The anatomy and physiology of the respiratory system is somewhat unique. There is a baseline level of involuntary activity necessary to sustain breathing during sleep as well as a conscious “override” that may be invoked. Brainstem nuclei transmit impulses through the anterior horn cells to initiate an inspiratory effort. Alternatively, respiratory centers in the cerebral cortex may stimulate a respiratory event through a conscious effort. There are established connections between both sides of the brainstem, including a described “cross phrenic phenomenon,” whereby a cord hemisection disrupting ipsilateral respiratory activity will be restored through a rerouting of impulses from the contralateral, uninjured side [4–6].

After descending to the upper cervical region (C3-5), the conduction proceeds extradural through the cervical roots and phrenic nerves, downward toward each hemidiaphragm (Fig. 10.2). The diaphragm is the primary inspiratory muscle, working in conjunction with several accessory respiratory muscles to expand the thoracic cavity in a vertical dimension, while intercostal muscles are primarily responsible for horizontal expansion of the ribcage. The entire process is a coordinated ensemble of contraction in the trunk musculature, including the trapezius, sternocleidomastoid, pectoralis major/minor, small strap muscles of the neck (hyoid musculature), intercostals, and abdominal muscles. The lung expands passively as a result of the facilitated increased thoracic domain, and an exchange of inspired gases occurs. The diaphragm maintains a critical role in this process through its action of increasing thoracic volume and opposing abdominal forces acting against it. The expiratory phase of breathing involves a different subset of muscles aimed at reversing the dimensions of the thoracic cavity back to its resting state.

The phrenic nerve is a peripheral nerve arising from C3-5 and contains primarily motor fibers, although there are a small group of sensory fibers innervating primarily the pericardium. The course of the nerve is deep in the neck, subjacent to the prevertebral fascia, and just above the anterior scalene muscle (Fig. 10.3). A majority of humans also have a smaller branch, called the accessory phrenic nerve, which runs a parallel but often variable course in the neck, typically joining the more dominant phrenic nerve proper at the base of the neck or in the mediastinum [7]. After entering the mediastinum, the phrenic nerve increases in caliber and travels between the lung and midline structures. In the region of the heart, the phrenic nerves on both sides are located close to or within the pericardial fat and descend within these tissues to reach their terminal insertions in the medial portions of each diaphragm. The nerves branch rather extensively within each hemidiaphragm in order to innervate all portions of these broad and wide muscles.

The primary respiratory muscle is skeletal in nature and is divided into two hemidiaphragms by its midline central tendon. The lateral attachments to each chest wall and its position in the center of the trunk account for its importance in body posture and stability. An excellent reference for the diaphragm’s role as a postural stabilizer [8]. The structural makeup of the diaphragm consists of approximately 50 % slow-twitch (type I) and fast-twitch (type II) muscle fibers according to postmortem human research [9, 10]. The resting thickness of the diaphragm muscle when measured at its so-called zone of apposition is estimated to be roughly 1.5 mm, expanding by 2 mm with functional activation [11].

The true incidence of diaphragmatic paralysis is currently unknown, in part because of the variety of etiologies. The most common peripheral etiologies are iatrogenic or traumatic events impacting the neck, mediastinum, or chest (Table 10.1). Cardiac surgery procedures such as coronary artery bypass or valve replacement have been associated with phrenic nerve injury or abnormal diaphragm findings in anywhere from 1 to 80 % of cases [12–14].

Interscalene nerve blocks performed for shoulder surgery previously resulted in a 100 % incidence of temporary diaphragmatic paralysis as a result of anesthetic effect on the phrenic nerve. However, altered dosing regimens and use of ultrasound guidance have reduced the risk [15, 16]. Permanent diaphragmatic paralysis after interscalene block has been reported, though the incidence has not been determined [17, 18]. Chiropractic neck manipulation also has been associated with phrenic nerve injury in the neck, likely a result of either a traction-type nerve injury from the sudden jolting or perhaps a post-inflammatory effect on the nerve, especially if recurrent treatments prevent complete internal healing to occur [19, 20]. Other surgical procedures in the neck that have been reported to have an association with diaphragmatic paralysis include: carotid-subclavian bypass, thoracic outlet surgery, and cervical lymphadenopathy [21].

