Fayçal Mouaffak

Abstract: Conversion disorder refers to the occurrence of neurological-like symptoms or deficits that are neither intentionally produced nor simulated. While it cannot be explained by an organic disease, it is often related to psychological events. CASE REPORT: We report the case of a 33-year-old patient with a fluctuating hysterical tetraplegia, which had started three years earlier. After the failure or the exhaustion of several biological (psychotropic medication, transcranial magnetic stimulation) and psychotherapeutic strategies, treatment with electroconvulsive therapy (ECT) was conducted. A total of thirty-five ECT sessions were performed. Whereas the patient's clinical state was initially characterized by a complete quadriplegia and an uncontrollable muscular hypertonia, we noted that the ECT sessions were associated with a slow, though remarkable, progress. At first, the sessions were followed by moments of altered consciousness during which the patient would be relaxed and could make simple movements. Secondarily, not only was our patient able to consciously move his four limbs, but he was also able to walk. However, those improvements remained partial and fluctuating, sometimes allowing the symptom to return temporarily secondary to frustrations or annoyances. Finally, our patient relapsed. Nevertheless, his clinical state presently remains better than that in which we first knew him. DISCUSSION: The treatment of conversion disorders has been the subject of few studies and predominantly remains symptomatic. Its main goals are: to lessen secondary gains impact by adopting a neutral behaviour towards the symptom and by encouraging physical rehabilitation; to lower the symptom by allowing the patient to understand the normal functioning of the diseased organ, and; to help the patient to deal with stressful situations. There is no evidence that hypnosis is superior to medical and other psychotherapeutic approaches. Pharmacological treatments may be helpful in the case of anxiety, impulsivity or depression, albeit delivered with caution. According to some case reports, transcranial magnetic stimulation has also been associated with clinical remission. Although the use of ECT in motor conversion disorders constitutes an uncommon procedure, and even if no clinical trial has evaluated its impact on such a pathological condition, several case reports suggest that electroconvulsive therapy can be efficient in the treatment of motor conversion disorders. This efficacy may rely on several hypotheses. ECT could induce neural modifications, and participate in the suppression of an active inhibition, which is responsible for hysterical symptoms. Indeed, conversion cerebral disorder correlates can be explored with the help of functional neuro-imaging techniques, which could therefore also identify ECT neural effects. ECT adverse effects on memory could lead to a new relationship with the symptom, and modulate the psychological conflict which has participated in its emergence. Narcoanalysis, ECT sessions could have an impact on consciousness by means of some dissolution and reorganization phenomenon. It could therefore participate in the ending of an emotional block, the psychic integration of traumatic events and the recovery of a voluntary motor control. Finally, ECT could be efficient thanks to its antidepressant properties, especially its ability to stimulate triaminergic, and particularly dopaminergic transmission. This case report reminds us how difficult it can be to deal with severe conversion disorders, and to navigate between two reefs, which are abstention, and therapeutic escalation.

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Abstract: Neuronal uncoupling proteins are involved in the regulation of reactive oxygen species production and intracellular calcium homeostasis, and thus, play a neuroprotective role. In order to explore the potential consequences of neuronal uncoupling proteins variants we examined their association in a sample of Caucasian patients suffering from schizophrenia and phenotyped them according to antipsychotic response.

Abstract: Mouchet-Mages S, Rodrigo S, Cachia A, Mouaffak F, Olie JP, Meder JF, Oppenheim C, Krebs MO. Correlations of cerebello-thalamo-prefrontal structure and neurological soft signs in patients with first-episode psychosis. Objective:  This study aimed at determining brain structural imaging correlates of neurological soft signs (NSS) in patients suffering from a first-episode psychosis. Method:  Fifty-two patients with a DSMIV diagnosis of first-episode psychosis (schizophrenia or schizophrenia spectrum disorder) were consecutively included. Subjects were assessed using a standardized neurological examination for motor coordination, motor integration and sensory integration. Anatomical magnetic resonance images (MRI) were analysed in the whole brain using optimized voxel-based morphometry. Results:  Neurological soft signs (NSS) total score (P-corrected = 0.013) and motor integration subscore (P-corrected = 0.035) were found to negatively correlate with grey matter structure of the dorsolateral prefrontal cortices. Motor coordination subscore was positively correlated with grey matter structure of the thalami (P-corrected = 0.002) and negatively with white matter structure of the cerebellum (P-corrected = 0.034). The addition of age and gender as covariate yielded similar results. We did not find any correlation between neither sensory integration subscore and grey matter structure nor NSS total score, motor integration subscore and voxel-based morphometry (VBM) white matter structure. Conclusion:  Structural alteration in the cerebello-thalamo-prefrontal network is associated with neurological soft signs in schizophrenia, a candidate network for 'cognitive dysmetria'.

Abstract: Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.

Abstract: Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.The Pharmacogenomics Journal advance online publication, 8 June 2010; doi:10.1038/tpj.2010.40.

Abstract: The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item.

