MRI lesion profiles in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes. METHODS: Pathologically confirmed sCJD cases with codon 129 genotype (MM, MV, and VV), PrP(Sc) type, and fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted imaging (DWI) were collected in seven countries. All MRI scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus, and cerebellum. RESULTS: MRI scans were evaluated in 211 CJD patients (98 MM1, 23 MM2, 19 MV1, 30 MV2, 9 VV1, and 32 VV2). Basal ganglia hyperintensities occurred most frequently in MV2, VV2, and MM1 subtypes (79, 77, and 70%). Wide cerebral cortical signal increase was most common in VV1, MM2, and MV1 subtypes (86, 77, and 77%). Thalamic hyperintensities occurred most often in VV2 (45%) and MV2 (43%). The most consistent finding across most subtypes was high signal in basal ganglia, with these abnormalities found in 63% (FLAIR) and 71% (DWI). CONCLUSION: Cortical signal increase and hyperintensities in the basal ganglia and thalamus are detected by MRI across all molecular sporadic Creutzfeldt-Jakob disease subtypes. Our findings argue that characteristic MRI lesion patterns may occur for each molecular subtype.

CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathies.

Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/microl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/microl and one of 20 cells/microl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/microl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests.

High incidence of genetic human transmissible spongiform encephalopathies in Italy.

OBJECTIVE: To assess the incidence and mortality rates of genetic transmissible spongiform encephalopathy (TSE) diseases in Italy. METHODS: The authors have sequenced the prion protein gene (PRNP) in 643 patients referred to the Italian Registry of Creutzfeldt-Jakob disease (CJD) and related disorders between 1993 and 2002. Crude age- and sex-specific incidence and mortality rates were calculated. Differences in morbidity from genetic TSE diseases in the 20 Italian regions were assessed by the standardized morbidity ratio (SMR). RESULTS: A total of 130 cases were classified as genetic TSE diseases with a mean yearly incidence rate of 0.28 cases per million people. Genetic TSE diseases represent 17.7% of all TSE diseases, including sporadic, iatrogenic, and variant CJD. The most frequent mutation was the V210I (n = 54), and the second most common the E200K (n = 42). Mortality rates for genetic TSE diseases did not increase in any of the age groups under examination over the 10 years of surveillance. The analysis of regional distribution of genetic cases by place of birth revealed that in Campania and Calabria regions the number of genetic TSE cases was higher than in other regions. CONCLUSIONS: In Italy the incidence of genetic transmissible spongiform encephalopathy (TSE) diseases is the second highest among European countries. Genetic analysis is important for a correct classification of patients with TSE.

Estimation of the conduction velocity of sympathetic sudomotor C fibres in healthy subjects: study of sympathetic skin reflex.

The aim of this study was to establish a simple method for estimating the conduction velocity (CV) of post-ganglionic sympathetic sudomotor C fibres (SSFCV) in the upper and lower limbs by simultaneously measuring the sympathetic skin reflex (SSR) in two distant sites. Fifty healthy volunteers were studied. SSRs were recorded with standard surface electrodes applied to both proximal (axilla and crural line) and distal sites for each limb (hand and foot). The CV of the efferent branch of the SSR was calculated by dividing the difference in the latencies of the response from two recording sites by the distance between the sites (axilla-hand for upper limb; crural line-foot for lower limb). Day-to-day reproducibility and intra-individual variability of the SSFCV were calculated. For the upper limbs, the SSFCV in the axilla-hand tract was 2.0+/-0.3 m/sec (range 1.6-2.4 m/sec). For the lower limb, the SSFCV in the crural line-foot tract was 1.4+/-0.4 m/sec (range 1.2-1.6 m/sec). Mean intra-individual variability of the SSFCV for the upper and lower limbs was 0.11 and 0.09, respectively. The coefficient of variation of the SSFCV for the upper and lower limbs was 5.1% and 5.4%, respectively. Our data show that this simple and non-invasive method can reliably be used to measure the CV of the sympathetic sudomotor fibres, in suitable temperature conditions, and may be useful when investigating the physiological functions of peripheral nerves in patients with peripheral neuropathies.