Mediastinal procedures such as thymectomy, especially for malignancy, have an association with phrenic nerve injury with a reported rate of 1–2 % [22, 23]. Aortic or mitral valve repairs/replacements may lead to phrenic nerve injury in the upper thoracic cavity. It is not yet known whether recently developed, minimally invasive methods of valve surgery will alter incidences of nerve injury. Phrenic nerve injury resulting from cardiac bypass surgery is most often due to either hypothermic damage from the use of heart cooling or direct injury during isolation and transfer of the internal mammary artery pedicle. Procedures performed to alleviate atrial fibrillation, such as the MAZE procedure and cardiac ablation, have both been reported to result in diaphragm paralysis. Patients with this etiology of phrenic nerve dysfunction have been evaluated, and their conditions are successfully reversed by the senior author (M.R.K) using techniques discussed below [3, 24].

Carcinoma of the lung requiring partial or complete resection may require intentional sacrifice of the phrenic nerve or, alternatively, result in diaphragmatic paralysis as an unintended consequence [25]. Patients undergoing lung transplantation may also suffer the effects of phrenic nerve injury due to the extensive restructuring of the thoracic cavity [26]. Trauma to the neck and chest may also lead to isolated phrenic nerve injuries or in combination with other neural structures, such as the brachial plexus or cranial nerves. A severe traction injury, when the shoulder is jolted forcefully in an opposite direction from the neck, puts substantial tension on the nerves coursing through the lower lateral cervical region [27]. Furthermore, there is often a resulting inflammatory process creating edema within the soft tissues of the neck. If this process does not resolve rather rapidly, the result is post-inflammatory fibrosis and adhesions.

Similar to other compression neuropathies in the upper and lower extremities, the phrenic nerve may easily be entrapped within the confines of its intra-fascial pathway, leading to conduction disturbances. A chronic, severe compression of any peripheral nerve may lead to segmental anoxia and axonal loss, a process that cannot be reversed spontaneously despite our inherent ability for nerve regeneration [28].

There may be certain patients who may be more susceptible to iatrogenic and traumatic phrenic nerve injury. The double–crush phenomenon, originally described by Upton and McKomas in 1973, describes the susceptibility of a second site of nerve injury along a neural pathway when one already exists [29]. For example, patients with cervical spine radiculopathy are more susceptible to carpal tunnel syndrome [30]. Similarly, patients with unilateral or bilateral phrenic nerve injuries resulting from trauma or surgery commonly present with degenerative cervical disease impacting the third through fifth cervical roots. We have also evaluated and treated numerous patients for diaphragmatic paralysis who have known, or subclinical cervical disease, but do not provide a clear traumatic or iatrogenic etiology. While the C-spine MRI often demonstrates foraminal narrowing or mild spinal stenosis in these patients, the only presenting clinical symptom is chronic dyspnea with exertion from a paralyzed diaphragm.

Idiopathic paralysis and viral neuritis (i.e., Parsonage-Turner syndrome) are other etiologies for diaphragmatic paralysis reported in the literature [31, 32]. Parsonage-Turner syndrome was originally described in 1948 as a condition that only affected the brachial plexus but is now used interchangeably, in addition to neuralgic amyotrophy, to describe isolated or combined insults to the brachial plexus and phrenic nerve(s) as a result of an inflammatory neuropathy. Although viral neuritis has very specific presenting sign and symptoms (e.g., fever, malaise, arm weakness, nausea/vomiting) that may be correctly diagnosed when exhibited in close temporal relation to the onset of dyspnea, idiopathic paralysis is truly a diagnosis of exclusion.

