Alterations in resting-state network dynamics along the Alzheimer's disease continuum.

Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer's disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with subjective cognitive decline (SCD), 10 patients with amnestic mild cognitive impairment (aMCI) and 10 patients with typical Alzheimer's disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. Correlations were sought between temporal properties of HMM states and participants' cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores, nor with the whole hippocampal volume. However, it correlated positively with the regional glucose consumption in the right dorsolateral prefrontal cortex (DLPFC). AD patients present alterations of posterior DMN power activation dynamics at rest that identify an additional electrophysiological correlate of AD-related synaptic and neural dysfunction. The right DLPFC may play a causal role in the activation of the posterior DMN, possibly linked to the occurrence of mind wandering episodes. As such, these data might suggest a neural correlate of the decrease in mind wandering episodes reported in pathological aging.

Tumor volume as a predictive parameter in the sequential therapy (induction chemotherapy) of head and neck squamous cell carcinomas.

PURPOSE: Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed. METHODS: Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter. RESULT: 65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%. CONCLUSION: The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method.

[An update on treatment of dementia and Alzheimer's diseases?] / Actualisation des traitements des démences et de la maladie d'Alzheimer.

Major and minor neurocognitive disorders are common and increase with age. In the 70s, similarities between " senile " and " presenile " dementia led to their homogenization in a unique illness, the Alzheimer's disease. Systematic specific psychosocial support of patients and caregivers is crucial and allows to discuss an advance care plan. We propose such a multidisciplinary program and discuss some of them. Various drugs and a variety of possible physiopathogenic targets are actually studied and should in the near future offer new therapeutics in dementia and Alzheimer's disease.

Les troubles neurocognitifs sont fréquents et augmentent avec l'âge. Dans les années 70, la similarité entre démences dites " séniles " et " préséniles " mena à leur homogénéisation en une maladie unique, la " maladie " ou " démence d'Alzheimer ". Un soutien psychosocial du patient et de ses proches sera toujours indispensable. Il s'accompagne et s'assimile de fait à une planification anticipée de soins en même temps qu'une actualisation de la prise en charge. Avec AREMIS et Alzheimer Belgique, l'hôpital Erasme propose un tel programme de soin mul tidisciplinaire aux patients présentant un syndrome démentiel. De très nombreuses molécules aux modes d'actions variées sont actuellement à l'étude et devraient ainsi nous offrir de nouvelles voies thérapeutiques dans la démence en général et la MA en particulier.

[Signs and symptoms of major neurocognitive disorders]. / Signes et symptômes precoces des troubles neurocognitifs majeurs.

Cognitive disorders are a common problem, especially for older people. Dementia, recently renamed "major neurocognitive disorder" in DSM-5 is a complex subject. Age, vascular risk factors, subjective decline and its objectivation, are all risk factor for such neurocognitive disorders. Face to minor neurocognitive disorder, decline seemed more associated with the presence of structural atrophy or functional metabolic modification. It seems however more and more clear that, at least actually, such a diagnosis should not be done as early as possible but well timely and individually correct. This patient-centred approach requires the peculiar involvement of its familial, general physician. But when early detection tools will be used, for any legitimate reason, it will also be important to address specialized teams. In case of neurocognitive disorders, particularly major, psychoeducative programs are the most effective therapeutic on both patient and caregiver qualities of live. Such multidisciplinary program of care for patients with neurocognitive disorder and his/her caregiver has just obtained a financial agreement via the specific protocol 3 and should be known to be efficient.

Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine.

OBJECTIVE: To compare early growth and developmental outcome of infants with in-utero exposure to low-dose methadone (<100 mg per day), high-dose methadone (⩾100 mg per day) and buprenorphine. STUDY DESIGN: A retrospective review of infants with in-utero methadone and buprenorphine exposure who were evaluated at the Southcoast Developmental Pediatric clinic in New Bedford, MA, USA was completed. Growth data and developmental testing results during infancy were compared among the groups. RESULT: Infants in the high-dose methadone group had lower head circumference z scores and a lower mean score on the Alberta Infant Motor Scale (AIMS). Regression results confirmed an association between methadone dose and head circumference z score and AIMS score. CONCLUSION: Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may have a negative impact on motor skill development during early infancy.

[Dementia, end of life and euthanasia]. / Troubles cognitifs, fin de vie et euthanasia.

