|Year : 2022 | Volume
| Issue : 1 | Page : 8-13
Could we Predict Respiratory Failure in Amyotrophic Lateral Sclerosis?
Ceren Cetin Akkoc1, Şeyma Aykaç1, Fikret Bademkıran1, İbrahim Aydoğdu1, Sezai Taşbakan2
1 Department of Neurology, Ege University Faculty of Medicine, Izmir, Turkey
2 Department of Chest Diseases, Ege University Faculty of Medicine, Izmir, Turkey
|Date of Submission||04-Nov-2021|
|Date of Decision||07-Dec-2021|
|Date of Acceptance||20-Dec-2021|
|Date of Web Publication||31-Mar-2022|
Ceren Cetin Akkoc
Department of Neurology, Ege University Faculty of Medicine, Bornova, Izmir 35100
Source of Support: None, Conflict of Interest: None
Introduction: Respiratory complications are important in the prognosis of amyotrophic lateral sclerosis (ALS). The aim of this study was to determine the electrophysiological findings that may predict respiratory failure. Methods: According to the Awaji electrodiagnostic criteria, 30 patients with ALS who were diagnosed with definite or probable ALS without respiratory failure were included in the study. Nerve conduction studies, needle electromyography (EMG), and single-breath count tests were performed in all patients. In addition, the pulmonary function tests, swallowing EMG, and arterial blood gas analysis of the patients were recorded and evaluated. The patients were followed until respiratory failure developed. Results: As a result of 18 months of follow-up, 26 of 30 patients developed respiratory failure. When the contribution of the accessory respiratory muscles to the respiratory effort before the development of respiratory failure was evaluated clinically and electrophysiologically, it was observed that the most common muscles involved in the respiratory effort were sternocleidomastoid (SCM), trapezius, and rectus abdominis. Before the development of respiratory failure, the latest neurogenic EMG findings were seen in the SCM (50% cases), trapezius (20% cases), and thoracic paraspinal muscles (17% of cases), respectively. It was thought that this finding could be an important early electrophysiologic marker in predicting the development of respiratory failure in ALS cases. Conclusions: To sum up, the presence of neurogenic changes in certain muscles in needle EMG and demonstration of the contribution of certain accessory respiratory muscles in respiration can be used as an electrophysiological marker to predict the development of respiratory failure.
Keywords: Amyotrophic lateral sclerosis, early electrophysiologic marker, electromyography, electrophysiological evaluation, respiratory failure
|How to cite this article:|
Akkoc CC, Aykaç &, Bademkıran F, Aydoğdu &, Taşbakan S. Could we Predict Respiratory Failure in Amyotrophic Lateral Sclerosis?. Neurol Sci Neurophysiol 2022;39:8-13
|How to cite this URL:|
Akkoc CC, Aykaç &, Bademkıran F, Aydoğdu &, Taşbakan S. Could we Predict Respiratory Failure in Amyotrophic Lateral Sclerosis?. Neurol Sci Neurophysiol [serial online] 2022 [cited 2022 Aug 15];39:8-13. Available from: http://www.nsnjournal.org/text.asp?2022/39/1/8/342366
| Introduction|| |
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that mainly affects the upper and lower motor neurons (LMN) in the cerebral cortex, brain stem, and spinal cord. The diagnosis is made based on the history of the disease, the neurological examination revealing the lower and upper motor neuron (UMN) findings, the extensiveness of findings in the supportive electrophysiological tests, and the exclusion of other diseases in the differential diagnosis. The revised El-Escorial and Awaji criteria are highly sensitive and specific criteria for the diagnosis of ALS disease.,, UMN findings can be determined clinically and lower motor neuron (LMN) findings can be detected clinically and electrophysiologically.
ALS is a progressive and fatal disease. After the diagnosis of the disease, the average life expectancy is estimated at 20–48 months. Patients usually die due to respiratory failure and pneumonia. Therefore, the detection of respiratory failure before the occurrence of complications is critical in terms of prognosis. Although there are many studies on ALS, there are not any sensitive biomarkers predicting the development of respiratory failure. Our study aims to determine the electrophysiological findings that may predict respiratory failure by detecting changes in electrophysiological tests in the follow-up of patients affected by ALS until respiratory failure develops.
| Methods|| |
Thirty patients who presented to general neurology and ALS outpatient clinics of the Department of Neurology of Ege University Faculty of Medicine Hospital and were diagnosed with definite or probable ALS according to the Awaji electrodiagnostic criteria and whose respiratory failure had not yet developed were included in the study. Patients who did not meet the Awaji electrodiagnostic criteria, patients with ALS who had developed respiratory failure, patients with cervical spondylotic myelopathy, spinal stenosis, craniocervical junction anomaly, patients with proven polyneuropathy, patients with malignancy or lymphoproliferative disease, patients with a pacemaker or similar electronic implants, and patients using anticoagulants were excluded. The patients included in the study were planned to be followed up every 3 months until respiratory failure developed. As a result, the obtained electrophysiological findings reflected the period before the occurrence of respiratory failure.
