BACKGROUND:Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a severe central nervous system involvement complicating LCH. ND-LCH is characterized by a cerebellar ataxia, pyramidal signs, pseudobulbar palsy, cognitive impairment, and behavioral disturbances. Cerebellar atrophy, the most common MRI finding, has been widely described in the literature. However, the natural history of volumetric changes in the cerebellum has never been examined. In this study, we aim to perform a quantitative analysis of cerebellar atrophy in ND-LCH patients compared to a control cohort. METHODS:MRI of patients with ND-LCH was compared to those of controls. An automated cerebellum analysis was performed using the Volbrain software (CERES) and a linear regression analysis was used to score the severity of cerebellar atrophy over time. RESULTS:We retrospectively analyzed the follow-up MRI of 16 adult patients with ND-LCH compared to those of 22 control patients. We examined an average of four MRIs per patient over a median follow-up period of six years. All patients with ND-LCH exhibit global and cortical cerebellar atrophy over time. The average atrophy rate is -1.86 cm3/year (range - 5.90 to 0.34) and is heterogeneous between patients. All cerebellar lobules are affected by atrophy. CONCLUSION:Longitudinal quantitative MRI analysis of the cerebellum in ND-LCH: (i) is feasible, (ii) confirms significant global and cortical cerebellar atrophy in patients with ND-LCH over time, (iii) estimates the rate of cerebellar atrophy, and (iv) could be useful as a therapeutic endpoint in a clinically slow-progressing disease. Further studies are needed to validate our findings.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by proliferation of tumor histiocytes that involves multiple organs including central nervous system. The physiopathologic process underlying degenerative neuro-LCH (i.e., DN-LCH) remains imperfectly settled. Since the main clinical features of DN-LCH are cerebellar ataxia and dysexecutive syndrome, eye movements might be disrupted and may help in disease diagnosis and monitoring. We retrospectively analyzed the medical records of twenty DN-LCH patients investigated using eye movement recording (EMR) in our hospital between 2015 and 2018. DN-LCH patients exhibited (i) abnormal gain in visually guided saccades including hypermetric saccades and excessive gain variability -45.0%-, (ii) increased mean antisaccade error rates -66.7%-, (iii) altered smooth pursuit -50.0%-, and (iv) excessive number of square wave jerks-25%- and gaze-evoked nystagmus. Our study suggests that DN-LCH patients present a peculiar pattern of eye movement impairments supporting cerebellar and prefrontal dysfunctions. As a non-invasive method, EMR could therefore be a useful tool for quantitative monitoring of DN-LCH patients. Further studies are warranted to support our findings.

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in longdistance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.

We report the case of a patient suffering from cortical blindness following bilateral occipital stroke, who recovered normal vision in his right visual field following injection of the local anesthetic mepivacaïne. The effect was transient but reproducible, allowing the patient to lead a normal life. Effect duration increased after adjunction of paroxetine. We provide anatomical and functional brain imaging correlates of this improvement, showing particularly how functional connectivity is restored between intact perilesional cortex and distant brain regions. This serendipitous finding may potentially benefit patients suffering from visual but also nonvisual handicap following brain lesions.

Langerhans cell histiocytosis (LCH) is a rare multisystemic disease. LCH is characterized by proliferation of myeloid progenitors with altered differentiation program and similar phenotypic features to epidermal dendritic cells termed Langerhans cell. LCH cells express CD1a+ and langerin and exhibit BRAF V600E mutation in ∼50% of cases. Neurological involvement or neuro-LCH is observed in 5 to 10% of cases. Three subtypes of neuro-LCH are individualized. The tumor type, accounting for 45% of neuro-LCH, affect mainly young adults. Tumor neuro-LCH is characterized by space occupying lesion(s) with contrast enhancement on MRI. Clinical symptoms are due to tumor brain location(s). Pathological examination of tumor neuro-LCH lesions reveals typical features of LCH. Treatment relies on surgical resection with/without chemotherapy. Degenerative neuro-LCH, accounting for 45% of cases, is usually revealed, mostly in children, by: (i) a cerebellar syndrome, (ii) a pyramidal syndrome, (iii) a pseubulbar palsy, and/or (iv) cognitive disorders. On MRI, several signs may coexist: (i) cortex atrophy, (ii) white matter T2 hyperintensities, and (iii) deep gray matter T1 hyperintensities. Pathological analysis of degenerative neuro-LCH lesions have been rarely performed and have never detected CD1a+ histiocytes but unspecific lesions (i.e. gliosis, neuronal loss and/or demyelination). Treatment of degenerative neuro-LCH patients is poorly standardized and poorly efficient. Functional rehabilitation and socio-educational care of these young patients are crucial. The mixed subtype of neuro-LCH combines clinico-radio-pathological characteristics of the first two first forms in the same patient, and represents 10% of neuro-HL. Neuro-HL, therefore, includes three very distinct entities with epidemiological, clinical, radiological and histological specific features requiring specific medical management.

