Comparison of Two Clinical Upper Motor Neuron Burden Rating Scales in ALS Using Quantitative Brain Imaging

Makary, Meena M.; Weerasekara, Akila; Rodham, Haley; Hightower, B. G.; Tseng, Chen‐Te; Chan, James; Chew, Sheena; Paganoni, Sabrina; Ratai, Eva‐Maria; Zürcher, Nicole R.; Hooker, Jacob M.; Atassi, Nazem; Babu, Suma

doi:10.1021/acschemneuro.0c00772

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…The secondary study outcomes included functional status measured through the ALSFRS-R and disease progression rate. ALSFRS-R is a questionnaire-based scale that measures the motor function and disease severity of ALS patients and is considered the gold standard measure of disability progression ( Makary et al, 2021 ). Higher ALSFRS-R score indicates better functional status.…”

Section: Methodsmentioning

confidence: 99%

Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis

Cui

Ingre

Yin

et al. 2022

eLife

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Immune response changes have been reported in amyotrophic lateral sclerosis (ALS), but their clinical relevance remains undetermined. Therefore, our aim is to evaluate the relationships between blood leukocyte subpopulations and prognosis of ALS.A longitudinal cohort of 288 ALS patients with up to 5 years of follow-up during 2015-2020 were recruited at the only tertiary referral center for ALS in Stockholm, Sweden. Routine differential leukocyte counts, and determination of lymphocyte subpopulations including an extended T cell panel with flow cytometry, were collected at diagnosis and at regular intervals thereafter. The primary outcome was risk of death (alternatively use of invasive ventilation) after diagnosis of ALS. The secondary outcomes included repeatedly measured functional status through Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) score and disease progression rate. Cox model was used to evaluate the associations between leukocytes and risk of death. Generalized estimating equation model (GEE) was used to assess the correlation between leukocytes and ALSFRS-R score and disease progression rate. The results showed that counts of leukocytes, neutrophils and monocytes increased gradually over time since diagnosis and were negatively correlated with ALSFRS-R score, but not associated with risk of death or disease progression rate. Focusing on lymphocyte subpopulations, increasing counts of natural killer (NK) cells (HR=0.61, 95% CI= [0.42-0.88] per SD increase) and proportions of Th2-diffrentiated CD4+ central memory (CM) T cells (HR=0.64, 95% CI= [0.48-0.85] per SD increase) were associated with a lower risk of death. Increasing proportions of CD4+ effector memory cells re-expressing CD45RA (EMRA) T cells (HR=1.39, 95% CI= [1.01-1.92] per SD increase) and CD8+ T cells (HR=1.38, 95% CI= [1.03-1.86] per SD increase) were associated with a higher risk of death. None of the lymphocyte subpopulations was correlated with ALSFRS-R score or disease progression rate. Our findings suggest a dual role of immune cells in ALS prognosis, where neutrophils and monocytes primarily reflect functional status whereas NK cells and different T lymphocyte populations act as prognostic markers for survival. The findings provide insights for cell-specific treatment for ALS.

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Section: Methodsmentioning

confidence: 99%

Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis

Cui

Ingre

Yin

et al. 2022

eLife

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“…To our knowledge, this is the first randomized, controlled, triple-blinded study of external herbal treatment for ALS. We used the ALSFRS-R score as the primary outcome, which is considered the gold standard for the staging and functional measurement of disease progression ( 34 , 35 ) and comparison with newly proposed scales ( 36 , 37 ). In our study, the decrease in the ALS-FRS-R was significantly lower in the JWLP group than in the PLAP group from the eighth week until the final examination after 20 weeks.…”

Section: Discussionmentioning

confidence: 99%

Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster–The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial

Schröder

Wang²,

Sima³

et al. 2022

Front. Neurol.

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BackgroundAmyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by gradually increasing damage to the upper and lower motor neurons. However, definitive and efficacious treatment for ALS is not available, and oral intake in ALS patients with bulbar involvement is complicated due to swallowing difficulties.Hypothesis/purposeThis study investigated whether the external plaster application of the herbal composition Ji-Wu-Li efficiently slows ALS progression because prior studies obtained promising evidence with oral herbal applications.Study designThe randomized, triple-blinded study compared the efficacy, safety, and tolerability of the application of Ji-Wu-Li plaster (JWLP) with placebo plaster (PLAP).MethodsIn total, 120 patients with definite ALS, clinically probable ALS, or clinically probable laboratory-supported ALS were randomized in a 1:1 ratio to receive JWLP or PLAP. Patients were treated and observed for 20 weeks. The primary outcome was the ALSFRS-R score, while the secondary outcomes were the ALS-SSIT score and weight loss.ResultsThe mean±SD decrease in the ALSFRS-R over 20 weeks differed by 0.84 points in a group comparison (JWLP, −4.44 ± 1.15; PLAP, −5.28 ± 1.98; p = 0.005). The mean increase in the ALS-SSIT over 20 weeks differed by 2.7 points in a group comparison (JWLP, 5.361.15; PLAP, 8.06 ± 1.72; p < 0.001). The mean weight loss over 20 weeks differed by 1.65 kg in a group comparison (JWLP, −3.98 ± 2.61; PLAP, −5.63 ± 3.17; p = 0.002). Local allergic dermatitis suspected as causal to the intervention occurred in 10 of 60 participants in the JWLP group and 9 of 60 participants in the PLAP group. Systemic adverse events were mild, temporary, and considered unrelated to the intervention.ConclusionThe JWLP showed clinical efficacy in the progression of ALS, as measured by the ALSFRS-R, ALS-SSIT, and weight loss in a randomized, placebo-controlled trial. Because skin reactions occurred in both groups, the covering material needs improvement. All of the Ji Wu Li herbal ingredients regulate multiple mechanisms of neurodegeneration in ALS. Hence, JWLP may offer a promising and safe add-on therapy for ALS, particularly in patients with bulbar involvement, but a confirmative long-term multicentre study is required.

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“…A novel component of the current study was the independent investigation of laughter and crying frequency components of the CNS-LS in combination with multi-modal neuroimaging in ALS, which appears overlooked in the existing literature ( 11 , 38 ). The current findings indicated stronger associations between CNS-LS laughter frequency with brainstem imaging metrics, compared to total score.…”

Section: Discussionmentioning

confidence: 99%

Brainstem Correlates of Pathological Laughter and Crying Frequency in ALS

Huang

Caga

et al. 2021

Front. Neurol.

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Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS (p = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A (R2 = 0.14, p = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem (R2 = 0.46, p < 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: R2 = 0.44, p < 0.01; right: R2 = 0.44, p < 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS. The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter.

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Comparison of Two Clinical Upper Motor Neuron Burden Rating Scales in ALS Using Quantitative Brain Imaging

Cited by 9 publications

References 51 publications

Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis

Correlation between leukocyte phenotypes and prognosis of amyotrophic lateral sclerosis

Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster–The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial

Brainstem Correlates of Pathological Laughter and Crying Frequency in ALS

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