Sudden Onset of Dyspnea Preceded by Shoulder and Arm Pain

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1 The Expert Clinician Section Editors: Peter Clardy, M.D., and Charlie Strange, M.D. Sudden Onset of Dyspnea Preceded by Shoulder and Arm Pain Anupam Kumar, Eduardo Mireles-Cabodevila, Atul C. Mehta, and Loutfi S. Aboussouan Respiratory Institute, Cleveland Clinic, Cleveland, Ohio Case Vignette A 61-year-old woman presented with breathlessness on exertion and when lying supine of 3 months duration. She denied cough, wheezing, and muscle weakness. Three weeks earlier, she had experienced an upper respiratory tract infection and developed right shoulder and arm pain. At the age of 17 years, she had experienced an episode of bilateral shoulder andarmpain,followedbyprofound weakness of both arms. No diagnosis was made at that time. Upper-extremity muscle strength returned to normal over a period of about 2 years. Fourteen months before the current presentation, she was hospitalized for neck and arm pain. A chest radiograph obtained at the time of that admission was normal (Figure 1), but a second chest radiograph obtained 3 weeks later showed elevation of the left diaphragm (Figure 2). She reported no respiratory symptoms at that time. Shoulder pain had resolved by the time of hospital discharge. On physical examination, vital signs were normal, and her arterial oxygen saturation was 96% while she breathed ambient air. She had vitiligo and total alopecia. Chest auscultation revealed symmetrical air entry bilaterally and no adventitious sounds. When she lay supine, she reported uncomfortable breathing, and we observed paradoxical movement of the anterior abdomen during tidal breathing. There was no apparent weakness of her extremities, and deep tendon reflexes were intact. Figure 1. Chest radiograph obtained 14 months before current presentation, showing normal position of both hemidiaphragms. Figure 2. Chest radiograph performed 3 weeks after the initial film, showing left diaphragmatic elevation. (Received in original form January 7, 2016; accepted in final form July 11, 2016 ) Correspondence and requests for reprints should be addressed to Anupam Kumar, M.D., Respiratory Institute, Cleveland Clinic, A90 desk, 9500 Euclid Avenue, Cleveland, OH drkumar83@gmail.com Ann Am Thorac Soc Vol 13, No 12, pp , Dec 2016 Copyright 2016 by the American Thoracic Society DOI: /AnnalsATS CC Internet address: Case Conferences: The Expert Clinician 2261

2 Table 1. PFT results PFT Predicted LLN Measured % FVC FEV FEV 1 /FVC ratio RV VC TLC RV/TLC DL CO DLVA MIP MEP Pulmonary function test results are shown in Table 1. Of note, she was unable to perform spirometry in the supine position because of profound orthopnea, which developed immediately on lying flat. A chest radiograph performed 3 weeks before the current presentation showed persistent left diaphragm elevation (Figure 3). A chest radiograph obtained on the day of presentation demonstrated bilateral diaphragm elevation (Figure 4). Definition of abbreviations: DL CO = diffusing capacity of carbon monoxide; DLVA = diffusing capacity adjusted by alveolar volume; LLN = lower limit of normal; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; PFT = pulmonary function test; RV = residual volume; TLC = total lung capacity. Figure 3. Chest radiograph obtained 3 weeks before the current presentation, showing persistent left diaphragmatic elevation. Figure 4. Chest radiograph obtained at the time of the current presentation, showing bilateral diaphragmatic elevation and low lung volumes. Questions 1. What is the most likely diagnosis? 2. What diagnostic studies can help confirm the diagnosis? 3. What is the natural history, and what are the therapeutic options? [Continue onto next page for answers] 2262 AnnalsATS Volume 13 Number 12 December 2016

