Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na(v)) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na(v) channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na(v) channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na(v) channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na(v) channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells.

Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinson's disease (PD) patients after subthalamic deep brain stimulation (STN-DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 +/- 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN-DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN-DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre-operative levodopa-equivalent daily dose, their reduction after STN-DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN-DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment.

No abstract

Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain metastases at the time of diagnosis. When surgical resection is not possible, whole brain radiotherapy is the standard of care, with a cerebral response rate of approximately 30%. We report our experience with an upfront association of carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m 2 , respectively), every 3 weeks, in 30 patients presenting with newly diagnosed brain metastases and NSCLC. Cerebral MRIs were performed every 6 -9 weeks. The radiologic response rates were assessed according to Response Evaluation Criteria in Solid Tumors. Overall survival was also determined. Twenty-six patients were evaluable for response, and the objective cerebral response rate (complete and partial response) in the intent-to-treat population was 40% (12 of 30 patients). Event-free survival was 31 weeks, and median overall survival was 39 weeks. The upfront association of carboplatin plus pemetrexed allows simultaneous treatment of cerebral and systemic disease in patients with NSCLC with newly diagnosed brain metastases and appears to be particularly interesting in terms of radiologic response and overall survival. Further clinical studies are warranted.

Functional independence in glioblastoma (GBM) patients is a key factor in measuring the quality of life. Progression free survival (PFS) and overall survival (OS) have been largely described. However, the evolution over time of the performance status during the patients' life remains understudied. We thus studied the time to loss of functional independence as assessed by a Karnosky Performance Status (KPS) below 70 % in GBM patients. We analysed all GBM patients treated in our institution between 2008 and 2013 and meeting the following criteria: age >18 years, supratentorial location, post-surgical KPS ≥ 70 %, initially treated with concomitant radiotherapy (RT) and Temozolomide. Within the 84 patients studied, the median PFS was 9 months and the median OS was 18.7 months. The median survival time with functional independence (KPS ≥ 70 %) was 14.5 months. On average, the patients spent 73 % of their lifespan with a KPS ≥ 70 %. Surgical resection and low steroid dosage were statistically associated with increased survival time with KPS ≥ 70 % (p = 0.015 and p = 0.03, respectively). Sixty-two (62) patients received one or several lines of chemotherapy at recurrence. Under treatment with Bevacizumab (42 Bev-based regimens), radiological responses were seen in 35 % and improvement in KPS occurred in 24 % whereas no response and rare improvement of KPS (3 %) were seen with other type of chemotherapy (97 non Bev-based regimens). In GBM patients, median survival with KPS ≥ 70 % largely exceeds PFS. Surgical resection and low steroids dosage at RT-onset appeared as good prognosis factors for survival with functional independence.