Weakness is a common complaint in the emergency department, and a most challenging one, because before the emergency physician can proceed with an evaluation, the complaint of weakness must be fully clarified to determine about what the patient is actually complaining. This article will focus on causes of acute generalized nontraumatic bilateral weakness. Evaluation begins with the history and physical examination, followed by diagnostic testing in some cases.
Key points
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True neuromuscular weakness needs to be distinguished from fatigue, asthenia, and malaise.
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Asking the patient what he or she can no longer is an excellent method of localizing weakness.
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Although many of the neuromuscular diseases discussed in this article are each relatively rare, as a combined entity they represent the largest percent of etiologies for neuromuscular weakness.
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Evaluation of acute generalized weakness in the emergency department begins with a broad differential that is systematically narrowed down with clues from the history, physical examination and diagnostic investigations.
Introduction
Weakness is a common complaint in the emergency department (ED), and a most challenging one, because before the emergency physician can proceed with an evaluation, the complaint of weakness must be fully clarified to determine about what the patient is actually complaining.
A prospective observational study from Switzerland underscores the vast differential diagnosis of the chief complaint of weakness. Of 79 consecutive patients presenting to the ED with generalized weakness, the spectrum of diagnoses spanned 14 distinct international classification of disease-10 codes. The most frequent were diseases of the respiratory system (18%), followed by endocrine, nutritional, and metabolic diseases (14%), and neoplasms (10%). Infections were the most common cause of generalized weakness. The authors attributed this to the median age of 78 in their cohort; this highlights the fact that older patients may not have fever, cough, or other specific signs of infection, but rather present with generalized weakness.
When patients complain about weakness, the first distinction that is important to make is whether it is true neuromuscular weakness, or rather feeling fatigue, malaise, or asthenia. Fatigue is the inability to continue performing a task after multiple repetitions; the muscle gets weak after sustained activity. Malaise is a general feeling of being ill or having no energy. Malaise is perhaps more properly described as asthenia, which is defined as a sense of weariness or exhaustion in the absence of muscle weakness. The key difference is that with true neuromuscular weakness, the patient is unable to partially or fully perform the task in the first place.
Weakness can be unilateral or bilateral. The most common cause of unilateral weakness is acute brain infarction or ischemia (stroke or transient ischemic attack) and intracerebral hemorrhage (including subarachnoid hemorrhage). As these entities are covered elsewhere in this issue, they will not be discussed here. Poisons are also a class of other potential contributors to weakness, which have their own vast separate discussion. The focus of this article will thus be causes of acute generalized nontraumatic bilateral weakness. Evaluation begins with the history and physical examination, followed by diagnostic testing in some cases.
Introduction
Weakness is a common complaint in the emergency department (ED), and a most challenging one, because before the emergency physician can proceed with an evaluation, the complaint of weakness must be fully clarified to determine about what the patient is actually complaining.
A prospective observational study from Switzerland underscores the vast differential diagnosis of the chief complaint of weakness. Of 79 consecutive patients presenting to the ED with generalized weakness, the spectrum of diagnoses spanned 14 distinct international classification of disease-10 codes. The most frequent were diseases of the respiratory system (18%), followed by endocrine, nutritional, and metabolic diseases (14%), and neoplasms (10%). Infections were the most common cause of generalized weakness. The authors attributed this to the median age of 78 in their cohort; this highlights the fact that older patients may not have fever, cough, or other specific signs of infection, but rather present with generalized weakness.
When patients complain about weakness, the first distinction that is important to make is whether it is true neuromuscular weakness, or rather feeling fatigue, malaise, or asthenia. Fatigue is the inability to continue performing a task after multiple repetitions; the muscle gets weak after sustained activity. Malaise is a general feeling of being ill or having no energy. Malaise is perhaps more properly described as asthenia, which is defined as a sense of weariness or exhaustion in the absence of muscle weakness. The key difference is that with true neuromuscular weakness, the patient is unable to partially or fully perform the task in the first place.
Weakness can be unilateral or bilateral. The most common cause of unilateral weakness is acute brain infarction or ischemia (stroke or transient ischemic attack) and intracerebral hemorrhage (including subarachnoid hemorrhage). As these entities are covered elsewhere in this issue, they will not be discussed here. Poisons are also a class of other potential contributors to weakness, which have their own vast separate discussion. The focus of this article will thus be causes of acute generalized nontraumatic bilateral weakness. Evaluation begins with the history and physical examination, followed by diagnostic testing in some cases.
History
Onset
The timing of weakness can sometimes provide a clue to diagnosis. Generally, weakness that develops minutes to hours prior to presentation is due to metabolic (electrolyte) or toxic disorders or stroke. Weakness that have begun within the last 24 hours includes etiologies such as acute porphyric neuropathy, Guillian Barre syndrome (GBS), myasthenia gravis (MG), and tick paralysis. Weakness that has been going on for a week or longer is often associated with peripheral nerve problems, and neuromuscular junction (NMJ) diseases. Weakness characterized by frequent relapses is suggestive of multiple sclerosis, periodic paralysis, and myasthenia gravis. Weakness that is transient in nature is seen with peripheral nerve entrapment problems, hemiplegic migraine, and periodic paralysis.
Description of Weakness
Asking the patient what he or she can no longer do or do without difficulty is a good start to localizing the problem. For example, difficulty combing one’s hair or climbing stairs suggests proximal muscle weakness, whereas difficulty buttoning one’s shirt, or turning a door knob indicate distal muscle weakness. Dysphagia, a nasal voice, and dysarthria are associated with bulbar muscle weakness and raise concern for impending airway compromise. Generally, proximal muscle weakness suggests a myopathic process, while distal muscle weakness indicates a (poly)neuropathy.
Comorbidities
Underlying systemic illnesses can contribute to the presentation of weakness. For example, diabetes and some rheumatic disorders cause neuropathy.
Family History
A family history of dystrophy, periodic paralysis, porphyria, paraneoplastic syndromes, and hereditary predisposition to pressure palsies can be important in generating an appropriate differential diagnosis. Sometime patients may not know the names of diseases, so asking about specific symptoms as in the patient history may be more useful.
Medications
A number of medications can cause myopathy (muscle disease), most notably the statins that are in widespread use. Box 1 summarizes some of the most common drugs associated with myopathies. Myopathies can also be inherited (eg, muscular dystrophies) or acquired.
HMG Co-A reductase inhibitors (statins)
Gemfibrozil
Alcohol
d -penicillamine
Interferon α
Procainamide
Zidovudine
Lamivudine
Germanium
Colchicine
Vincristine
Quinine drugs
Amiodarone
Emetine
Ipecac
Corticosteroids
Hydroxyurea
Leuprolide
Sulfonamides
Physical examination
Motor Nervous System
Weakness can be caused by problems affecting upper motor neurons (UMNs), lower motor neurons (LMNs), NMJ, or the muscle itself ( Fig. 1 ).
The LMNs are comprised of anterior horn cells and innervate the skeletal muscle. UMNs provide impulses and regulate the activity of lower motor neurons. The neuromuscular junction is a chemical synapse formed by the contact between the motor neuron and a muscle fiber.
The motor neuronal pathway originates in the primary motor cortex (precentral gyrus) of the cerebral cortex. The corticobulbar and corticospinal tracts are the 2 main pathways of motor conduction, with the majority of axons from the corticospinal tract. Corticobulbar fibers terminate in the brain stem. Corticospinal fibers pass through the internal capsule; most of them cross to the contralateral side in the brain stem (pyramidal decussations of the medulla) and continue as lateral corticospinal tract in the spinal cord. They ultimately terminate in the gray matter of the spinal cord. Peripheral nerves (LMNs) arising from the spinal cord supply skeletal muscle. LMN disorders affect a particular muscle that is innervated by that nerve. Signs of LMN disease include decreased muscle tone, hyporeflexia, fasciculations, and an absent Babinski sign ( Table 1 ). The Babinski sign is extension, (rather than the normal flexion response) of the hallux (great toe) in response to stimulation of the sole of the foot with a blunt instrument.
| Sign | UMN | LMN |
|---|---|---|
| Reflexes | ↑ | ↓ |
| Atrophy | _ | + |
| Weakness | + | + |
| Fasciculations | _ | + |
| Tone | ↑ | ↓ |
| Extensor | + | _ |
Examples of LMN problems include: poliomyelitis, lower spinal cord injury (L4-S2) with nerve root compression, amyotrophic lateral sclerosis (ALS), progressive spinal muscular atrophy, spondylotic myelopathy, and radiation myelopathy. Problems that affect the peripheral nerves include
Trauma (including entrapment)
Toxins such as lead, alcohol, and many drugs
Infectious causes such as diphtheria, Lyme disease, and human immunodeficiency virus (HIV)
Inflammatory polyneuropathies such as GBS
Metabolic derangements such as diabetes and porphyria
Vascular problems such as autoimmune arteritis
Nutritional disturbances such as vitamin B1 or B12 deficit or pyridoxine toxicity
Heredity conditions such as Charcot-Marie-Tooth disease
Neoplasms
Abnormal proteins (amyloidosis).
