Delayed diagnosis in ALS: The problem continues ☆ Hipolito Nzwalo a , Daisy de Abreu b , Michael Swash c,d,f , Susana Pinto d , Mamede de Carvalho d,e, ⁎ a Department of Neurology, Hospital de Faro, Centro Hospitalar do Algarve EPE, Algarve, Portugal b Department of Statistics, Faculty of Sciences, University of Lisbon, Lisbon, Portugal c Department of Neurology, Royal London Hospital, UK d Translational Clinical Physiology Unit, Instituto de Medicina Molecular, Institute of Physiology, Faculty of Medicine, University of Lisbon, Portugal e Department of Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal f Barts and the London School of Medicine, Queen Mary University of London, UK abstract article info Article history: Received 4 March 2014 Received in revised form 30 April 2014 Accepted 2 June 2014 Available online 12 June 2014 Keywords: Amyotrophic lateral sclerosis Diagnosis delay General practitioner Motor neuron disease Neurologist We studied the limitations to early diagnosis in amyotrophic lateral sclerosis (ALS). The diagnostic process was assessed in 120 consecutive patients, including onset, interval to diagnosis, investigations, specialist assessment and pre-diagnostic management. Times from onset to first consultation (T1), second consultation (T2) and diagnosis (TD) were considered. Predictors of diagnostic delay were determined by multivariate logistic regres- sion, adjusted for gender, age, clinical manifestations, and specialism of the first and second consultants. There were 101 consecutive ALS patients with complete datasets (69% men; median age at diagnosis 61.5 years). The mean TD and median TD were respectively 10.1 and 9.5 months. In 55%, the first consultant was a general prac- titioner (GP), in 16% a neurologist and in 14% an orthopedist. The diagnosis of ALS was made by non-neurologists in 9 patients. The odds of delayed diagnosis (≥12 months) were higher (1.56; 0.19–12.56) in younger patients (≤45 years) (p b 0.05). Female gender (0.56; 0.29–1.70) and bulbar-onset (0.56; 0.29–1.70) were independently associated with earlier diagnosis (p b 0.05). Assessment by a neurologist at the first (0.32; 0.19–2.46) or second consultation (0.87; 0.21–1.21) was associated with a shorter diagnosis time (b 12 months) (p b 0.05). We conclude that diagnostic delay mainly resulted from delayed referral from non-neurologist physicians to a neurologist. Moreover, incomplete neurophysiological investigation had a relevant impact. © 2014 Elsevier B.V. All rights reserved. 1. Introduction The diagnosis of amyotrophic lateral sclerosis is a clinical exercise, supported by neurophysiological studies, neuroimaging and other tests used to exclude other possible diagnoses [1,2]. Early diagnosis and management in specialized ALS clinics providing multidisciplinary patient care positively impacts quality of life and prolongs survival [3]. Delayed diagnosis, a major concern in the care of patients with ALS, derives from clinical uncertainty at presentation, lack of a simple diagnostic test, and inappropriate referral to other specialists. The lag-time to diagnosis, a mean of 11 months irrespective of different healthcare systems [4,5], remains close to that first reported [6,7]. In addition to delaying management, delayed diagnosis delays patient entry into clinical trials [3,7]. Any new drug therapy for ALS would probably have its major impact in the early phase of the disease. Thus, understanding the diagnostic pathway is fundamental to identifying and mitigating factors leading to diagnostic delay. 2. Patients and methods We reviewed the medical records of 120 consecutive ALS patients followed most recently in our multidisciplinary ALS clinic in Lisbon, to evaluate their progress from symptom onset to a diagnosis of ALS. Diag- nosis was determined by expert neurological and neurophysiological examination (MdeC/SP) in accordance with the revised El Escorial criteria and utilizing the Awaji guidelines for neurophysiological assess- ment [1,2]. To complement or clarify this information, patients were interviewed in person or by telephone. Data focusing on early clinical manifestations, the time interval to diagnosis, complementary investi- gations (in particular, CT or MR imaging, and neurophysiologic studies), the specialty of the evaluating physicians and their diagnostic pathway, as well as pre-diagnostic management were analyzed. Specifically, time from symptom onset to first consultation (T1), time from symptom onset to second consultation (T2) and the time from symptom onset to definite diagnosis (TD) were analyzed. For the purpose of this report, misdiagnosis was considered when any neurological or condition other than ALS was diagnosed in affected patients. Differences between groups were explored with the Mann– Whitney U test. Age (≤ 45 vs N 45 years) and time to diagnosis (b 12 vs ≥ 12 months) cutoffs were established as defined by other au- thors [8,9]. Multivariate logistic regression (stepwise forward and Journal of the Neurological Sciences 343 (2014) 173–175 ☆ All authors made a substantial contribution to the manuscript. ⁎ Corresponding author at: Institute of Physiology, Faculty of Medicine, University of Lisbon, Av. Professor Egas Moniz, 1648-028 Lisbon, Portugal. Tel./fax: +351 21 7805219. E-mail address: mamedemg@gmail.com (M. de Carvalho). http://dx.doi.org/10.1016/j.jns.2014.06.003 0022-510X/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns