Differences in Frontal Activation in Adult Patients with Schizophrenia and in Psychotic Adolescents with Schizophrenic Symptoms in Two Fmri Tasks

Background: Language processing abnormalities and inhibition difficulties are hallmark features of schizophrenia. The objective of this study is to asses the blood oxygenation level-dependent (BOLD) response at two different stages of the illness and compare the frontal activity between adolescents and adults with schizophrenia. Methods: 10 adults with schizophrenia (mean age 31,5 years) and 6 psychotic adolescents with schizophrenic symptoms (mean age 16,2 years) underwent functional magnetic resonance imaging while performing two frontal tasks. Regional activation is compared in the bilateral frontal areas during a covert verbal fluency task (letter version) and a Stroop task (inhibition task). Results: Preliminary results show poorer task performance and less frontal cortex activation during both tasks in the adult group of patients with schizophrenia. In the adolescent patients group, fMRI analysis show significant and larger activity in the left frontal operculum (Broca's area) in the verbal fluency task and greater activity in the medium cingulate during the inhibition phase of the Stroop task. Conclusions: These preliminary findings suggest a decrease of frontal activity in the course of the illness. We assume that schizophrenia contributes to frontal brain activity reduction.

Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment.

RATIONALE: Dopamine D2 receptors are the main target of antipsychotic drugs. In the brain, D2 receptors coexpress with adenosine A2A and CB1 cannabinoid receptors, leading to functional interactions. OBJECTIVES: The protein and messenger RNA (mRNA) contents of A2A, D2, and CB1 receptors were quantified in postmortem prefrontal cortex of subjects with schizophrenia. MATERIALS AND METHODS: The study was performed in subjects suffering schizophrenia (n=31) who mainly died by suicide, matched with non-schizophrenia suicide victims (n=13) and non-suicide controls (n=33). The density of receptor proteins was evaluated by immunodetection techniques, and their relative mRNA expression was quantified by quantitative real-time polymerase chain reaction. RESULTS: In schizophrenia, the densities of A2A (90+/-6%, n=24) and D2-like receptors (95+/-5%, n=22) did not differ from those in controls (100%). Antipsychotic treatment did not induce changes in the protein expression. In contrast, the immunodensity of CB1 receptors was significantly decreased (71+/-7%, n=11; p<0.05) in antipsychotic-treated subjects with schizophrenia but not in drug-free subjects (104+/-13%, n=11). The relative mRNA amounts encoding for A2A, D2, and CB1 receptors were similar in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls. CONCLUSIONS: The findings suggest that antipsychotics induce down-regulation of CB1 receptors in brain. Since A2A, D2, and CB1 receptors coexpress on brain GABAergic neurons and reductions in markers of GABA neurotransmission have been identified in schizophrenia, a lower density of CB1 receptor induced by antipsychotics could represent an adaptative mechanism that reduces the endocannabinoid-mediated suppression of GABA release, contributing to the normalization of cognitive functions in the disorder.

La thérapie actuelle du rhabdomyosarcome orbitaire de l'enfant [Update of orbital rhabdomyosarcoma therapy in children]

INTRODUCTION: Rhabdomyosarcoma is the most frequent primitive orbital malignant tumor in children. If the treatment is started as soon as possible after discovery of the disease, the vital prognosis is considerably better than otherwise. The goal of this paper is to present the new therapeutic protocol and to report our experience in this field. MATERIAL AND METHOD: During the past 35 years, 102 cases of orbital tumors were collected in children under 15 years of age: 5 cases of rhabdomyosarcoma were cared for in our department. At the time of tumor diagnosis, the age of our patients ranged from 3 weeks to 13 years. After a biopsy or excision biopsy, all our cases were treated by chemotherapy with or without radiotherapy. Medication was mostly vincristine, ifosfamide and actinomycine D. When the result of the treatment was not satisfactory, carboplatine and epirubicine, vincristine as well as ifosfamide were given. Radiotherapy was performed only in particular cases or in recurrences. CONCLUSION: Rhabdomyosarcoma is a highly malignant tumor. Although rare, it is the most frequent of malignant tumors in children. It is important to keep it in mind in order to perform a biopsy enabling quick diagnosis and treatment following the modern protocol giving the highest chances of survival to these patients: about 98% in 3 years.

False recognition following frontal lobe damage: The role of encoding factors

This paper reports a series of experiments on patient JB, a man with memory difficulties following damage to the left frontal lobe. The primary characteristic of JB's recognition memory impairment is a high level of false recognition together with a normal hit rate. The hypothesis that JB's false recognition reflects an over-reliance on familiarity is considered, but discounted on the basis that the false alarm rate is not affected by increasing the similarity between distracters and targets, and remains high when nonword stimuli are used. It is suggested, instead, that JB relies on a poorly focused memory description, which lacks item-specific detail but contains more general, low-level properties of the target items-these properties being held by many distracter items as well. This deficit is considered to arise because of damage to frontally mediated control processes involved in the selection of elements for memory encoding. An encoding deficit is supported by the fact that JB's false recognition is significantly reduced by orienting instructions, and is eliminated when his remote memory is subjected to recognition testing. In contrast, it is shown that manipulations at the level of retrieval (e.g. restricting the number of "old" responses) have little effect on his false recognition.

