Weakness

Introduction

Weakness is a subjective term that patients use to describe feelings of malaise, fatigue or frailty experienced as the result of myriad medical and psychological conditions. The Oxford Dictionary defines ‘weak’ as ‘lacking the power to perform physically demanding tasks; having little physical strength or energy’.

In this chapter, we mainly consider the assessment and management of patients presenting with acute-onset, generalized, symmetrical or rapidly progressive weakness, primarily in the context of neuromuscular disease. Conditions that cause focal or unilateral weakness are not discussed in any great depth, nor is weakness related to non-neuromuscular causes. It should, however, be remembered that the latter group affects the majority of patients presenting to the emergency department (ED) complaining of weakness.

Aetiology and pathogenesis

Weakness is essentially due to a neuromuscular problem or something else. The primary goal in ED is to determine if there is actual quantitative loss of muscle strength indicative of a neuromuscular cause or whether the weakness results from a non-neuromuscular cause. The latter cases are often the result of multiple system disorders—for example, endocrine, cardiac and metabolic factors.

Neuromuscular weakness may reflect deficits anywhere along the neural pathway from the cerebral cortex to the myocyte. This pathway includes the pyramidal system as upper motor neurons (UMNs) synapse with lower motor neurons (LMNs) of the anterior spinal cord. LMN axons then descend through the anterior spinal cord to exit and synapse with myocytes. At the neuromuscular junction, LMNs release the presynaptic neurotransmitter acetylcholine (Ach) into the synaptic cleft, and post-synaptic Ach receptors then trigger depolarization of the motor end plate and contraction of the muscle cell. Pathology at any level of this neural pathway will result in weakness. An intact myelin nerve sheath, functioning calcium and sodium channels and the presence of acetylcholinesterase to limit the response are all necessary for normal neuromuscular function.

Specific signs—such as altered deep tendon reflexes (DTRs) and tone, muscle atrophy, fasciculations and distribution of weakness—aid in localizing the site of the neuromuscular pathology ( Table 8.7.1 ).

Non-neuromuscular causes of weakness are myriad and generally reflect a combination of age, general physical and mental health factors and specific systemic disorders that co-exist to result in a general feeling of weakness or malaise ( Table 8.7.2 ).

Pathology

Diverse pathological processes may underlie neuromuscular weakness. Of these, genetic, autoimmune and toxic causes predominate in the ED ( Table 8.7.3 ). Patients with congenital genetic syndromes, such as muscular dystrophies or mitochondrial disorders, are rarely seen in the ED unless they are suffering from acute respiratory decompensation in the context of an acute reversible precipitant, such as pneumonia. Management of these cases will be guided by consideration of the clinical context, the stage of disease and disability and any advance care directives from the patient or their advocates.

In industrialized countries such as Australia, Guillain-Barré syndrome (GBS) is the most common cause of acute-onset neuromuscular weakness. GBS variants, multiple sclerosis (MS) and myasthenia gravis (MG) are other autoimmune disorders that precipitate ED presentations, either as de novo diagnoses or in the context of acute exacerbations. Toxic triggers—such as organophosphates, tetanus, botulism and envenomations—are relatively rare but can be fatal if not recognized and treated aggressively.

Other pathologies, such as paraneoplastic syndromes (Eaton-Lambert syndrome [ELS]) and electrolyte disturbances (e.g. hypokalaemic periodic paralysis), should be considered if the clinical context is suggestive. Poliomyelitis is an example of an infectious disease that was previously a major cause of acute-onset weakness. It has been eradicated in the Western world and is well on the way to eradication in the developing world. Post-polio syndrome is a rare late complication seen in ED.

Differential diagnosis

The differential diagnosis of weakness in the ED is very broad and it may not be possible to arrive at a definitive diagnosis during one ED visit. Recognition of neuromuscular disorders that have the potential to deteriorate rapidly and require intensive supportive care with assisted ventilation is the most crucial element of ED diagnosis. In particular, GBS, MS exacerbations, myasthenic crises and intoxications, such as botulism, must be recognized early.

Clinical features

The diagnosis of neuromuscular disease is dependent on history, examination and specific investigation findings. A starting point for diagnosis should include a thorough history, noting in particular the following:

• Known underlying neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), muscular dystrophy, MS or MG

• Pre-existing medical conditions, such as malignancy suggesting a paraneoplastic syndrome, monoclonal gammopathy associated with chronic inflammatory polymyopathy (CIDP) or HIV infection/post-transplant immunosuppressive states associated with CIDP, polyradiculopathy or HIV myopathy

• Recent infections (diarrhoeal, viral) or major surgery associated with GBS.

• Recent exposures/ingestions suggestive of intoxications, for example botulism, organophosphate, ciguatera toxin.

Clinical findings generally reflect the site of the lesion within the motor unit (see Table 8.7.1 ).

Clinical investigations

Given the broad differential diagnosis possible for weakness, a broad screen of laboratory parameters—including full blood count (for anaemia or inflammation), electrolytes and renal function, liver function, thyroid function plus muscle creatine kinase (CK), inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) as indicated—should be performed. An ECG should be obtained urgently if an electrolyte imbalance is possible. A rheumatoid screen may be suggested by clinical signs. Lumbar puncture (LP) may be indicated and can be performed to corroborate the diagnosis of GBS or MS if there are no contraindications. Specific investigations—such as brain stem evoked potentials and magnetic resonance imaging (MRI) scanning for MS—should be arranged by specialist neurology services. Chest x-ray or a computed tomography (CT) scan may be indicated to exclude thymoma in association with MG.

Treatment and prognosis

The mainstay of treatment for weakness caused by neuromuscular disorders is supportive care with a particular focus on ventilatory support commenced early rather than later, as emergency intubations are associated with higher complication rates. General supportive measures will also include maintenance of homeostasis with respect to normothermia, euglycaemia, normotension and control of any other autonomic dysregulation, such as paralytic ileus and urinary retention.

Prophylaxis against peptic ulcers and deep vein thrombosis as well as pressure area care are all crucially important in the mechanically ventilated and sedated patient. This will require admission to an ICU, but treatment is usually commenced in the ED. Early neurological consultation and ICU review are crucial, especially for conditions in which there are effective interventions, such as plasmapheresis or intravenous immunoglobulin (IVIG) administration for GBS. For acute envenomations or intoxications, supportive care is still the priority in combination with anti-venoms or antidotes when indicated.

For non-neuromuscular causes of weakness, the treatment priority is to address the underlying disease state. This will variously include electrolyte reconstitution, rehydration, correction of thyroid function, treatment of systemic diseases and infections, optimization of organ function and psychological assessment as indicated by clinical assessment and investigations. Appropriate referral should follow. In cases where no apparent cause can be found for a complaint of weakness, an expectant approach is warranted.

The prognosis for neuromuscular disease depends on the specific condition .

Criteria for diagnosis

Table 8.7.3 summarizes the key pathophysiology, assessment findings to elucidate and management strategies for the conditions likely to present to the ED with weakness as a predominant feature.

Specific conditions