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Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation

Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation
Literature review current through: Jan 2024.
This topic last updated: Jul 24, 2023.

INTRODUCTION — Several types of neuromuscular disease can be complicated by respiratory muscle weakness (table 1) [1,2].

The clinical manifestations and evaluation of respiratory muscle weakness due to neuromuscular disease will be reviewed here. The management and outcomes of patients with respiratory muscle weakness are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management".)

Our approach is similar for the most part to guidelines issued by the American College of Chest Physicians [3].

INCIDENCE — Respiratory muscle weakness can be a serious problem among patients with neuromuscular disease. The incidence varies with the underlying disorder. For example, many patients with amyotrophic lateral sclerosis (ALS) die from progressive chronic respiratory failure. In addition, it is estimated that 15 to 28 percent of patients with myasthenia gravis and 20 to 30 percent of patients with Guillain-Barré syndrome require invasive mechanical ventilation at some point during their illness [4-6].

The incidence of respiratory failure due to respiratory muscle weakness in common neuromuscular disorders is discussed separately. (See "Clinical manifestations of myasthenia gravis" and "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis" and "Epidemiology and pathogenesis of amyotrophic lateral sclerosis" and 'Investigating the underlying disorder' below.)

MUSCLES OF RESPIRATION AND COUGH — Good working knowledge of the muscles of respiration is important since affected muscles determine the clinical presentation (table 2). (See 'Symptoms and signs' below.)

Inspiratory muscles include the diaphragm, external intercostals, scalenes, sternocleidomastoids, and trapezii.

Expiratory muscles include the internal and external obliques, rectus abdominis, transverse abdominis, and internal intercostals.

Upper airway muscles, important for bulbar function, include the lips, tongue, palate, pharynx, glottis, and larynx.

Neuromuscular control of cough is complex. An effective cough consists of three sequential phases [7].

The inspiratory phase generates a rapid and large tidal volume through an open glottis. Inspiratory muscle weakness decreases the tidal volume inspiration, limiting the volume and flow of gas during the subsequent expiratory phase. Upper airway muscle weakness results in inadequate glottic opening, thereby also decreasing the inspiratory tidal volume and subsequent expiratory flow.

The compressive phase is characterized by glottic closure resulting in a dramatic increase in positive intrathoracic pressure required for adequate expectoration. Upper airway muscle weakness causes inadequate glottic closure. Inadequate glottic closure results in a less effective inspiratory phase (due to leak of some of the inspired tidal volume) and a poor compressive phase.

The expiratory phase is where the glottis opens permitting high peak expiratory flow due to the sudden release of pressurized gas and airway compression that dislodges mucus adhering to airway walls. Expiratory muscle weakness limits the increase in positive intrathoracic pressure, reducing peak expiratory flow and dynamic airway compression.

CLINICAL MANIFESTATIONS — Inspiratory, expiratory, and upper airway muscle weakness due to neuromuscular disease can cause symptoms of hypoventilation, ineffective cough, and upper airway dysfunction (ie, bulbar dysfunction), respectively (table 2) [8]. In most patients the underlying neuromuscular disorder is known, although some patients present without a diagnosis (eg, Guillain-Barré syndrome).

Timing of onset — The duration of symptom onset varies with the underlying diagnosis (table 1).

Acute – Symptoms commonly develop acutely in patients with Guillain-Barré syndrome, acute spinal cord or phrenic nerve trauma or infarction, epidural abscess, acute poisoning, medications, metabolic disturbances, tetanus or other infections, or acute myasthenic crisis.

Chronic – Patients with other disorders may present slowly over months. These include patients with amyotrophic lateral sclerosis (ALS), multiple sclerosis, spinal cord tumors, myasthenia gravis, syringomyelia, muscular dystrophy, and myotonic dystrophy.

Relapsing or acute-on-chronic – Symptoms in patients with multiple sclerosis and myasthenia gravis may be intermittently relapsing. When patients with a chronic neuromuscular disorder develop a complication such as aspiration pneumonia, acute-on-chronic symptoms may also be seen.

Progressive – Some neuromuscular disorders are progressive such as ALS, spinal muscular atrophy, post-polio syndrome, and syringomyelia.

