Assessment of respiratory functions by spirometry and phrenic nerve studies in patients of amyotrophic lateral sclerosis
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)
- et al.
Consensus guidelines for the design and implementation of clinical trials in ALS. World Federation of Neurology committee on research
J Neurol Sci
(1999) - et al.
Predicting respiratory insufficiency in amyotrophic lateral sclerosis: the role of phrenic nerve studies
Clin Neurophysiol
(2009) - et al.
The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III)
J Neurol Sci
(1999) - et al.
Spirometry in the supine position improves the detection of diaphragmatic weakness in patients with amyotrophic lateral sclerosis
Chest
(2002) Amyotrophic lateral sclerosis (ALS): evaluation of respiratory function
Rev Neurol (Paris)
(2006)- et al.
Changes of the phrenic nerve motor response in amyotrophic lateral sclerosis: longitudinal study
Clin Neurophysiol
(2009) - et al.
Amyotrophic lateral sclerosis
N Engl J Med
(2001) - et al.
Management of respiration in MND/ALS patients: an evidence based review
Amyotroph Lateral Scler
(2006) - et al.
Motor neuron disease presenting with respiratory failure
J Neurol Sci
(1996) - et al.
Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS practice parameters task force
Neurology
(1999)
Spirometry in amyotrophic lateral sclerosis
Arch Neurol
Forced vital capacity (FVC) as an indicator of survival and disease progression in an ALS clinic population
J Neurol Neurosurg Psychiatry
Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis
Brain
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
An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease
J Neurol Neurosurg Psychiatry
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