In the evaluations, the onset pattern of the disease, its progression, and findings of UMN and LMN involvement detected in the affected body regions were noted. The presence of respiratory distress at rest and during exercise was questioned. The single-breath count test was performed. The ALS Functional Rating Scale (ALSFRS-R) score, which also includes respiratory complaints, was calculated to determine the functional status of the cases.
Nerve conductive studies and needle electromyography (EMG) were performed on an electrophysiological examination. We performed nerve conduction studies in the following nerves: median-ulnar sensory and motor, fibular-posterior tibial motor and sural nerve, and bilateral phrenic nerves. Particularly, the decreases in motor compound muscle action potential (CMAP) amplitudes in limb muscles and diaphragm muscle were taken into consideration. In addition to at least three muscles innervated by different myotomes in the bilateral lower and upper limbs, the abdominal muscles, thoracic and cervical paraspinal muscles, intercostal muscles, trapezius, and sternocleidomastoid (SCM) muscles, which are accessory respiratory muscles, were examined with needle EMG. Each muscle was first observed at rest, and the presence of abnormal spontaneous activity was evaluated. Then, the presence of pathological motor unit potential (MUP) was recorded, considering the duration, amplitude, phase, rise time, turn, and satellite potentials of the MUP that emerged during the slight voluntary muscle contraction. Finally, whether there is an interference in the maximal contraction, recruitment pattern, or the presence of single oscillation examples were evaluated. Furthermore, whether all the above-mentioned accessory respiratory muscles contribute to the respiratory effort were examined both with physical examination and electrophysiologically. The bursts of activity observed during needle EMG in the accessory respiratory muscles, showing the characteristics of the patient's breathing and coinciding with the respiratory effort, were evaluated as a contribution to breathing. The obtained findings were compared after clinical visits, and altered electrophysiological and clinical findings were determined.
Pulmonary function tests (PFT), swallowing EMGs, and arterial blood gas analyses performed during the clinical follow-up were recorded from the patients' files. Changes in these tests were noted at each evaluation. The cases with respiratory failure were defined as those who could not count up to 15 in the single-breath count test and could not lie flat on their back and had hypercarbia-hypoxia in blood gas analysis. Pathological findings detected in electrophysiological tests were evaluated together with clinical and other laboratory findings indicating the development of respiratory failure. Moreover, it was tried to determine the early electrophysiological markers that could indicate respiratory failure.
All electrophysiological tests were performed by two clinical Neurophysiologists at the Neurophysiology Laboratory of the Department of Neurology of Ege University Faculty of Medicine between December 2017 and July 2019. Our study was approved by the Ege University Faculty of Medicine Bioethical Committee on April 20, 2017 and decision number 17-4/16. Nerve conduction and needle EMG studies were performed using the Medelec Synergy EMG device. In needle EMG studies, a separate, sterile disposable concentric needle electrode (50 mm × 26G) (TECAelite, disposable Concentric Needle Electrodes 50 mm × 26G) was used at each visit. The Statistical Packages for the Social Sciences (version 21.0; SPSS Chicago, IL, USA) was used for statistical analysis of all data. Descriptive findings were presented as frequency, percentage, minimum, and maximum values. The mean, standard deviation, and median were given as measures of central distribution. Comparative data analysis was performed using the Wilcoxon signed-rank test. Results were considered statistically significant if P < 0.05.
| Results|| |
From the recruited patients, 19 patients (63.3%) were male and 11 (36.7%) were female. The mean age of onset of symptoms was 59.3 ± 9.6 years. Twenty patients (66.7%) had spinal onset and 10 patients (33.3%) had bulbar onset patterns. The initial symptom was often weakness in the distal muscles of the upper limb in patients with spinal onset and dysarthria in patients with bulbar onset. The mean time elapsed between the onset of symptoms and the diagnosis of ALS was 12.56 ± 8.1 months. This period was 8.9 ± 5.8 months in patients with the bulbar onset and 14.4 ± 8.5 months in patients with spinal onset.
The patients were examined 3 or 4 times on average at 3-month intervals. After 18 months of follow-up, 26 (86.7%) of 30 patients developed respiratory failure, and these patients were rapidly taken to noninvasive mechanical ventilator support. The mean time elapsed between the onset of the initial symptom and the development of respiratory failure was 31 ± 13.81 months. The mean time was 37.17 ± 13.2 months in patients with spinal onset, while this period was shorter in patients with bulbar onset, being 26.66 ± 12.84 months [Table 1].
|Table 1: The time elapsed between the onset of the disease and the development of respiratory failure (months)|
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The mean ALSFRS-R score at the beginning of the follow-up was found to be 32.77 ± 8.12[12–44], and the mean ALSFRS-R score after the development of respiratory failure was 20.15 ± 9.1 (5–37). There was a statistically significant decrease in the ALSFRS-R scores calculated at the end of the 18-month follow-up of the patients.