Predicting the sensory consequences of saccadic eye movements likely plays a crucial role in planning sequences of saccades and in maintaining visual stability despite saccade-caused retinal displacements. Deficits in predictive activity, such as that afforded by a corollary discharge signal, have been reported in patients with schizophrenia, and may lead to the emergence of positive symptoms, in particular delusions of control and auditory hallucinations. We examined whether a measure of delusional thinking in the general, non-clinical population correlated with measures of predictive activity in two oculomotor tasks. The double-step task measured predictive activity in motor control, and the in-flight displacement task measured predictive activity in trans-saccadic visual perception. Forty-one healthy adults performed both tasks and completed a questionnaire to assess delusional thinking. The quantitative measure of predictive activity we obtained correlated with the tendency towards delusional ideation, but only for the motor task, and not the perceptual task: Individuals with higher levels of delusional thinking showed less self-movement information use in the motor task. Variation of the degree of self-generated movement knowledge as a function of the prevalence of delusional ideation in the normal population strongly supports the idea that corollary discharge deficits measured in schizophrenic patients in previous researches are not due to neuroleptic medication. We also propose that this difference in results between the perceptual and the motor tasks may point to a dissociation between corollary discharge for perception and corollary discharge for action.

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Efficacy of treatment with lithium is largely demonstrated in many indications. Its polyvalent effect is due to heterogenous pharmacological mechanisms on systems of neurotransmission and on complex cellular mechanisms. These effects explain both regulation of neurotransmission and neuroprotection. Clinicians are confronted with crucial question: Monotherapy or polytherapy where lithium is associated with one or several mood stabilizers. This decision is relevant for prevention of manic or depressive episodes, treatment of acute episodes, treatment of comorbidity and of resistant states in particular bipolar depression. In our reflexion, we underline that both polytherapy and polytherapy are recommended in clinical practice in more or less defined indications. Rigorous and rational decision should be based on complex neurochemical pharmacological effects of lithium in association with other psychotropic drugs: Synergical effects, neuroprotective effects and negative drug interactions. (C) 2014 Published by Elsevier Masson SAS.

Nous avons tous une humeur qui oscille entre « des hauts et des bas ». Mais certaines personnes passent d’un veritable etat d’excitation a des phases de depression profonde. On dit qu’elles sont « bipolaires ». Les troubles bipolaires sont-ils une simple variante de la normalite, une fantaisie psychologique ou au contraire une pathologie cerebrale ? Comment les soigner ? Si les sels de lithium ont depuis longtemps prouve leur efficacite, d’autres strategies de soin existent, medicamenteuses ou psychotherapeutiques. Au plus pres des dernieres avancees scientifiques, le docteur Marc Masson livre ici, a la lumiere de son experience clinique, une synthese sur l’origine et les principales manifestations des troubles bipolaires, qui touchent en France plus d’un million de personnes. Avec les temoignages de Veronique Dufief, Gerard Garouste et Danielle Steel.

31 32 33 Background 34 Studies of visual backward masking have frequently revealed an elevated masking 35 threshold in schizophrenia. This finding has frequently been interpreted as indicating a low36 level visual deficit. However, more recent models suggest that masking may also involve late 37 and higher-level integrative processes, while leaving intact early “bottom-up” visual 38

A briefly presented target shape can be made invisible by the subsequent presentation of a mask that replaces the target. While varying the target-mask interval in order to investigate perception near the consciousness threshold, we discovered a novel visual illusion. At some intervals, the target is clearly visible, but its location is misperceived. By manipulating the mask's size and target's position, we demonstrate that the perceived target location is always displaced to the boundary of a virtual surface defined by the mask contours. Thus, mutual exclusion of surfaces appears as a cause of masking.