Among legislative criteria granting the right to practice euthanasia or assisted suicide, there are systematically four major elements. Precisely, any request must be voluntary, persistent, to be well thought and well informed. Such euthanasia raises numerous difficult questions in case of dementia. It also justifies thinking about possibilities that can offer specific arrangements of anticipated demands in such peculiar cases. Empirical experiences show us that it applies with difficulties in practice. Finally, to avoid that a big majority of these demands would find themselves not applied in practice, it would certainly be necessary to add to it structural valuation of advance care planning, and assure its recognition and development. These should not be limited to a single pathological target but would address all of us to increase advance care planning initiation, which remains the most limiting factor of such any early but continuous procedure.

[Biomarkers of the Alzheimer's disease: concepts and clinical case]. / Les biomarqueurs de la maladie d'Alzheimer: concepts et cas clinique.

Concepts and knowledge evolve gradually our ways of diagnosing and treating many diseases, but also our views and some kind of stigmatization that could be associated with them. Alzheimer's disease seems to evolve over several years before leading any perceptible clinical sign. To redefine its semantics seems thus essential. This way, new diagnostic criteria should allow refining diagnosis in case of dementia but also and especially before the apparition of any clinical manifestations or in case of mild suggestive cognitive disorders. Moreover, they allow, in case of other cognitive disorders presentations (aphasia or apraxia), diagnosing its unusual atypical form. However, the possibility that they also offer to set such diagnosis of Alzheimer's disease to people who do not present any slights clinical signs raises numerous ethical considerations, especially in view of the current absence of curative treatment. Noteworthy that, in theory, a biomarker is the objective indicator of a biological process associated with the pathogenicity. In Alzheimer's disease, pathogenicity and scientific bases to propose these biomarkers remains at least controversial. All of these crucial questions leading to their exclusive use by team specialized in their practices and interpretations. An exemplary clinical case is presented.

The Addenbrooke's Cognitive Examination Revised is as effective as the original to detect dementia in a French-speaking population.

INTRODUCTION: This paper presents the validation of the French version of the Addenbrooke's Cognitive Examination Revised (ACE-R). METHODS: The variability of the 3 versions of the ACE-R (A, B and C), performed by the same observer, hence mainly 2 or 3 times on 119 patients showing no progression, was first calculated by Cronbach's alpha coefficient, t test and linear regression. The alpha coefficients of the 3 versions were obtained showing that the ACE-R versions can be considered as one, and an analysis of the interobserver variability was performed by Cohen's kappa coefficient, t test and linear regression on 12 patients. Eventually, we performed a receiver operating characteristic (ROC) analysis to compare the sensitivities and specificities to detect dementia of the ACE, the ACE-R and Mini Mental State Examination on 319 consecutive patients. RESULTS: The ROC areas of sensitivities and specificities of the ACE and ACE-R were very similar. Two cutoffs were identified at 83/100 and 89/100 with a specificity to normality of 98.6% if the ACE-R score was ≥83 and a sensitivity to dementia of 98.4% if the ACE-R score was ≤89. CONCLUSION: ACE-R in French is as reliable and valid as the original version to detect dementia.

[Evaluation of our psycho-educative program by participating caregivers]. / Evaluation de notre programme de psychoéducation par les accompagnants de patients déments.

Facing difficulties due to dementia syndromes, systemic care is necessary. Amongst therapies assessed specifically to caregivers, psychoeducative steps seem to be the strongest effective one on neuropsychiatrics symptoms. Psychoeducations tend to teach the caregivers to modify their interactions with patients via a better understanding of illnesses and patients. Our training "Pour mieux vivre avec la maladie d'Alzheimer", applied in groups of eight to twelve persons, consists in twelve sessions of two hours each. To assure the biggest possible availability, we recently incorporated the concomitant coverage of patients into artistic workshops. These sessions of art-therapy realized in parallel to our psychoeducative program will thus be estimated according to the same rigorous methodology. The critical evaluations realized by participants at the end of our program reflect the outcome of our main objective (to teach to modify interactions with the patients) while contributing to the improvement of social contacts and to the learning of calling to existing helps. These preliminary results strongly argue for the pursuit and even extension of this kind of caregiver's management.

[New promising caregiver's psychoeducation training program: a Belgian experience in dementing disorders]. / La psychoéducation des accompagnants de patients déments comme nouvelle approche thérapeutique à l'efficacité démontrée.

