Lungs Work, Diaphragm Doesn't: Respiratory Distress in ALS

CASE

History

HM is a 56-year-old male with a past medical history of hyperlipidemia, hypertension, OSA on CPAP since 2010, and approximately two years of progressive shortness of breath who presents with an acute worsening of his shortness of breath. He used to walk with coworkers around his workplace and began noticing he was having trouble keeping up and catching his breath. Since then, his activity tolerance has continued to decrease, and he noticed that he had trouble lying flat about one year ago. In early February, he presented to the ED with these symptoms, and his workup was largely negative – no signs of lung disease on imaging and preserved cardiac function on TTE. However, his symptoms had gotten to the point that CPAP was not enough to keep him feeling comfortable while he slept, so he was transitioned to volume assured pressure support (VAPS). During this hospitalization, he also endorsed trouble swallowing and feeling like he was getting weaker, not stronger during his weightlifting sessions.

ED Course

Today, his SOB, which is usually episodic, is constant. He is tripoding and looks uncomfortable. Chest x-ray, CBC, pro-BNP, TSH, and electrolytes are all unremarkable. Given his progressive weakness despite clear imaging and labs, we were concerned about neuromuscular disorders, particularly ALS. We decided to evaluate his diaphragm excursion using ultrasound M-mode and find his diaphragm is markedly still. He is admitted and leaves the hospital with an official ALS diagnosis.

Clinical Question: What are the emergent presentations commonly associated with ALS, and are there unique considerations in evaluating their respiratory status?

Amyotrophic lateral sclerosis (ALS) is defined by its progressive involvement of both upper and lower motor neuronsultimately culminating in respiratory failure or other complications as a result of weakness. It is invariably fatal, with approximately half of patients succumbing within 14-18 months after diagnosis(1). Emergent presentations include presentations include presentations include: .Emergent presentations include:

acute respiratory failure requiring intubation
aspiration pneumonia
choking episodes
gastrointestinal tube issues
trauma related to extremity weakness(2,3)

Respiratory failure is by far the most common cause of death in ALS patients, but its mechanisms, and therefore predictive measures(4), are different from most hypoxic patients seen in the ED.

SUMMARY OF EVIDENCE

Guimaraes-Costa et al. (2019) investigated how well commonly used measures of respiratory function such as FVC correlated with diaphragmatic atrophy.

Inclusion criteria: The patients were a subset in the RespiStimALS study whose forced vital capacity (FVC) when sitting was 60–80% of predicted, age >18 years and fulfilment of the revised El Escorial criteria (formerly the gold standard diagnostic criteria) for laboratory-supported probable, clinically probable, or clinically definite ALS.
Measures: These patients all underwent laparoscopic insertion of intradiaphragmatic electrodes, and 50 of 74 patients also consented to diaphragmatic biopsies. In addition to diaphragm studies, patients had preoperative measurements of spirometry, maximal inspiratory pressure (MIP), and maximal sniff nasal inspiratory pressure (SNIP) performed. They found that all patients had significant atrophy of both slow- and fast-twitch muscle fibers.
Results: Notably, their analyses showed poor correlation of atrophy with FVC, MIP, and SNIP, though these measures are commonly used as prognostic markers for impending respiratory muscle failure in outpatient ALS care. Inspiratory capacity (IC) correlated significantly with both diaphragm atrophy and reinnervation of myofibers, a marker of motor function preservation in the limbs. Higher reinnervation in the diaphragm was associated with greater IC.
Conclusion: Ultimately, while FVC, MIP, and SNIP are still valuable ways of assessing global respiratory muscle strength, they fail to accurately represent diaphragmatic involvement.

Hermann et al. (2022) asked how ultrasound measures of diaphragm excursion and thickness compared with routine clinical diagnostics for evaluating respiratory impairment.

Inclusion criteria: Adult patients with definite, probable, or possible ALS according to the revised El Escorial criteria, and patients with genetically proven 5q-associated spinal muscular atrophy (SMA).
Measures: Forced expiratory volume (FEV1), vital capacity (VC), and established motor function scoring schemes in ALS, the revised ALS Functional Rating Scale (ALSFRS-R) in dyspnea, orthopnea, and mechanical ventilation.
Results: They found that diaphragm excursion during breathing at rest was the most correlated with clinical measures of respiratory function, especially in the ALS cohort. The images below show how using M-mode on the ultrasound allows for evaluation of the excursion of diaphragm across a single point. In the following images, we can see the waves associated with normal diaphragm movement versus the blunted appearance of a weak or paralyzed diaphragm(7).
Conclusion: POC ultrasound for evaluating diaphragm movement and thickness is a reliable option for approximating respiratory function in ALS patients without lung function testing data.

Finally, before late-stage ALS, patients are likely to present with perfectly normal blood gases. Much like in severe asthma exacerbations, the normality of the numbers belies the respiratory muscle weakness that can no longer compensate for increasing CO2 and should not be sufficient to be reassured of the patient’s stability. FVC is not highly correlated with diaphragm atrophy, but values less than 25mL/kg are associated with higher risk of aspiration pneumonia and respiratory failure(2).

RECOMMENDATIONS

When presented with an ALS patient in the ED complaining of dyspnea, the key is remembering that the patient’s lung parenchyma is likely normal. Therefore, labs like VBG are often falsely reassuring because they don’t measure respiratory muscle strength.
If your patient has a pre-existing diagnosis of ALS, it would be helpful to find if they’ve had pulmonary function testing recently to use FVC as a risk-stratifying measure. If not, or if you’re concerned about their respiratory effort, getting a look at their diaphragm’s movement using ultrasound can clue you in to how much their chest, abdomen, and neck muscles are working to compensate for diaphragmatic dysfunction.
At the end of the day, comfort with the assessment of ABC’s and airway management will be the tools you need to keep ALS patients with respiratory distress safe.

REFERENCES

Mayo Clinical Staff (2023) Amyotrophic lateral sclerosis (ALS), Mayo Clinic. Available at: https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022
Gipson, J. (2017) Amyotrophic lateral sclerosis: A focused emergency medicine review, emDOCs.net - Emergency Medicine Education. Available at: http://www.emdocs.net/amyotrophic-lateral-sclerosis-focused-emergency-medicine-review/
Meininger, V., Padat, P.F. and Corcia, P. (2007) Amyotrophic lateral sclerosis, Orphanet. Available at: https://www.orpha.net/data/patho/Pro/en/Emergency_AmyotrophicLateralSclerosis.pdf
Development of a prognostic model of respiratory insufficiency or death in amyotrophic lateral sclerosis Jason Ackrivo, John Hansen-Flaschen, E. Paul Wileyto, Richard J. Schwab, Lauren Elman, Steven M. Kawut European Respiratory Journal Apr 2019, 53 (4) 1802237; DOI: 10.1183/13993003.02237-2018
Guimaraes-Costa R, Similowski T, Rivals I, et al. Human diaphragm atrophy in amyotrophic lateral sclerosis is not predicted by routine respiratory measures. Eur Respir J 2019; 53: 1801749.
Hermann W, Langner S, Freigang M, Fischer S, Storch A, Günther R, Hermann A. Affection of Respiratory Muscles in ALS and SMA. J Clin Med. 2022 Feb 22;11(5):1163. doi: 10.3390/jcm11051163. PMID: 35268254; PMCID: PMC8910994.
Wang, B., Yin, Q., Wang, Yy. et al. Diaphragmatic dysfunction associates with dyspnoea, fatigue, and hiccup in haemodialysis patients: a cross-sectional study. Sci Rep 9, 19382 (2019). https://doi.org/10.1038/s41598-019-56035-4