Natural history of upper motor neuron-dominant ALS

Sorarù, Gian Domenico; Ermani, Mario; Logroscino, Giancarlo; Palmieri, Arianna; Ascenzo, Carla D'; Orsetti, Valeria; Volpe, M; Cima, Valentina; Zara, Gabriella; Pegoraro, Elena; Angelini, C.

doi:10.3109/17482960903300867

Cited by 33 publications

(26 citation statements)

References 14 publications

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“…The statistical analysis, model-building process or completeness of reporting were judged to be inadequate in six studies, resulting in 'moderate' to 'high' [20], [21], [22], [25], [28], [30] (n = 3,660) 0 [ 20], [25], [28], [30] Mixed effects model [21] Multiple linear regression [22] Multiple linear analysis (only results from univariate analysis reported) [20], [21], [22], [25], [28], [ Frontotemporal syndrome = comorbid FTD or executive dysfunction in a patient without dementia J Neurol risk of bias. Some of the studies reviewed only presented results from univariate analysis on the prognostic factor(-s) studied, thus causing the data quality assessment to be downgraded [22,26,29,31]. One study could be classified as 'low' risk of bias on all quality domains [23].…”

Section: Methodological Quality Of Included Studiesmentioning

confidence: 98%

Prognostic factors for the course of functional status of patients with ALS: a systematic review

et al. 2014

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The progressive course of amyotrophic lateral sclerosis (ALS) results in an ever-changing spectrum of the care needs of patients with ALS. Knowledge of prognostic factors for the functional course of ALS may enhance clinical prediction and improve the timing of appropriate interventions. Our objective was to systematically review the evidence regarding prognostic factors for the rate of functional decline of patients with ALS, assessed with versions of the ALS Functional Rating Scale (ALSFRS). Two reviewers independently assessed the methodological quality of the thirteen included studies using the Quality in Prognosis Studies (QUIPS) tool. The overall quality of evidence for each prognostic factor was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, considering risk of bias, imprecision, inconsistency, indirectness, and publication bias. The quality of evidence for the prognostic value of age at onset, site of onset, time from symptom onset to diagnosis, and ALSFRS-Revised baseline score was low, mainly due to the limited data and inconsistency of results in the small number of studies included. The prognostic value of initial rate of disease progression, age at diagnosis, forced vital capacity, frontotemporal dementia, body mass index, and comorbidity remains unclear. We conclude that the current evidence on prognostic factors for functional decline in ALS is insufficient to allow the development of a prediction tool that can support clinical decisions. Given the limited data, future prognostic studies may need to focus on factors that have a predictive value for a decline in ALSFRS(-R) domain scores, preferably based on internationally collected and shared data.

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Section: Methodological Quality Of Included Studiesmentioning

confidence: 98%

Prognostic factors for the course of functional status of patients with ALS: a systematic review

et al. 2014

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“…Thus, the diagnosis of PLS should be made only after four years of disease duration (8). PLS may stabilize after a few years of progression (12), although similar stabilization may occur in UMN-dominant ALS (UMN-D ALS) (11,13). Frontotemporal dementia (FTD), cognitive impairment and altered behavior occur in PLS comparably to ALS (14).…”

Section: Clinical Phenotypesmentioning

confidence: 98%

Deciphering amyotrophic lateral sclerosis: What phenotype, neuropathology and genetics are telling us about pathogenesis

Ravits¹,

Appel²,

Baloh³

et al. 2013

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

151

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Amyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. However, they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they are mostly characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Overall, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS – and ALS is a syndrome. Since, however, multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principal component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms could be identified and understood, ALS therapy could rationally target progression and stop the disease – a goal that seems increasingly achievable.

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“…Neuromuscular ultrasound abnormalities may aid in the diagnosis of ALS and also in distinguishing between ALS phenotypes (e.g., UMND vs. PLS patients), which has major prognostic implications …”

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confidence: 99%