Spread Direction and Prognostic Factors in Limb-Onset Sporadic Amyotrophic Lateral Sclerosis

Abstract

Objective: To investigate the spread direction and prognostic factors in limb-onset sporadic amyotrophic lateral sclerosis (sALS). Methods: Medical records of 128 patients with sALS were reviewed. Variables studied were age at symptom onset, gender, region and lateralization of onset, onset to diagnosis interval (ODI), progression direction, bulbar-involved, time from onset to bulbar-involved, ALSFRS-r, upper motor neuron (UMN) signs and progression rate. Results: First, the horizontal and vertical directions are major spreading directions in limb-onset sALS. Second, in crossed and interposed groups, while ODI is shorter, the progression rate is faster and UMN signs are more pronounced (p < 0.05). Third, ALSFRS-r, UMN signs and progression rate have significant differences between with-bulbar-involved and without-bulbar-involved (p < 0.05). The progression rate is related to the time from onset symptoms to bulbar-involved (correlation coefficient -0.535, p = 0.00). Fourth, in multivariate regression analysis, progression rate could respectively increase by about 1.14 and 3.89 times with shorter ODI and bulbar-involved in limb-onset sALS patients. Conclusions: The horizontal and vertical directions are the major spread directions in limb-onset sALS. Except for ALSFRS-r and ODI, bulbar-involved is an adverse factor for ALS progression, and progression rate is related to the time from onset symptoms to bulbar-involved.

Spreading in ALS: The relative impact of upper and lower motor neuron involvement

“…Moreover, UMN involvement seems important in shortening the time for cranial-caudal spread, but not in caudal-cranial progression. This is contrary to Hu et al 7 observation that UMN signs had no influence on the rate of progression. Ravits et al, 1 described preferential involvement of the ipsilateral leg following arm onset in patients with predominant UMN signs, but we did confirm this observation.…”

“…18 Noncontiguous progression has been associated with a poor prognosis. 6,7 Analysing the AUC, which incorporates both of disease spread and rate, spread of bulbar and lower limb onsets to adjacent regions had higher probabilities than to more distant regions. The disease tended to follow a caudal progression; the AUC from upper limbs to lower limbs was higher than its converse, and this was most influenced by UMN involvement.…”

“…Only three are prospective, 1,2,3 others rely on chart reviews, 4,5,6,7 patient self-administered questionnaire at one time point, 8 or EMG studies. 9 Only four investigators 1,5,7,8 studied the impact and distribution of UMN dysfunction on the pattern and rate of progression of the disease. All these studies, except one 6 were carried out in single centers, and none included patients with frontotemporal dementia (FTD).…”

Regional spreading of symptoms at diagnosis as a prognostic marker in amyotrophic lateral sclerosis: a population-based study

“…The pattern of disease spreading has been related to survival30; for example, in lower limb-onset, the time to involvement of the following limb has been shown to be a prognostic factor regardless of the initial direction of spread 31. Besides, the time to bulbar involvement in spinal onset patients,32 the time to generalisation (ie, the time of spreading of the clinical signs from spinal or bulbar localisation to both)33 and the interval from onset to involvement of the second region have been reported to correlate with survival 21…”

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

“…Serial MRI studies could provide a measure for the rate of progression in neurological diseases and may also demonstrate the spread of pathology to different brain regions (Hu, Jin et al 2016). However, the few longitudinal DTI studies of ALS have small numbers of subjects and inconsistent findings , Zhang, Schuff et al 2011, Keil, Prell et al 2012.…”