Comparing the EMG findings of the respiratory muscles at the beginning of the follow-up with the EMG findings at the end of the follow-up, there were significant neurogenic EMG findings showing LMN involvement in all examined accessory respiratory muscles. This finding was correlated with clinically observed respiratory failure in most cases. Comparison data are summarized in [Table 2]. Before the development of respiratory failure, the latest neurogenic EMG findings were seen in the SCM (50% cases), trapezius (20% cases), and thoracic paraspinal muscles (17% of cases), respectively. Moreover, it was thought that this finding could be an important early electrophysiological marker in predicting the development of respiratory failure. When we looked at the time of the occurrence of these neurogenic EMG findings in the mentioned muscles, it was determined that neurogenic fındings developed in the SCM, trapezius, and thoracic paraspinal muscles after an average of 8, 7, and 8 months from the beginning of the follow-up, respectively.
|Table 2: Comparison of the initial and final electromyography findings of the accessory respiratory muscles|
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Assessing the contribution of the accessory respiratory muscles to the respiratory effort before the development of respiratory failure clinically and electrophysiologically, it was observed that the most common muscles involved in the respiratory effort were the SCM, trapezius, and rectus abdominis [Table 3]. In addition, it was noted that the mentioned muscles participated in respiratory effort after an average of 12, 11, and 11 months, respectively.
|Table 3: Muscles involved in the respiratory effort before the development of respiratory failure|
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Low amplitude and prolonged latency of CMAP were recorded on phrenic nerve conduction studies in nine patients (65.8%) at the initial assessment and 21 patients (80.8%) at the final assessment. This difference indicates a statistically significant decrease.
In the single-breath count test, there was a statistically significant decrease in the number that the patients could count at the initial and final assessments. During the initial examination, the patients could count up to 15.5 ± 12.9, and at the final examination, they could count up to 6.5 ± 8.5. Thirteen (50%) patients could not perform the test when respiratory failure developed. Fourteen of 26 (46.7%) patients who developed respiratory failure could not perform PFT effectively due to muscle weakness. The initial measurable forced vital capacity (FVC) results of the patients decreased on average by 77.0 ± 11.1% compared to the predictive value, and the last measurable FVC results showed a mean decrease of 46.5 ± 18.0% compared to the predictive value. This decrease was found to be statistically significant. Swallowing EMG was found to be pathological in all patients with respiratory failure. In swallowing EMG, 17 patients (65.7%) had severe dysphagia, 4 (15.3%) moderate dysphagia, and 5 (19.2%) mild dysphagia.
| Discussion|| |
ALS is a disease characterized by progressive degeneration of upper and LMNs. It usually starts between the ages of 39–80. It is more common in males than in females (M/F: 1.7/1). The initial symptoms of the disease are usually asymmetric weakness and atrophy, which may be localized in a particular part of a limb and often begin distally. The most common form is spinal onset. On the other hand, the bulbar onset form is observed in 20%–30% of the patients. There is no sensitive and specific biomarker in the diagnosis of ALS. Diagnosis is made based on the Revised El-Escorial and Awaji diagnostic criteria., In a 10-year prospective population-based study conducted by Chiò et al., the time from the onset of symptoms to the diagnosis of ALS was found to be 10–18 months. In our study, spinal onset was observed in 20 (66.7%) and bulbar onset in 10 (33.3%) of 30 definite or probable ALS cases according to the Awaji electrodiagnostic criteria. The mean time to a definitive diagnosis of ALS was determined to be 12.56 ± 8.1 months in accordance with the literature.
Respiratory complications are known to be an important cause of death in patients with ALS. The respiratory muscles are usually affected before the symptoms of respiratory failure appear. This subclinical involvement of respiratory muscles can be detected by EMG, and neurophysiological examinations may play an important role in determining the cause of dyspnea and predicting the development of respiratory failure. Based on this, there are studies in the literature on electrophysiological evaluation of accessory respiratory muscles that may guide the diagnosis and follow-up of ALS. It has been reported that pathological needle EMG findings in C6 and T5 paraspinal muscles are associated with low FVC value and diaphragm denervation, and these findings may be used in the follow-up of respiratory failure. The rectus abdominis muscle was evaluated by needle EMG, and it was found that active denervation findings were more common in ALS patients with dyspnea than those without this symptom. It was stated that the pathological findings in the rectus abdominis muscle would guide the evaluation of the subclinical involvement of the thoracic LMN in patients with suspected ALS. In another study, it was found that spontaneous denervation potentials detected in rectus abdominis needle EMG were directly related to respiratory failure and dyspnea. In a study by Pinto and de Carvalho, it was noted that the weakness in the diaphragm muscle was an indicator of respiratory failure and poor prognosis in ALS, and the weakness in the SCM muscle was parallel with the weakness of the diaphragm.
Respiratory failure developed in 26 (86.7%) of 30 patients at the end of 18 months. The mean time elapsed between the onset of the disease and the development of respiratory failure was 31 ± 13.81 months. We found that respiratory failure developed in patients with bulbar-onset ALS an average of 11 months earlier compared to patients with spinal-onset ALS. Based on the studies carried out, the trapezius, SCM, rectus abdominis, cervical-thoracic paraspinal, and intercostal muscles were selected as accessory respiratory muscles and evaluated electrophysiologically in our study. The abnormal results in needle EMG of all these accessory respiratory muscles grew significantly as the disease advanced. Since ALS patients with definitive diagnoses were included in our study, the contribution of the mentioned muscles to the diagnosis was not evaluated. It was observed that the muscle in which the most recent neurogenic EMG findings were detected before the development of respiratory failure in half of the patients was frequently SCM. Moreover, the neurogenic EMG findings in the SCM muscle were detected after an average of 8 months of follow-up. Based on this result, it was thought that pathological EMG findings detected in the SCM muscle could be a marker for predicting the development of respiratory failure.
Electrophysiological examinations performed in cases with ALS are mostly aimed at detecting neurogenic findings in the muscles being tested. Apart from this, there are very few studies in the literature that have specifically evaluated the contribution of the accessory respiratory muscles in respiration electrophysiologically, considering its relationship with respiratory activity. In a study by de Carvalho et al., it was reported that the needle EMG recordings of the thoracic paraspinal muscles of patients with low FVC values show bursts of activity that coincided with the respiratory effort, showing the characteristic features of the diaphragm recordings and this finding occurs when there was a significant respiratory muscle weakness. Similar to the literature, when respiratory failure developed, the bursts of activity were observed in our study during needle EMG examinations of all the accessory respiratory muscles that show characteristic features with the patient's respiratory activity and coincide with respiratory effort [Figure 1]. Since consent could not be obtained from the patients due to possible complications, simultaneous needle EMG recording of the diaphragm muscle could not be performed. However, the bursts of muscle activity detected on the accessory muscles being examined were clinically rhythmic and synchronous with the respiratory pattern of the patients. Unlike the previous study, we showed that this finding occurs more frequently in some accessory respiratory muscles in the subclinical period before respiratory failure develops in our study. Therefore, electrophysiological demonstration of the respiratory contribution pattern in the SCM, trapezius, and rectus abdominis muscles, especially in the subclinical period when respiratory failure did not develop, suggested that these patients should be closely monitored for the development of respiratory failure.
|Figure 1: Bursts of activity of the sternocleidomastoid muscle associated with the respiratory effort observed during needle electromyography|
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Phrenic nerve CMAP amplitude reflects the number of excitable motor units in the diaphragm. Low CMAP amplitude is significant for predicting hypoventilation, and it is stated that it may be employed as a marker. Studies have reported that the phrenic nerve CMAP amplitude decreases in correlation with PFT and may be used in the follow-up of patients who cannot perform PFT due to facial weakness and cognitive impairment. In our study, there was a decrease in phrenic nerve CMAP amplitudes proportional to respiratory involvement. As phrenic nerve conduction studies were generally normal at the initial visits, it was assumed that this examination in the early period was not a good indicator of respiratory involvement.
In addition to respiratory failure, swallowing difficulty is also a major clinical concern in ALS. Dysphagia-associated aspiration pneumonia that develops after the symptoms progress may complicate respiratory failure. Therefore, swallowing assessment is also vital to prevent exacerbation of respiratory failure in such cases. From this point of view, swallowing EMGs of all patients in our study with respiratory failure showed dysphagia. Nutritional training was provided in cases with mild-to-moderate dysphagia. Patients with advanced dysphagia were advised to receive nutrition through a percutaneous endoscopic gastrostomy to avoid aspiration pneumonia.
| Conclusions|| |
Respiratory complications are crucial in the follow-up of patients with ALS. In our study, we found that the pathological needle EMG findings in the SCM, as well as subclinical recording of the respiratory contribution of SCM, rectus abdominis, and trapezius using EMG, might be used to predict the development of respiratory failure. We believe that these electrophysiological findings will guide clinicians in the evaluation of respiratory failure in the early period in patients with ALS.
The authors report no conflicts of interest. There is no foundation. The paper has not been presented at a meeting. Special thanks to Bulten Tugay, MD for her contribution to the English editing of the article.
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[Table 1], [Table 2], [Table 3]