Stimulus-induced, sleep-bound, focal seizures: a case report.

STUDY OBJECTIVES: In nocturnal frontal lobe epilepsy (NFLE), seizures occur almost exclusively during NREM sleep. Why precisely these seizures are sleep-bound remains unknown. Studies of patients with nonlesional familial forms of NFLE have suggested the arousal system may play a major role in their pathogenesis. We report the case of a patient with pharmaco-resistant, probably cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that could be elicited by alerting stimuli and were associated with ictal bilateral thalamic and right orbital-insular hyperperfusion on SPECT imaging. DESIGN: Case report. SETTING: University Hospital Zurich. PATIENTS OR PARTICIPANTS: One patient with pharmaco-resistant epilepsy. CONCLUSION: This case shows that the arousal system plays a fundamental role also in cryptogenic non-familial forms of NFLE.

Flujos de detritos recientes en la cordillera frontal de Mendoza: Un ejemplo de riesgo natural en la ruta 7 = Recent debris flows in the Frontal Cordillera of Mendoza: An example of natural risk on the Road 7

In this paper is presented a study dealing with the debris flows that reached the national road 7 in January 2005, in the km 1,118.5, Mendoza province. The area is located in the Frontal Cordillera near the limit of the Precordillera. A detailed geomorphologic map has been realized for this study using a Quickbird satellite imagery of the year 2006. Various calculations of volumes, velocities and peak discharges have been performed with the field data and using a geographic information system (GIS). The geomorphologic survey has permitted to propose three propagation scenarios in case of a new event. These allowed creating a map of debris flows susceptibility for the stretch of the road that has been studied. Finally, it has been proposed protection and mitigation measures, based on the results of the study, to protect the road from a new event.

Metastases orbitaires de melanome malin. [Orbital metastasis in malignant melanoma]

We report the case of a 60-year-old man presenting bilateral progressive proptosis with diplopia, weight loss, tachycardia, nervosity, and stomach pain. These signs seemed at first to favor a diagnosis of Graves'ophthalmopathy. Thyroid tests were negative and the initial orbital CT scan was considered normal. A new radiological investigation 4 months later in our hospital revealed typical hypertrophy of the extraocular muscles compatible with orbital metastasis. The systemic investigations demonstrated a pulmonary tumor, multiple hepatic lesions, and several pigmented nodules of gastric mucosa. The pathology of pulmonary and gastric specimens confirmed the diagnosis of malignant melanoma. The primary lesion remains unknown. The authors discuss the differential diagnoses of orbital metastasis and the radiological characteristics of orbital metastasis in malignant melanoma.

Accuracy and predictability in use of AO three-dimensionally preformed titanium mesh plates for posttraumatic orbital reconstruction: a pilot study.

The aim of this study was to prospectively evaluate the accuracy and predictability of new three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction.We analyzed the preoperative and postoperative clinical and radiologic data of 10 patients with isolated blow-out orbital fractures. Fracture locations were as follows: floor (N = 7; 70%), medial wall (N = 1; 1%), and floor/medial wall (N = 2; 2%). The floor fractures were exposed by a standard transconjunctival approach, whereas a combined transcaruncular transconjunctival approach was used in patients with medial wall fractures. A three-dimensional preformed AO titanium mesh plate (0.4 mm in thickness) was selected according to the size of the defect previously measured on the preoperative computed tomographic (CT) scan examination and fixed at the inferior orbital rim with 1 or 2 screws. The accuracy of plate positioning of the reconstructed orbit was assessed on the postoperative CT scan. Coronal CT scan slices were used to measure bony orbital volume using OsiriX Medical Image software. Reconstructed versus uninjured orbital volume were statistically correlated.Nine patients (90%) had a successful treatment outcome without complications. One patient (10%) developed a mechanical limitation of upward gaze with a resulting handicapping diplopia requiring hardware removal. Postoperative orbital CT scan showed an anatomic three-dimensional placement of the orbital mesh plates in all of the patients. Volume data of the reconstructed orbit fitted that of the contralateral uninjured orbit with accuracy to within 2.5 cm(3). There was no significant difference in volume between the reconstructed and uninjured orbits.This preliminary study has demonstrated that three-dimensionally preformed AO titanium mesh plates for posttraumatic orbital wall reconstruction results in (1) a high rate of success with an acceptable rate of major clinical complications (10%) and (2) an anatomic restoration of the bony orbital contour and volume that closely approximates that of the contralateral uninjured orbit.

