Christine Delmaire

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 Cohens 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.

Validity of Presurgical Functional Localization

Over the last decade, presurgical mapping using functional neuroimaging techniques — and in particular fMRI — has made considerable progress. FMRI is now approaching clinical practice and is no longer just used for research applications. One of the best established clinical applications is presurgical functional neuroimaging with its contributions to surgical planning and performance and possibly to the prediction of postoperative outcome.

Patterns of response to crizotinib in recurrent glioblastoma according to ALK and MET molecular profile in two patients

Two patients with an unmethylated MGMT promoter and IDH1 (R132H) wild-type recurrent glioblastoma were treated with crizotinib. Prolonged stabilization of the disease (17 months) was achieved in the first case. Interestingly, anaplastic lymphoma kinase (ALK) expression and c-MET protein overexpression was observed. Conversely, no response to crizotinib was obtained in the second case with MET protein overexpression and c-MET amplification but no ALK expression or ALK gene amplification. These case studies suggest that novel targeted ALK inhibitors may provide relevant clinical benefit in selected cases in which driver mutations are demonstrable.