Facing difficulties due to dementia syndromes, systemic care is necessary. But nevertheless, caregivers are generally lacking in medical welfare. Therapies assessed specifically to caregivers are missing. Amongst these, psychoeducative steps seem to be the strongest effective's one on neuropsychiatrics symptoms. Psychoeducations tend to learn to caregivers to modify their interactions with patients via a better understanding of illnesses and patients. Our training "Pour mieux vivre avec la maladie d'Alzheimer ", done in groups of eight to twelve persons, is constituted of twelve sessions of two hours each. Complete formation includes behavioural and cognitive aspects of the disease and proposes some multidimensional approach which content at least pedagogical, psychological and cognitivo behavioural aspects. We illustrate here with the use of two peculiar cases that our program can reach its objectives. These preliminary results strongly argue for the pursuit and even extension of this kind of caregiver's management.

[An unusual hospitalization under constraint]. / Une mise en observation peu ordinaire.

The case report describes a 45-year old man presenting of the behavioral problems and an aphasia of Wernicke, hospitalized under constraint. The urinary screening in the search of psychotropic substances is positive for the cannabis and the amphetamines. The neurological localization is confirmed by cerebral CT-scan. The discussion relates on the differential diagnosis between a schizophasia and an aphasia of Wernicke, on the difficulty of a somatic diagnosis among patients agitated under the effect of a drug and to the tendency to hospitalize those too quickly under constraint, on the noxious effect of drugs on the brain.

Effect of age, feeding, and omeprazole administration on gastric tonometry in healthy neonatal foals.

BACKGROUND: Gastric tonometry is commonly used in humans as an assessment of intestinal mucosal perfusion. Values in healthy foals are currently unknown. HYPOTHESIS: Age, enteral feeding, and omeprazole administration would significantly alter gastric tonometry measurements in neonatal foals. ANIMALS: Nine clinically normal foals were used to assess the effect of age and feeding, and 8 similar foals were used to assess the effect of omeprazole. METHODS: At 1, 7, and 14 days of age, gastric intramucosal PCO2 (PgCO2) and arterial blood gas samples were obtained at baseline, immediately after feeding milk, and 1 and 2 hours after fasting for calculation of the intramucosal-arterial PCO2 difference (DeltaCO2). To evaluate the effect of omeprazole, foals were evaluated twice as above, 2 hours after fasting, comparing administration of omeprazole to no drug. RESULTS: There was a significant effect of age and feeding on PgCO2 and DeltaCO2, whereas arterial PCO2 was not significantly affected by these factors. Postfeeding DeltaCO2 values were significantly lower than fasted values. Baseline and postfeeding DeltaCO2 increased with age. There was no significant effect of age on data collected after 1 or 2 hours of fasting. The 90% reference interval for DeltaCO2 data collected after fasting was 0-54 mmHg. Foals had a significantly higher mean gastric pH and significantly higher DeltaCO2 and PgCO2 following omeprazole relative to no treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Because of the high and variable DeltaCO2, which is exacerbated by omeprazole administration, the reference interval in foals is extremely wide.

[The central island tongue flap for the reconstruction of the anterior floor of the mouth]. / Der zentral gestielte myomucosale Zungenlappen zur Rekonstruktion des anterioren Mundbodens.

BACKGROUND: There are several techniques described for the reconstruction of the anterior floor of mouth after tumour surgery. Here, we point out the advantages of the central island tongue flap for this indication. PATIENTS AND METHODS: We report on 20 patients with medium sized defect in the anterior floor of mouth, which was reconstructed with the central island tongue flap. Besides this surgical technique, we discuss the results of oral rehabilitation after a follow-up period of at least 3 months. RESULTS: There was now flap necrosis or loss, and the median time for flap formation was less than 45 min. In the follow-up we found successful oral rehabilitation in speech and swallowing.

[Misdiagnosis of sinus thrombosis with reversible posterior leucoencephalopathy]. / Thrombose ou hypoplasie veineuse cérébrale avec leucoencéphalopathie postérieure réversible.

Reversible posterior leucoencephalopathy and cerebral venous thrombosis share many symptoms. Both of them may lead to coma, and cause epilepsy or focal neurological signs. Moreover, diffuse leucoencephalopathy can be observed in both cases. Cerebral venous thrombosis needs anticoagulation which is not a riskless treatment. We describe a case of reversible posterior leucoencephalopathy in an hypertensed, seventy-year old man, presenting with a left lateral sinus hypoplasia whose clinical history and paramedical results first suggested a cerebral veinous thrombosis. Our case shows the misleadings a congenital vascular asymmetry can induce when confronted with a subacute coma.