Symptoms and signs — The clinical features of respiratory muscle weakness are those associated with inadequate ventilation, ineffective cough, and bulbar dysfunction. The contribution of inspiratory, expiratory, and upper airway involvement varies with the underlying disorder (table 1) and determines which symptoms predominate (table 2).

Inadequate ventilation — In patients who have chronic respiratory muscle weakness, inadequate ventilation during sleep is often the first manifestation (ie, nocturnal hypoventilation). If respiratory muscle weakness is acute in onset or progressive, symptoms of hypoventilation can also be present during waking hours.

Nocturnal hypoventilation — Nocturnal hypoventilation may present as choking during sleep, daytime hypersomnolence, morning headaches, fatigue, impaired cognition or affect, and, rarely, insomnia (ie, symptoms similar to those of obstructive sleep apnea). These symptoms result from upper airway obstruction due to bulbar dysfunction, as well as decreased inspiratory muscle activity during rapid eye movement (REM) sleep. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Clinical features'.)

Awake hypoventilation — Insufficient ventilation during awake hours may result in the following symptoms or signs:

Dyspnea

Orthopnea

Rapid shallow breathing (ie, tachypnea with decreased tidal volume)

Accessory respiratory muscle use

Thoracoabdominal paradox (inward motion of the abdomen during inspiration; worse when supine)

Patients with acute hypercapnia may also develop mental status changes such as delirium, paranoia, and confusion, which progress to coma (carbon dioxide [CO2] narcosis) as hypercapnia progresses. Asterixis, myoclonus, seizures, and papilledema are later manifestations of acute hypercapnia. (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure", section on 'Clinical features of hypercapnia'.)

The principal cause of insufficient daytime ventilation is weakness of the inspiratory muscles (diaphragm, external intercostals, scalenes, sternocleidomastoids, and trapezii). Tidal volume decreases and respiratory frequency increases in an effort to compensate and maintain alveolar ventilation. Because patients with respiratory muscle weakness rely on gravity to assist diaphragmatic movement, orthopnea develops. As patients progress, tachypnea with short, shallow breathing and poor chest expansion may be seen. Late signs include accessory respiratory muscle use and thoracoabdominal paradox.

Ineffective cough — Poor cough is caused by weakness of the upper airway, inspiratory, and expiratory muscles. Patients with a poor cough are predisposed to retention of secretions, aspiration, and pneumonia [9,10]. The physiology of cough is discussed above. (See 'Muscles of respiration and cough' above.)

Bulbar dysfunction — Bulbar dysfunction is due to impairment of the upper airway muscles including the lips, tongue, palate, pharynx, glottis, and larynx. Bulbar dysfunction may present with drooling, dysarthria, dysphagia, weak mastication, facial weakness, nasal speech, abnormal secretion clearance, or a protruding tongue. Patients may present acutely with aspiration, and chronically with the features of nocturnal hypoventilation. (See "Aspiration pneumonia in adults" and 'Nocturnal hypoventilation' above.)

DIAGNOSTIC EVALUATION — In patients with neuromuscular disease who are suspected of having respiratory muscle weakness, we perform objective testing.

Testing includes pulmonary function tests (PFTs), tests of respiratory muscle strength (in particular, maximal inspiratory and expiratory pressure [MIP, MEP] and sniff nasal inspiratory pressure [SNIP]), and arterial blood gas analysis. (See 'Pulmonary function testing' below and 'Respiratory muscle strength testing' below and 'Arterial blood gas analysis' below.)

When diaphragmatic weakness is suspected, we perform an upright chest radiograph and test diaphragmatic strength. (See 'Diaphragmatic function' below.)

If patients have sleep-related symptoms, sleep-related hypoventilation is suspected, or respiratory muscle weakness is confirmed, we typically have patients undergo a sleep study (polysomnogram). (See 'Sleep study' below.)

Last, in those with a suspected weak cough we assess cough strength to confirm respiratory muscle weakness and inform future therapy. (See 'Assessing cough strength' below.)

