Epilepsie et shizophrénie: association ou antagonisme?

The relationship between epilepsy and schizophrenia is complex. In 1934, von Meduna proposed camphorinduced convulsions in the treatment of schizophrenia and concluded that there was a biological antagonism between epilepsy and schizophrenia. From the1950s on, the prevalence of psychosis in epileptic patients has been studied repeatedly. The work of Slater et al. (1969) had a profound impact. Over a few years, they collected 69 cases of inter-ictal psychosis (schizophrenia-like psychosis) among epileptics. The onset of seizures preceded the development of mental deterioration by an interval of several years. Temporal lobe epilepsy was overrepresented. Although the patients exhibited at times all the cardinal features of schizophrenia, the psychoses observed deviated from schizophrenic norms in some respects. Conversely, the occurrence of seizures and/or epilepsy in schizophrenics was documented many years ago and was not considered a major problem. Using modern diagnostic criteria of schizophrenia and epilepsy, Gelisse et al. (1999) confirmed that the prevalence of epilepsy and acute symptomatic seizures was low in schizophrenics, which points to a possible relative “ resistance ” to factors of epileptic seizures. In this article, we discuss the relationship between epilepsy and schizophrenia and hypothesize that there is an antagonism between seizures (not epilepsy) and schizophrenia. However, there is a link between longstanding and drug-resistant epilepsy and interictal psychosis, so epilepsy and schizophrenia-like psychosis can be associated.Les relations entre épilepsie et psychoses ont été le sujet de nombreuses discussions et controverses. En 1934, von Meduna proposa le camphre pour induire des crises convulsives dans le traitement de la schizophrénie et conclut qu’il y avait un antagonisme biologique entre l’épilepsie et la schizophrénie. Cependant, une association entre épilepsie et psychoses a été évoquée au début du siècle mais avec de considérables incertitudes. A partir des années 1950, de nombreux travaux ont été consacrés a à ce sujet. Les psychoses schizophréniformes de l’épilepsie (schizophrenia-like psychosis des auteurs anglo-saxons) se développeraient au bout de plusieurs années d’évolution d’une épilepsie temporale mal contrôlée. La prévalence s’échelonne de 0,74 % à 9,25 %. Des différences culturelles et d’époque quant à la définition de la schizophrénie et de l’épilepsie temporale explique en partie la variabilité des résultats. Beaucoup d’études ont fait l’objet de biais méthodologiques en considérant l’épilepsie temporale comme un syndrome homogène décrit à l’époque comme épilepsie « psychomotrice » mais aussi en présélectionnant des populations de malades épileptiques graves consultant des centres spécialisés. C’est ainsi que Slater et al. (1969) concluaient à une relation en trouvant une fréquence de survenue d’une psychose schizophréniforme supérieure à celle de la population générale. Le début des crises précédait le développement d’une psychose de plusieurs années. Les épilepsies temporales « psychomotrices » étaient surreprésentées. Slater et al. (1963) avaient remarqué que si tous leurs patients avaient présenté à un moment ou à un autre, un des signes cardinaux de la schizophrénie, leur tableau ne correspondait pas à une vraie schizophrénie. Une histoire familiale de schizophrénie et une personnalité schizoïde prémorbide étaient relativement rares dans leur population. Cette opinion que ces patients ne présentent pas une schizophrénie typique est partagée par d’autres auteurs. Inversement, la survenue de crises ou d’une épilepsie chez des patients schizophrènes n’a jamais été considérée comme un véritable problème. En utilisant des critères modernes de diagnostic de schizophrénie et d’épilepsie, Gélisse et al. (1999) ont confirmé que la prévalence de l’épilepsie et des crises symptomatiques aiguës étaient rares chez ces patients et ceux malgré l’utilisation de psychotropes. Dans cet article, nous discutons les relations entre épilepsie et schizophrénie. Nous émettons l’hypothèse qu’il y a un antagonisme entre les crises d’épilepsie et la schizophrénie. Cependant, il y a un lien entre une épilepsie pharmacorésistante évoluant depuis de nombreuses années et une psychose shizophréniforme intercritique, ainsi schizophrénie (shizophrénie like-psychosis) et épilepsie peuvent être associées

Rabies Postexposure Prophylaxis in Routine Practice in View of the New Centers for Disease Control and Prevention and World Health Organization Recommendations

Under real-life conditions rabies post-exposure prophylaxis is often administered in a suboptimal manner. In this study, 6.7% of previously non-immune patients did not develop adequate antibody levels after 4 doses of rabies vaccin

A Phase 1 Trial of MSP2-C1, a Blood-Stage Malaria Vaccine Containing 2 Isoforms of MSP2 Formulated with Montanide® ISA 720

Background: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2), parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naïve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion. Methodology/Principal Findings: The trial was designed to include three dose cohorts (10, 40, and 80 μg), each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 μg dose; no subjects received the 80 μg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 μg and 40 μg dose cohorts, with antibody levels by ELISA higher in the 40 μg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI) of parasite growth. Conclusions/Significance: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation of MSP2 in an alternative adjuvant. Trial Registration: Australian New Zealand Clinical Trials Registry 12607000552482

Genome-Wide Copy Number Variation in Epilepsy: Novel Susceptibility Loci in Idiopathic Generalized and Focal Epilepsies

Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

OBJECTIVE: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. METHODS: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. RESULTS: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. CONCLUSIONS: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutationsjournal articleresearch support, non-u.s. gov't2012 Nov 202012 10 17importedComment in : Paroxysmal disorders associated with PRRT2 mutations shake up expectations on ion channel genes. [Neurology. 2012

Remembering Joseph Roger, 1918–2012

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