Introduction This is a well-done study of ALS patients, but it will not provide new information to specialists in the field.
The survival time of patients after a diagnosis of ALS is variable, although death generally occurs about 2 to 5 years after the onset of symptoms, with a mean survival of 20 to 50 months, and only about 5 to 10% of those affected survive 10 years or more. In addition, earlier age at symptom onset and diagnosis, spinal onset, higher initial ALSFRS-R score, or higher body mass index (BMI) have been associated with longer survival. In contrast, older age, bulbar onset, cognitive impairment or depression, and poorer nutritional status are associated with shorter survival.
Although several authors have described the clinical and epidemiological characteristics and factors related to the survival of patients with ALS, few studies have been conducted in the Spanish population. This study is therefore one of the few to evaluate the epidemiological and clinical characteristics and prognostic factors of ALS in Spain, and it provides similar results to previous population studies.
A population-based registry data analysis over a long study period provides up-to-date, representative, and complete information on patients with ALS, which is useful for planning the necessary resources for affected individuals and their families. Therefore, this study aimed to determine the incidence and prevalence of patients with ALS, as well as their main characteristics, and to analyze the factors associated with the evolution and survival of these individuals using information from the Rare Disease Registry in the Region of Murcia (RM), located in the southeast of Spain.
Study population
An observational study was conducted on patients with a confirmed or probable diagnosis of ALS according to the El Escorial criteria and registered in the Rare Disease Information System (SIER) of the RM from January 2008 to December 2021. The data collected from each patient included the following:
- Data include gender, country of birth, date of birth, death of the patient (yes/no) and date of death.
- Family history of the disease, i.e. those including a family member with a diagnosis of ALS. The associated genetic mutation was collected in patients who underwent genetic study.
- Characteristics included year of diagnosis, date of symptom onset, and initial disease presentation (bulbar, spinal, bulbospinal, or respiratory). Time from symptom onset to diagnosis (years) and from symptom onset to death (years) were also recorded.
- Initial clinical manifestations collected were: muscle weakness (cervical, upper limbs, lower limbs, or both), dysarthria, dysphagia, dyspnea, gait alteration and clumsiness, muscle atrophy (upper limbs, lower limbs, or all limbs), muscle cramps, loss of dexterity, fasciculations (lingual, upper limbs, lower limbs, mixed), spasticity, and emotional lability (Citation35).
- Information on riluzole treatment, family support, palliative care, and the patient's last wishes were obtained. Finally, data were collected on the recognition of disability and/or dependency.
Statistical analysis
Demographic, genetic, and clinical characteristics of people with ALS were summarized using descriptive statistics. In addition, different hypothesis contrast tests were used depending on the type of variables and the normality of their data distribution. Survival was calculated from the age of symptom onset to the age of death (end event) or until December 31, 2021, or until loss to follow-up.
Results
781 cases of ALS were recorded in the SIER, 508 were of which were classified as confirmed or probable cases, including 374 incidents from 2008 to 2021.
The standardized incidence rate (SIR) was approximately 2/100,000 person-years. It was higher in men than in women. An increase in incidence was observed with age, with a maximum of data between 75 and 84 years, followed by an overall decrease. However, in men, the highest incidence was in the 65-74 age group.
Throughout the study, incidence rates ranged from 2/100,000 person-years in 2008 to 2.77/100,000 in 2021), with the latter year being the year with the highest incidence recorded.
There was a family history of the disease in 28 patients (7.5%). Among patients for whom information on the causative genetic mutation was available, 55.5% were associated with the C9orf72 gene, 22.2% with the FUS gene, and the remaining 22.2% with other genes.
According to the site of onset, spinal ALS was predominant in half of the patients, followed by bulbar ALS in one-third of the cases. Dual pathologies (bulbar and spinal) were considerably less frequent and cases where the onset of the disease was characterized by respiratory symptoms were rare. In the remaining 8.3% of the cases, this information was not available.
The more frequent site of onset in men was spinal ALS, while in women it was bulbar ALS but less clearly. In analyses by age group, spinal onset predominated up to 74 years, after which bulbar onset had the highest incidence.
The mean time from symptom onset to diagnosis was less than 1 year, with no significant differences between the sexes. However, when analyzed by site of onset (bulbar or spinal), the diagnostic delay was slightly shorter for bulbar ALS.
Overall, the most common clinical manifestations at disease onset were muscle weakness (71.1%), followed by fasciculations (66.0%), muscle atrophy (61.2%), and gait alteration/clumsiness (53.0%). Patients with bulbar ALS had more dysarthria and dysphagia as their initial symptom (over 80% in both cases), while those classified as spinal ALS had mainly muscle weakness, atrophy, fasciculations, and gait alteration/clumsiness.
Interestingly, only 9 out of 10 patients were treated with riluzole, and more distressingly, less than half of the cases had their disability recognized. The average time from diagnosis of ALS to recognition of disability was one year, and the average time to dependency was one and a half years.
Half of the patients received palliative care, three-quarters of them had family support, and more than a third recorded their last wishes. Among these, most of them refused to receive palliative measures but accepted final sedation, while 15% of them on the contrary accepted any measure that could have prolonged their life.
During the study period, 297 people died (8 out of 10), half of them were men, and the average age at death was 70 years, without significant differences between genders.
The mean number of years between the onset of symptoms and death was 2.6 and the median was 2 years (there were more early deaths than deaths after these two years). 85% of patients survived more than 1 year after diagnosis, 12% more than 5 years, and 1% more than 10 years, which is lower than the 5 to 10% reported by other authors.