[Clinical overview of auto-inflammatory diseases]. / Panorama des maladies auto-inflammatoires.

Monogenic auto-inflammatory diseases are characterized by genetic abnormalities coding for proteins involved in innate immunity. They were initially described in mirror with auto-immune diseases because of the absence of circulating autoantibodies. Their main feature is the presence of peripheral blood inflammation in crisis without infection. The best-known auto-inflammatory diseases are mediated by interleukines that consisted in the 4 following diseases familial Mediterranean fever, cryopyrinopathies, TNFRSF1A-related intermittent fever, and mevalonate kinase deficiency. Since 10 years, many other diseases have been discovered, especially thanks to the progress in genetics. In this review, we propose the actual panorama of the main known auto-inflammatory diseases. Some of them are recurrent fevers with crisis and remission; some others evaluate more chronically; some are associated with immunodeficiency. From a physiopathological point of view, we can separate diseases mediated by interleukine-1 and diseases mediated by interferon. Then some polygenic inflammatory diseases will be shortly described: Still disease, Schnitzler syndrome, aseptic abscesses syndrome. The diagnosis of auto-inflammatory disease is largely based on anamnesis, the presence of peripheral inflammation during attacks and genetic analysis, which are more and more performant.

[Multiple facets of ADA2 deficiency: Vasculitis, auto-inflammatory disease and immunodeficiency: A literature review of 135 cases from literature]. / Les multiples facettes du déficit en ADA2, vascularite, maladie auto-inflammatoire et immunodéficit : mise au point à partir des 135 cas de la littérature.

Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.

Substance abuse and suicidality in schizophrenia: a common risk factor linked to impulsivity.

Lifetime substance abuse comorbidity is frequent in schizophrenic patients, but the clinical correlates remain unclear. We have explored the chronological relations between substance abuse and course of schizophrenia, and compared several clinical characteristics and personality dimensions in 50 schizophrenic patients with or without lifetime substance abuse or dependence. Abuse occurred mainly after the first prodromal symptoms and just before the first psychotic episode. Substance-abusing patients were not different from non-substance-abusing patients on the Chapman Physical Anhedonia Scale, PANSS total score, negative subscore or depression item, CGI, treatment response and demographic variables. In contrast, substance-abusing patients had higher scores on the Barratt Impulsivity Scale (total, cognitive and non-planning scores) and had attempted suicide more often. In patients with schizophrenia, as in the general population, substance abuse or dependence appears associated with higher impulsivity and suicidality. High impulsivity could facilitate substance abuse as a maladaptive behavior in response to prodromal symptoms, precipitating the onset of a characterized psychosis.

Impairment of predictive saccades in schizophrenia.

Using infrared oculography, we compared saccades toward predictable and pseudo-random visual targets in 19 neuroleptic-free patients with schizophrenia (including 13 neuroleptic-naïve patients) and in 29 age- and gender-matched healthy volunteers. Externally driven saccades were not different between patients and controls, whether or not the target was predictable. Anticipated saccades were specifically less accurate in the patients compared to the controls. The difference between primary gain of anticipated and non-anticipated saccades was markedly higher in the patients compared to controls (p=0.003). These results point to a deficit in the early step of internally driven oculomotor planning in schizophrenia.

Validation and factorial structure of a standardized neurological examination assessing neurological soft signs in schizophrenia.

Although neurological soft signs (NSS) have been consistently reported in patients with schizophrenia, their clinical relevance, the actual impact of treatment or their evolution during the disease are not well clarified, possibly because of methodological limitations of the available tools. We have developed a new standardized examination integrating the assessment of 23 NSS selected from the literature and the rating of well-validated scales for assessment of extra-pyramidal symptoms. We examined 161 subjects (controls, n=48; patients with schizophrenia, n=95; or recurrent mood disorder, n=18). Half of the patients were neuroleptic-free. Schizophrenic patients had significantly higher total score (14. 6+/-8) than mood disorder patients (12.0+/-7) and controls (5.0+/-2). Internal consistency (Cronbach's alpha=0.85) and inter-rater reliability were good. Principal component analysis found five consistent factors ('motor coordination', 'motor integrative function', 'sensory integration', 'involuntary movements or posture', 'quality of lateralization'). This scale thus confirmed a factorial structure in agreement with the conceptual areas of interest explored by NSS and should be a useful tool for assessment of the different dimensions of neurological dysfunction in schizophrenia.

[Clinical dimensions and visually guided saccades in schizophrenia]. / Dimensions cliniques et saccades visuellement guidées dans la schizophrénie.

Eye movement anomalies are more frequent in schizophrenic patients than in healthy subjects. This study deals with visually guided saccadic eye movements in seventeen schizophrenic patients [ten untreated (neuroleptic-naive or free), seven treated patients] and their correlations between symptoms presented by patients and oculomotor performances. There was no significant difference between the patients and the control group in visually guided saccades tasks. However, negative correlations between oculomotor performance and positive or disorganisation symptomatology were found. Thus, although no major oculomotor dysfunction in response to external stimulus was seen in schizophrenic patients, some symptoms were linked to oculomotor performance impairment. Thus psychiatric symptoms might share some common cerebral circuits which those involved in oculomotor tasks.