A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Correlation of age and haematoma volume in patients with spontaneous lobar intracerebral haemorrhage

Background Lobar intracerebral haemorrhage (LH) is gaining importance in the ageing population, but there are only limited data regarding specific clinical characteristics and risk factors of older patients with LH. Methods This retrospective analysis of patients with spontaneous supratentorial haemorrhage included 174 consecutive patients (78 LH and 96 deep ICH (DH)). Clinical data including the preadmission status, neuroradiological findings, initial presentation, treatment and outcome were evaluated using institutional databases, patients' medical charts and mailed questionnaires. Logistic regression analyses were calculated for initial parameters predisposing LH and for treatment and outcome parameters associated with LH. Results Age-stratified volume analysis revealed increasing haematoma volumes for LH (≤70 years: 26.2 ml; 70–80 years: 37 ml; >80 years: 61.3 ml), whereas DH showed no relation between volume and age (≤70 years: 10.1 ml; 70–80 years: 23.2 ml; >80 years: 12.1 ml). DH patients had significantly higher HbA1c levels. Post-ICH seizures were more frequent after LH. Logistic regression analyses identified the parameters: age, haematoma volume and post-ICH seizures to be associated with LH, whereas intraventricular haemorrhage, extraventricular drainages and elevated HbA1c were related to DH. Conclusion Haematoma volumes are substantially increasing in LH patients who are older than 70 years. Pathological HbA1c levels are significantly associated and predisposing for DH. These findings further support the ongoing debate of different disease entities for supratentorial ICH (ie, association of cerebral amyloid angiopathy and lobar ICH versus diabetes induced atherosclerosis in deep ICH). Future studies should focus on identifying specific pathological characteristics and risk factors for both bleeding sites to implement specific preventive measures, that is amyloid angiopathy modulating therapies for LH, and to avoid risk factors that are specific for each haemorrhage location

Origin of the Mutations in the parkin Gene in Europe: Exon Rearrangements Are Independent Recurrent Events, whereas Point Mutations May Result from Founder Effects

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder