Factors affecting the diagnostic delay in amyotrophic lateral sclerosis
Introduction
Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the adult life, characterized by a progressive loss of spinal, bulbar and cortical motor neurons and, consequently, muscle wasting, dysphagia, dysarthria, and respiratory impairment. Death usually occur within 3–5 years after onset, the main cause being the respiratory failure [1]. Although the established pharmacological therapy for ALS, i.e. riluzole, allows an increase in survival [2], patients greatly benefit from the highly specialized palliative care, which is now best provided by tertiary referral Centres [3], [4], [5].
The diagnosis of ALS is mainly based on a clinical approach and supported by negative neuroimaging. Full nerve conduction studies and conventional EMG are very important in the diagnostic workup [6], [7]. A recent consensus conference held by the Awaji Group established the equivalence of electrophysiological signs of lower motor neuron dysfunction to the clinical signs, making redundant the early category of “Laboratory-supported probable ALS” [7]. In addition, in the same conference it was established the equivalence, as a sign of acute denervation, between the fasciculation potentials and the fibrillation potentials and acute sharp waves [7]. Taken together, these two suggestions should increase the sensitivity of the diagnostic criteria and allow earlier diagnosis [7].
As ALS shows almost invariably a subtle onset, early diagnosis can be difficult in ALS, despite the growing number of clinical trials which undoubtedly encourage researchers to put much effort on a timely identification of the disorder. Previous studies have shown, in fact, little change in the diagnostic delay in ALS, with a median delay from onset to diagnosis of about 9–13 months [5], [8], [9], [10], [11].
The concept of “earlier is better” in the diagnosis of ALS bears significant implications in order to access to an appropriate management and care. Besides the available pharmacologic therapy, a high-quality and appropriate palliative care has been demonstrated to have a positive impact on the disease course, and hence on the patients’ quality of life and survival [12], [13], [14], [15], [16].
The objective of the present study was to describe those factors that may delay the diagnosis in ALS and to discuss the potential for improvement.
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Patients and methods
Two-hundred and sixty clinically probable or definite ALS patients (M/F = 1.32) were diagnosed according to El-Escorial/WFN criteria [6] and followed by our Tertiary Referral Centre during a seven-years period (2000–2007).
We made a complete diagnostic work-up in 97 patients (37.3%), while the remaining 163 patients (62.7%) were referred to us from other Centres/Hospitals. All patients underwent a complete clinical evaluation, EMG and nerve conduction studies, brain and/or cervical MRI (the
Results
Table 1 shows the demographic and clinical characteristics of the 260 ALS patients included in this study. 148 (57%) were men and 112 (43%) were women, with a M/F ratio of 1.32. Patients were stratified by site of disease onset: 65 were bulbar (25%, M/F = 0.8) and 195 were spinal (75%, M/F = 1.56). Dysphagia and dysarthria were almost invariably the symptoms at onset in the bulbar patients. Among the spinal-onset group, first symptoms (e.g., weakness, fasciculations) were almost equally distributed
Discussion
This retrospective study involved a cohort of 260 ALS patients followed in a single tertiary referral centre, and it showed that the diagnostic delay is less than one year being slightly shorter in bulbar-onset patients. This appears to be similar to the findings of previous studies [5], [8], [9], [10], [11], [13], [17], [18], [19], [20], and it is in part related to misdiagnoses, the most frequent being discal hernia/cervical myelopathy and vascular pseudobulbar palsy. Furthermore, an early
Acknowledgements
This work was supported by a research grant of the Italian Ministry of Health (no. G71J07000010001). We thank Mr. Martin Russell for the revision of the English language.
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