Bulbar impairment score and survival of stable amyotrophic lateral sclerosis patients after noninvasive ventilation initiation

There is general agreement that noninvasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS) and that the main cause of NIV failure is the severity of bulbar dysfunction. However, there is no evidence that bulbar impairment is a contraindication for NIV. The aim of this study was to determine the effect of bulbar impairment on survival in ALS patients with NIV.ALS patients for whom NIV was indicated were included. Those patients who refused NIV were taken as the control group.120 patients who underwent NIV and 20 who refused NIV were included. The NIV group presented longer survival (median 18.50 months, 95% CI 12.62–24.38 months) than the no-NIV group (3.00 months, 95% CI 0.82–5.18 months) (p<0.001) and also in those patients with severe bulbar dysfunction (13.00 months (95% CI 9.49–16.50 months) versus 3.00 months (95% CI 0.85–5.15 months), p<0.001). Prognostic factors for ALS using NIV, adjusted for NIV failure, were severity of bulbar dysfunction (hazard ratio (HR) 0.5, 95% CI 0.92–0.97; p=0.001) and time spent with oxygen saturation measured by pulse oximetry <90% (%sleepSpO2<90) using NIV (HR 1.12, 95% CI 1.01–1.24; p=0.02).Severe bulbar impairment in ALS does not always prevent NIV from being used, but the severity of bulbar dysfunction at NIV initiation and %sleepSpO2<90 while using NIV appear to be the main prognostic factors of NIV failure in ALS.

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Unstable control of breathing can lead to ineffective noninvasive ventilation in amyotrophic lateral sclerosis

ERJ Open Research ◽

10.1183/23120541.00099-2019 ◽

2019 ◽

Vol 5 (3) ◽

pp. 00099-2019 ◽

Cited By ~ 2

Author(s):

Jesús Sancho ◽

Enric Burés ◽

Santos Ferrer ◽

Ana Ferrando ◽

Pilar Bañuls ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Noninvasive Ventilation ◽

Upper Airway ◽

Control Of Breathing ◽

Controller Gain ◽

Central Origin ◽

Als Patients ◽

Bulbar Dysfunction ◽

Lateral Sclerosis

Upper airway obstruction with decreased central drive (ODCD) is one of the causes of ineffective noninvasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). The aim of this study is to determine the mechanism responsible for ODCD in ALS patients using NIV.This is a prospective study that included ALS patients with home NIV. Severity of bulbar dysfunction was assessed with the Norris scale bulbar subscore; data on upper or lower bulbar motor neuron predominant dysfunction on physical examination were collected. Polysomnography was performed on every patient while using NIV and the ODCD index (ODCDI: number of ODCD events/total sleep time) was calculated. To determine the possible central origin of ODCD, controller gain was measured by inducing a hypocapnic hyperventilation apnoea. Sonography of the upper airway during NIV was performed to determine the location of the ODCD.30 patients were enrolled; three (10%) had ODCDI >5 h−1. The vast majority of ODCD events were produced during non-rapid eye movement sleep stages and were a consequence of an adduction of the vocal folds. Patients with ODCDI >5 h−1 had upper motor neuron predominant dysfunction at the bulbar level, and had greater controller gain (1.97±0.33 versus 0.91±0.36 L·min−1·mmHg−1; p<0.001) and lower carbon dioxide (CO2) reserve (4.00±0.00 versus 10.37±5.13 mmHg; p=0.043). ODCDI was correlated with the severity of bulbar dysfunction (r= −0.37; p=0.044), controller gain (r=0.59; p=0.001) and CO2 reserve (r= −0.35; p=0.037).ODCD events in ALS patients using NIV have a central origin, and are associated with instability in the control of breathing and an upper motor neuron predominant dysfunction at the bulbar level.

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A Retrospective Study of the Clinical Phenotype and Predictors of Survival in non-Caucasian Hispanic Patients with Amyotrophic Lateral Sclerosis.

10.21203/rs.2.11620/v4 ◽

2019 ◽

Author(s):

Claudia Marisol Sánchez-Martínez ◽

José Alberto Choreño-Parra ◽

Lilia Nuñez-Orozco ◽

Noel Isaías Placencia-Álvarez ◽

Laura Marcela Alvis-Cataño ◽

...

Keyword(s):

Overall Survival ◽

Amyotrophic Lateral Sclerosis ◽

Prognostic Factors ◽

Retrospective Study ◽

Survival Time ◽

Clinical Characteristics ◽

Clinical Phenotype ◽

Age At Onset ◽

Als Patients ◽

Lateral Sclerosis

Abstract Background. Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS. Methods. We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test. Results. We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival. Conclusions. The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.

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Significance of Serological Markers in Neurological Function and Progression Rate of Amyotrophic Lateral Sclerosis

10.21203/rs.3.rs-667353/v1 ◽

2021 ◽

Author(s):

Xiaowen Chen ◽

Junrong Li ◽

Yingying Lv ◽

Wei Zhang ◽

xiujian Xu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Creatine Kinase ◽

Uric Acid ◽

Total Cholesterol ◽

Cystatin C ◽

Control Group ◽

Progression Rate ◽

Cholesterol Levels ◽

Als Patients ◽

Lateral Sclerosis

Abstract Objective The present study was to investigate the significance of creatinine, uric acid, creatine kinase, total cholesterol, triglyceride, HCY (Homocysteine), and cystatin C in neurological function and progression rate of amyotrophic lateral sclerosis. Methods According to the diagnostic criteria of EI-Escorial (2000), 103 patients with ALS were enrolled. All patients were given corresponding serological tests at the initial diagnosis. The Revised ALS Functional Rating Scale (ALSFRS-R) and Disease Progression Rate (DPR) were evaluated. The detected indexes in blood tests included creatinine, uric acid, creatine kinase, total cholesterol, triglycerides, homocysteine, and cystatin C. All data were input into the computer, and the data analysis was performed by SPSS22.0 statistical software.Results 1. There were significant differences in creatinine, uric acid, creatine kinase, total cholesterol, HCY and cystatin C between the two groups (P<0.05). The levels of uric acid and creatinine of ALS group were lower than those of the control group, and the levels of creatine kinase, total cholesterol, triglyceride, HCY and cystatin C were higher than that in the control group. 2. The results from correlation analysis demonstrated that there was a significant correlation between ALSFRS-R and creatinine (P<0.01), the correlation coefficient was 0.567 (positive correlation); There was also a significant correlation between DPR and creatinine (P<0.01), and the correlation coefficient was -0.808 (negative correlation). The correlations of DPR with triglyceride and total cholesterol were significantly negative correlated (P<0.05), with -0.201 and -0.210 of correlation coefficients, respectively. The remaining indexes did not show any correlation with ALSFRS-R and DPR. Conclusions 1. Uric acid and creatinine of ALS patients were lower than that in healthy people. Creatine kinase, triglyceride, total cholesterol, HCY, and cystatin C in ALS patients were higher than those in health controls. There were significant metabolic abnormalities in ALS patients. 2. Creatinine level is an independent risk factor affecting ALSFRS-R. The creatinine and total cholesterol levels are also the independent risk factors affecting DPR. Creatinine and total cholesterol levels could be used as reliable indicators to evaluate the ALSFRS-R and DPR of ALS patients.

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Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis

10.21203/rs.3.rs-1114560/v1 ◽

2021 ◽

Author(s):

Xintong Guo ◽

Xiaoxuan Liu ◽

Shan Ye ◽

Xiangyi Liu ◽

Xu Yang ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Eye Movement ◽

Smooth Pursuit ◽

Oculomotor System ◽

Control Group ◽

Clinical Markers ◽

Square Wave ◽

Movement Parameters ◽

Als Patients ◽

Lateral Sclerosis

Abstract Background and Purpose It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and the corresponding pattern has not yet been established. Furthermore, bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. Methods Patients with clinically definite, probable or laboratory-supported probable ALS (n=60) and a control group composed of their caregivers (n=30) underwent clinical assessments and standardized evaluations of the oculomotor system using videonystagmography. The gaze test, reflexive saccade test and smooth pursuit test were administered to all subjects. Results Eye movement abnormalities such as square-wave jerks, abnormal cogwheeling during smooth pursuit, and saccade hypometria were observed in ALS patients. Square-wave jerks (p<0.001) and abnormal cogwheeling during smooth pursuit (p=0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (p=0.004) and abnormal cogwheeling during smooth pursuit (p=0.031) were found to be more common in ALS patients with bulbar involvement (n=44) than in those without bulbar involvement (n=16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n=12) and spinal-onset patients (n=48). Conclusion ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. These abnormalities were observed more common in the ALS patients with bulbar involvement. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.

