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 myositis

Subtypes 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], while other neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) have a more chronic, progressive course [Table S2, Supplemental Digital Appendix]. 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.

Medication type	Examples	Comments
Antibiotics
Fluoroquinolones	Ciprofloxacin Levofloxacin	Fluoroquinolones, macrolides and aminoglycosides should be avoided if alternatives are available; penicillin, sulfa drugs and cephalosporins are considered safe alternatives
Macrolides	Telithromycina Azithromycin
Aminoglycosides	Gentamicina Neomycin
Antimalarials	Chloroquinea	NIL
Cardiovascular agents
Beta-blockers/ calcium channel blockers	Labetalol Metoprolol Verapamil	Can be used with caution
Antiarrhythmics	Procainamidea Quinidinea	Class 1a antiarrhythmics, in particular, should be avoided
Antirheumatic drugs	Penicillaminea	Can cause de novo myasthenia
	Hydroxychloroquinea	NIL
Neuromuscular blocking agents	Atracuriuma Succinylcholinea	Avoid neuromuscular blockade; if needed, use rocuronium with reversal agent and neuromuscular monitoring
Cancer treatment drugs
Immune checkpoint inhibitors	Nivolumab Pembrolizumab	Can cause de novo myasthenia
Other drugs	Magnesiuma	Exercise caution, especially in parenteral administration
	Corticosteroidsa	Avoid high dosesb
	Botulinum toxina	NIL

^aDrugs with a stronger association with precipitating myasthenia. ^bIf a high dose is needed, initiate treatment concurrently with intravenous immunoglobulins/plasmapheresis.

Table 2.

Other non-neuromuscular differentials for acute weakness.

Condition	Key features on history	Key features on examination
Central nervous system diseases
Stroke	• Acute-onset hemiparesis or limb weakness • Cardiovascular risk factor history such as hypertension, hyperlipidaemia, diabetes mellitus, smoking history	• Hemiparesis with or without cortical signs (anterior circulation infarcts) • Brainstem/cerebellar signs/decreased conscious level (posterior circulation infarcts) Note: Brainstem lesions can result in dysphagia, respiratory depression, complex ophthalmoplegia or ptosis and mimic MG
Multiple sclerosis/other neuroinflammatory diseases	• History of previous episodes of weakness or visual loss with variable extent of recovery • History of other systemic features of autoimmunity	• Spasticity and upgoing plantar response in chronically affected limbs; acutely weak limb/limbs may not have clear upper motor neuron signs until later • Paraparesis with a sensory level and sphincter dysfunction may be present in acute myelitis • Relative afferent pupil defect in the eye affected by optic neuritis
Spinal cord lesion (acute)	• May present with flaccid paraparesis, mimicking GBS • May have a history of back pain	Presence of sphincter disturbance (lax anal tone), flaccid bilateral lower limb weakness with a spinal sensory level
Hemiplegic migraine	• History of migraine headache associated with onset of weakness • Onset with other migraine aura features such as visual symptoms, speech deficits, sensory symptoms (usually paraesthesia rather than numbness) • May have family history of hemiplegic migraine	Hemiparesis; may also have other variable signs (e.g. speech deficits and sensory loss)
Post-ictal (Todd’s) paralysis	History of epilepsy or a witnessed seizure episode	• Post-ictal drowsiness • Other neurological features (speech deficits, gaze preference) dependent on epileptic focus
Rhombencephalitis	Fever, headache and/or seizures with neurological deficits localising to the brainstem	Confused patient with the presence of neurological deficits localising to the brainstem (e.g. cranial nerve deficits with crossed hemiparesis), with or without meningism
Non-neurological causes
Hypoglycaemia	• Background history of diabetes mellitus with insulin–meal mismatch or oral hypoglycaemic agents–meal mismatch • Associated with non-specific symptoms such as fatigue, giddiness and sweating	Weakness can be generalised or focal Note: Easily diagnosed and reversible by a bedside point-of-care blood glucose test
Sepsis	Fever, symptoms of infective focus (e.g. cough, abdominal pain, dysuria)	• Fever with localising signs (e.g. lung crepitations, suprapubic/ renal angle tenderness, localised erythema and tenderness) • Hypotension
Adrenal insufficiency	• Generalised weakness with other symptoms such as nausea, vomiting, abdominal pain, fatigue, lethargy and/or altered mental status • May have a history of exogenous steroid intake with sudden withdrawal	• Generalised weakness and hypotension • Can be associated with abdominal tenderness, hyperpigmentation and/or fever
Electrolyte disorders	History of conditions or medications (e.g. diuretics) that may be associated with electrolyte derangements	Non-focal weakness; electrocardiographic changes (e.g. ‘U’ waves in hypokalaemia)
Other organ system involvement	• Renal failure—decreased urine output, history of predisposing factors for renal disease • Liver failure—alcohol intake, hepatitis history/exposure • Heart failure/ACS: breathlessness, chest discomfort (some patients may present without typical features of ACS)	• Renal failure: oedema, hypertension, pruritus, anorexia • Liver failure: jaundice, pruritus, anorexia, ascites • Heart failure: oedema, pulmonary congestion, elevated jugular venous pressure

ACS: acute coronary syndrome, GBS: Guillain–Barré syndrome, MG: myasthenia gravis

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.

Variable	Features on history	Features on examination	Bedside testing	Definitive testing
Overall weakness	Rapid worsening: development of significant weakness within days	Significant limb or neck weakness, e.g. limbs that are unable to overcome gravity	Inability to walk 10 m independently	–
Bulbar	Frequent choking and nasal regurgitation, excessive drooling, change in speech quality	• Increased sensation of choking when supine • Weak cough • Speech with nasal quality	Bedside swallowing test—swallowing 90 mL of water causes coughing, choking or ‘wet’ sounding voice	Formal speech therapist review
Respiratory	Dyspnoea at rest or on minimal exertion, orthopnoea	• Shallow and rapid breaths • Weak neck flexion/extension • Paradoxical abdominal movements • Altered mental state	• Single breath count test—inability to count to 20 in a single breath after maximum inspiration (~ 2 s per count) • Negative inspiratory force of <−30 cmH2O or serial worsening	Spirometry: • Slow vital capacity of ≤20 mL/kg • Peak cough flow assessment: ≥160 L/min indicates effective cough; <270 L/min is linked to secretion retention/increased infection risk
Autonomic	Headaches, giddiness, palpitations, fever	Marked fluctuations or extremes in heart rate or blood pressure	Arrhythmias on electrocardiogram Postural blood pressure testing	• Continuous cardiac monitoring • Invasive blood pressure monitoring via arterial line

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 (<20 mL/kg) and peak cough flow (<160 L/min) can predict the need for invasive ventilation.[11,12]

Autonomic dysfunction

The autonomic nervous system regulates involuntary bodily functions such as heart rate, blood pressure, respiration, sweating, digestion and urination. Sympathetic and parasympathetic fibres or peripheral neurotransmitter function may be affected, manifesting as cardiac, vasomotor, sudomotor, gastrointestinal or genitourinary dysfunction.

In approximately 40% of patients, GBS is associated with dysautonomia, purportedly due to disruption of afferent fibres from arterial baroreceptors and efferent fibres that mediate various autonomic functions. In GBS, dysautonomia generally manifests during the plateau phase before motor improvement. It is associated with severe manifestations of GBS (quadriparesis, bulbar/respiratory failure) and increased mortality.[18]

Cardiovascular autonomic dysfunction can be life threatening. Managing labile blood pressure fluctuations requires close monitoring in high-dependency or intensive care units (ICUs) and treatment with vasopressor or antihypertensive infusions. Complications include posterior reversible encephalopathy syndrome,[18] which manifests as hypertensive urgency, encephalopathy and seizures. Tachyarrhythmias, such as ventricular tachycardia and atrial fibrillation, are more common than bradyarrhythmia in GBS. Patients suspected of arrhythmias should have continuous cardiac monitoring for life-threatening events, which may require emergent interventions. Procedures such as tracheal suctioning can induce arrhythmias and should be performed with caution. Intubation should be performed by proficient operators, minimising the risk of prolonged tracheal stimulation that may provoke arrhythmias or cardiac arrest.[19]

Gastrointestinal ileus and urinary retention, which are among the most common autonomic features in GBS,[18] are managed by adequate bowel disimpaction and urinary catheterisation, respectively. Medications that slow gastrointestinal transit or cause urinary retention, such as opiates or anticholinergics, should be avoided.