3 Clinical Reasoning and Diagnosis In a patient with orthopnea and paradoxical inward movement of the abdomen during inspiration, the diagnosis of diaphragmatic paralysis should be considered. The reduction in our patient s FVC and total lung capacity, combined with a reduced maximal inspiratory pressure (MIP), increased the suspicion for bilateral diaphragmatic paralysis. Our patient was unable to perform pulmonary function testing in the supine position because of profound orthopnea. The symptoms, together with the presence of sequential diaphragmatic elevation on serial chest radiographs, led to a presumptive diagnosis of bilateral diaphragm paralysis. A traumatic cause for denervation was excluded by the absence of any recent cervical or thoracic surgery. The clinical presentation, absence of bulbar symptoms, limb weakness, and intact reflexes reduced our suspicion for a systemic neuromuscular condition such as amyotrophic lateral sclerosis, Guillain-Barre syndrome, poliomyelitis, and myasthenia gravis. All laboratory studies were unremarkable, including antinuclear antibody and myositis antibodies. Computed tomographic imaging of the neck and chest excluded anatomic pathology such as a tumor causing compression of a phrenic nerve. The history of unprovoked upperextremity pain of sudden onset followed by exertional shortness of breath was suspicious for neuralgic amyotrophy. Phrenic nerve conduction studies demonstrated absent bilateral phrenic nerve motor responses. A simultaneous ultrasound examination showed no detectable movement of the diaphragm on either side. The diaphragm electromyogram demonstrated changes suggestive of subacute or chronic axon loss neuropathy. Thus, a diagnosis of neuralgic amyotrophy causing phrenic neuropathy and bilateral diaphragmatic paralysis was confirmed. Discussion Bilateral diaphragmatic paralysis commonly results from neck manipulation, neck trauma, or systemic neuromuscular diseases such as Guillain-Barre syndrome, amyotrophic lateral sclerosis, and poliomyelitis (1). Neuralgic amyotrophy (Parsonage-Turner syndrome) is an underrecognized cause of diaphragmatic paralysis. This is thought to be a unifocal or multifocal peripheral nerve inflammatory condition. Neuralgic amyotrophy classically involves the long thoracic nerve or one or more roots of the brachial plexus. Typically, the condition presents with acute shoulder and arm pain followed within 1 day to 2 weeks or more by weakness and loss of muscle function in the area of innervation (2). Involvement of thelongthoracicnervecausesparalysisof the serratus anterior muscle, resulting in winging of the scapula. This is best observedbyaskingapatienttolean forward with both hands pressed against awall. There are many variations on the classic form, including bilateral shoulder and arm injury and involvement of the lumbosacral plexus, recurrent laryngeal nerve, and one or both phrenic nerves. Phrenic nerve involvement with neuralgic amyotrophy is estimated to occur in 5 10% of patients (2, 3). The phrenic neuropathy may be isolated (unilateral or bilateral), or may occur in combination with the involvement of other nerves (3). Triggers such as respiratory infections, exercise, surgery, puerperium, and vaccinations are reported frequently (4). These insults are thought to initiate an autoimmune reaction, causing degeneration or demyelination of nerve axons and leading to neuralgic amyotrophy (4, 5). Our patient s vitiligo and alopecia lend support to an autoimmune pathophysiology. Although most cases of neuralgic amyotrophy are idiopathic in nature, a few cases are hereditary, with an autosomal-dominant mode of transmission (4). Neuralgic amyotrophy sometimes unfolds in a staggering fashion, with episodes of activity and consequent nerve injury occurring in similar or different locations over time. Thus, it is possible that one or both of our patient s previous episodes of upper-extremity nerve injury were also caused by neuralgic amyotrophy. In the absence of other concomitant respiratory problems, patients with unilateral diaphragmatic weakness may be asymptomatic. For instance, our patient did not report any significant symptoms until both diaphragms were paralyzed. In contrast, patients with bilateral phrenic nerve impairment typically present with dyspnea, precipitated mostly by exertion and orthopnea (6). Patients may also report shortness of breath during bending or when they are immersed in water with the level reaching abdomen (caused by pressure on the paralyzed diaphragm pushing it in cephalad direction) (1). Patients may manifest sleepdisordered breathing and nocturnal desaturations with nonspecific symptoms such as morning headaches and daytime sleepiness. This is the result of hypoventilation during sleep, which is worsened by muscular hypotonia during REM sleep (7). Some patients will develop hypercapnia when accessory respiratory muscles are unable to compensate (7, 8). The characteristic finding on physical examination of patients with bilateral diaphragmatic paralysis is paradoxical abdominal movement ( abdominal paradox ). There is inward movement of the abdomen while the rib cage expands outward during inspiration (1). Paradoxical breathing is distinguished from flail chest, which is characterized by inward collapse of the rib cage and normal outward movement of the abdominal wall during inspiration. Abdominal paradox is not specific for bilateral diaphragm paralysis, but it is typically not seen in unilateral diaphragmatic paresis because of compensatory movement by the contralateral normal hemidiaphragm. In most cases, a diagnosis of diaphragmatic paralysis can be made on the basis of history, physical examination, and pulmonary function test abnormalities. Chest radiographs are abnormal in unilateral paralysis, with an acceptable sensitivity of 90% but limited specificity (44%) (9). Cephalad movement of the elevated hemidiaphragm observed on fluoroscopy during a sniff inspiration is more specific. However, false-negatives are described in bilateral diaphragmatic paralysis caused by the caudal displacement of the diaphragm from the compensatory response of the accessory muscles (1, 10). During pulmonary function testing, a baseline reduction in FVC may be noted, suggesting restriction. In healthy subjects, Case Conferences: The Expert Clinician 2263