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Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis (sALS): correlation with prognostic factors

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci.2011.006 ◽

2011 ◽

Vol 6 (1) ◽

Author(s):

Gisella Gargiulo Monachelli ◽

Maria Meyer ◽

Gabriel Rodríguez ◽

Laura Garay ◽

Roberto E. Sica ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Prognostic Factors ◽

Neurodegenerative Disorder ◽

Neuronal Damage ◽

Sporadic Amyotrophic Lateral Sclerosis ◽

Sporadic Als ◽

Bulbar Onset ◽

Als Patients ◽

Short Time ◽

Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short time between onset and diagnosis. Progesterone (PROG) has been associated with neuroprotective and promyelinating activities in injury, ischemia and degeneration of the central and peripheral nervous system. Cortisol is connected to the response to stress situations and could contribute to neuronal damage. The goals of this study were: (i) to investigate whether PROG levels are modified by ALS prognostic factors and (ii) to determine whether cortisol follows the same pattern. We determined serum steroid levels in 27 patients with sporadic ALS (sALS) and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients versus controls (mean±SEM: PROG ALS vs. control: 0.54±0.05 vs. 0.39±0.04 ng/mL, p<0.05; cortisol ALS vs. control: 17.02±1.60 vs. 11.83±1.38 μg/dL, p<0.05).

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Rapid Voice Tremor, or “Flutter,” in Amyotrophic Lateral Sclerosis

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949210100612 ◽

1992 ◽

Vol 101 (6) ◽

pp. 511-518 ◽

Cited By ~ 37

Author(s):

Arnold E. Aronson ◽

William S. Winholtz ◽

Lorraine Olson Ramig ◽

Sandra R. Silber

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Matched Control ◽

Normal Subjects ◽

Control Group ◽

Fast Fourier Transform Analysis ◽

Frequency Components ◽

Low Levels ◽

Frequency Modulations ◽

Als Patients ◽

Lateral Sclerosis

In an attempt to clarify the origin and frequency characteristics of a rapid voice tremor, or “flutter,” in patients with amyotrophic lateral sclerosis (ALS), eight patients (four men and four women; ages 42 to 70 years) who had ALS and rapid voice tremor and an age-and sex-matched control group of eight subjects were asked to sustain the vowel /a/ and their voices were recorded for later analysis. Each segment of phonation was demodulated into amplitude and frequency components. From each subject's 8-second amplitude and frequency signals, a fast Fourier transform analysis was done on a 1-second segment previously identified perceptually as having the most apparent tremor or flutter. The results showed that patients with ALS had multiple combinations of levels and frequencies for amplitude and frequency modulations in comparison with control subjects, who had consistently low levels of modulations. In an attempt to quantify the tremor or flutter in ALS, amplitude and frequency modulations were not clearly or predominantly represented at one point along the spectrum. Nevertheless, these frequency and amplitude modulations are more prominent in patients with ALS than in normal subjects. The origins of these aberrant frequency and amplitude modulations in ALS patients remain obscure, although speculation is that they are of peripheral rather than central nervous system origin.

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Open Randomized Clinical Trial on JWSJZ Decoction for the Treatment of ALS Patients

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/347525 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Weidong Pan ◽

Xiaojing Su ◽

Jie Bao ◽

Jun Wang ◽

Jin Zhu ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Control Group ◽

Efficacy And Safety ◽

Significant Difference ◽

Als Patients ◽

And Control ◽

Lateral Sclerosis ◽

Basic Treatment

Objective. To investigate the efficacy and safety of the traditional Chinese medicine Jiawei Sijunzi (JWSJZ) decoction for the treatment of patients with amyotrophic lateral sclerosis (ALS).Methods. Forty-eight patients with ALS were divided into a JWSJZ group (n=24) and a control group (n=24) using a randomized number method. Together with the basic treatment for ALS, JWSJZ decoction was added to the treatment regimen of patients in the JWSJZ group or Riluzole was administered to the control group for 6 months. Neurologists evaluated the treated and control patients using the ALS functional rating scale (ALSFRS) before, 3 and 6 months after starting the additional treatments.Results. The ALSFRS scores in both groups were lower 3 and 6 months after treatment than before. There was a significant difference at 6 months after treatment between the subgroups of patients with ALS whose limbs were the initial site of attack. No serious adverse effects were observed in the JWSJZ group.Conclusion. JWSJZ decoction may be a safe treatment for ALS, and may have delayed the development of ALS, especially in the subgroup of patients in whom the limbs were attacked first when compared with Riluzole treatment.

