Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis.

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis.

Our objective was to characterize the structural and metabolic changes of the corticospinal tract (CST) in ALS patients using combined diffusion tensor imaging (DTI) and magnetic resonance spectroscopic imaging (MRSI). Fourteen patients (male:female, 6:8; mean age, 54 years) and 14 controls (male:female, 8:6; mean age, 53 years) underwent imaging. Four regions of the CST were evaluated: precentral gyrus, corona radiata, posterior limb of the internal capsule, and cerebral peduncle. DTI and MRSI indices tested included fractional anisotropy (FA), apparent diffusion coefficient (ADC), and the ratio of N-acetylaspartate to choline (NAA/Cho) and creatine (NAA/Cr). In the precentral gyrus, NAA/Cho was reduced 18% (p<0.001), NAA/Cr was reduced 9% (p=0.01), and FA was reduced 3% (p=0.02). NAA/Cho and NAA/Cr were reduced in the corona radiata (p<0.001). Reduced NAA/Cho in the precentral gyrus correlated with shorter symptom duration (r=0.66, p=0.02) and faster disease progression (r=-0.65, p=0.008). Increased spasticity correlated with higher ADC in the precentral gyrus (R=0.52, p=0.005). In conclusion, both MRSI and DTI provided in vivo evidence of intracranial degeneration of the CST in ALS that was most prominent rostrally in the precentral gyrus.