Pneumonia and hypercapnic respiratory failure

Discussion

Neuromuscular respiratory failure (NRF) is the most serious complication of neuromuscular disorders. Prompt recognition of NRF and determination of the cause are essential. When the cause of NRF cannot be identified and the diagnosis on discharge remains unknown, outcomes are usually poor with high rates of severe disability. Among 85 adults admitted to the ICU with acute NRF over a 6-year period, the most frequent causes were myasthenia gravis (myasthenic crisis), Guillain–Barré syndrome, myopathies and amyotrophic lateral sclerosis (27, 12, 12 and 12 patients, respectively) [1]. Respiratory failure is rarely the presenting feature of a neuromuscular disorder. More often, it results from disease progression or exacerbation by a superimposed respiratory disease when the compensatory mechanisms are overwhelmed [2].

Myasthenia gravis, the most common disorder of neuromuscular transmission, is an autoimmune disease in which autoantibodies bind to AChR or other functionally related molecules and impair transmission in the postsynaptic membrane at the neuromuscular junction [3]. Most patients (80–90%) have antibodies AChR; approximately half of those without AChR antibodies have antibodies directed to MuSK. Patients without detectable AChR or MuSK antibodies are referred to as having seronegative myasthenia gravis [4].

The annual incidence of myasthenia gravis is approximately 8–10 cases per million and the prevalence is about 150–250 per million [5].

The main clinical feature is fluctuating weakness and fatigability of the skeletal muscles, which is the sole manifestation of the disease. Weakness can be generalised or confined to ocular muscles, resulting in ptosis and/or diplopia, which is the classic initial presentation of myasthenia gravis. About half of the patients presenting with ocular myasthenia gravis will develop generalised disease within 2 years. Other frequently involved muscle groups include bulbar, facial, neck and limb muscles with predominantly proximal weakness. Respiratory muscles can also be involved, producing the most serious symptoms of myasthenia gravis. It is usually seen with advanced disease and respiratory failure is rarely the initial presentation of myasthenia gravis [3, 6].

Diagnosis is based on clinical and serological testing, as well as electrophysiological tests. The presence of AChR or MuSK antibodies on serological assays provides the laboratory confirmation of myasthenia gravis [6]. The most commonly used electrophysiological test, due to its wide availability, is RNS, in which a motor nerve of a muscle is stimulated and the compound muscle action potential (CMAP) amplitude of that muscle is recorded. In myasthenia gravis, there is a progressive decline in the CMAP amplitude with the first four to five stimuli (a decremental response). RNS is considered positive if the decrement is >10%. SFEMG, a more technically demanding and less widely available test than RNS, is the most sensitive clinical test for myasthenia gravis. In SFEMG, the action potentials of two muscle fibres innervated by the same axon are recorded. The variability in time of the second action potential relative to the first is called “jitter”. Disorders with impaired transmission at the neuromuscular junction, such as myasthenia gravis, will produce increased jitter [7].

The four main types of treatment for ­myasthenia gravis include symptomatic, chronic immunosuppressive and rapid immunomodulatory therapy, and thymectomy. The initial therapy for most patients with mild to moderate symptoms is with an acetyl­cholinesterase inhibitor. Pyridostigmine is most commonly used. Neostigmine and ambenonium chloride are available, but are less effective than ­pyridostigmine. If full clinical remission is not achieved with symptomatic therapy, immunosuppressive therapy with prednisone or a combination with azathioprine is added. ­Mycophenolate mofetil is an alternative option, with methotrexate, ­cyclosporine and tacrolimus being alternative secondary immunosuppressive drugs [3, 4, 8]. ­Rituximab might be a potential treatment option for myasthenia gravis, with small case series showing substantial improvement in patients with insufficient response to prednisolone and ­azathioprine [9]. In myasthenia gravis patients with thymoma, thymectomy should be performed, as it is associated with better outcomes [3]. In patients with severe worsening of muscle weakness involving the respiratory muscles and causing NRF, also termed myasthenic crisis, rapid therapy with plasma exchange or intravenous immune globulin is used, both having similar efficacy [10].

Any time there are difficulties weaning patients from mechanical ventilation due to neuromuscular pathology, critical illness polyneuropathy (CIP) must be considered. CIP is a symmetric distal axonal sensory–motor polyneuropathy affecting limb and respiratory muscles. It is a relatively common cause of neuromuscular weakness in critically ill patients in the ICU, along with critical illness myopathy. CIP is usually a consequence of severe sepsis and multiorgan failure or treatments required in the intensive care setting. It is usually discovered with difficulty in weaning a patient from mechanical ventilation that cannot be explained by pulmonary or cardiac pathology [11].

Contrary to myasthenia gravis, which is a classic autoantibody-mediated autoimmune disease, the pathogenesis of CIP is less well understood. Impaired microcirculation and mitochondrial function, and increased secretion of stress hormones, cytokines and nitric oxide during critical illness are probable mechanisms. Excitable tissues, such as peripheral nerves and muscle, require energy to maintain function, and are probably damaged by the combination of ischaemic and cytopathic hypoxia, resulting in axon degeneration [11, 12]. Reduction of nerve excitability by inactivation of sodium channels may also play a role [13].

The main clinical features of CIP are flaccid and symmetrical weakness that can range from moderate paresis with reduced deep-tendon reflexes to severe quadriplegia with no deep-tendon reflexes, muscle wasting and hypotonia with or without involvement of respiratory muscles. The cranial nerves are usually spared. Distal and proximal muscles are usually equally affected. Sensory impairment can also occur, with distal loss of pain, temperature and vibration senses [12, 14].

Findings on electrophysiological tests are consistent with primary axonal degeneration and show a reduction in CMAP and sensory nerve action potential amplitudes. Contrary to myasthenia gravis, there is no progressive decline in CMAP amplitude with repetitive stimulation (no decremental response) [12].

Whereas there are multiple treatment options in myasthenia gravis, no specific treatment has yet been effective in the case of CIP. Treatment is mainly supportive. Aggressive treatment of sepsis and early rehabilitation play an important role [14].

Here, we present a case report of a patient diagnosed with myasthenia gravis, presenting with bulbar dysfunction, bilateral vocal cord paresis and hypercapnic respiratory failure, which is rarely the initial presentation of the disease. There are a few reports of bilateral vocal cord paresis and respiratory failure as an initial presentation of myasthenia gravis [15, 16]. In some cases of persistent bilateral vocal cord paresis due to myasthenia gravis, it is not possible to evacuate the tracheostomy tube and long-term (permanent) tracheostomy may be needed despite adequate treatment, as was the case with this patient [17].