4 the FVC measured in the supine position may be up to 10% lower than the FVC measured in the upright measurement. The drop in FVC usually does not exceed 30% in unilateral paralysis, whereas it is usually.30% with bilateral involvement (1). Indeed, many patients, including ours, are unable to perform the maneuver when lying supine. FVC measurement is a key parameter to be used for follow-up of patients with diaphragm weakness. An improvement in FVC may be a marker of regaining diaphragmatic function, whereas a decline in FVC (especially to less than 50%) may be an indication to consider noninvasive positive pressure ventilation (7, 8). The MIP in patients with bilateral diaphragm paralysis is also reduced (1). Ultrasound has also emerged as an effective tool to diagnose and to monitor for recovery of diaphragm function (11). Electromyographic studies of phrenic nerve conduction can demonstrate nerve conduction blockage in a primary neuropathic disorder. Prolongation of nerve conduction time on electromyography may help distinguish neuropathy from myopathy as the cause of diaphragm paralysis (6). Measurement of transdiaphragmatic pressure is considered the gold standard for the diagnosis of diaphragm weakness, but it is rarely used because a diagnosis can usually be made with less invasive tests (1, 2). Arterial blood gases are also important to assess for the elevation of the Pa CO2 caused by alveolar hypoventilation and to look for hypoxemia caused by atelectasis of the lung above an elevated hemidiaphragm. Physicians should also consider formal sleep assessment of patients with diaphragmatic paralysis. In patients with nocturnal or diurnal hypoventilation, noninvasive positive pressure support (bilevel positive pressure ventilation) should be initiated. Many patients with mild to moderate dyspnea from unilateral diaphragmatic paralysis improve spontaneously. About 70% of patients with neuralgic amyotrophy and phrenic neuropathy may experience some recovery of function (12). However, the recovery is slow (1 to 3 yr) and usually incomplete (11, 12). In a series reported by Hughes and colleagues, only 50% of the patients with bilateral diaphragmatic paralysis caused by neuralgic amyotrophy had improvement to 50% of the lower limit of normal (12). Moreover, up to 25% of subjects may experience a recurrence of neuralgic amyotrophy, as demonstrated by our patient (4). For those patients with unilateral diaphragmatic paralysis who have troubling symptoms such as orthopnea or whodonotimproveaftermonitoringfor spontaneous recovery, surgical plication of the diaphragm can be considered and has been shown to improve ventilation and gas exchange (13, 14). Other therapeutic modalities are limited. For instance, diaphragmatic/phrenic nerve stimulation is generally indicated for individuals with an intact phrenic nerve and diaphragm, such as subjects with hypoventilation in the context of spinal cord injury or central apnea rather than neuralgic amyotrophy (1), and current treatment algorithms exclude subjects with neuralgic amyotrophy from phrenic nerve reconstruction surgery (15). Answers 1. What is the most likely diagnosis? Bilateral diaphragm paralysis caused by neuralgic amyotrophy. 2. What diagnostic studies can help confirm the diagnosis? The combination of clinical history, physical examination findings, pulmonary function test results, and chest radiographs can generally confirm a diagnosis of bilateral diaphragmatic paralysis. Neuralgic amyotrophy is a clinical syndrome characterized by acute onset of pain in the neck, shoulders, or arms, followed by weakness. Electromyography may show changes of axonal degeneration affecting the muscles of the proximal arm, thumb, or diaphragm. Compressive nerve injury caused by trauma or mass lesions, as well as systemic neuromuscular disorders, must be excluded. 3. What is the natural history, and what are the therapeutic options? Recovery of function can occur in about 70% of subjects, but the course of recovery is often prolonged. Nocturnal noninvasive pressure support with bilevel positive pressure ventilation should be instituted, especially in patients in whom the diaphragm impairment results in significant hypoventilation. Follow-Up With an initial FVC of 1.04 L (35% predicted) and an inability to breathe comfortably in the supine position, the patient was started on noninvasive bilevel pressure support ventilation. The patient reported improvement in dyspnea. During her most recent visit, approximately 2 years after diagnosis, her FVC had improved to 1.44 L (50%), although she still complained of orthopnea and exertional dyspnea. Insights 1. Orthopnea, together with abdominal paradoxical movement during inspiration in the supine position, is highly suggestive of bilateral diaphragmatic paralysis. 2. Neuralgic amyotrophy is a clinical diagnosis and should be suspected in patients with a history of acute or subacute extremity pain followed by neuromyopathy. Neuralgic amyotrophy may be recurrent in some patients. 3. Phrenic neuropathy causing diaphragmatic paralysis may be seen in up to 10% of patients with neuralgic amyotrophy. Dyspnea, worsened by exertion and supine position, should prompt evaluation of diaphragmatic function. 4. The degree of drop in vital capacity from a sitting to a recumbent position can distinguish unilateral from bilateral diaphragmatic paralysis. Bilateral diaphragmatic paralysis usually results in a.30% decrease in the VC. The MIP in patients with bilateral diaphragm paralysis is often,30% predicted. 5. Recovery of diaphragmatic function is slow and often incomplete. Serial monitoring of FVC is recommended for assessment. 6. Patients with diaphragmatic paralysis should be evaluated for hypoventilation and, if present, considered for noninvasive positive pressure ventilation. n Author disclosures are available with the text of this article at AnnalsATS Volume 13 Number 12 December 2016

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