The diagnostic pathway and prognosis in bulbar-onset amyotrophic lateral sclerosis
Introduction
Understanding the clinical heterogeneity inherent in amyotrophic lateral sclerosis (ALS) remains an important challenge that might have some bearing on the disappointing results from clinical therapeutic trials for this degenerative disorder of cerebral and spinal motor neurons. Despite a median survival of 2–3 years from symptom onset in most clinic-based series, there is a skewed distribution with a significant number surviving beyond 10 years, a small minority of which also have bulbar-onset (BO) of their symptoms [1]. BO patients constitute up to 25% of most ALS clinic populations, and generally this phenotype is associated with more rapid progression [2]. It has been observed that older female patients are over-represented in BO patients [3], [4], [5], which links to the independent observation that the female:male ratio in ALS increases with each decade [5], [6], [7].
The insidious onset of symptoms in ALS, the lack of a diagnostic test, erroneous referral to other specialists [8], and even unnecessary surgery in some cases [9], are all factors involved in the consistent delay from symptom onset to formal diagnosis in ALS (frequently beyond 12 months [2]). This interval might represent a missed opportunity for a more effective therapeutic intervention. True ‘mimics’ of ALS are rare, possibly even more so for BO patients, who are observed to reach ALS clinics sooner after symptom onset than limb-onset patients [10], though this may simply reflect more rapid progression of symptoms. We have informally observed that BO patients are frequently referred to otolaryngology and stroke clinics prior to diagnosis in our tertiary centre, sometimes undergoing unnecessary investigations as a result.
Finally, we also recognise a group of patients, often female, who despite the relatively rapid development of anarthria, remain ambulant for months thereafter, and may derive proportionately a greater benefit from interventions such as enteral feeding.
In this retrospective analysis we sought to characterise the diagnostic pathway and aspects of clinical heterogeneity affecting survival in bulbar-onset ALS patients.
Section snippets
Methods
Patients with ALS seen at a tertiary referral centre since August 2003 were prospectively recorded in a database as part of routine clinical care. Since 2009 attendees have provided written informed consent for the use of anonymised clinical data for research and publication, and approval for the retrospective use of deceased patients (or those lost to follow up) was granted through application to the Ireland Health and Social Care Research Ethics Committee 2 (09/NIR02/35).
The diagnosis of ALS
Results
A total of 49 patients with bulbar-onset were identified from 262 sporadic ALS cases recorded in the database. The results are summarised in Table 1.
Discussion
This retrospective descriptive study of a group of bulbar-onset ALS patients confirms the long-recognised lower median survival overall, whilst specifically noting that nearly 10% of patients survived beyond 4 years from symptom onset (the upper limit of median survival in a review of prognostic factors in ALS [2]). We confirmed a higher proportion of females and higher mean age of symptom onset, and demonstrated that the development of anarthria is strongly predictive of the time to eventual
Acknowledgements
We would like to thank all the staff of the Oxford MND Care Centre (www.oxfordmnd.net), which receives funding from the MNDA, for their ongoing work in the care of ALS patients. MRT is supported by the MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellowship.
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These authors contributed equally to the manuscript.