Objective tests for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS).

OBJECTIVE

To develop objective markers for upper motor neuron (UMN) involvement in ALS, the value of single-voxel MR spectroscopy (MRS) and transcranial magnetic stimulation (TMS) was studied.

METHODS

Test results of 164 ALS patients who had MRS only (n = 91), TMS only (n = 13), or both (n = 60) were analyzed; also, 11 autopsy examinations were evaluated.

RESULTS

Abnormal test results consistent with UMN involvement were found in 134 patients with clinical UMN signs: 86% on MRS, 77% on TMS, and 70% on MRS and TMS together. Among 30 patients with solely LMN signs (progressive muscular atrophy), UMN results were found in 63% on MRS, 63% on TMS, and 46% on both tests together. There was a significant association of the degree of abnormal N-acetyl aspartate/creatine ratios with UMN signs (p = 0.01). The sensitivity to detect UMN involvement was 0.86 for MRS (specificity 0.37) and 0.77 for TMS (specificity 0.38). At autopsy, all 11 patients had pathologic UMN abnormalities, including 4 with normal MRS and 1 with normal TMS in life.

CONCLUSIONS

MRS is highly sensitive, somewhat more than TMS, and shows good correlation with clinical UMN signs. Combining MRS and TMS results in the same patient with further refinement may help in the early diagnosis of ALS.