The addition of objective, observer-independent magnetic resonance imaging (MRI) measures to clinical evaluations significantly enhanced the accuracy of 18-month prognosis in patients diagnosed with amyotrophic lateral sclerosis (ALS) in a study published recently in BMC Neurology.1
The investigators from Trinity College in Dublin, Ireland, prospectively enrolled 69 consecutive patients with ALS from January 2011 to June 2015 from the Biomarker Initiative at the Academy of Neurology at Trinity, and 69 healthy controls. Of the 63 patients with ALS who participated in the study, 33 survived to the 18-month end point. The investigators randomly selected a subgroup of 30 survivors, designating 80% as a training sample (whose results were compared directly with the controls) and the remaining 20% as a validation sample.
Demographic and observable clinical features of ALS, including older age at onset, rapid weight loss, bulbar or respiratory onset, recent symptom onset prior to diagnosis, significant motor impairment, and comorbid executive dysfunction, are all characteristics that have been previously linked to shorter survival.2-5 Although imaging biomarkers have been proposed, the current study is the first to identify specific ALS anatomical measures on MRI and positron emission tomography (PET) scans that correspond to clinical datasets.
The group identified ALS-specific core white matter pathological brain regions for comparison between the training sample and healthy controls: the superior corona radiata, inferior corona radiata, anterior and posterior limbs of the internal capsule, cerebral peduncles (mesencephalic crus) and the genu, and body and splenium of the corpus callosum. Group comparisons showed high degrees of cortical thinning of the precentral and paracentral gyri as well as significant white matter degeneration of the corticospinal tract and corpus collosum. In addition, the patients in the short-survival group demonstrated the most diffuse white matter changes to the cortical region compared with controls.
The use of combined clinical data and MRI measures of ALS-specific regions correctly identified 75% of patients who survived less than 18 months and 83.3% of patients who lived longer than 18 months. The addition of MRI measures improved the accuracy of prediction of mortality at 18 months to 79.17% overall with the combination analysis, compared to 66.67% for evaluation of clinical data alone and 77.08% for MRI alone. Sensitivity and specificity also increased from 62.50% and 70.84%, respectively, to 79.16% for clinical measures and 75% for MRI. The combination led to 75% sensitivity and 83.34% specificity.
Subjective perception factored into misprediction according to clinical measures. Patients who were inaccurately predicted to survive less than 18 months had lesser degrees of physical impairment, with higher revised ALS Functional Rating Scale (ALSFRS-R) scores, while those inaccurately predicted to survive longer than 18 months had a much longer disease duration. This was corrected by the addition of MRI, which showed no real differences between misclassified patients.
For a disease with no cure or effective disease-modifying therapies, the benefit of more accurate prognostic prediction are evident in the timing of supportive measures, discussion of end-of-life decisions, and better-managed palliative care to offer the highest quality of life for the longest period of time.
- Schuster C, Hardiman O, Bede P. Survival prediction in amyotrophic lateral sclerosis based on MRI measures and clinical characteristics [published online April 17, 2017]. BMC Neurol. doi:10.1186/s12883-017-0854-x
- Gordon PH, Salachas F, Lacomblez L, et al. Predicting survival of patients with amyotrophic lateral sclerosis at presentation: a 15-year experience. Neurodegener Dis. 2012;12(2):81-90.
- Elamin M, Phukan J, Bede P, et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology. 2011;76:1263-1269.
- Wolf J, Safer A, Wöhrle JC, et al. Factors predicting one-year mortality in amyotrophic lateral sclerosis patients–data from a population-based registry. BMC Neurol. 2014;14:197.
- Chio A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009;10:310-323.