ISIS Survey: an international study on the diagnostic process and its implications in amyotrophic lateral sclerosis

Abstract

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are often clinically confused with each other because they share a rapid disease progression, parkinsonism that responds poorly or transiently to levodopa therapy, and associated signs (e.g., ocular abnormalities, pyramidal signs and cognitive involvement). To improve the accuracy in diagnosing these disorders, this study examined the clinical features of 51 patients pathologically diagnosed with PSP and CBD. Logistic regression analysis identified two sets of predictors (models) for CBD patients, one consisting of asymmetric parkinsonism, cognitive disturbances at onset and instability and falls at first clinic visit, and the other one of asymmetric parkinsonism, cognitive disturbances at symptom onset and speech disturbances. While PSP patients often had severe postural instability at onset, symmetric parkinsonism, vertical supranuclear gaze palsy, speech and frontal lobe-type features, CBD patients presented with lateralized motor (e.g., parkinsonism, dystonia or myoclonus) and cognitive signs (e.g., ideomotor apraxia, aphasia or alien limb). On the other hand, CBD patients presenting with an alternate phenotype characterized by early severe frontal dementia and bilateral parkinsonism were generally misdiagnosed. PSP patients without vertical supranuclear gaze palsy were misdiagnosed. Recognizing the features which differentiate these disorders and the less obvious disease presentations as well as developing an increased index of suspicion will improve the diagnostic accuracy of these disorders.

Rate of disease progression: a prognostic biomarker in ALS

“…Utilising Kaplan-Meier plots, the median survival from symptom onset was estimated to be 2.7 years (95% CI 2.3 to 3.1 years), while the median survival time from diagnosis of ALS was 1.7 years (95% CI 1.5 to 2.0 years), and that from initial visit to the clinic 1.4 years (95% CI 1.2 to 1.6 years). In addition, the percentage of patients surviving at 1, 2, 3 and 5 years after initial assessment in the clinic was 59±3.9%, 33±3.8%, 23±3.6%, and 21±3.5%, respectively, and is in keeping with previous studies 3 10 15…”

EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives

“…Diagnosing the disease early in the disease when the patient has only limited focal symptoms from one or two regions (bulbar, upper limb, truncal, lower limb) may be difficult and depends on the presence of signs in other affected regions and a number of investigations (Wilbourn, 1998; Meininger, 1999). The mean time from onset of symptoms to confirmation of diagnosis of ALS is 13–18 months (Chio, 1999). Delays may arise from a complex referral pathway, and early symptoms are often intermittent and non‐specific and may be denied or go unrecognized by the patient.…”

“…Delays may arise from a complex referral pathway, and early symptoms are often intermittent and non‐specific and may be denied or go unrecognized by the patient. However, three studies have shown that the longest delay occurs after the patient actually has seen the neurologist (Chio, 1999). There are four cogent reasons for making the diagnosis as early as possible:…”

Region‐specific atrophy of precentral gyrus in patients with amyotrophic lateral sclerosis

“…We used disease duration of 12 months as a cutoff to stratify patients into early and late stage . According to the patients' medical record, 22 people had a disease duration of 12 or less than 12 months (early‐stage, ALS‐e) and six had a disease duration for more than 12 months (late‐stage, ALS‐l) (Table ); the symptom onset suggested that 16 patients had a left limb onset, 8 had a right limb onset, 3 had a bulbar onset, and one patients was not clearly recorded; clinical phenotypes indicated that 23 of the ALS patients had upper limb function impairment.…”

“…Epidemiological statistics have revealed that the median survival time since symptom onset is 2.9 years in ALS patients, and 50% of the patients died within 3 years of symptom onset . The diagnosis of ALS is very challenging if UMN signs are absent or ignored, especially in its early stages . In clinical practice, except for neurological examinations, abnormal signal changes of corticospinal tract (CST) or precentral gyrus (PrCG) on conventional high‐field magnetic resonance imaging (MRI) has also been advocated as markers of UMN compromise in ALS, especially for patients at an advanced stage .…”