Objective testing is important since, in some neuromuscular conditions, there is no correlation between the respiratory muscle weakness and the degree of peripheral muscle weakness, although this is not true for amyotrophic lateral sclerosis [11]. Diagnostic testing also helps identify patients who need specific therapies (eg, assisted coughing aids, ventilatory support). (See "Respiratory muscle weakness due to neuromuscular disease: Management".)

Pulmonary function testing — In patients with suspected respiratory muscle weakness, we perform PFTs in the supine and upright position. This includes spirometry, lung volumes, and diffusing capacity for carbon monoxide (DLCO); maximum voluntary ventilation (MVV) is not typically performed unless needed for cardiopulmonary exercise testing. The degree of pulmonary dysfunction generally correlates with severity of the respiratory muscle weakness.

Some patients with severe bulbar dysfunction may have trouble with testing due to an inability to create a tight seal with their lips at the mouthpiece. In such cases, the operator may manually facilitate a tight seal for the patient; alternatively, the SNIP may be used as an indicator of respiratory muscle weakness. (See 'Respiratory muscle strength testing' below.)

The diagnosis of respiratory muscle weakness is based upon a constellation of abnormalities that include one or more of the following [12]:

A pattern of restriction on spirometry – Restriction is typical in patients with respiratory muscle weakness. It is identified as a reduced forced expiratory volume in one second (FEV1), reduced forced vital capacity (FVC) and vital capacity (VC), normal FEV1/FVC ratio (greater than 70 percent of predicted), and reduced total lung capacity (TLC). Patients with predominantly expiratory muscle weakness also demonstrate a reduced expiratory reserve volume (ERV) and an increased residual volume (RV) such that the RV/TLC ratio is normal or increased [13]. (See "Overview of pulmonary function testing in adults".)

The VC (also known as slow VC) may be a more reliable indicator of respiratory muscle weakness than the FVC since it is unaffected by coexisting airflow obstruction. The VC is the maximum volume of gas that can be expelled from full inspiration while the FVC measures the same thing, only the patient is exhaling with maximal speed and effort. In patients with concurrent obstruction, the VC is usually higher than the FVC, with the difference being directly related to the degree of obstruction.

Reduced FVC or VC in the upright and supine position – Obtaining PFTs in the supine position can be pragmatically challenging. When feasible, a supine FVC or VC that is more than 10 percent lower than an upright FVC or VC is supportive of a diagnosis of respiratory muscle weakness (normal is 5 to 10 percent lower [14]).

A fall in VC greater than 30 percent when supine compared to the upright posture is indicative of isolated or disproportionate bilateral diaphragm weakness and may be more reliable that the maximal inspiratory pressure (PImax) in this regard [15,16]. However, a decreased VC is less specific for respiratory muscle weakness compared with the PImax [17,18].

Noteworthy is that the VC falls late in progressive neuromuscular disease (eg, amyotrophic lateral sclerosis) while the PImax falls earlier and correlates better with disease progression [19]. (See "Tests of respiratory muscle strength", section on 'Clinical course and criteria for detecting change' and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Pulmonary tests'.)

The marked change in VC is a result of the action of gravity on the abdominal contents and thoracic blood flow and the change in diaphragm geometry and load (figure 1).

Reduced MVV – MVV is the volume of air that can be maximally and rapidly inhaled and exhaled within one minute (it is typically measured over 15 seconds). MVV is typically reduced in patients with respiratory muscle weakness and is most valuable when measured during exercise.

Preserved DLCO – DLCO is typically preserved in patients with neuromuscular weakness, provided there is no coexisting pulmonary parenchymal (eg, interstitial lung disease or atelectasis), obstructive, or vascular disease resulting in ventilation/perfusion mismatch. (See "Diffusing capacity for carbon monoxide".)

Respiratory muscle strength testing — In patients with suspected respiratory muscle weakness, we perform the MIP, MEP, and SNIP. For patients in whom diaphragmatic weakness is suspected, we also perform investigations targeted at testing diaphragmatic strength. Assessing cough strength can confirm respiratory muscle weakness and inform future therapies. Values that indicate respiratory muscle weakness are briefly described in the sections below while reference values, differential, and interpretation are discussed elsewhere. (See "Tests of respiratory muscle strength".)

