Psychiatric burden in a cohort of adults with Niemann Pick type C disease: from psychotic symptoms to frontal lobe behavioral disorders.

OBJECTIVES: To describe Niemann-Pick type C (NP-C) behavioral symptoms (focusing on psychotic symptoms) and its relation to frontal lobe functioning. METHODS: We retrospectively reviewed medical charts of NP-C-patients followed in the Lysosomal Diseases reference center in Paris Pitié-Salpêtrière. We collected demographic data, psychiatric clinical manifestations, psychometric scales, and extended neuropsychological data including executive and behavioral frontal lobe functions evaluations. RESULTS: Nineteen patients were included in the study with ten of them having experienced at least one acute psychotic episode, being inaugural for six of them. Most of the patients suffered from behavioral (15/17) and cognitive disorders (18/19) (including executive dysfunction (11/12), apathy (13/17), impaired social cognition (11/13) and stereotyped behaviors (5/10). For five patients, quality of life was significantly impaired by these abnormal behaviors. Concerning frontal neuropsychological evaluation, Facial emotion recognition was by far the most performed neuropsychological test (n = 8) and the score was always abnormal. It is noteworthy that psychotic symptoms were often drug resistant (8/9) and that Miglustat was associated with a better control of psychotic symptoms. CONCLUSIONS: We report a high frequency of psychiatric symptoms in NP-C encompassing acute psychotic manifestations, often presenting early in the course of the disease with atypical features. We also report disabling behavioral manifestations related to frontal dysfunction.

Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy-related apathy.

BACKGROUND AND PURPOSE: The symptomatic effect of zolpidem on apathy has been reported in neurological disorders such as strokes and post-anoxic brain injuries, but not in white-matter disease of the brain. METHODS: A 38-year-old patient presenting with severe apathy related to a genetic leukoencephalopathy but showing marked improvement of apathy after taking 10 mg of zolpidem was studied. To understand what may mediate such a clinical effect, a multimodal neurometabolic approach using 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) and a dedicated magnetic resonance spectroscopy (MRS) sequence for gamma aminobutyric acid (GABA) and glutamine + glutamate metabolism was undertaken. RESULTS: Pre-zolpidem FDG-PET showed hypometabolism in the orbitofrontal cortex, dorsolateral cortex and basal ganglia compared to healthy controls. Post-zolpidem, FDG-PET displayed increased metabolism in the orbitofrontal cortex together with improvement in the emotional and auto-activation domains of apathy. There was no improvement in the cognitive domain of apathy, and no change in metabolism in the dorsolateral frontal cortex. Post-zolpidem, MRS showed increased GABA and glutamine + glutamate levels in the frontal cortex and pallidum. CONCLUSION: Our multimodal neurometabolic study suggests that the effects of zolpidem on apathy are related to increased metabolism in the orbitofrontal cortex and basal ganglia secondary to GABA modulation. Zolpidem may improve apathy in other white-matter disorders.

Solubilisation of chlorinated solvents by cyclodextrin derivatives: a study by static headspace gas chromatography and molecular modelling.

The capacity of alpha-cyclodextrin (alpha-CD) and four beta-cyclodextrins (beta-CDs) in reducing the volatility of volatile organic compounds (VOCs) and particularly carbon tetrachloride (CT), chloroform (TCM) and dichloromethane (DCM) is investigated by using static headspace gas chromatography (HSGC). The experiments allowed the determination of Henry's law constant (H(c)) in absence and in presence of cyclodextrins (CDs). The use of CDs may lead to a reduction of 95% of the Henry's law constant for some VOCs. The association constants of the inclusion complexes formed between CDs and the three guests are determined using a new method involving an algorithmic treatment bringing the shortening of experimental time required for the determination of the stability constant. The complementarities of the host and the guest are investigated by molecular modelling. The complexation energies obtained are in good agreement with the experimental formation constants. Furthermore, this study shows the effectiveness of CDs in trapping pollutants and reducing their volatility in the viewpoint of pollution prevention.

Study of the local atomic strain field in a Zr-doped TiAl intermetallic alloy by EXAFS and ab initio FLAPW calculations.

The mechanical properties of gamma-TiAl-based intermetallic alloys are strongly influenced by Ti d-Ti d and Al p-Ti d hybridizations. These directional bonds supply good mechanical properties at high temperature but they are also associated with a low ductility at room temperature. Small amounts (about 3%) of additional elements can improve this behaviour noticeably and modify the mechanical properties. In the present case, the addition of zirconium in the gamma-TiAl-based alloys has been reported to increase their ductility at low temperature. Beyond the modifications of the directional bonds which come directly from the band structure, the different atomic volumes of the solute atoms induce local deformation fields which interact with the dislocations. We present ab initio calculations (FLAPW method) compared with an EXAFS study which the aim is to determine the site preference of zirconium in the TiAl lattice and the deformation fields around the solute atoms.