Assessment of respiratory functions by spirometry and phrenic nerve studies in patients of amyotrophic lateral sclerosis

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Abstract

Objective

Spirometry is the most common test recommended to monitor respiratory dysfunction in patients of amyotrophic lateral sclerosis (ALS). However, the test depends on the patient's efforts and may be difficult to conduct in patients with faciobulbar weakness. We aimed to study the role of phrenic nerve-electrophysiological studies to predict respiratory dysfunction and correlate it with the forced vital capacity (FVC) in patients of ALS.

Methods

Forty-three unselected patients (32 male, 25 with limb-onset ALS, age 50 ± 15 years) with clinically definite or probable ALS were included. They were evaluated at entry and after a period of 6 months with the ALS functional rating scale (ALSFRS), their respiratory subscores (ALS-FRSr), their FVC values as determined by spirometry, and phrenic nerve studies.

Results

Six patients could not perform a satisfactory spirometry at the onset and during the course of illness. All the six patients had severe faciobulbar weakness. Respiratory abnormalities on spirometry were found in 85% of patients, whereas only 30% were symptomatic for respiratory dysfunction. In patients with severe respiratory dysfunction (FVC < 60%), the phrenic nerve motor amplitudes (PNAMPs) were significantly reduced compared to those with mild-to-moderate respiratory dysfunction (FVC  60%). The FVC value showed a significant correlation with the PN-AMP. Nine patients had a poor outcome (death or severe disability) at the end of a period of 6 months. Low levels of both FVC and PN-AMP were predictors of poor outcome for patients at the end of 6 months.

Conclusion

We conclude that respiratory dysfunction, as determined by spirometry, is common in patients of ALS. However, only about one-third of patients show symptoms of respiratory distress. Clinical symptoms of respiratory distress are unreliable predictors of respiratory failure in ALS. Measurement of PN-AMP at the time of presentation may be an additional tool to assess respiratory dysfunction in ALS. Reduced PN-AMP values may be indicative of low FVC and may have some role in the assessment of respiratory function in patients in whom a routine spirometry is not possible due to limitations arising from the illness. Both low FVC and reduced PN-AMP at the time of presentation are predictors of poor outcome for patients at the end of 6 months.

Introduction

Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease. It is a prime example of a neurodegenerative disease and is the most devastating of the neurodegenerative disorders. The disease affects motor neurons in the brain, brainstem, and spinal cord and manifests as a linear decline in muscular function, which eventually leads to paralysis, speech deficits, and dysphagia. The involvement of the motor neurons responsible for the functioning of respiratory muscles leads to weakness of these muscles, resulting in dyspnoea and respiratory failure. Death generally occurs within years of the onset of disease, and respiratory failure remains the most common cause of death [1]. Patients usually succumb from hypoventilation, with hypoxemia and hypercapnia (Type-2 respiratory failure) often associated with aspiration and pneumonia [2]. Although symptoms of respiratory failure are generally not noticed until an advanced stage of illness, the disease may present as respiratory failure [3]. Due to the delay in the occurrence of respiratory symptoms and the poor prognosis after the appearance of respiratory symptoms, monitoring of respiratory functions assumes great importance to detect early abnormalities. Many different tests have been studied thoroughly for the assessment of respiratory functions in ALS to predict the prognosis of the disease. However, at present, no single test has been shown to reliably detect early respiratory insufficiency and to correlate well with respiratory failure in ALS [4]. However, regular assessment of forced vital capacity (FVC) by spirometry has been recommended by the American Academy of Neurology to monitor respiratory functions in patients with ALS [5]. FVC has also been shown to predict the prognosis [6], [7]. Because FVC assesses the strength of the inspiratory muscles and does not take into account the important prognostic role of the expiratory muscles, additional measures, such as sniff nasal pressure, maximum inspiratory pressure, and maximum expiratory pressure, may be also needed to assess the global respiratory function in patients with ALS. The accuracy of these measurements is highly dependent on the subject's effort and cooperation and on the training of the evaluator. Consequently, there is a clear need for more objective tests, which do not depend on the patients' efforts, for monitoring respiratory functions in ALS. Various respiratory function tests have been shown to have significant predictive value for hypercapnia in spinal-onset ALS patients [8]. However, no test had satisfactory predictive value in bulbar-onset ALS patients [9].

The objective of our study was to evaluate the role of phrenic nerve latency and amplitude in predicting the low FVC and poor outcome in patients after 6 months of follow-up. Phrenic nerve studies can be easily carried out in both limb-onset and bulbar-onset ALS and do not depend on the patient's efforts. They provide objective and discrete information, which can be easily compared and monitored over time, especially in patients with bulbar involvement where faciobulbar weakness may invalidate conventional respiratory function tests. Our study has implications for making decisions regarding starting of ventilatory support (invasive or noninvasive) for ALS patients.

Section snippets

Patients and methods

This study was conducted between March 2009 and August 2010 in the Department of Neurology of the Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. Our institution is a tertiary-care medical facility catering to an approximate population of 100 million in North India. The institutional ethics committee approved the study protocol. Written informed consent to participate in the study was obtained from all patients or their legal guardians.

Results

A total of 49 patients fulfilled the inclusion criteria; among these, 43 were included in the study (causes of exclusion were as follows: presence of degenerative spine disease in one, coronary artery disease in one, diabetes mellitus in one, pulmonary tuberculosis in one; two were smokers). The mean age of the patients was 50 years (± 15 years, range 17–80 years). The number of males (n = 32) was 2.9 times that of females (n = 11). Among these, 22 had definite and 21 had probable ALS. The disease was

Discussion

Despite the availability of many sophisticated and advanced tests for measurement of respiratory dysfunction, the FVC value obtained from commonly available spirometry remains a strong tool for assessing respiratory insufficiency in ALS [6], [16], [17]. Previous studies have shown that the FVC, that was < 75% predicted, is an excellent and simple test for quantifying diaphragmatic function and can replace more invasive and intensive procedures, such as esophageal pressure and transdiaphragmatic

Acknowledgement

Authors thank Mr Sunny Razzaq for his crucial assistance in conducting spirometry in our patients.

References (30)

  • R.J. Fallat et al.

    Spirometry in amyotrophic lateral sclerosis

    Arch Neurol

    (1979)
  • A. Czaplinski et al.

    Forced vital capacity (FVC) as an indicator of survival and disease progression in an ALS clinic population

    J Neurol Neurosurg Psychiatry

    (2006)
  • R.A. Lyall et al.

    Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis

    Brain

    (2001)
  • B.R. Brooks et al.

    World Federation of Neurology research group on motor neuron diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis

    Amyotroph Lateral Scler Other Motor Neuron Disord

    (2000)
  • C.P. Douglass et al.

    An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease

    J Neurol Neurosurg Psychiatry

    (2010)
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