Maximal inspiratory and expiratory pressure (MIP, MEP) — In patients with inspiratory muscle weakness, MIP is reduced, and in patients with expiratory muscle weakness MEP is reduced. Occasionally, MIP is reduced but MEP is relatively spared (eg, respiratory muscle weakness isolated to the diaphragm). Muscles that control respiration and the diagnosis of diaphragmatic paralysis are discussed separately. (See 'Muscles of respiration and cough' above and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Pulmonary function testing' and "Tests of respiratory muscle strength", section on 'Maximal inspiratory pressure (PImax)' and "Tests of respiratory muscle strength", section on 'Maximal expiratory pressure (PEmax)'.)

Diagnosis of diaphragmatic paralysis is discussed separately. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Pulmonary function testing'.)

Sniff nasal inspiratory pressure (SNIP) — In patients with inspiratory muscle weakness, the SNIP is typically lower than predicted. It is particularly useful in those with bulbar dysfunction who may have difficulty creating a seal with the mouthpiece for the performance of routine PFTs, MIPs, and MEPs [20]. However, SNIP may be more variable than adequate measurements of lung volume. In addition, SNIP is not suitable for patients with hyperinflation due to severe airway obstruction. This is because the transmission of intrathoracic pressure to the nose is impaired in those with hyperinflation such that SNIP generally underestimates inspiratory muscle strength; consequently, MIP may be more reliable in this population. (See "Tests of respiratory muscle strength", section on 'Sniff nasal inspiratory pressure (SNIP)'.)

Other tests — In most patients the maximal inspiratory pressure, maximal expiratory pressure and sniff nasal pressure are sufficient to make a diagnosis of respiratory muscle weakness when taken together with other clinical features. However, when the diagnosis of respiratory muscle weakness is in doubt, more invasive testing can be performed, depending on availability and need. These complex measurements are best made in specialist centers and can reliably diagnose and quantify respiratory muscle weakness. The decision to perform invasive tests such as these is also best made in conjunction with a pulmonologist and/or neurologist.

Sniff esophageal and gastric pressure — Similar to SNIP, sniff esophageal pressure is a good test of overall inspiratory muscle strength that may be valuable in patients with hyperinflation due to obstructive airways disease [21].

Gastric pressure, measured with a pressure catheter in the stomach following maximal cough efforts, reflects expiratory (particularly abdominal) muscle strength [22]. Non volitional abdominal (expiratory) muscle strength can be measured by recording gastric pressure following surface magnetic stimulation posteriorly in the mid-line at the level of T10 [23].

Diaphragmatic function — For patients in whom diaphragmatic weakness is suspected (eg, spinal tumor or trauma), common tests that are performed include the following:

Chest imaging (eg, upright chest radiography and chest computed tomography)

Diaphragmatic electromyography (EMG)

Diaphragmatic imaging (eg, fluoroscopic sniff test, diaphragmatic ultrasound movement or thickness [24,25])

Phrenic nerve stimulation (electric or magnetic) [26-28]

Combined phrenic nerve stimulation and diaphragmatic EMG measures phrenic nerve latency and the amplitude of the compound muscle action potential (CMAP) [29]

Sniff transdiaphragmatic pressure (Sniff Pdi)

Twitch mouth pressure is an uncommon test that needs further validation [30]

Testing in patients with suspected diaphragmatic dysfunction is discussed in detail separately. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Imaging studies' and "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Measurement of transdiaphragmatic pressure' and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Imaging'.)

Arterial blood gas analysis — In patients with suspected respiratory muscle weakness, we routinely obtain an arterial blood gas (ABG) analysis. An ABG is typically drawn at rest during awake hours to determine whether daytime hypercapnia is present. However, hypercapnia may be evident during sleep only. The latter may require ABG analysis at the end of sleep or determined using end-tidal or transcutaneous capnography during sleep measured at home or in a sleep laboratory [31]. In all cases when hypercapnia is present, it should be determined whether it is acute, chronic, or acute-on-chronic. (See "Arterial blood gases" and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure", section on 'Distinguishing acute and chronic hypercapnia'.)

