Gustatory and olfactory dysfunctions in ALS-patients

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterised by progressive loss of motor function due to cell death of upper as well as lower motor neurons, resulting ultimately in death due to ventilatory and respiratory insufficiency. Due to lack of specific clinical tests and the absence of reliable biomarkers, ALS remains a diagnosis of exclusion, the workup is complex and thus time consuming, which can be emotionally challenging for the patient and potentially causes treatment delays. Since on the one hand evidence of olfactory and to a lesser extent gustatory dysfunction has emerged in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease and on the other hand non-motor symptoms in ALS have come to light, this study wanted to investigate potential olfactory and gustatory dysfunctions respectively in ALS patients; in case such dysfunctions existed, olfactory or gustatory testing could be used as a further diagnostic tool potentially facilitating the difficult diagnostic process. We enrolled 36 participants (23 ALS patients and 13 neurologically healthy controls) into a case-control study. Both groups underwent thorough olfactory and gustatory testing, using validated testing kits manufactured by "Burghart Messtechnik". Gustatory testing was performed in lateralised manner and assessed sweet, sour, bitter and salty taste in 4 different flavour concentrations. Incidence of hyposmia and hypogeusia were evaluated for each group and a potential link between gustatory performance and disease progression was assessed. There were no significant differences between ALS patients' and controls' results in olfactory and gustatory testing – with the exception of the second lowest concentration of sour flavour, likely a false-positive finding. Accordingly, incidence of hyposmia and hypogeusia did not differ between groups. Gustatory performance was inversely correlated with age in both groups. This study has clearly demonstrated the feasibility of olfactory and gustatory testing in ALS patients, which to the best of our knowledge is a novel undertaking in ALS. Among its further strengths are a detailed characterisation of the participant collective, since the olfactory and gustatory testing was embedded into the creation of a cohort of ALS patients ("DESCRIBE ALS") that collected detailed information on the patients, in some cases even including structural magnetic resonance imaging findings. The study did not show any evidence of gustatory or olfactory dysfunction in ALS and based upon our data it is admissible with a reasonable level of certainty to deduce that in fact there are none. However, our study was limited by a small sample size and underpowered to show subtle differences in gustation and olfaction respectively. Another limitation was the lack of umami flavour in our gustatory testing as well as the lack of longitudinal data. Further research has to be undertaken to determine with absolute certainty the absence of gustatory and olfactory dysfunctions as possible non-motor findings in ALS.