Expression of NPP1 is regulated during atheromatous plaque calcification.

Mutations of the ENPP1 gene encoding ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) are associated with medial calcification in infancy. While the inhibitory role of matrix proteins such as osteopontin (OPN) with respect to atherosclerotic plaque calcification has been established, the role of NPP1 in plaque calcification is not known. We assessed the degree of plaque calcification (computed tomography), NPP1 and OPN localization (immunohistochemistry) and expression (RT-PCR) in a cohort of 45 patients undergoing carotid endatherectomy for significant stenosis of the internal carotid artery and in normal arteries (N= 50). We correlated NPP1 and OPN expression levels to the degree of plaque calcification, to pro-atherogenic factors and statin therapy. NPP1 was demonstrated in the base and in the shoulder of atherosclerotic plaques. Compared to normal arteries and non-calcified plaques, in calcified plaques NPP1 mRNA was decreased (P < 0.0001). OPN mRNA levels were up-regulated in carotid atheroma. NPP1 and OPN expression levels positively correlated with the degree of plaque calcification (R= 0.54, P= 0.00019 and R= 0.46, P= 0.017, respectively) and with risk factors of atherosclerosis. Expression of the calcification inhibitor NPP1 is down-regulated in calcified atherosclerotic plaques. Our correlation data point to a counter-active mechanism, which in the end turns out to be insufficient to prevent further progression of calcification.

Apical temporal lobe resection; "tailored" hippocampus-sparing resection based on presurgical evaluation data.

BACKGROUND: It is the aim of epilepsy surgery in patients with lesional epilepsy for the surgeon to not only remove the lesion itself, but also the epileptogenic zone. Here, we report our experience with a modified temporal resection technique confined to the apical temporal lobe, i.e., sparing the hippocampal formation in patients with epileptogenic lesions in the anterior part of the temporal lobe. This apical temporal lobe resection (aTLR) includes tailored lesionectomy, amygdalectomy, and resection of the mesial structures only in the apex of the temporal lobe. This paper presents our surgical technical details and the outcome of aTLR. METHODS: Between 2001 and 2008, aTLR was performed in 61 patients. All patients underwent comprehensive presurgical evaluation including video-EEG monitoring, magnetic resonance imaging (MRI), and neuropsychological testing. All patients had a lesion in the apex of the temporal lobe and a normal hippocampus as seen in MRI, as well as intact memory functions in neuropsychological examination. There were 33 males (54.1%) and 28 females (45.9%). The mean age in years at epilepsy onset was 20.2 ± 13.4, the mean age at epilepsy surgery was 32.1 ± 11.9, the mean preoperative epilepsy duration was 11.8 ± 8.8 years and the mean duration of follow-up was 2.1 ± 1.3 years (range 0.5-6 years). RESULTS: Fifty-four (88.5%) of 61 patients were in Engel Class 1 at 6 months, 38 (80.9%) of 47 at 2 years and nine (81.8%) of 11 at the 5 year follow-up. Histopathological examination showed tumors in 31 patients, FCD in ten patients, amygdala sclerosis in seven patients, cavernomas in six patients, unspecific reactions in eight patients, and gliosis in one patient. Surgical complications occurred in four patients: one had a permanent and three had transient complications which could be successfully treated. Fifty (82%) resections were considered to be complete resections as evaluated by serial postoperative MRI, seven patients (11.5%) had incomplete resection of the preoperative MRI lesion and in four patients (6.6%) it remained unclear. Fifteen patients (29.4%) were withdrawn from antiepileptic drugs for more than 2 years without relapse. Postoperative neuropsychological examination revealed worsening of memory performance in two patients (3.2%) and improved or no changes in the rest of the patients. CONCLUSIONS: Apical temporal resection sparing the mesial temporal structures is an effective procedure with good long-term seizure outcome in patients with refractory epilepsy due to lesions confined to the apex of the temporal lobe.