Effect of one-year Dextromethorphan/Quinidine treatment on management of respiratory impairment in Amyotrophic Lateral Sclerosis

ObjectivesTo assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the early phases of the disease.MethodsThe study cohort included all ALS patients in Piemonte/Valle d’Aosta in the 2007–2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated.ResultsOf the 712 patients, 620 (87.1%) were included in the study. Patients ’ survival was related to the mean monthly percentage of weight loss at diagnosis (p<0.0001), but not to pre-morbid BMI or BMI at diagnosis. Spinal onset patients with dysphagia at diagnosis had a median survival similar to bulbar onset patients. About 20% of spinal onset patients without dysphagia at diagnosis had severe weight loss and initial respiratory impairment, and had a median survival time similar to bulbar onset patients.ConclusionsThe rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms.

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Frontotemporal degeneration in amyotrophic lateral sclerosis (ALS): a longitudinal MRI one-year study

CNS Spectrums ◽

10.1017/s109285292000005x ◽

2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Francesca Trojsi ◽

Federica Di Nardo ◽

Mattia Siciliano ◽

Giuseppina Caiazzo ◽

Cinzia Femiano ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Functional Connectivity ◽

Disease Progression ◽

Resting State ◽

Diffusion Tensor ◽

Middle Temporal Gyrus ◽

Multisystem Disease ◽

Longitudinal Changes ◽

One Year ◽

Lateral Sclerosis

Abstract Objective. Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis. Methods. Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year. Results. During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P = .003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points. Conclusion. Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.

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Triage of Amyotrophic Lateral Sclerosis Patients during the COVID-19 Pandemic: An Application of the D50 Model

Journal of Clinical Medicine ◽

10.3390/jcm9092873 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2873

Author(s):

Robert Steinbach ◽

Tino Prell ◽

Nayana Gaur ◽

Beatrice Stubendorff ◽

Annekathrin Roediger ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Similar Time ◽

Comparable Amount ◽

Aggressive Disease ◽

Progression Model ◽

Risk Patients ◽

One Year ◽

Novel Coronavirus ◽

Als Patients ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, the management of which requires the continuous provision of multidisciplinary therapies. Owing to the novel coronavirus disease (COVID-19) pandemic, regular contact with ALS patients at our center was severely restricted and patient care was at risk by delay of supportive therapies. We established a triage system based on the D50 disease progression model and were thus able to identify a prospective cohort with high disease aggressiveness (D50 < 30). Thirty-seven patients with highly aggressive disease were actively offered follow-up, either via telephone or on-site, depending on their disease-specific needs and abilities. We describe here the procedures, obstacles, and results of these prescient efforts during the restrictions caused by COVID-19 in the period between March and June 2020. In conclusion, four patients with highly aggressive disease were initiated with non-invasive ventilation and two received a gastrostomy. We could show that a comparable amount of advanced care was induced in a retrospective cohort within a similar time period one year prior to the COVID-19 outbreak. Our workflow to identify high-risk patients via D50 model metrics can be easily implemented and integrated within existing centers. It helped to maintain a high quality of advanced care planning for our ALS patients.

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Dyspnea in amyotrophic lateral sclerosis: The Dyspnea-ALS-Scale (DALS-15) essentially contributes to the diagnosis of respiratory impairment

Respiratory Medicine ◽

10.1016/j.rmed.2019.06.014 ◽

2019 ◽

Vol 154 ◽

pp. 116-121 ◽

Cited By ~ 1

Author(s):

S. Vogt ◽

S. Schreiber ◽

K. Kollewe ◽

S. Körner ◽

H.-J. Heinze ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Respiratory Impairment ◽

Lateral Sclerosis

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Profile of Respiratory Impairment in Patients With Amyotrophic Lateral Sclerosis at Initial Admittance

Neurosurgery Quarterly ◽

10.1097/wnq.0b013e318201c316 ◽

2010 ◽

Vol 20 (4) ◽

pp. 288-291 ◽

Cited By ~ 1

Author(s):

