Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease.

The methionine (M)-valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.

Clinical Outcome of Ischemic Stroke in Old Patients Versus Oldest-Old.

BACKGROUND: It is unclear whether very old patients benefit from stroke unit. The aim of our work was to compare the clinical outcome of patients with ischemic stroke aged either 70 or 80 (G 1) versus oldest-old greater than or equal to 81 years (G 2). METHODS: Of 1187 patients admitted with stroke during 5 years in our stroke unit, we included 252 patients with independent functional status (modified Rankin scale, [mRS] ≤ 2) before the stroke. All patients underwent clinical examination, blood test, electrocardiography, brain imaging, and cerebrovascular ultrasound. Clinical outcome was assessed with the mRS and National Institutes of Health Stroke Scale (NIHSS) at discharge. We considered favorable outcome mRS 0-2 at discharge. RESULTS: Of 252 patients included, 55% were male, 150 (59.5%) patients belonged to G1 and 102 (40.5%) G2. We detected a significant increase of atrial fibrillation, bronchoaspiration, mortality, higher NIHSS at admission, and worse functional status at discharge in G2. No significant differences in other demographic, vascular risk factors, hospital stay, NIHSS at discharge or subtype of stroke were found. NIHSS at discharge was the only independent predictor of good functional status (odds ratio 0.4; 95% confidence interval, 0.3-0.6; P < .001). CONCLUSIONS: Oldest-old patients showed similar NIHSS at discharge than younger patients despite having higher neurological severity at admission. Our results support the hypothesis that oldest-old patients have good recovery potential, and should not be excluded from the stroke unit. The worse functional status detected at discharge in these patients could be attributed to others factors and not to neurological severity.

Predictors of occult cancer in acute ischemic stroke patients.

BACKGROUND: We investigated the prevalence of occult malignancy (OM) in acute ischemic stroke patients to evaluate if any biological marker could help to detect the presence of OM. METHODS: We retrospectively reviewed all ischemic stroke patients during 48 months. We did not perform any screening for OM. Demographic data, vascular risk factors, routine blood chemistry with fibrinogen and C-reactive protein (CRP), National Institutes of Health Stroke Scale (NIHSS), and etiological subtype of stroke according to Trial of Org 10172 in Acute Stroke Treatment criteria were analyzed. The patients were divided into 2 groups (Non-OM versus OM). RESULTS: We analyzed 631 patients with acute ischemic stroke. The mean age was 69.7 ± 12.7 years, and 59% were men. The distribution of vascular risk factors, etiological subgroups, and NIHSS was comparable between both groups. We detected 13 cases (2.1%) with OM, and this percentage was higher in patients with stroke of undetermined etiology (5.3%). We detected significant higher levels of fibrinogen and CRP in patients with stroke of undetermined cause with OM. Receiver operating characteristic curves showed a sensitivity of 75% and specificity of 96% for levels of CRP more than 20 mg/L, and a sensitivity of 67% and specificity of 91% for fibrinogen levels greater than 600 mg/dL. CONCLUSIONS: OM was present in 2.1 % of overall patients, and 5.3% of patients with stroke of undetermined cause. Baseline levels of fibrinogen more than 600 mg/dL or CRP greater than 20 mg/L in patients with undetermined stroke might be good predictors of OM.