By contrast, UMN disorders have widespread manifestations and a more complicated pathophysiology. Signs of UMN disease include increased muscle tone (spasticity), hyper-reflexia, and a positive Babinski. Examples of problems associated with UMN disease include cerebrovascular accidents, intracranial tumor, cervical spine injury (C1-C6), transverse myelitis, HIV, ALS, cerebral palsy, multiple sclerosis, and spinal stenosis.
Diseases of the NMJ are characterized by fluctuating strength based on muscle use. The classic examples of NMJ diseases are myasthenia gravis, where repeated contractions result in decreasing power, and Lambert Eaton myasthenic syndrome, in which repeated contractions result in increasing power. Botulism and organo phosphate poisoning are other examples.
Diseases that cause myopathy include
Congenital problems such as muscular dystrophy
Infection such as trichinosis
Connective tissue disease such as polymyositis, scleroderma, and mixed connective tissue disorder
Endocrine derangements such hypo/hyperthyroidism, hyperparathyroidism, and hypo/hyperadrenalism
Neoplastic diseases
Drug-induced diseases
Elements of the Motor Examination
The motor component of the neurologic examination comprises of 4 main elements : muscle bulk, tone, strength, and stretch reflexes. These assist in localizing the lesion responsible for the weakness.
Bulk
To ascertain muscle bulk, careful inspection of the muscles bilaterally is required. Decreased muscle bulk (atrophy) is seen in denervation disorders involving the peripheral nerves. Fasciculations (rapid twitching of the muscle) can also be noticed in the atrophic muscle. Non-neurological disorders can also result in atrophy (eg, disuse, and patient history can help in this regard.
Tone
Passive movement of the muscles can elucidate the tone, which is basically a resistance in the movements. Tone can be normal, increased, or decreased. A slight resistance is observed in normotonic muscle. Hypertonicity most commonly presents in the form of rigidity or spasticity. Rigidity is constant increase in tone over the entire range of motion, also described as lead pipe. Spasticity on the other hand is a variable increase in the tone and is dependent on velocity, also known as the clasp knife form. Rigidity is classically associated with a basal ganglia disorder, whereas spasticity is commonly observed in diseases involving corticospinal tracts. Hypotonicity (decreased muscle tone) is seen in lower motor neuron disorders.
Assessment of muscle strength
Strength (power) of the muscle can be graded per The British Research Council system ( Table 2 ).
| Grade | Description |
|---|---|
| Grade 5 | Normal strength |
| Grade 4 | Reduced strength but can still move joints against resistance |
| Grade 3 | Movements against gravity but not against resistance |
| Grade 2 | Movements only with the elimination of gravity |
| Grade 1 | Only fasciculations are noticed, and no movement is observed |
| Grade 0 | No muscle contractions. |
Stretch reflexes
Stretch reflexes are muscle contractions occurring when the tendon is percussed over a stretched muscle. They can be normal, decreased (lower motor neuronal disorders), or increased (upper motor neuronal disorders). They are graded on the basis on intensity of contraction: 4, clonus (very brisk); 3, brisk but normal; 2, normal; 1, minimal and 0, absent.
Emergency department management
The first priority with any patient presenting to the ED for any complaint always includes the ABCs of airway, breathing, and circulation. In this immediate assessment, a quick mental checklist of life-threatening causes of weakness (not necessarily true neuromuscular weakness) is helpful ( Box 2 ) to decide which further investigations might be warranted. In general, obtaining a complete blood cell (CBC) count, chemistry, and urinalysis covers a broad scope. If there is any respiratory compromise, an arterial blood gas and an inspiratory pressure (or negative inspiratory force, NIF) should be obtained also. CPK is useful when considering rhabdomyolysis. Blood cultures and lactate are obtained when sepsis is in the differential diagnosis. For most cases of acute generalized weakness, brain imaging will be of low yield, unless an acute stroke is still in the differential (discussed elsewhere in this issue). A lumbar puncture is helpful for diagnosing encephalitis. Once initial stabilization is complete, focusing on a detailed history and physical examination can provide clues as to which specific disease entity may be present ( Table 3 ).