Thermoregulatory dysfunction is managed with antipyretics or warming, after excluding infectious causes. Sudomotor dysfunction and pupillary dysfunction are unlikely to require direct intervention, but they signal a need to monitor for other autonomic symptoms. Apart from GBS, other neuromuscular conditions may feature dysautonomia. Although autonomic dysfunction is rare in MG,[20] it is well recognised in Lambert–Eaton myasthenic syndrome, where it manifests as dry mouth or erectile dysfunction.[21]

RESPIRATORY SUPPORT AND INTUBATION CONSIDERATIONS

Having identified patients at risk of decompensation, management invariably involves consideration of either NIV or endotracheal intubation. In GBS, intubation is preferred over NIV as patients needing ventilatory support are unlikely to improve for days to weeks. Dysautonomia increases the risk of unplanned emergent endotracheal intubation.[19,22] Elective intubation should be considered for patients who show a deteriorating trajectory, especially when bulbar, respiratory or autonomic failure is identified.

In contrast, patients with MG without bulbar dysfunction may benefit from a trial of NIV, with the aim of avoiding intubation. Appropriate use of NIV shortens ICU stay and hospitalisation, and is associated with lower rates of atelectasis and pneumonia.[11,22] However, if patients become hypercapnic or develop difficulty managing secretions, intubation should be performed.

Depolarising neuromuscular blocking agents (NMBAs) such as succinylcholine should be avoided, when possible, in muscular dystrophies and conditions with motor neuron loss, as acetylcholine receptors (AChr) are upregulated at the muscle end plate. When succinylcholine activates upregulated AChR, muscle fibre depolarisation results in excess potassium efflux, producing life-threatening hyperkalaemia.[23] In MG, destruction and blockade of AChR by antibodies causes resistance to depolarising NMBAs and sensitivity to non-depolarising NMBAs.[24] Plasma exchange treatment targeting pathological AChR antibodies inadvertently removes proteins that degrade paralytic agents, further prolonging neuromuscular blockade. If NMBAs are clinically necessary, rocuronium or vecuronium is preferred, with intraoperative neuromuscular monitoring and subsequent reversal with sugammadex.[24]

ESTABLISHING A DEFINITIVE DIAGNOSIS

Obtaining an immediate definitive diagnosis for a patient in crisis is often challenging and should not take precedence over managing deteriorating respiratory and bulbar weakness. However, once the patient is stabilised, further investigations to confirm MG, GBS or other neuromuscular disorders should be conducted, thereby allowing for disease-specific treatment to be initiated without delay. These tests include creatinine kinase (elevated in various myopathies), AChR antibody/anti-MuSK antibody (for MG) and anti-ganglioside antibodies (for GBS).

A 3 Hz repetitive nerve stimulation test demonstrating an abnormal decremental response can aid in confirming MG. Nerve conduction studies may be normal in early stages of GBS, as features such as axonal loss, conduction block or velocity slowing typically become more apparent a few weeks after symptom onset. Hence, GBS is diagnosed early based on clinical presentation, using early electrodiagnostic studies to exclude other causes of acute neuromuscular weakness. Subsequently, electrodiagnostic studies may help in prognostication by assessing the extent of axonal damage. In myopathic processes, electromyography may show typical features of early motor unit recruitment, as well as irritability suggestive of muscle fibre necrosis. Cerebrospinal fluid analysis is frequently needed to exclude infective or malignant processes affecting the nerve roots or leptomeninges. Raised cerebrospinal fluid protein without corresponding pleocytosis is consistent with GBS.

CONCLUSION

An overall approach to the diagnosis and management of neuromuscular weakness is summarised in Figure 2. In general, MG or GBS crisis is treated with immunomodulatory therapy.[1,2] This includes intravenous immunoglobulins or plasmapheresis for both conditions, and steroids for MG. Management requires specialist care and close monitoring in an inpatient setting.

Figure 2.

Chart shows the approach to diagnosis and management of neuromuscular weakness.

TAKE HOME MESSAGES

1. Conditions such as GBS and MG can lead to respiratory, bulbar and/or autonomic complications.

2. Bedside testing should include assessment of neck flexion, accessory muscle use, speech, swallowing and NIF. Close monitoring is needed to look for blood pressure fluctuations and life-threatening arrhythmias.