Maladie d'Alzheimer : Etude des marqueurs pathologiques dans le cortex frontal humain et corrélations anatomo-cliniques

La maladie d'Alzheimer (MA), forme de démence la plus fréquente, est caractérisée précocement par des troubles de la mémoire, puis par une détérioration cognitive progressive, corrélée avec la progression des lésions cérébrales que sont les dépôts de protéine ß-amyloïde, notamment dans les plaques séniles, et la dégénérescence neurofibrillaire qui touche en priorité les grands neurones pyramidaux de l'hippocampe et du cortex cérébral. La perte ou les dommages synaptiques sont aussi prépondérants et conduisent à la mort neuronale et à la perte de réseaux fonctionnels notamment au niveau des protéines présynaptiques comme la synaptophysine et postsynaptiques comme PSD-95 (Leuba et al. 2008), ainsi que des récepteurs NMDA (NMDAR) liés à PSD-95 et jouant un rôle prédominant dans le fonctionnement synaptique. Notre étude s'est portée une des régions du cortex frontal correspondant à l'aire de Brodmann 10, encore peu étudiée dans la littérature scientifique, qui peut être touchée de manière plus ou moins importante dans la MA, entraînant des troubles de l'humeur et du comportement ainsi que des répercussions sur les fonctions exécutives. L'étude a pour but d'identifier et de quantifier les dépôts de protéine ß-amyloïde et les lésions neurofibrillaires ainsi que les changements de protéines synaptiques et de récepteurs NMDA dans cette région entre une population contrôle et AD, et de la comparer avec d'autres régions déjà partiellement étudiées dans le laboratoire, notamment l'aire 9 qui lui est adjacente et les aires cingulaires 24 et 25. L'analyse est faite de manière qualitative et semi-quantitative au microscope optique sur des coupes colorées avec des méthodes immunohistochimiques. De possibles corrélations anatomo-cliniques sont recherchées dans les cas AD. La région FC10 est touchée par la MA avec une présence de plaques séniles et de dégénérescences neurofibrillaires plus marquées chez les cas atteints de la MA ce qui n'est pas le cas des protéines synaptiques. Le comportement des deux marqueurs pathologiques dans FC10 est comparable aux autres régions cérébrales étudiées notamment à la région adjacente, FC9, contrairement aux marqueurs synaptiques qui selon la région ont un comportement plus variable. L'effet de l'âge dans l'évolution de la physiopathologie de la MA pour les marqueurs pathologiques a été mis en évidence dans la région FC10. Les régions EC et FC9 n'ont pas montré de microhémorragie synonyme d'une possible contribution vasculaire. L'étude de cette région a permis de mettre en évidence l'implication de FC10 dans la MA. Elle montre des points communs avec les autres régions cérébrales notamment vis-à-vis des plaques séniles et des DNF.

Rehabilitation of orbital cavity after total orbital exenteration using oculofacial prostheses anchored by osseointegrated dental implants posed as a one-step surgical procedure

BACKGROUND: Total orbital exenteration is a radical surgical procedure, which typically involves the removal of the entire contents of the orbit including the periorbita, leaving the patient with a deep orbital deformity and results in devastating cosmetic, functional, and psychological consequences requiring difficult and challenging procedures for oculoplastic surgeons. Oculofacial prostheses retained by endosseous dental implants present an attractive and viable alternative when aesthetic and functional demands are beyond the capacity of local reconstructive efforts. PATIENTS AND METHODS: A 72-year-old woman presenting a malignant melanoma of the right eyelids and a 77-year-old man presenting a sebaceous carcinoma of the left upper eyelid underwent a total exenteration followed by positioning of endosseous implants (Straumann system Dental implants) as an integrated one-step combined surgical procedure. The oculofacial prosthesis was placed after epithelialization of the orbital cavity. RESULTS: The implants were perfectly osseointegrated without any complications, providing sufficient retention of the prostheses. A satisfactory aesthetic outcome has been achieved for both patients. CONCLUSIONS: Oculofacial prostheses anchored by osseointegrated dental implants placed as one-step surgical procedure ensure an adequate aesthetic result as well as a considerably decreased rehabilitation time and present a satisfactory solution when reconstruction is not a suitable option.

Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein

We investigated how synaptic plasticity is related to the neurodegeneration process in the human dorsolateral prefrontal cortex. Pre- and postsynaptic proteins of Brodmann's area 9 from patients with Alzheimer's disease (AD) and age-matched controls were quantified by immunohistochemical methods and Western blots. The main finding was a significant increase in the expression of postsynaptic density protein PSD-95 in AD brains, revealed on both sections and immunoblots, while the expression of spinophilin, associated to spines, remained quantitatively unchanged despite qualitative changes with age and disease. Presynaptic protein alpha-synuclein indicated an increased immunohistochemical level, while synaptophysin remained unchanged. MAP2, a somatodendritic microtubule protein, as well as AD markers such as amyloid-beta protein and phosphorylated protein tau showed an increased expression on immunosections in AD. Altogether these changes suggest neuritic and synaptic reorganization in the process of AD. In particular, the significant increase in PSD-95 expression suggests a change in NMDA receptors trafficking and may represent a novel marker of functional significance for the disease.