Sedat Kuleci ◽

Filiz Koç ◽

Ismail Hanta

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Respiratory Impairment ◽

Lateral Sclerosis

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A Controlled One-Year Trial of Dextromethorphan in Amyotrophic Lateral Sclerosis

Clinical Neuropharmacology ◽

10.1097/00002826-199619020-00009 ◽

1996 ◽

Vol 19 (2) ◽

pp. 189-192 ◽

Cited By ~ 34

Author(s):

O. Blin ◽

J. P. Azulay ◽

C. Desnuelle ◽

F. Billé-Turc ◽

D. Braguer ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

One Year ◽

Lateral Sclerosis

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Cortical drive to breathe in amyotrophic lateral sclerosis: a dyspnoea-worsening defence?

European Respiratory Journal ◽

10.1183/13993003.01686-2015 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1818-1828 ◽

Cited By ~ 29

Author(s):

Marjolaine Georges ◽

Elise Morawiec ◽

Mathieu Raux ◽

Jésus Gonzalez-Bermejo ◽

Pierre-François Pradat ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Respiratory Failure ◽

Spontaneous Breathing ◽

Neck Muscle ◽

Compensatory Mechanism ◽

Respiratory Impairment ◽

Als Patients ◽

Lateral Sclerosis ◽

Diaphragm Weakness ◽

Severe Dyspnoea

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing diaphragm weakness that can be partially compensated by inspiratory neck muscle recruitment. This disappears during sleep, which is compatible with a cortical contribution to the drive to breathe. We hypothesised that ALS patients with respiratory failure exhibit respiratory-related cortical activity, relieved by noninvasive ventilation (NIV) and related to dyspnoea.We studied 14 ALS patients with respiratory failure. Electroencephalographic recordings (EEGs) and electromyographic recordings of inspiratory neck muscles were performed during spontaneous breathing and NIV. Dyspnoea was evaluated using the Multidimensional Dyspnea Profile.Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. Pre-inspiratory potentials were attenuated during NIV (p=0.04). Patients without pre-inspiratory potentials presented more advanced forms of ALS and more severe respiratory impairment, but less severe dyspnoea. Patients with pre-inspiratory potentials had stronger inspiratory neck muscle activation and more severe dyspnoea during spontaneous breathing.ALS-related diaphragm weakness can engage cortical resources to augment the neural drive to breathe. This might reflect a compensatory mechanism, with the intensity of dyspnoea a negative consequence. Disease progression and the corresponding neural loss could abolish this phenomenon. A putative cognitive cost should be investigated.

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γ' Fibrinogen as a Predictor of Survival in Amyotrophic Lateral Sclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.715842 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ana Catarina Pronto-Laborinho ◽

Catarina S. Lopes ◽

Vasco A. Conceição ◽

Marta Gromicho ◽

Nuno C. Santos ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Positive Impact ◽

Enzyme Linked Immunosorbent Assay ◽

Fibrinogen Concentration ◽

Respiratory Impairment ◽

Increased Risk ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder related to neuroinflammation that is associated with increased risk of thrombosis. We aimed to evaluate γ' fibrinogen plasma level (an in vivo variant of fibrinogen) as a biomarker in ALS, and to test its role as a predictor of disease progression and survival. Sixty-seven consecutive patients with ALS were followed and the results were compared with those from 82 healthy blood donors. Patients were clinically evaluated at the time of blood sampling and on follow-up (every 3 months for the beginning of the follow-up until death) by applying the revised ALS Functional Rating Scale. Human plasma γ' fibrinogen concentration was quantified using a specific two-site sandwich kit enzyme-linked immunosorbent assay. We found, for the first time, a positive association between γ' fibrinogen concentration and survival in ALS patients: patients with higher γ' fibrinogen plasma levels survived longer, and this finding was not influenced by confounders such as age, gender, respiratory impairment, or functionality (ALSFRS-R score). Since increased levels have a positive impact on outcome, this novel biomarker should be further investigated in ALS.

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