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Prognosis of amyotrophic lateral sclerosis patients undergoing tracheostomy invasive ventilation therapy in Japan

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-322213 ◽

2020 ◽

Vol 91 (3) ◽

pp. 285-290 ◽

Cited By ~ 3

Author(s):

Naoki Hayashi ◽

Naoki Atsuta ◽

Daichi Yokoi ◽

Ryoichi Nakamura ◽

Masahiro Nakatochi ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Prognostic Factors ◽

Propensity Score ◽

Survival Time ◽

Propensity Score Matching ◽

Invasive Ventilation ◽

Propensity Score Matching Analysis ◽

Als Patients ◽

Prospective Longitudinal ◽

Lateral Sclerosis

ObjectiveThe aim of this study is to describe and clarify the factors affecting the prognosis of Japanese patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy invasive ventilation (TIV) therapy.MethodsWe conducted a prospective longitudinal observational case-control study using a multicentre registry. ALS patients who started TIV therapy after registration (TIV group) and those who did not receive TIV (non-TIV group) were included. We compared the survival time between the TIV group and the non-TIV group using a propensity score matching analysis and evaluated the prognostic factors in the TIV group.ResultsFrom February 2006 to January 2018, 190 patients in the TIV group and 1093 patients in the non-TIV group were included in this study. The mean age of disease onset and usage rate of gastrostomy and non-invasive ventilation therapy differed between the groups. In the propensity score matching analysis using known prognostic factors, the median overall survival time of the TIV group was significantly greater than that of the non-TIV group (11.33 years vs 4.61 years; p<0.001). Analysis using the Cox proportional hazard model suggested that older age of onset and respiratory onset was an independent factor for poor prognosis after starting TIV therapy.ConclusionWe showed that there was a significant difference of approximately 7 years in life expectancy between Japanese ALS patients who did and did not receive TIV therapy.

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A retrospective study of the clinical phenotype and predictors of survival in non-Caucasian Hispanic patients with amyotrophic lateral sclerosis

BMC Neurology ◽

10.1186/s12883-019-1459-3 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Claudia Marisol Sánchez-Martínez ◽

José Alberto Choreño-Parra ◽

Lilia Nuñez-Orozco ◽

Noel Placencia-Álvarez ◽

Laura Marcela Alvis-Castaño ◽

...

Keyword(s):

Overall Survival ◽

Amyotrophic Lateral Sclerosis ◽

Prognostic Factors ◽

Retrospective Study ◽

Survival Time ◽

Clinical Characteristics ◽

Clinical Phenotype ◽

Age At Onset ◽

Als Patients ◽

Lateral Sclerosis

Abstract Background Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS. Methods We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test. Results We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival. Conclusions The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.

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Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis

Neurology ◽

10.1212/wnl.49.5.1292 ◽

1997 ◽

Vol 49 (5) ◽

pp. 1292-1298 ◽

Cited By ~ 145

Author(s):

Ulf Ziemann ◽

Martin Winter ◽

Carl D. Reimers ◽

Karin Reimers ◽

Frithjof Tergau ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Cortex ◽

Silent Period ◽

Intracortical Inhibition ◽

Control Group ◽

Cortical Silent Period ◽

Healthy Control ◽

Als Patients ◽

Period Duration ◽

Lateral Sclerosis

We investigated 14 patients with amyotrophic lateral sclerosis (ALS) by paired conditioning-test transcranial magnetic stimulation to test the hypothesis that the motor cortex is hyperexcitable in ALS. Intracortical(corticocortical) inhibition was significantly less in the ALS group than in an age-matched healthy control group (85.3 ± 27.0% versus 45.2± 15.5%, respectively; p < 0.0001). In contrast, intracortical facilitation, motor threshold, and cortical silent period duration in the ALS patients were not different from the control group. We suggest that the selective abnormality of intracortical inhibition is best compatible with an impaired function of inhibitory interneuronal circuits in the motor cortex that in turn renders the corticomotoneuron hyperexcitable.

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