Clinical · Healthcare · Insights · Scientific

Epidemiology, associations and prognostication in ALS

The session began with an overview of epidemiology of ALS in China. Dr Liying (China) gave a first glimpse into clinical and genetic characteristics of 461 Chinese patients with ALS. When compared to Western literature on ALS, Chinese patients tend to be younger at the time of diagnosis (mean 52.4) and less likely to have bulbar onset. Cultural differences were also found to have important implications to management of ALS in China. For example, only half of the newly diagnose patients were informed of the diagnosis, while 86% of families were made aware. It is perceived that withholding this information protects from causing anxiety. In addition, majority of the patients were prescribed herbal remedies or vitamin supplements as clinicians felt pressured by the patients to provide at least some treatment for this incurable disease. Genetic differences of the familial forms of ALS were also noted with SOD1 and FUS being common genotypes in China while c9orf72 was found to be rare. Dr Liying finished the talk by presenting a case of ALS caused by H46R mutation, a new mutation discovered by her team.

Following this lecture, the focus of the session moved onto the risk factors and associations with ALS. Dr. Weisskopf (USA) examined the relationship between military service and the likelihood of developing ALS using a population based dataset. The study found an overall risk ratio of 1.23 (CI 0.98-1.53), which was not statistically significant. However, when participants were grouped based on the time of service (WW1, WW2, Vietnam war and Korean war), men who served in WW2 were found to have 47% higher risk of developing ALS, which was statistically significant. Although the reasons for these observations are not clear, Dr. Weisskopf suggested that this could be related to higher deployment rates during WW2 and longer follow period. The jury is still out regarding the association between service in other wars and development of ALS. It is hoped that the answer will be available in next 10 years.

The relationship between diabetes mellitus and ALS was investigated in detailed in a Swedish ALS population by Dr. Mariosa (Sweden). The association is not as straightforward as one might have thought. It was observed that if diabetes is diagnosed before the age of 30, there is a significantly increased risk of ALS. However, the picture is reverse if the diagnosis of diabetes is after the age of 30, which is protective against ALS. It is yet to be shown whether this is as a result of age at the time of diagnosis of diabetes or different types of diabetes (type 1 and 2).

Another study presented by Dr. Fournier (USA) employed mixed methods including epidemiological and post-mortem examination to investigate the effects of head injury prior to to diagnosis of ALS on disease progression and neuropathological changes. Dr. Fournier found no significant correlation between head injury and disease progression after adjusting for a number of confounders. In addition, the study disproved previous speculations that head injury may be responsible for concomitant accumulation of TDP-43 and tau proteins, which are known to play key roles in ALS pathophysiology.

Last two plenaries presented the data on the prognostic factors for ALS progression. Both studies aimed to produce simple and robust clinical tools, which would aid clinicians in prognosticating the rate of progression. Dr. Elamin identified three factors associated with poor outlook including respiratory/bulbar onset, high ALSFRS-slope and loss of executive function. Combining these three factors allows calculating a score which accurately  predicts which patients are low, medium and high risk of progression. Similar robust score (ALS-Survival Score) was developed by the Italian team led by Dr. Lunetta, which included age at diagnosis, ALSFRS total score, BMI, Disease duration, AST and creatinine. The latter two laboratory markers were speculated to represent skeletal muscle damage.

The plenary received a great amount of attention and was filled with interesting discussions ranging from speculations for causal mechanisms of physical activity, diabetes and head injury on ALS. It is impressive the amount of evidence can be uncovered using robust statistical analyses from epidemiological studies in ALS.