Central nervous system disorders may also cause diaphragmatic paralysis, often with bilateral muscle dysfunction, resulting in the need for oxygen supplementation or dependency on mechanical ventilation. Rates of ventilator dependence in high cervical spinal cord injury can reach as high as 71 % [33]. It is estimated that 20 % of these injuries will also result in Wallerian degeneration within the phrenic nerves as a result of the loss of anterior horn cells.

Amyotrophic lateral sclerosis (ALS) and other bulbospinal neuropathies lead to demyelination and axonal loss within the phrenic nerves. Diaphragmatic paralysis in ALS almost universally results in complete ventilator dependency in later stages of the disease and, ultimately, is one of the leading causes of mortality [34]. Other CNS conditions that are associated with diaphragmatic paralysis include: central hypoventilation syndrome, brainstem tumor, stroke, and cervical cord compression [35, 36].

Unilateral diaphragmatic paralysis will rarely result in a need for mechanical ventilation. However, in this clinical scenario, there is often a co-diagnosis of sleep-disordered breathing for which nocturnal positive pressure oxygen may be necessary [37]. Individuals with this disorder typically report dyspnea with exertion, orthopnea, and easy fatigability [38]. Quality of life assessments reveal disturbances on measures of physical functioning and indicate that traditional perceptions suggesting one can live unaffected by a paralyzed diaphragm have underestimated the significance of the problem [3]. Other presenting symptoms of unilateral paralysis include: gastroesophageal reflux for left-sided diaphragmatic paralysis, chest wall discomfort, abdominal bloating, chronic cough, breathlessness, depression,and postural asymmetries/pain.

On examination, the most obvious finding is diminished breath sounds at the base on the involved side when auscultating the lung fields. Occasionally, there will be a Tinel’s sign in the supraclavicular region of the neck, supporting the diagnosis of a phrenic neuropathy in the cervical region. Unless the diagnosis is due to a major insult to the cervical roots and/or brachial plexus, examination of the upper extremities will be unremarkable. Alternatively, traumatic injury to the brachial plexus has a reported association with diaphragmatic paralysis due to phrenic nerve injury in 10–20 % of cases [39].

Spirometry evaluation in patients with diaphragmatic paralysis will typically reveal a restrictive ventilatory deficit, though well-conditioned individuals with unilateral paralysis may often have the percent predicted values within a normal range for their age. Alternatively, there are other patients with diaphragmatic paralysis who develop secondary pulmonary disorders, such as asthma or sleep-disordered breathing, and demonstrate mixed restrictive-obstructive deficits on spirometry testing. When bilateral diaphragmatic dysfunction is present, for example, in patients with cervical stenosis, the results of spirometry testing will usually indicate much more severe restrictive ventilatory deficiencies.

Radiographic imaging using CT or MRI modalities is almost always appropriate to rule out organic pathology, such as degenerative cervical disease or tumor, and should be recommended based on the particulars of patient history. For example, individuals with a history of neck or back pain, especially with concomitant upper extremity weakness or paresthesias, require cervical MRI to look for cord compression. Alternatively, patients with diaphragmatic paralysis, whose history is significant for benign or malignant tumors of the thyroid, thymus, breast, or lung, require imaging to eliminate tumor pathology causing neural injury.

Electrodiagnostic evaluation is important for quantifying the extent of phrenic nerve injury and severity of muscle atrophy and is discussed more thoroughly in its own chapter. The phrenic nerve conduction study is often performed in conjunction with an upper extremity evaluation to assess conduction velocity and latency. Normative values have been described. In cases of unilateral paralysis, the normally functioning side is often used as the baseline for comparison [40]. Diaphragm electromyography is included in a comprehensive evaluation to assess motor amplitude deficits and assists in stratifying those patients that may be candidates for phrenic nerve reconstruction. The technical difficulty of this assessment supersedes that of most other electrodiagnostic testing due to the muscle not being readily accessible transcutaneously and the inherent risk of pneumothorax.