3. Arterial blood gases can remain normal until a late stage of respiratory failure.

4. In patients suspected to have neuromuscular causes of weakness, NMBAs should be avoided if possible.

5. Non-invasive ventilation should be used selectively in the management of GBS. In the presence of bulbar dysfunction and respiratory failure, intubation is required.

Closing Vignette

You assessed the patient to be in respiratory distress as she was speaking only in short phrases and using accessory muscles of respiration. She had a nasal speech and was unable to swallow her secretions without coughing. Her NIF was –25 cmH₂O. You decided to intubate her semi-electively, avoiding NMBAs. Electrophysiological studies showed abnormal decremental response suggesting a neuromuscular junction transmission defect, and blood tests returned positive for antibodies against AChR. She received plasma exchange during her ICU stay and was successfully extubated a week later.

Conflicts of interest

See KC is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article.

Supplemental digital content

Appendix at http://links.lww.com/SGMJ/A257

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 27 February 2026

Question: Answer True or False
1. A good history and physical examination are important to differentiate true neuromuscular weakness from other systemic causes of generalised weakness.
2. Fatigable ptosis and fatigable proximal limb weakness are suggestive of a neuromuscular junction disorder, such as myasthenia gravis (MG).
3. A prior history of upper respiratory tract infection in a patient with symmetrical weakness and absent reflexes suggests a diagnosis of Guillain–Barré syndrome (GBS).
4. Fluoroquinolones can be used safely in a patient with MG.
5. Painful swallowing and the sensation of incomplete swallowing are suggestive of oropharyngeal dysphagia associated with neuromuscular weakness.
6. Weakness of neck flexion and the use of accessory muscles of respiration are suggestive of respiratory compromise.
7. The presence of paradoxical abdominal movements, observed when the patient is in a supine position, suggests severe diaphragmatic weakness.
8. A normal arterial blood gas test result in a patient with neuromuscular weakness is reassuring, indicating that the patient is not at risk of respiratory failure.
9. The measurement of negative inspiratory force can be done as an objective assessment of respiratory function.
10. Arterial blood gases in decompensating patients typically indicate respiratory acidosis.
11. Formal spirometry testing is always required to diagnose respiratory failure in a patient acutely deteriorating from MG.
12. Spirometry shows an obstructive pattern in patients with neuromuscular weakness.
13. A negative inspiratory force of−30 cmH2O is concerning for respiratory muscle weakness.
14. Dysautonomia in patients with GBS is associated with more severe forms of the condition and a higher mortality.
15. If a patient with GBS has arrhythmias, the patient should be monitored in the high-dependency unit with continuous cardiac monitoring.
16. Urinary retention and gastrointestinal ileus can occur in patients with GBS.
17. Patients with GBS should be electively intubated early when there are early signs of bulbar or respiratory failure, or if the clinical trajectory is declining.
18. Non-invasive ventilation can be used selectively in certain patients with MG crisis.
19. In a patient with MG who has hypercapnia or difficulties with secretion management, non-invasive ventilation should be selected over intubation.
20. Depolarising neuromuscular blocking agents (e.g. succinylcholine) should be avoided during intubation for patients with suspected neuromuscular disorders.

APPENDIX

Table S1.

