Factors affecting the diagnostic delay in amyotrophic lateral sclerosis

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Abstract

Background

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy).

Objective

To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it.

Methods

We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007.

Results

The median time from onset to diagnosis was 11 months (range: 6–21) for the whole ALS cohort, 10 months (range: 6–15) in bulbar-onset (n = 65) and 12 months (range: 7–23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75–24.25] vs ALS, n = 179, median delay, 9 months [6–15.25], p < 0.001).

Conclusions

The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis.

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.

Section snippets

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.

References (30)

  • G.D. Borasio et al.

    Breaking the news in amyotrophic lateral sclerosis

    J Neurol Sci

    (1998)
  • T. Okita et al.

    Can Awaji criteria earlier diagnosis than the revised El Escorial criteria

    J Neurol Sci

    (2011)
  • R. Spataro et al.

    Causes and place of death in Italian patients with amyotrophic lateral sclerosis

    Acta Neurol Scand

    (2010)
  • R.W. Orrell

    Motor neuron disease: systematic reviews of treatments for ALS and SMA

    Br Med Bull

    (2009)
  • R.G. Miller et al.

    Practice parameter update: The care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review)

    Neurology

    (2009)
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