The demonstration of hypercapnia, which is the hallmark of inadequate ventilation, is important when investigating patients for respiratory muscle weakness. Early in the course of chronic disease, ventilation may be adequate to maintain a normal partial pressure of carbon dioxide (PaCO2). However, under stress (eg, fever, infection) or with disease progression, ventilation cannot be sufficiently increased and PaCO2 rises (acute for stress, chronic for disease progression).

Hypoxemia frequently accompanies insufficient ventilation and is multifactorial. A small contribution is due to insufficient ventilation itself while a more significant contribution is typically due to atelectasis-induced shunt from rapid, shallow breathing. Patients get caught in a vicious cycle because hypoxemia from chronic atelectasis increases the work of breathing and predisposes the patient to worsening respiratory muscle fatigue, thereby aggravating hypoventilation. (See "Measures of oxygenation and mechanisms of hypoxemia", section on 'Hypoventilation' and "Measures of oxygenation and mechanisms of hypoxemia", section on 'Right-to-left shunt'.)

Other tests

Sleep study — In those with sleep-related symptoms or when sleep-related hypoventilation is suspected and respiratory muscle weakness is confirmed, we typically obtain a sleep study.

Many patients with neuromuscular disease hypoventilate during sleep and some may have overt obstructive sleep apnea. Given the potential complexity of sleep disordered breathing in patients with neuromuscular disorders, most experts prefer to perform in-laboratory sleep testing with polysomnography rather than home testing, unless patients have trouble sleeping in, or cannot access, a sleep laboratory.

The evaluation of sleep-disordered breathing in patients with neuromuscular disease and diagnosis of sleep apnea are discussed in detail separately. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Diagnostic tests' and "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders".)

Assessing cough strength — Several tests can identify patients with an ineffective cough. (See 'Diagnostic evaluation' above and "Tests of respiratory muscle strength".)

Maximum expiratory pressure – A MEP less than 60 cm H2O suggests that the patient's cough is ineffective [32]. (See "Tests of respiratory muscle strength", section on 'Maximal expiratory pressure (PEmax)'.)

Peak cough flow – The peak cough flow (PCF) is measured by having the patient inspire fully and then cough forcibly through a mask or mouthpiece attached to a peak flow meter. A PCF less than 160 L/min identifies patients with an ineffective cough. Patients with a PCF between 160 and 270 L/min are at risk for respiratory tract infections, which can further reduce muscle strength [33-35].

Expiratory cough flow tracings – The absence of transient increases in expiratory flow above the maximal flow-volume loop (ie, cough spikes) is associated with decreased cough effectiveness (figure 2) [36].

Other – Gastric pressure is an invasive test that can be assessed following cough efforts or stimulation and reflects abdominal muscle strength.

Miscellaneous — Surrogate markers of lung function should be considered when respiratory physiologic measurements cannot be obtained. As an example, a single breath count test (SBC) is performed by the patient taking full inhalation and then counting, for as long as possible, at a rate of two counts per second. Studies in patients with myasthenia gravis and Guillain-Barré Syndrome have shown a correlation between SBC testing and vital capacity with lower counts indicating more severe respiratory dysfunction. SBC values <20 indicate abnormal respiratory function [37-39].

Neck flexor strength, graded using the modified Medical Research Council grading scale, is also correlated with forced vital capacity [39].

DIAGNOSIS

Differential diagnosis — During assessment, several etiologies need to be ruled out before confirming a diagnosis of respiratory muscle weakness.

Patients with restrictive lung disease – Patients with restriction on their pulmonary function may have pleural, alveolar, interstitial, or thoracic cage disease (including obesity) to explain the restriction. Distinguishing these may be achieved by the following:

History and examination – While symptoms such as dyspnea may overlap between etiologies associated with restriction, dry cough is unusual in those with respiratory muscle weakness unless chronic aspiration is present. In addition, symptoms of nocturnal hypoventilation are uncommon in patients with pleural, alveolar, and interstitial lung disease.

