles as Contrast Agents in Magnetic Resonance Imaging.

We describe the synthesis, characterization and application as contrast agents in magnetic resonance imaging of a novel type of magnetic nanoparticle based on Gd-Si oxide, which presents high Gd3+ atom density. For this purpose, we have used a Prussian Blue analogue as the sacrificial template by reacting with soluble silicate, obtaining particles with nanorod morphology and of small size (75 nm). These nanoparticles present good biocompatibility and higher longitudinal and transversal relaxivity values than commercial Gd3+ solutions, which significantly improves the sensitivity of in vivo magnetic resonance images.

Gd-Si oxide mesoporous nanoparticles with pre-formed morphology prepared from a Prussian blue analogue template.

A novel approach to the synthesis of Gd-Si oxide mesoporous nanoparticles with a high Gd(3+) atom density and pre-formed morphology is presented. Prussian blue analogue Gd(H2O)4[Fe(CN)6], a metal organic framework that crystallizes in the orthorhombic system, is used for the first time as a sacrificial template by a reaction with soluble silicate. Simultaneous and stoichiometric condensation of gadolinium hydroxide and silica takes place, leading to dense and monodispersed nanoparticles that preserve the original shape and size of the Prussian blue analogue crystals. Then, porosity is developed by incorporation of cetyltrimethylammonium bromide under hydrothermal conditions. The obtained Gd-Si mesoporous oxide particles present a dual morphology of nanocrosses and nanorods and large surface areas.

Hearing colors: an example of brain plasticity.

Sensory substitution devices (SSDs) are providing new ways for improving or replacing sensory abilities that have been lost due to disease or injury, and at the same time offer unprecedented opportunities to address how the nervous system could lead to an augmentation of its capacities. In this work we have evaluated a color-blind subject using a new visual-to-auditory SSD device called "Eyeborg", that allows colors to be perceived as sounds. We used a combination of neuroimaging techniques including Functional Magnetic Resonance Imaging (fMRI), Diffusion Tensor Imaging (DTI) and proton Magnetic Resonance Spectroscopy ((1)H-MRS) to study potential brain plasticity in this subject. Our results suggest that after 8 years of continuous use of this device there could be significant adaptive and compensatory changes within the brain. In particular, we found changes in functional neural patterns, structural connectivity and cortical topography at the visual and auditive cortex of the Eyeborg user in comparison with a control population. Although at the moment we cannot claim that the continuous use of the Eyeborg is the only reason for these findings, our results may shed further light on potential brain changes associated with the use of other SSDs. This could help to better understand how the brain adapts to several pathologies and uncover adaptive resources such as cross-modal representations. We expect that the precise understanding of these changes will have clear implications for rehabilitative training, device development and for more efficient programs for people with disabilities.

Epidermoid cyst with a metabolite pattern mimicking a brain abscess. A magnetic resonance spectroscopy study.

BACKGROUND AND PURPOSE: Intracranial epidermal cysts are benign uncommon lesions. Such lesions arise from an inclusion of an ectodermal element during neural tube closure, in which dermal elements become trapped in the suture line, diploe, meninges, or scalp. Reports have extensively demonstrated the typical magnetic resonance (MR) spectra with the presence of large lactate signals with a virtual absence of healthy brain metabolites. METHODS: A 20-year-old male patient with a parietal lobe brain lesion was studied by magnetic resonance imaging and magnetic resonance spectroscopy in a 1.5-T Philips scanner. RESULTS: The lesion presented atypical MR spectra with presence of alanine (1.46 ppm), lactate (1.31 ppm), and amino acids such as valine, isoleucine (0.97 ppm), and glicine (3.52 ppm). No evidence of normal parenchyma tissue metabolites (N-acetylaspartate, creatine, and choline) or succinate and acetate signals was observed. This spectral pattern was unexpected being proposed the differential diagnosis of brain abscess versus epidermoid cyst. Finally, surgical total excision biopsy confirmed the diagnosis of epidermal cyst. CONCLUSIONS: In this report, we describe a case of an epidermal cyst with an unusual metabolic pattern observed by magnetic resonance spectroscopy mimicking a brain abscess.