Examples of acute neuromuscular causes of weakness

Condition	Key Features on history	Key Features on examination
Neuromuscular junction disorders
Myasthenia Gravis	Fluctuating weakness, that is more marked towards the end of the day. Weakness improves with rest and cold.	Fatigable muscle weakness Fatigable ptosis and diplopia Reflexes may be preserved or slightly reduced No sensory loss
Lambert-Eaton myasthenic syndrome (LEMS)	Progressive, proximal weakness, +/- autonomic dysfunction (e.g. dry mouth) Association with small cell lung cancer (paraneoplastic LEMS)	Post-exercise improvement of muscle strength and recovery of lost deep tendon reflexes with vigorous, brief muscle activation
Organophosphate poisoning	Appropriate history suggesting exposure to organophosphates (pesticides)	Features of cholinergic excess - salivation, lacrimation, bronchospasm, diarrhoea, bradycardia, miosis Subsequently followed by proximal weakness, areflexia and respiratory insufficiency
Botulism	Exposures include contaminated canned food, injection drug use	Cranial neuropathies with symmetric descending weakness and respiratory insufficiency
Neuropathies
Guillain Barre Syndrome	Acute progressive, symmetric and classically ascending muscle weakness (involving limbs, and / or facial and bulbar muscles) with paraesthesia occurring within a few days Can be preceded by antecedent event e.g. infection (upper respiratory tract infection, gastroenteritis), vaccination	Flaccid proximal and distal limb weakness, with possible involvement of facial (lower motor neuron cranial nerve VII pattern) and bulbar muscles and hyporeflexia / areflexia Autonomic dysfunction (e.g. labile blood pressure and heart rate) Presence of sensory symptoms and signs
Miller Fisher syndrome (GBS- variant)	Acute onset of diplopia, unsteady gait following an antecedent event (e.g. infection, vaccination)	Triad of ophthalmoplegia, areflexia and ataxia
Vasculitic neuropathies	Usually painful, stepwise and asymmetric development of weakness and/or numbness May be associated with other features of systemic vasculitis	Asymmetric flaccid weakness and/or numbness in a ’mononeuropathy multiplex’ pattern
Anterior horn cell disorders
Poliomyelitis	Acute onset pain and weakness following a febrile illness / meningitis	Weakness without sensory loss. May affect one or more limbs, and may result in quadriplegia and respiratory failure
Muscle Disorders
Acute myopathies	Subacutely progressive, proximal weakness Associated with cutaneous changes e.g. in Dermatomyositis Drug related - e.g. Statins, Colchicine Metabolic and mitochondrial myopathies can have episodes of acute decompensation (e.g. exercise induced rhabdomyolysis) Rarer causes: Sporadic late onset nemaline myopathy (consider if age > 40, monoclonal gammopathy, respiratory compromise)	Proximal weakness, usually symmetric No objective sensory loss Photosensitive rash and cutaneous changes are usually present in Dermatomyositis, interstitial lung disease may also occur in MDA5 myositis Muscle soreness
Periodic Paralysis	Usually young male patient, with history of previously self- resolving episodes Weakness precipitated by exercise / carbohydrate rich meal May be associated with hyperthyroidism, hyper or hypokalemia	Usually symmetric weakness / quadriparesis without sensory loss Respiratory and bulbar function usually not involved Spontaneous recovery
Critical Illness myopathy/neuropathy/ neuromyopathy	Frequent complication for prolonged admission to intensive care for critically ill patients, complicating recovery Essential to exclude other causes of weakness and failure to wean ventilatory support before ascribing to critical illness neuromyopathy	Diffuse weakness involving facial, bulbar, and respiratory muscles, but commonly sparing extraocular movements. In critical illness neuropathy, there may be sensory involvement, areflexia and muscle wasting.

Table S2.

Examples of chronic neuromuscular causes of weakness

Condition	Key Features on history	Key Features on examination
Polyradiculoneuropathies
Chronic demyelinating polyneuropathy	Chronic, progressive weakness and sensory loss worsening over months typically affecting both proximal and distal limbs	Flaccid proximal and distal limb weakness, with hyporeflexia / areflexia
Polyneuropathies
Diabetic neuropathy	Sensory predominant symptoms manifesting with a glove-and- stocking pattern over years. There is usually concomitant diabetic retinopathy and diabetic nephropathy.	Predominantly length-dependent sensory loss with hyporeflexia
Anterior horn cell disorders
Amyotrophic lateral sclerosis	Pure motor symptoms which may start with isolated limb weakness, bulbar weakness, or respiratory insufficiency, and gradually progress to involve adjacent body regions over a duration of weeks to months.	Fasciculations (tongue, limbs), weakness without sensory loss, with mixed upper and lower motor neuron features
Muscle Disorders
Heritable metabolic disease (e.g. alpha glucosidase deficiency / pompe disease, acid maltase deficiency)	Subtle difficulties in childhood with athletic performance, exercise induced myalgia or cramping. These disorders may present for the first time in adulthood with respiratory insufficiency or weakness.	Proximal weakness, usually symmetric with no objective sensory loss

Funding Statement

Nil.