Diaphragmatic weakness; Phrenic nerve palsy; Respiratory muscle weakness
Definition and Characteristics
Inspiratory muscle weakness that results from any disease process affecting the diaphragm or the neural structures that innervate the diaphragm. Disorders of the lower motor neuron (Phrenic nerve, neuromuscular junction or muscle) are most common, but diaphragmatic paralysis may also result from injury to upper motor neuron pathways.
There are no epidemiological studies, in part because diaphragmatic paralysis is not a unitary disease entity, but rather a clinical syndrome with many diverse causes.
Diaphragmatic paralysis may be associated with a number of different genetic disorders including the hereditary motor and sensory neuropathies (Charcot-Marie Tooth disease)  and the metabolic myopathies, notably acid maltase deficiency [2,3]. Although diaphragmatic weakness may be found in several of the autosomal dominant inherited neuropathies, it is most characteristic of CMT-2C (linkage to chromosome 12q23-q24; unknown gene product) . Acid maltase deficiency (autosomal recessive) is due to mutations in the gene coding for the acid α-1,4-glucosidase protein (chromosome 17q23).
Molecular and Systemic Pathophysiology
Pathophysiology varies depending on etiology. Phrenic neuropathy may result from direct trauma to the phrenic nerve during cardiothoracic surgery, from anterior horn cell dysfunction (amyotrophic lateral sclerosis), from immune-mediated inflammation as part of an acute brachial neuritis (Parsonage-Turner syndrome), from endoneurial ischemia as part of a mononeuritis multiplex secondary to large artery vasculitis (Takayasu’s or giant cell arteritis), as part of inflammatory demyelination (as seen in the Guillain-Barre syndrome) or from dysmyelination secondary to an inherited disorder to myelin proteins (Charcot-Marie Tooth disease). Diaphragmatic weakness may also result from impaired neuromuscular transmission (myasthenia gravis, Lambert-Eaton myasthenic syndrome, botulism) and from primary disorders of muscle (inflammatory and metabolic myopathies).
Shortness of breath when supine (orthopnea) is the most common symptom of diaphragmatic paralysis. The characteristic finding on examination is paradoxical inward movement of the abdomen with inspiration, most readily visible in the supine position [4,5]. Direct measurement of transdiaphragmatic pressure (Pdi) is the most accurate method of assessing diaphragmatic function, but requires the placement of balloon catheters in the esophagus and stomach . The clinical utility of Pdi measurements is limited, therefore, by the invasive nature of the test. Elevation of a hemidiaphgram may be apparent on chest x-ray and fluroscopy in the posteroanterior and lateral positions may show absent or paradoxical movement of the diaphragm in response to a sniff maneuver . These imaging techniques are most useful in the evaluation of hemi-diaphragmatic paralysis. Ultrasound may be used to measure diaphragmatic thickness and the change in thickness (representing diaphragmatic shortening with contraction) with inspiration. Atrophy and lack of shortening (i.e., little change in thickness) with inspiration are signs of diaphragmatic paralysis [6,7]. Reduced forced vital capacity (FVC) is the characteristic finding on lung function testing, especially when supine FVC is <75% of erect FVC . Reductions in maximum inspiratory and expiratory pressures (MIPs and MEPs) are also characteristic of diaphragmatic weakness, but like the FVC the diagnostic utility of these static lung volumes is limited by the effort-dependence of these measurements. Several electrophysiological techniques have been used to assess diaphragmatic function including phrenic nerve conduction studies (in response to either electrical or magnetic stimulation) and diaphragmatic electromyography (EMG) . The technical difficulty of these electrophysiological tests limits their diagnostic utility.
Symptomatic treatment takes the form of mechanical ventilation when diaphragmatic weakness is sufficiently severe to result in respiratory failure. Specific treatment depends on the underlying cause. Diaphragmatic paralysis due to the Guillain-Barre Syndrome is treated with either intravenous immunoglobulin (IVIg)  or plasma exchange (PE) . Myasthenia gravis is also treated with IVIg  or PE , often in combination with steroids  and cholinesterase inhibitors.