High resolution chest computed tomography – Most pleural, alveolar, interstitial, and thoracic cage disorders can be appreciated on chest computed tomography (CT) and are typically absent in patients with neuromuscular weakness, unless they have concurrent disease (eg, polymyositis). Additional investigation may be needed (eg, lung biopsy, drainage of an effusion) before confirming the presence of respiratory muscle weakness. (See "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Pleural fluid analysis in adults with a pleural effusion".)

Pulmonary function testing – In patients with respiratory muscle weakness, the forced vital capacity (FVC) is reduced relative to the total lung capacity (TLC). When the expiratory muscles are involved, the residual volume (RV) is increased, the RV/TLC ratio may be increased, and the expiratory reserve volume (ERV) is decreased. In patients with interstitial lung disease, the FVC and TLC should be similarly reduced, the RV/TLC ratio is reduced, and ERV is normal.

Obese patients with a body mass index (BMI) >40 kg/m2 have similar pulmonary function texts (PFTs) to some patients with respiratory muscle weakness (ie, normal or increased RV/TLC ratio and reduced ERV). Obesity can be identified by calculating the BMI.

Patients with a preserved diffusing capacity for carbon monoxide (DLCO) with reduced lung volumes may have respiratory muscle weakness or conditions of the chest wall or pleura, which are typically readily distinguished by chest CT. (See "Chest wall diseases and restrictive physiology".)

Respiratory muscle strength – Indicators of poor respiratory muscle strength are typically normal in patients with restrictive lung disease who do not have respiratory muscle weakness. (See 'Respiratory muscle strength testing' above.)

Etiologies of hypercapnia – Similarly, etiologies that can result in hypercapnia should be reasonably excluded using routine laboratories (eg, thyroid function testing, metabolic disturbances) and clinical history and examination (table 3). (See "Mechanisms, causes, and effects of hypercapnia".)

Heart failure – For patients who present with dyspnea and orthopnea, an echocardiogram is reasonable to differentiate respiratory muscle weakness from heart failure. Notably, heart failure can also occur as a manifestation of some neuromuscular disorders, such as a Duchenne muscular dystrophy. (See "Transthoracic echocardiography: Normal cardiac anatomy and tomographic views" and "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis", section on 'Cardiomyopathy'.)

Poor effort – When the maximum inspiratory and expiratory pressure (MIP, MEP), sniff nasal inspiratory pressure (SNIP), and/or maximum voluntary ventilation (MVV) are reduced, in some cases the low results may reflect poor effort or difficulties with performing the maneuvers. A low MVV may also be seen in restrictive lung disease. Diagnostic accuracy for inspiratory muscle weakness is improved when MIP and SNIP are both measured and when interpreted in the appropriate clinical context. The interpretation of abnormal respiratory muscle strength testing is discussed elsewhere. (See "Tests of respiratory muscle strength".)

Sleep-disordered breathing – Symptoms of nocturnal hypoventilation should prompt a sleep study which can distinguish central from obstructive events and prompt appropriate therapy. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders".)

Diagnosis — The diagnosis of respiratory muscle weakness is made using a constellation of supportive clinical, physiologic, and gas exchange findings. For example, the diagnosis can be confidently made in most patients with a known neuromuscular disorder who have consistent symptoms, nocturnal or daytime hypercapnia, restriction on PFTs and evidence of respiratory muscle strength weakness. However, a definitive diagnosis is more challenging in those with only some supportive features (eg, no known neurologic disorder or normal daytime arterial carbon dioxide tension) or those with other cardiopulmonary comorbidities. In such cases, clinicians should rely on clinical suspicion and subtle findings to support the diagnosis, such as nocturnal hypoventilation or unexplained decline in PFTs. (See "Approach to the patient with muscle weakness".)