The pathological processes responsible for diaphragmatic paralysis typically involve one or more sites of insult to the neuromuscular pathway. This pathway originates in the brain and cervical spine, emerges through the cervical roots 3–5, extends down the phrenic nerve, and terminates beyond the neuromuscular junction in the diaphragm itself. Aside from the central nervous system disorders previously described, e.g., stroke, spinal cord injury, and ALS, direct injury to the cervical roots and/or phrenic nerve may occur in any number of ways.

Peripheral nerve injury can result from complete transection or alternatively can be the consequence of traction, (hypo-)thermal, compression, or pharmacological injury. Regardless of the manner in which the injury is sustained, in all non-transection processes, the end result is usually segmental nerve anoxia leading to demyelination and, ultimately, axonal loss. This description follows the nerve injury classification system of Seddon and Sunderland that has gained universal acceptance and forms the basis for current surgical treatment algorithms [41].

Continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP) are two treatment modalities for respiratory sleep disorders that effectively maintain airway patency and reduce or prevent apneic events. The reduction in inspiratory muscle force that occurs with diaphragmatic paralysis commonly leads to sleep abnormalities detectable on polysomnography. Positive airway pressure supplementation using either CPAP or BiPAP is a recommended treatment, although the ability to maintain higher pressures during inspiration and then provide a lower level during the expiratory phase would seem to favor BiPAP for an inspiratory muscle disorder. This may distinguish sleep disorders due to isolated diaphragmatic paralysis from obstructive sleep apnea patients with upper airway obstruction that could benefit from higher pressures during both phases of breathing. Khan et al. (2014) retrospectively reviewed 66 patients with unilateral or bilateral diaphragmatic paralysis, all of whom exhibited abnormal sleep studies consistent with sleep-disordered breathing [42]. Patients exhibited demonstrable improvements using positive airway pressure supplementation. Unsurprisingly, less than 40 % tolerated CPAP with the rest requiring BiPAP.

This section will focus on mechanics, method, timing, and results of diaphragmatic plication. The surgical restructuring of the diaphragm attempts to expand the thoracic volume and eliminate paradoxical motion in order to improve ventilation mechanics and pulmonary function and decrease symptomatic dyspnea. Diaphragmatic plication is indicated when symptomatic dyspnea occurs secondary to permanent phrenic nerve paralysis, and other methods of reinnervation or pacing are not available. Contraindications are relative and depend on the severity of the comorbidity and the significance of the dyspnea.

The vital role of the diaphragm in respiration is obvious, though its contribution varies based on position and sleep. The diaphragm is responsible for 56 % of the tidal volume in the awake, supine patient and up to 81 % during periods of deep sleep [43]. The aim of plication is to minimize the loss of thoracic space and prevent paradoxical motion. Plication decreases atelectasis of the involved lung and improves ventilation perfusion mismatch [44, 45]. Wright et al. demonstrated this diaphragmatic correction results in a significant increase in total lung capacity, vital capacity, expiratory reserve volume, functional residual capacity, and arterial PaO₂. Diaphragm plication has also been found to improve spirometry results when testing is performed in both sitting and supine positions [46].

The traditional approach is through standard posterolateral thoracotomy [46–49]. With the advent of modern, minimally invasive surgery, a video-assisted thoracic surgical (VATS) approach has slowly replaced open thoracotomies [49, 50]. Gazala and colleagues examined 126 studies on diaphragmatic paralysis, reviewing 13 representing the best evidence of repair, and compared VATS approach with thoracotomy. They found that a VATS approach achieves similar results based on pulmonary function tests (PFTs), dyspnea scores and functional assessment with shorter length of stay, lower complications rates, and mortality rate [51]. Several authors have supported a laparoscopic approach [52–54]. Both VATS and laparoscopic approaches are minimally invasive and offer unique benefits. There is no clear benefit of either, and the approach should be dictated by the surgeon’s preference and experience [54]. The technique involves a suture line running parallel to the thoracotomy that is repeated until appropriate tension is created [46, 47]. Others have described a series of horizontal mattress sutures with or without pledgets in varying directions [44, 50, 52, 54].