Response to immunotherapy in CLIPPERS: clinical, MRI, and MRS follow-up.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system disorder responsive to steroids with characteristic magnetic resonance imaging (MRI) features. We report a 69-year-old man presenting with gait ataxia with the characteristic MRI features of CLIPPERS and describe the clinical, MRI, and magnetic resonance spectroscopy (MRS) follow-up after treatment with glucocorticosteroids. Brain and spine MRI showed punctate enhancement peppering the brainstem, cerebellar peduncles, and upper cervical cord. In MRS, the ratio of N-acetyl aspartate to creatine (NAA/Cr) was significantly decreased in the pons and both thalami. An extensive evaluation found no alternative diagnoses. Treatment with steroids led to rapid clinical improvement. Repeat MRI and MRS showed complete resolution of gadolinium-enhancing lesions and recovery of NAA/Cr levels in the pons and thalami. After 1 month of tapering oral steroids, weekly oral methotrexate was started and the patient has remained stable for the past 6 months.

Brain edema dynamics in patients with overt hepatic encephalopathy A magnetic resonance imaging study.

UNLABELLED: The aim of our study was to investigate the dynamics of brain water content assessed by magnetic resonance imaging (MRI) applications in patients with cirrhosis and overt episodic hepatic encephalopathy (HE). METHODS: Twenty-four patients with cirrhosis and overt HE, 9 healthy controls and 9 controls with cirrhosis but without HE were included. All patients underwent laboratory analysis, MRI and (1)H MRS in the first 24h after the diagnosis of encephalopathy. Five of them were studied again 5days after the resolution of HE. RESULTS: The values of glutamine/glutamate (Glx) increased progressively (healthy controls: 1.8; cirrhotic controls: 2.4; HE: 4.4; p=0.0001). Values of myo-inositol were lower among cirrhotics than in healthy controls (healthy: 0.6; cirrhotic: 0.3; HE: 0.4; p=0.01). Patients with overt HE showed a decrease in MTR in several brain locations. A significant correlation was observed between MTR values and Glx/creatine ratios (r=-0.54; P=0.004). Five days after the resolution of HE, there were no changes in brain Glx/Cr or MTR but a significant decrease of median ADC in parietal grey matter was observed (acute HE: 121.9 vs. 5days later: 100.5; p<0.05). CONCLUSIONS: Cirrhotic patients with overt HE have a disturbance in the brain osmolyte homeostasis, reflecting a low-grade brain edema. Shortly after the clinical resolution of the episode of HE low-grade brain edema still persists, but there is a decrease in the ADC value in the parietal grey matter, suggesting water flux from extracellular to intracellular compartments and the existence of a vasogenic brain edema.

Proton magnetic resonance spectroscopy (1H-MRS) reveals the presence of elevated myo-inositol in the occipital cortex of blind subjects.

This paper is addressed to investigate whether proton magnetic resonance spectroscopy ((1)H-MRS) may provide the means to investigate changes associated to alterations of neural activity and sensory experience in the blind. We examined the relationships between different brain metabolite levels in 10 blind volunteers and 10 sighted subjects matched for age and gender. Adjusted levels of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), glutamate/glutamine (Glx) and myo-inositol (mIno) in the occipital cortex region were quantified in the water-suppressed spectrum using the AMARES estimation algorithms. An unpaired two-tailed t-test was used to determine any significant difference in metabolite ratios. Our results show that none of the blind volunteers presented atrophy or any other MRI detectable degenerative change of the occipital cortex. The main finding was a significant increase of myo-inositol (mIno), a glial marker, in blind subjects compared to sighted controls. This simple sugar-like molecule can be found mainly within astrocytes, and cannot cross the blood-brain barrier. Therefore its increase could reflect glial proliferation or an increase in glial cell size. These results show that (1)H-MRS may help to understand the complex mechanisms involved in brain plasticity and suggest an active role of glial cells in the reorganization of the brain in response to visual deprivation.

The pre-transmembrane region of the HCV E1 envelope glycoprotein: interaction with model membranes.

The previously identified membranotropic regions of the HCV E1 envelope glycoprotein, a class II membrane fusion protein, permitted us to identify different sequences which might be implicated in viral membrane fusion, membrane interaction and/or protein-protein binding. HCV E1 glycoprotein presents a membrano-active region immediately adjacent to the transmembrane segment, which could be involved in membrane destabilization similarly to the pre-transmembrane domains of class I fusion proteins. Consequently, we have carried out a study of the binding and interaction with the lipid bilayer of a peptide corresponding to segment 309-340, peptide E1PTM, as well as the structural changes which take place in both the peptide and the phospholipid molecules induced by the binding of the peptide to the membrane. Here we demonstrate that peptide E1(PTM) strongly partitions into phospholipid membranes, interacts with negatively-charged phospholipids and locates in a shallow position in the membrane. These data support its role in HCV-mediated membrane fusion and suggest that the mechanism of membrane fusion elicited by class I and II fusion proteins might be similar.