Abstract: INTRODUCTION: Preliminary studies have suggested that balneotherapy (BT) is an effective and well-tolerated treatment for generalized anxiety disorder (GAD) and psychotropic medication withdrawal syndrome. We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD. METHOD: We compared BT to paroxetine in terms of efficacy and safety in a randomized multicentre study lasting 8 weeks. Patients meeting the diagnostic criteria of GAD (DSM-IV) were recruited. Assessments were conducted using the Hamilton Rating Scale for Anxiety (HAM-A) and other scales, by a specifically trained and independent physician. The primary outcome measure was the change in the total HAM-A score between baseline and week 8. RESULTS: A total of 237 outpatients were enrolled in four centres; 117 were assigned randomly to BT and 120 to paroxetine. The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine (-12.0 vs -8.7; p<0.001). Remission and sustained response rates were also significantly higher in the BT group (respectively 19% vs 7% and 51% vs 28%). CONCLUSION: BT is an interesting way of treating GAD. Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies.

Abstract: SUMMARY: Developmental anomalies have been identified as risk factors for a future schizophrenic illness: low weight at birth, congenital malformations, delayed motor and social learning. Cognitive deficits and neurological soft signs belong to the indices of the schizophrenic spectrum. Neuroimaging has visualized various structural abnormalities present from the very beginning of schizophrenia. These structural changes may represent an exacerbation of normal neurodevelopmental processes. Moreover, vulnerability genes for schizophrenia are involved at different stages of neurodevelopment: the best studied associations are dysfunctional variants of DISC-1 and neuroregulin-1 genes, the role of other genes (dysbindin, BDNF, reelin...) remaining more widely debated. Lastly, the observation of structural chromosomal anomalies in 15% of patients suffering from schizophrenia (versus 5% of controls), more frequent in early onset schizophrenia (32% of cases) suggests a neurodevelopmental cause. Such a dynamic understanding of schizophrenia is consistent with what we know about cerebral plasticity along the life span. This does not preclude the search for cues of degenerative mechanisms. The issue now is a better characterization of the vulnerable phenotype for screening procedures to be implemented prior to disease onset.

Abstract: Although the benefits of clozapine have been well demonstrated in resistant schizophrenia, the frequency of adverse events is of particular concern: up to 76% of patients to whom clozapine was prescribed experienced an adverse event, with a discontinuation rate of 17%. In addition to its major clinical side effect, agranulocytosis, clozapine is reported to induce inflammatory syndromes with polyserositis. Apart from sparse case reports, no study has yet addressed this particularly interesting issue. With the aim of improving the outcome of clozapine-treated patients, we undertook a review of the literature to characterize the clinical features of clozapine-induced serositis, its pathophysiology, and to propose strategies of clinical management.

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Abstract: Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.

Abstract: BACKGROUND: Several studies have reported an increase of dermatoglyphic anomalies in schizophrenic patients compared to controls. However, the recognition of specific dermatoglyphic variables related to this disorder and their genetic and/or environmental component are still controversial. METHOD: We conducted a dermatoglyphic analysis in a new sample of 617 individuals: 205 patients with schizophrenia-spectrum disorders, 224 healthy first degree relatives and 188 healthy controls. The dermatoglyphic variables studied were: the total a-b ridge count (TABRC) and its fluctuating asymmetry (FAABRC), and the presence of ridge dissociations (RD) and abnormal palmar flexion creases (APFC). RESULTS: Patients, relatives and controls did not differ in TABRC. However, within the patients group those with a low birth weight or absence of psychiatric family history showed lower TABRC than the others. The frequency of ectodermic derivates abnormalities (RD and/or APFC) appeared to be higher in patients and relatives than in controls, while first degree relatives did not differ from patients. Males showed an increased rate of ectodermic derivates abnormalities compared to females in all groups and male patients also presented higher FAABRC than female patients. CONCLUSIONS: Our results suggest a different relative weight of genetic and environmental factors on each dermatoglyphic variable analyzed: i) TABRC may be a sensitive marker to environmental factors in schizophrenia, ii) ectodermal derivates abnormalities appear to be influenced by genetic risk factors, which could be involved both in the disrupted development of ectodermic derivates like dermatoglyphics and central nervous system and in the vulnerability for schizophrenia.

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Abstract: BACKGROUND: Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy. OBJECTIVES: The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines. RESULTS: Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations. CONCLUSION: Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.

Abstract: BACKGROUND: Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine. OBJECTIVE: The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials. CONCLUSION: Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.

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Abstract: Mahmoud el Materi was undoubtedly, one of the main leading figures of contemporary tunisian history. Open and brillant, he detained a vast knowledge, but was nevertheless a man of moderation and humility, and a humanist who dedicated his entire professional and militating life to the service of the people of Tunisia. In a country, stricken then by poverty and widespread human misery, he was a remarkable militant who fought for independence and greatly contributed to the rebirth of modern Tunisia.

Abstract: Ismael Jorjanio (d. 1137), the Persian physician and philosopher, received his medical training in the most famous schools of the Iranian province of khawarizm. He wrote several works in which he dealt with medicine and the natural sciences. We are interested in the work dealing with the classification of ulcerations as proposed by Ismael Jorjani in function with their clinical characteristics and evolution as well as with their technical aspects.