Infantile Convulsions with Paroxysmal Dyskinesia (ICCA Syndrome) and Copy Number Variation at Human Chromosome 16p11

BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome); the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105) located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions

Somatosensory evoked potentials at rest and during movement in Parkinson's disease: evidence for a specific apomorphine effect on the frontal N30 wave.

Studies attempting to relate the abnormalities of the frontal N30 components of the somatosensory evoked potentials (SEPs) to motor symptoms in Parkinson's disease (PD) have shown contradictory results. We recorded the frontal and parietal SEPs to median nerve stimulation in 2 groups of PD patients: a group of 17 patients presenting the wearing-off phenomenon, and a group of 10 untreated PD patients. The results were compared with a group of 13 healthy volunteers of the same age and with a group of 10 non-parkinsonian patients. All parkinsonian and non-parkinsonian patients were studied before ("off" condition) and after a subcutaneous injection of apomorphine ("on" condition). The gating effects of a voluntary movement (clenching of the hand) on the SEPs were also studied for the wearing-off group of PD patients (in states off and on) in comparison with the healthy subjects. At rest and in the off condition the amplitude of the frontal N30 was significantly reduced in the 2 groups of PD patients. We demonstrate that the movement gating ability of the PD patient is preserved in spite of the reduced amplitude of the frontal N30. This result suggests that the specific change in the frontal N30 in PD is not the consequence of a continuous gating of the sensory inflow by a motor corollary discharge. Clinical motor improvement induced by apomorphine was associated with a significant enhancement of the frontal N30 wave. In contrast, the subcortical P14 and N18 waves and the cortical N20, P22, P27 and N45 were not statistically modified by the drug. Apomorphine infusion did not change the absolute reduced voltage of the N30 reached during the movement gating. While the frontal N30 component of the non-parkinsonian patients was significantly lower in comparison to healthy subjects, this wave did not change after the apomorphine administration. In the wearing-off PD patient group the frontal N30 increment was positively correlated with the number of off hours per day. This specific apomorphine sensitivity of the frontal N30 was interpreted as a physiological index of the dopaminergic modulatory control exerted on the neuronal structures implicated in the generation of the frontal N30.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Traitement médicamenteux des épilepsies: actualité

Medical treatment of epilepsy has evolved during the last ten years. The "Epileptic Syndrome Classification" established in 1989 and new antiepileptic drugs account for these changes. This article recalls the principal rules of medical treatment of epilepsy and reviews new antiepileptic drugs available in Belgium.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase II study of an intensive combination chemotherapy with cisplatin, adriamycin, etoposide and cyclophosphamide (CAVE) in small cell lung cancer

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A Phase III randomized study comparing a chemotherapy with cisplatin and etoposide to a etoposide regimen without cisplatin for patients with extensive small-cell lung cancer

Introduction: In a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57-0.66] and for those including etoposide (HR 0.65; 0.61-0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide. Methods: Extensive small-cell lung cancer patients were randomized between cisplatin-etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013. Results: 176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68-1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49-0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49-0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65-1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE. Conclusion: Combination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580. © 2017 Berghmans, Scherpereel, Meert, Giner, Lecomte, Lafitte, Leclercq, Paesmans and Sculier