Diagnosis and management of acute neuromuscular weakness

Opening Vignette A 26-year-old woman was admitted to the general medical ward for progressive generalised weakness and breathlessness lasting over a week. She had no past medical history and was not on medications. Chest X-ray, electrocardiogram and lab test results were unremarkable. Shortly after hospitalisation, she experienced increasing dyspnoea and a sensation of choking when supine. Her vital signs were as follows: temperature 36.7°C, pulse rate 105 beats/min, blood pressure 105/65 mmHg and respiratory rate 25 breaths/min.IDENTIFYING NEUROMUSCULAR WEAKNESS Diagnosing non-specific complaints such as generalised weakness necessitates a myriad of potential diagnostic considerations. Non-neurological conditions, such as hypothyroidism, renal or liver impairment and cardiorespiratory disorders (e.g., heart failure and obstructive sleep apnoea), can present with generalised weakness. A systematic history and physical examination can differentiate these from neurological disorders, particularly neuromuscular causes. A general approach to physical examination for lower motor neuron conditions is shown in Figure 1. The following discussion focuses on specific acute presentations. Myasthenia gravis (MG) typically affects ocular muscles (causing diplopia and ptosis), as well as bulbar, neck, respiratory and proximal limb muscles.[1] Difficulty with specific tasks such as rising from a chair or lifting laundry overhead suggests proximal weakness, while difficulty in opening jars or tripping over one’s feet suggests distal weakness. Fatigability may be elicited when examining for ptosis and on testing proximal limb power. Ptosis improves with cold and can be tested by applying an ice pack over the eyelid. There is no sensory loss in MG. Weakness in Guillain–Barré syndrome (GBS) typically affects upper and lower limbs symmetrically, with diminished or absent reflexes and ascending sensory loss. Facial, bulbar and respiratory weakness can also complicate GBS.[2] Similar to MG, myopathies can present acutely with constant proximal weakness, without fatigability or sensory loss. Assessment of swallowing and breathing is important, as these functions may complicate various types of neuromuscular weakness.Figure 1: Chart shows the neuro-localisation for lower motor neuron features. aLook additionally for bulbar, facial, ocular and respiratory muscle weakness. FSHD: facioscapulohumeral muscular dystrophy, IBM: inclusion body myositisSubtypes of MG and GBS exhibit variations in the distribution of muscle weakness. For example, patients with anti-muscle specific kinase MG often present with early, prominent respiratory and bulbar dysfunction.[1] Likewise, pharyngeal–cervical–brachial variant of GBS presents with predominant upper limb and bulbar weakness.[2] Hence, bulbar and respiratory involvement without substantial limb weakness may be the incipient presentation of MG or GBS. Defining the time course of symptoms also aids in determining aetiology. Symptoms with subacute onset are consistent with inflammatory diseases such as MG or GBS [Table S1, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A257], while other neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) have a more chronic, progressive course [Table S2, Supplemental Digital Appendix at https://links.lww.com/SGMJ/A257]. In some instances, ALS presents with acute weakness during episodes of decompensation, while MG demonstrates fatigability, with symptoms often worsening at the end of the day. Infectious and drug exposures can be associated with the onset of neuromuscular diseases. Certain drugs may precipitate a flare of MG and should be documented in the drug history[3] [Table 1]. Patients with GBS should be asked for a history of preceding respiratory infection or diarrhoea.[4] Central nervous system (CNS) disorders [Table 2] may mimic features of neuromuscular disease,[4,5] such as bulbar or ocular dysfunction due to brainstem lesions, or quadriparesis due to cervical cord lesions. In patients with risk factors for CNS disorders (e.g. atherosclerotic risk factors for stroke), urgent CNS imaging may be indicated.Table 1: Commonly used drugs to avoid in myasthenia gravis.Table 2: . Other non-neuromuscular differentials for acute weakness.In patients with existing medical conditions, comorbid neuromuscular aetiologies contributing to weakness, and respiratory or swallowing difficulties should be considered, especially if the patient does not respond appropriately to treatment. For example, fever and breathlessness may be attributable to pneumonia, but the presence of disproportionately severe or persistent weakness or bulbar signs should prompt a workup for an undiagnosed neuromuscular condition. If an acute neuromuscular diagnosis is suspected in the ambulatory setting, further management may require urgent inpatient care or outpatient follow-up. Minor symptoms such as ptosis or diplopia from ocular MG can be safely managed with outpatient treatment; however, red flags [Table 3] such as rapidly worsening or significant weakness, bulbar or respiratory involvement and haemodynamic concerns[6,7] indicate an urgent need for inpatient monitoring.Table 3: Red flag features for acute neuromuscular disorders predicting severe disease.IDENTIFYING IMPENDING DECOMPENSATION FROM NEUROMUSCULAR WEAKNESS Life-threatening decompensation of neuromuscular conditions can occur due to bulbar, respiratory muscle or autonomic dysfunction. A targeted history and examination, supplemented by point-of-care tests, are needed to identify the following features that may herald deterioration, enabling timely interventions to stabilise the patient. Bulbar dysfunction Identification of bulbar dysfunction entails evaluation of swallowing, secretion management and speech.[8,9] Dysphagia due to neuromuscular weakness involves the oropharyngeal phase of swallowing, affecting both liquids and solids. It must be differentiated from painful swallowing (odynophagia) and the sensation of incomplete swallowing (globus sensation) caused by oesophageal lesions. Patients with bulbar weakness often complain of nasal regurgitation and coughing or choking when drinking due to weakness of the soft palate.[8,9] Excessive drooling occurs, as patients are unable to swallow saliva.[8] These are exacerbated in the recumbent position. Saliva pooling at the posterior pharynx causes choking when supine, and care must be taken before placing patients in the supine position. Weakness of muscles of mastication causes fatigue when chewing.