Lower Motor Neuron Phenotype Research Articles

Subclinical upper motor neuron involvement at the diagnosis may predict disease progression in a cohort of lower motor neuron syndromes from Southern Italy

BackgroundOnly few epidemiological studies on survival of Lower Motor Neuron (LMN) phenotype (LMNP) are available and with controversial results. AimsTo prospectively evaluate a cohort of LMNP patients and assess the possible contribute on survival or disease's progression according to the presence of subclinical Upper Motor Neuron (UMN) impairment at the diagnosis. MethodsForty LMNP among 176 consecutive incident ALS cases observed in our tertiary center from the ALS-Apulia Register were enrolled in the study. Each patient underwent to a neurophysiological study with transcranial magnetic stimulation (TMS) at diagnosis. The primary outcome was the impact of abnormalities at TMS on survival time (from symptoms onset or diagnosis to death, tracheostomy or 30 June 2020, as censoring time). Secondary outcome was time to reach the King's 4 stage. ResultsApproximately one half of LMNP reached the primary outcome during the study period. No difference was found in median survival times and 4 years survival rates according to the presence of TMS impairment. On the other hand, a shorter median time to reach the King's 4 from onset was observed in the group of LMNP with TMS abnormalities (16 months versus 50 months; p = 0.008). Consistently, TMS abnormalities were associated with a 3.5 times higher risk for reaching King's 4 stage (Hazard Ratio: 3.5; 95% Confidence Interval: 1.1–10.9; p = 0.03). ConclusionOur data suggest a role of TMS abnormalities as potential indicator of disease progression and multidistrectual involvement in patients with pure clinical LMN phenotype at the diagnosis.

Motor-evoked potentials in amyotrophic lateral sclerosis: potential implications in detecting subclinical UMN involvement in lower motor neuron phenotype

BackgroundIn amyotrophic lateral sclerosis (ALS), the involvement of lower motor neuron is well defined by electromyography, whereas a reliable marker of upper motor neuron (UMN) damage still lacks. Aim of the study was to estimate the role of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) as marker of subclinical UMN involvement.MethodsClinical evidence of UMN damage was prospectively compared to MEPs in 176 ALS patients diagnosed between 2011 and 2014, and classified according to existing diagnostic criteria. Finally, we evaluated the appearance of clinical UMN signs and the level of diagnostic certainty in ALS after 1 year of follow-up.ResultsAt presentation, abnormal MEPs were found in 80% of patients with clinical evidence of UMN damage and in 72% of patients without clinical involvement of UMN. Among these latter, 61% showed appearance of UMN clinical signs after 1 year. Approximately 70% of patients with clinical lower motor neuron (LMN) phenotype showed MEP abnormalities, while they were considered not classifiable ALS according to Airlie house or Awaji criteria. Furthermore, abnormal MEPs in absence of clinical UMN signs at baseline were found in 80% of spinal ALS that after 1-year developed UMN signs at limbs, compared to 50% of bulbar ALS.ConclusionsTMS is a reliable marker of subclinical UMN damage particularly among LMN phenotype and ensure an early ALS diagnosis in ~ 70% of such cases.

Patterns of symptom development in patients with motor neuron disease

Objective: To investigate whether symptom development in motor neuron disease (MND) is a random or organized process. Methods: Six hundred patients with amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor neuron (LMN) phenotypes were invited for a questionnaire concerning symptom development. A binomial test was used to examine distribution of symptoms from site of onset. Development of symptoms over time was evaluated by Kaplan-Meier analysis. Results: There were 470 respondents (ALS = 254; LMN = 100; UMN = 116). Subsequent symptoms were more often in the contralateral limb following unilateral limb onset (ALS: arms p = 1.05 × 10−8, legs p < 2.86 × 10−15; LMN phenotype: arms p = 6.74 × 10−9, legs p = 6.26 × 10−6; UMN phenotype: legs p = 4.07 × 10−14). In patients with limb onset, symptoms occurred significantly faster in the contralateral limb, followed by the other limbs and lastly by the bulbar region. Patterns of non-contiguous symptom development were also reported: leg symptoms followed bulbar onset in 30%, and bulbar symptoms followed leg onset in 11% of ALS patients. Conclusions: Preferred spread of symptoms from one limb to the contralateral limb, and to adjacent sites appears to be a characteristic of MND phenotypes, suggesting that symptom spread is organized, possibly involving axonal connectivity. Non-contiguous symptom development, however, is not uncommon, and may involve other factors.