scholarly journals Two Distinct Clinical Phenotypes of Bulbar Motor Impairment in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaila L. Stipancic ◽  
Yana Yunusova ◽  
Thomas F. Campbell ◽  
Jun Wang ◽  
James D. Berry ◽  
...  

Objective: Understanding clinical variants of motor neuron diseases such as amyotrophic lateral sclerosis (ALS) is critical for discovering disease mechanisms and across-patient differences in therapeutic response. The current work describes two clinical subgroups of patients with ALS that, despite similar levels of bulbar motor involvement, have disparate clinical and functional speech presentations.Methods: Participants included 47 healthy control speakers and 126 speakers with ALS. Participants with ALS were stratified into three clinical subgroups (i.e., bulbar asymptomatic, bulbar symptomatic high speech function, and bulbar symptomatic low speech function) based on clinical metrics of bulbar motor impairment. Acoustic and lip kinematic analytics were derived from each participant's recordings of reading samples and a rapid syllable repetition task. Group differences were reported on clinical scales of ALS and bulbar motor severity and on multiple speech measures.Results: The high and low speech-function subgroups were found to be similar on many of the dependent measures explored. However, these two groups were differentiated on the basis of an acoustic measure used as a proxy for tongue movement.Conclusion: This study supports the hypothesis that high and low speech-function subgroups do not differ solely in overall severity, but rather, constitute two distinct bulbar motor phenotypes. The findings suggest that the low speech-function group exhibited more global involvement of the bulbar muscles than the high speech-function group that had relatively intact lingual function. This work has implications for clinical measures used to grade bulbar motor involvement, suggesting that a single bulbar measure is inadequate for capturing differences among phenotypes.

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.


2017 ◽  
pp. 15-32
Author(s):  
Satish V. Khadilkar ◽  
Rakhil S. Yadav ◽  
Bhagyadhan A. Patel

2020 ◽  
Vol 10 (3) ◽  
pp. 58 ◽  
Author(s):  
Owen Connolly ◽  
Laura Le Gall ◽  
Gavin McCluskey ◽  
Colette G Donaghy ◽  
William J Duddy ◽  
...  

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.


2007 ◽  
Vol 8 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Marie‐Odile Habert ◽  
Lucette Lacomblez ◽  
Philippe Maksud ◽  
George EL Fakhri ◽  
Jean‐FranÇois Pradat ◽  
...  

Data in Brief ◽  
2020 ◽  
Vol 29 ◽  
pp. 105229 ◽  
Author(s):  
Peter Bede ◽  
Rangariroyashe H. Chipika ◽  
Eoin Finegan ◽  
Stacey Li Hi Shing ◽  
Kai Ming Chang ◽  
...  

2013 ◽  
Vol 9 (3) ◽  
pp. 260-263 ◽  
Author(s):  
Giulio E. Lancioni ◽  
Nirbhay N. Singh ◽  
Mark F. O’Reilly ◽  
Jeff Sigafoos ◽  
Gabriele Ferlisi ◽  
...  

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