Interhypothalamic adhesion and multiple cerebral abnormalities in a 2-year-old boy.

International audienceInterhypothalamic adhesion (IHA) is a band of tissue spanning the anterior recess of the third ventricle, linear in the transverse and frontal planes. Recently described, in 2008 [1] in a patient with a Chiari type II malformation, IHA is commonly associated with multiple congenital anomalies [2] particularly midline disorders but can also be isolated. IHA is related with hypothalamo-pituitary dysfunctions and seizures in most of patient, but asymptomatic patients have been reported [3]. Here, we present a case of IHA associated with corpus callosum agenesis (CCA)

Mean Arterial Pressure Change Associated with Cerebral Blood Flow in Healthy Older Adults

We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 +/- 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R(2) = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&amp;cond=depression&amp;cntry=FR&amp;rank=

A MANBA mutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant

<p>Abstract</p> <p>Background</p> <p>β-Mannosidosis (OMIM 248510) is a rare inborn lysosomal storage disorder caused by the deficient activity of β-mannosidase, an enzyme encoded by a single gene (<it>MANBA</it>) located on chromosome 4q22-25. To date, only 20 cases of this autosomal recessive disorder have been described and 14 different <it>MANBA </it>mutations were incriminated in the disease. These are all null mutations or missense mutations that abolish β-mannosidase activity. In this study, we characterized the molecular defect of a new case of β-mannosidosis, presenting with a severe neurological disorder.</p> <p>Methods</p> <p>Genomic DNA was isolated from peripheral blood leukocytes of the patient to allow <it>MANBA </it>sequencing. The identified mutation was engineered by site-directed mutagenesis and the mutant protein was expressed through transient transfection in HEK293T cells. The β-mannosidase expression and activity were respectively assessed by Western blot and fluorometric assay in both leukocytes and HEK293T cells.</p> <p>Results</p> <p>A missense disease-associated mutation, c.1922G>A (p.Arg641His), was identified for which the patient was homozygous. In contrast to previously described missense mutations, this substitution does not totally abrogate the enzyme activity but led to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression studies in transfected cells also resulted in 7% residual activity.</p> <p>Conclusion</p> <p>Correlations between MANBA mutations, residual activity of β-mannosidase and the severity of the ensuing neurological disorder are discussed. Whether the c.1922G>A mutation is responsible for a yet undescribed pseudodeficiency of β-mannosidase is also discussed.</p

Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Radioanatomie du langage

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Dépots de Gadolinium dans le cerveau : où en sommes nous?

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Imagerie de l’hypophyse

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Produits de contraste et cerveau

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Suivi neuro-oncologique

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