Identification of the membrane-active regions of hepatitis C virus p7 protein: biophysical characterization of the loop region.

We have identified the membrane-active regions of the hepatitis C virus p7 protein by performing an exhaustive study of membrane rupture, hemifusion, and fusion induced by a p7-derived peptide library on model membranes having different phospholipid compositions. We report the identification in p7 of a highly membranotropic region located at the loop domain of the protein. Here, we have investigated the interaction of a peptide patterned after the p7 loop (peptide p7(L)), studying its binding and interaction with the lipid bilayer, and evaluated the binding-induced structural changes of the peptide and the phospholipids. We show that positively rich p7(L) strongly binds to negatively charged phospholipids and it is localized in a shallow position in the bilayer. Furthermore, peptide p7(L) exhibits a high tendency to oligomerize in the presence of phospholipids, which could be the driving force for the formation of the active ion channel. Therefore, our findings suggest that the p7 loop could be an attractive candidate for antiviral drug development, because it could be a target for antiviral compounds that may lead to new vaccine strategies.

Interaction of a peptide from the pre-transmembrane domain of the severe acute respiratory syndrome coronavirus spike protein with phospholipid membranes.

The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein, a Class I viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. In order to gain new insight into the protein membrane alteration leading to the viral fusion mechanism, a peptide pertaining to the putative pre-transmembrane domain (PTM) of the S glycoprotein has been studied by infrared and fluorescence spectroscopies regarding its structure, its ability to induce membrane leakage, aggregation, and fusion, as well as its affinity toward specific phospholipids. We demonstrate that the SARS-CoV PTM peptide binds to and interacts with phospholipid model membranes, and, at the same time, it adopts different conformations when bound to membranes of different compositions. As it has been already suggested for other viral fusion proteins such as HIV gp41, the region of the SARS-CoV protein where the PTM peptide resides could be involved in the merging of the viral and target cell membranes working synergistically with other membrane-active regions of the SARS-CoV S glycoprotein to heighten the fusion process and therefore might be essential for the assistance and enhancement of the viral and cell fusion process.

Characterization of the interaction of two peptides from the N terminus of the NHR domain of HIV-1 gp41 with phospholipid membranes.

The HIV-1 gp41 envelope glycoprotein is responsible for the membrane fusion between the virus and the target cell. According to recent models, the N-terminal coiled-coil (NHR) region of gp41 is involved in forming the interfaces between neighboring helices in the six-helix bundle, as well as in membrane binding and perturbation. In order to get new insights into the viral membrane fusion mechanism, two peptides, pFP15 and pFP23, pertaining to the first part of the gp41 NHR domain were studied regarding their structure and their ability to induce membrane leakage, aggregation, and fusion, as well as their affinity toward specific phospholipids by a variety of spectroscopic methods. Our results demonstrate that the first part of the NHR domain interacts with negatively charged phospholipid-containing model membranes, modifies the phase behavior of membrane phospholipids, and induces leakage and aggregation of liposomes, suggesting that it could be involved directly in the merging of the viral and target cell membranes working synergistically with other membrane-active regions of the gp41 glycoprotein to boost the fusion process. On the other hand, we suggest that this region of the NHR domain could be involved in the first steps of the destabilization of the HIV-1 gp41 six-helix bundle after its interaction with negatively charged phospholipid headgroups.

Two-dimensional infrared correlation spectroscopy study of the interaction of oxidized and reduced cytochrome c with phospholipid model membranes.

We have used two-dimensional infrared correlation spectroscopy (2D-IR) to study the interaction and conformation of cytochrome c in the presence of a binary phospholipid mixture composed of a zwitterionic perdeuterated phospholipid and a negatively-charged one. The influence of the main temperature phase transition of the phospholipid model membranes on the conformation of cytochrome c has been evaluated by monitoring both the Amide I' band of the protein and the CH(2) and CD(2) stretching bands of the phospholipids. Synchronous 2D-IR analysis has been used to determine the different secondary structure components of cytochrome c which are involved in the specific interaction with the phospholipids, revealing the existence of a specific interaction between the protein with cardiolipin-containing vesicles but not with phosphatidic acid-containing ones. Interestingly, 2D-IR is capable of showing the existence of significant changes in the protein conformation at the same time that the phospholipid transition occurs. In summary, 2D-IR revealed an important effect of the phospholipid phase transition of cardiolipin on the secondary structure of oxidized cytochrome c but not to either reduced cytochrome c or in the presence of phosphatidic acid, demonstrating the existence of specific intermolecular interactions between cardiolipin and cytochrome c.

