Motor neuron dysfunctions in the frontotemporal lobar degeneration spectrum: a clinical and neurophysiological study

Abstract

Background: Although only a few frontotemporal lobar degeneration (FTLD) patients develop frank amyotrophic lateral sclerosis (ALS), motor neuron dysfunctions (MNDys) occur in a larger proportion of patients. The aim of this study is to evaluate MNDys and ALS in a sample of consecutively enrolled sporadic FTLD patients.

Methods: Clinical and neurophysiological evaluations (i.e. needle electromyography) assessed lower (LMN) and upper (UMN) motor neuron function at the baseline in 70 probable FTLD patients (i.e., 26 behavioural variant-bvFTD, 20 primary progressive aphasias-PPAs and 24 corticobasal syndrome-CBS). To obtain a more accurate estimation, quantitative scales were also applied (i.e. ALSFRS-r and UMN scale). Patients were screened for MAPT, GRN and C9orf72 mutations. A mean clinical follow-up of 27.8±22.4 months assessed MNDys progression and the clinical presentation of ALS.

Results: Five genetic cases were identified. Within the sample of sporadic patients, a relative low rate of FTLD patients was diagnosed as probable ALS (5%), while a higher proportion of patients (17%) showed clinical and neurophysiological MNDys. Thirteen patients (20%) presented with isolated clinical signs of LMN and/or UMN dysfunction, and 8 patients (12%) showed neurogenic changes at the electromyography. No differences in FTLD phenotype and disease duration were found between MNDys positive and negative patients. Clinical MNDys were highly associated with positive electromyographic findings. At follow-up, no MNDys positive patient developed ALS.

Conclusion: Neurophysiological and clinical examinations revealed mild MNDys in FTLD patients not fulfilling criteria for ALS. This condition did not evolve at a mean follow-up of two years. These results, indicating a subclinical degeneration of corticospinal tracts and lower motor neurons, suggest that FTLD patients may be more at risk of MNDys than the general population.

Keywords: Amyotrophic lateral sclerosis; Electromyography; Frontotemporal dementia; Frontotemporal lobar degeneration; Motor neuron dysfunction; Pyramidal signs.