Cerebral degeneration predicts survival in amyotrophic lateral sclerosis

Objective

To determine the relationship of cerebral degeneration with survival in amyotrophic lateral sclerosis (ALS).

Methods

Patients with probable or definite ALS underwent magnetic resonance spectroscopic imaging (MRSI) of the brain between July 1996 and May 2002, and were followed prospectively until March 2004. Creatine (Cr), choline (Cho) and the neuronal marker N‐acetylaspartate (NAA) were quantified as ratios in the motor cortex.

Results

In 63 patients compared with 18 healthy people, NAA/Cho was reduced by 13% (p<0.001), NAA/Cr was reduced by 5% (p = 0.01) and Cho/Cr was increased by 8% (p = 0.01). NAA/Cho was used for survival analysis, given its larger effect size and superior test accuracy (a sensitivity of 67% and a specificity of 83%). Median survival after MRSI was 24 months. Multivariate analysis showed reduced survival for lower NAA/Cho (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.08 to 0.72, p = 0.01), older age (HR 1.03, 95% CI 1.00 to 1.06, p = 0.04) and shorter symptom duration (HR 0.96, 95% CI 0.93 to 0.99, p = 0.01). Patients with NAA/Cho <2.11 had a reduced survival of 19.4 v 31.9 months (HR 2.05, 95% CI 1.12 to 4.03, p = 0.02).

Conclusions

Cerebral degeneration is predictive of reduced survival in ALS.The extent to which cerebral involvement contributes to shortened life expectancy in amyotrophic lateral sclerosis (ALS) has been difficult to elucidate. The clinical evaluation of upper motor neurone (UMN) integrity as an index of motor cortex degeneration falls short owing to the possible masking of UMN signs by the loss of lower motor neurones (LMNs). Indeed, autopsy series have shown UMN degeneration in cases of LMN‐predominant motor neurone disease that would not have otherwise met the clinical criteria for ALS.¹ The identification of prognostic indicators would aid in selecting patients for clinical trials who are predicted to behave in a homogeneous manner with respect to disease progression and, potentially, pathogenesis. Prognostic indicators would also have clinical value in counselling patients.Proton magnetic resonance spectroscopy (MRS) studies in ALS have consistently shown evidence of neuronal loss or dysfunction in the motor cortex by the finding of decreased N‐acetylaspartate (NAA), a neuronal marker.^2,3We aimed to determine whether cerebral neurochemical abnormalities quantified by MRS correlated with survival.