Investigating the underlying disorder — In most patients, the neuromuscular disorder in known. However, in some patients, a diagnostic evaluation for a suspected neuromuscular disorder needs to be undertaken. These details are found separately:

Diaphragmatic paralysis (see "Diagnostic evaluation of adults with bilateral diaphragm paralysis" and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults")

Amyotrophic lateral sclerosis (ALS) (see "Symptom-based management of amyotrophic lateral sclerosis", section on 'Respiratory function management')

Guillain-Barré syndrome (see "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Ventilatory status')

Myasthenic crisis (see "Myasthenic crisis", section on 'Assessment of respiratory function')

Myotonic dystrophy (see "Myotonic dystrophy: Etiology, clinical features, and diagnosis", section on 'Respiratory function' and "Myotonic dystrophy: Treatment and prognosis", section on 'Respiratory function and sleep')

Spinal muscular atrophy (see "Spinal muscular atrophy", section on 'Pulmonary')

Multiple sclerosis (see "Manifestations of multiple sclerosis in adults", section on 'Sleep disorders')

SUMMARY AND RECOMMENDATIONS

Respiratory muscle weakness can be a serious problem among patients with several types of neuromuscular disorders (table 1). The incidence varies with the underlying disorder. (See 'Introduction' above and 'Incidence' above.)

Presenting clinical features may be acute, chronic, acute-on-chronic, relapsing, or progressive depending upon the etiology. The contribution of inspiratory, expiratory, and upper airway involvement varies with the underlying disorder (table 2) and determines which symptoms predominate (table 2). In general, respiratory muscle weakness is worse during sleep. (See 'Clinical manifestations' above and 'Timing of onset' above.)

In patients with chronic respiratory muscle weakness, nocturnal hypoventilation is often the first manifestation, presenting as choking during sleep, daytime hypersomnolence, morning headaches, fatigue, impaired cognition or affect, and insomnia (ie, symptoms similar to obstructive sleep apnea). (See 'Nocturnal hypoventilation' above.)

In patients with acute or progressive disease, daytime hypoventilation may present as dyspnea, orthopnea, rapid, shallow breathing, accessory muscle use, and thoracoabdominal paradox. (See 'Awake hypoventilation' above.)

Ineffective cough is evident in those with inspiratory, expiratory, and upper airway muscle weakness (eg, bulbar dysfunction). Such patients present with poor secretion clearance and aspiration pneumonia. Patients with bulbar dysfunction may additionally present with drooling, dysarthria, dysphagia, weak mastication, facial weakness, nasal speech, or a protruding tongue. (See 'Ineffective cough' above and 'Bulbar dysfunction' above.)

Patients with suspected respiratory muscle weakness should have pulmonary function testing (PFTs) performed to demonstrate restriction, and respiratory muscle strength testing to demonstrate respiratory muscle weakness (eg, maximal inspiratory and expiratory pressure and sniff nasal inspiratory pressure). An arterial blood gas and/or carbon dioxide monitoring during sleep should be obtained to demonstrate hypercapnia. For other patients in whom diaphragmatic dysfunction, sleep-disordered breathing, or weak cough is suspected, chest imaging, tests of diaphragmatic function, an in-laboratory sleep study, or tests of cough strength may be warranted. (See 'Diagnostic evaluation' above and "Tests of respiratory muscle strength".)

The diagnosis of respiratory muscle weakness is made using a constellation of supportive clinical, physiologic, and gas exchange findings. (See 'Diagnosis' above.)

The diagnosis can be confidently made in most patients with a known neuromuscular disorder who have consistent symptoms, nocturnal or daytime hypercapnia, restriction on PFTs, and evidence of respiratory muscle weakness on strength testing. (See 'Diagnosis' above.)

Patients with restriction should have pleural, alveolar, interstitial, or thoracic cage disease (including obesity) excluded by history, examination, PFTs, and high resolution chest computed tomography. In addition, etiologies associated with hypercapnia should be reasonably excluded (table 3) and patients who present with dyspnea and orthopnea should have an echocardiogram to rule out congestive heart failure. (See 'Differential diagnosis' above.)

Additional evaluation for a suspected neuromuscular disorder, if unknown may be needed. Investigating for disorders such as diaphragm paralysis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenic crisis, myotonic dystrophy, and spinal muscular atrophy are described separately. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis" and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults" and 'Investigating the underlying disorder' above and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Respiratory function management' and "Myasthenic crisis", section on 'Assessment of respiratory function' and "Myotonic dystrophy: Etiology, clinical features, and diagnosis", section on 'Respiratory function' and "Spinal muscular atrophy", section on 'Pulmonary' and "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Ventilatory status'.)

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Topic 5121 Version 26.0

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