Site Of Onset And Spreading Pattern In Amyotrophic Lateral Sclerosis: A Clinical Study In 233 Cases

Background:Amyotrophic Lateral Sclerosis is one of the neurodegenerative diseases which majorly affects motor system including both upper and lower motor neurons.Patients with ALS usually present with weakness of a particularly limb or a focal region and the symptoms gradually evolve to other limbs and bulbar region.Patiens with bulbar-onset conut for a small part,dysarthria or dysphagia may be their first complains.Respiratory muscles can also be affected,which indicates poor prognosis.Although there remains studies concerning onset region and spread patterns overseas,it's relatively deficient in Chinese ALS patients.Objectives:To explore the natural history of ALS including site at onset,directionality of evolvement,patterns of spread,survival time and prognosis.Methods:A total of 233 sporadic ALS patients were included in our study.All of them were diagnosed in the department of neurology of Peking Union Medical College Hospital in China.Gender,age at onset,diagnosis delay,ALS function rating scales and the onset order were collected at the time of diagnosis.Follow-ups were conducted at least once a year,mainly through telephone.Survival datas were analysed using Kaplan-Meier and Cox regression analysis.Results:Of all the 233 ALS patients,the ratio between male and female was 1.38:1.The mean age at symptom onset was 52.6±10.7 years.Diagnostic delay was 14.4±8.1 months in average and 12 months in median.The percentage of bulbar-onset,upper limb-onset and lower limb-onset was 24.5%,51.9%,23.6%.Survival time was not significantly different between phenotyeps.The most frequent directionality of initial spread with limd-onset patients was to an adjacent horizontal region as observed 56.2%in upper limb-onset and 69.7%in lower limb-onset patients.Among all the upper limb-onset patients,rostral progression indicated poor prognosis and gender made difference in the evolving directionality(p<0.05).210 patients evolved contiguously,which meant evolving to adjacent neurological function domain,while 23 patients did not.Contiguous-pattern included Bulbar-cervical-lumbar pattern(21.5%),Cervical-lumbar-bulbar pattern(21.0%),Lumbar-cervical-bulbar pattern(17.6%),Limb-reentry pattern(from unilateral limb to adjacent domain then back to contralateral limb)(15.5%)and Cervical-bulbar-lumbar pattern(14.6%)from greatest to least.Non-contiguous pattern could be further categorised into Limb-crossing pattern(from unilateral cervical to contralateral lumbar or vice versa)(5.6%),Bulbar-lumbar pattern(3.0%),Lumbar-bulbar pattern(1.3%).Survival time between Contiguous pattern and Non-contiguous pattern showed no significantly difference.Patients with Cervical-lumbar-bulbar pattern had the best prognosis in all the five Contiguous patterns while the Cervical-bulbar-lumbar poorest,the rest three patterns lay between these two.Other factors influenced survival in Cox regression analysis included age at onset,diagnositic delay from symptoms onset,the rate of decline in ALSFRS-R score.Conclusions:1.Patients with bulbar,upper limb and lower limb onset showed no significantly difference in survival time.2.Patient with limb-onset most frequently evolved horizontally.3.Contiguously spreading was the most common spreading pattern in ALS patients.There were no significantly difference in survival time between Contiguous pattern and Non-contiguous pattern.Patients with Cervical-lumbar-bulbar pattern had significantly better prognosis than Cervical-bulbar-lumbar pattern.