Structure of the C-terminal domain of the pro-apoptotic protein Hrk and its interaction with model membranes.

The protein harakiri (Hrk) is a pro-apoptotic BH3-only protein which belongs to the Bcl-2 family. Hrk appears associated to the mitochondrial outer membrane, apparently by a putative transmembrane domain, where it exerts its function. In this work we have identified a 27mer peptide supposed to be the putative membrane domain of the protein at the C-terminal region, and used infrared and fluorescence spectroscopies to study its secondary structure as well as to characterize its effect on the physical properties of phospholipid model membranes. The results presented here showed that the C-terminal region of Hrk adopts a predominantly alpha-helical structure whose proportion and destabilization capability varied depending on phospholipid composition. Moreover it was found that the orientation of the alpha-helical component of this C-terminal Hrk peptide was nearly perpendicular to the plane of the membrane. These results indicate that this domain is able of inserting into membranes, where it adopts a transmembrane alpha-helical structure as well as it considerably perturbs the physical properties of the membrane.

The membrane-active regions of the hepatitis C virus E1 and E2 envelope glycoproteins.

We have identified the membrane-active regions of the full sequences of the HCV E1 and E2 envelope glycoproteins by performing an exhaustive study of membrane leakage, hemifusion, and fusion induced by 18-mer peptide libraries on model membranes having different phospholipid compositions. The data and their comparison have led us to identify different E1 and E2 membrane-active segments which might be implicated in viral membrane fusion, membrane interaction, and/or protein-protein binding. Moreover, it has permitted us to suggest that the fusion peptide might be located in the E1 glycoprotein and, more specifically, the segment comprised by amino acid residues 265-296. The identification of these membrane-active segments from the E1 and E2 envelope glycoproteins, as well as their membranotropic propensity, supports their direct role in HCV-mediated membrane fusion, sustains the notion that different segments provide the driving force for the merging of the viral and target cell membranes, and defines those segments as attractive targets for further development of new antiviral compounds.

Location and orientation of Triclosan in phospholipid model membranes.

Triclosan is a hydrophobic antibacterial agent used in dermatological preparations and oral hygiene products. Although the molecular mechanism of action of this molecule has been attributed to inhibition of fatty acid biosynthesis, earlier work in our laboratories strongly suggested that the antibacterial action of Triclosan is mediated at least partly through its membranotropic effects. In order to assess its location in phospholipid membranes, high-resolution magic-angle spinning natural abundance (13)C NMR of Triclosan embedded within egg yolk lecithin model membranes has been used to obtain (13)C spin-lattice relaxation times for both Triclosan and lecithin carbon atoms in the presence of Gd(3+ )ions. The results indicate that Triclosan is localized in the upper region of the phospholipid membrane, its hydroxyl group residing in the vicinity of the C = O/C2 carbon atoms of the acyl chain of the phospholipid, and the rest of the Triclosan molecule is probably aligned in a nearly perpendicular orientation with respect to the phospholipid molecule. Intercalation of Triclosan into bacterial cell membranes likely compromises the functional integrity of those membranes, thereby accounting for at least some of this compound's antibacterial effects.

A MAS-NMR study of the location of (+)-totarol, a diterpenoid bioactive molecule, in phospholipid model membranes.

(+)-Totarol, a diterpenoid isolated from Podocarpus spp., is a potent antioxidant and antibacterial agent. Although the mechanism of action of this hydrophobic molecule is poorly understood, recent work from our laboratories suggests that it could be due to membranotropic interactions. The location of (+)-totarol in membranes and its interaction with membrane components is therefore of considerable interest. High resolution magic angle spinning (MAS) natural abundance 13C nuclear magnetic resonance studies were undertaken to assess the location of (+)-totarol in model membranes composed of egg yolk phosphatidylcholine (EYL). 13C spin-lattice relaxation times (T(1)) of both the phospholipid and (+)-totarol molecules in the presence of Gd(3+) were measured to obtain information on molecular distances. Our results indicate that (+)-totarol is situated in the upper region of the membrane, with its hydroxyl group located in the vicinity of the C-3/4 carbon atoms of the phospholipid acyl chain, and nearly perpendicular with respect to the phospholipid acyl chain axis. Such a location of (+)-totarol in the membrane would be expected to compromise the functional integrity of the membrane and account, at least in part, for its antibacterial effects.