[8,9] As such, patients with chronic, progressive neuromuscular diseases, such as ALS, may develop weight loss from inadequate caloric intake. Speech disturbances may be present due to weakness of facial muscles responsible for articulation or palatal weakness resulting in nasal speech. Standardised swallowing assessments are useful for detecting subtle bulbar dysfunction. Various validated protocols exist,[10] commonly requiring the patient to swallow around 90 mL of water, followed by assessment for coughing, choking or altered voice quality. Comprehensive swallowing assessments are conducted by speech therapists, often necessitating a videofluoroscopic study, although this is seldom offered in the acute setting. Management of bulbar dysfunction in the acute setting involves consideration of airway protection with pre-emptive intubation. Medications that exacerbate secretions—notably pyridostigmine for MG—should be reviewed. When swallowing is significantly impaired, increased secretions due to its cholinergic effects exacerbate swallowing difficulties; hence, pyridostigmine should be avoided until the patient’s condition has improved. In neuromuscular diseases with significant bulbar and respiratory dysfunction, aggressive chest physiotherapy with regular suctioning, cough assist machines and anticholinergic medications (e.g. glycopyrrolate/atropine) offer symptomatic relief and reduce chest infection. Respiratory muscle dysfunction In neuromuscular conditions, respiratory muscle dysfunction can lead to ventilatory failure. The muscles of respiration include the diaphragm, which is responsible for approximately 70% of ventilation at rest, and the accessory muscles of respiration—intercostals, scalene and sternocleidomastoids. Due to physiological reserves of respiration, respiratory failure sets in when respiratory muscle strength decreases to 25%–30% of normal.[11,12] The perception of dyspnoea is especially marked when respiratory dysfunction occurs acutely. Dyspnoea is exacerbated when supine (orthopnoea), as the diaphragm loses the aid of gravity when descending and abdominal contents restrict the descending diaphragm. When chronic respiratory insufficiency is partially compensated, carbon dioxide retention during sleep causes early morning headaches. Daytime somnolence suggests the possibility of sleep-disordered breathing, and these symptoms should be routinely assessed. Respiratory drive decreases during sleep and with sedating medications. Respiratory load increases with superimposed pneumonia, fluid overload or atelectasis, which decreases the efficiency of gas transfer and lung compliance.[12] These factors may precipitate decompensation, and should therefore be identified during history-taking and physical examination and addressed early. Subtle early signs of respiratory insufficiency may precede decompensation. This includes shallow breathing with increased respiratory rate. Physical examination includes assessing neck flexion, which uses the sternocleidomastoid and scalene muscles that mirror diaphragmatic weakness. The single-breath count test is a surrogate for vital capacity. It involves counting to 20 in a normal speaking voice (approximately two counts per second).[13] The inability to do so correlates with reduced vital capacity. Peripheral oxygen saturation measurement is not a reliable early indicator of neuromuscular respiratory failure due to compensatory mechanisms. Hypoxia is a late feature and suggests that decompensation is well established. Patients with marked respiratory failure appear overtly breathless, have difficulty speaking in full sentences and use accessory muscles of respiration. Paradoxical abdominal movements, observed when the patient is supine, suggest significant diaphragmatic weakness. This occurs as the weak diaphragm does not descend during inspiration, but is instead drawn up, pulling the abdominal contents inwards. Without prompt intervention, increasing hypercapnia can lead to confusion and obtundation. Intubation is then unavoidable when patients become comatose. Patients with established respiratory failure may present either with agitation and acute respiratory distress or as obtunded and hypoxic. Further history is limited, and physical examination is confounded by lack of cooperation. Priority is given to stabilising the patient, correcting hypoxia and securing the airway.[14] Further investigations may provide clues pointing to a neuromuscular cause. A normal chest radiograph excludes differentials such as pneumonia, pulmonary oedema, pleural effusion and pneumothorax. If hypoxaemia is easily corrected with low levels of supplemental oxygen, large pulmonary emboli causing ventilation–perfusion mismatch are less likely.[15] In decompensating patients, arterial blood gases typically show respiratory acidosis (low pH/high partial pressure of carbon dioxide), with or without hypoxaemia.[16] However, these findings occur late, as patients initially compensate by increasing the respiration rate to overcome low tidal volumes due to respiratory muscle weakness.[11,12] Hence, a normal-looking blood gas test result in the context of respiratory distress should not provide false reassurance. In chronic compensated respiratory acidosis (e.g. ALS), the blood pH may be normal with elevated arterial carbon dioxide level and bicarbonate concentration. Objective assessment of respiratory function includes the measurement of negative inspiratory force (NIF).[11,12,17] Using a hand-held device, respiratory therapists instruct the patient to form a tight lip seal around the mouthpiece and inspire after maximal expiration. The negative pressure, measured in cmH2O, is obtained, and readings across three attempts are recorded. The reliability of this measure depends on the patient’s ability to provide maximal effort and maintain a good seal. There is a range of normal values, with females generating less force. Normal NIF is more negative than −60 cmH2O. Markedly decreased readings (less negative than −30 cmH2O) or serially declining measurements are concerning for progressive respiratory muscle weakness. Compared to NIF, spirometry produces more objective and robust measurements. For chronic or progressive neuromuscular diseases, spirometry measurements guide decisions regarding non-invasive ventilation (NIV) or tracheostomy. Spirometry has limited utility in acutely deteriorating patients and is seldom conducted in acute settings. Nonetheless, in cases of neuromuscular weakness, spirometry shows a restrictive pattern (reduction in forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC], with preserved FEV1/FVC ratio) and reduced supine versus seated vital capacity by ≥10%. If bedside spirometry is available, measuring slow vital capacity (