Approach to Acute
We akn es s
Deena Khamees, MD, William Meurer, MD*
KEYWORDS
Weakness Neurologic emergency Stroke Neuromuscular CNS Motor
Malaise
INTRODUCTION, HISTORY, DEFINITIONS, AND BACKGROUND
Background
Weakness can represent the initial stage of many emergency conditions. The differen-
tial diagnosis is broad and includes many etiologies that are decidedly non-neurologic.
In this review, we discuss a general emergency medicine approach to neurologic
causes of weakness. Our focus is on both common neurologic conditions and uncom-
mon conditions with a high likelihood of morbidity or mortality if the diagnosis is
delayed.
Definitions
We consider a variety of external and internal causes of neurologic weakness. We
define weakness as decreased or lost muscular strength resulting in an inability to
act with normal or desired force.1 Neurologic weakness, specifically, is due to specific
dysfunction in any of the following locations: the neuromuscular junction, peripheral
nerves (including brachial plexus), spinal cord, or brain. We do not discuss generalized
malaise, often referred to as “weakness” by patients, because this entity is most
frequently attributable to or associated with a primary medical cause such as anemia
or hypoglycemia. We define external causes to represent infectious diseases, trauma,
and toxins (including drug effects). Internal causes broadly include autoimmune,
vascular (including stroke), neoplastic, metabolic, and genetic. Idiopathic causes
might represent as yet undefined internal or external causes. Localization is the pro-
cess by which we use the signs and symptoms to determine what part or parts of
the nervous system are likely to be the source of the new problem.
History
The now-known causes of weakness were, at some point in history, newly discovered
or described. This continues today, because new diseases may present with
Emergency Medicine, University of Michigan Medical School, 1500 East Medical Center Drive,
Ann Arbor, MI 48109-5303, USA
* Corresponding author.
E-mail address: wmeurer@med.umich.edu
Emerg Med Clin N Am 39 (2021) 173–180
https://doi.org/10.1016/j.emc.2020.09.010 emed.theclinics.com
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174 Khamees & Meurer
weakness of unclear etiology. Acute flaccid myelitis, particularly in children, is an
example.2 Evolving technologies, such as methods to isolate viruses and other path-
ogens or molecular techniques to detect pathologic antibodies that lead to autoimmu-
nity, continue to uncover such previously unknown or unclear etiologies. This historical
context importantly highlights that the inability to identify a cause in the emergency
department does not mean there is no medical or organic etiology.
DISCUSSION
History Features
As with all neurologic conditions, a careful, focused history can assist in organizing
areas to query further with physical examination and diagnostic testing. Ask the pa-
tient or accompanying history-provider about the location of the weakness, duration
and pattern of symptoms, and association with other symptoms such as blurry vision
or pain. Ask about particular tasks or movements that are most impaired or that high-
light the weakness. For example, difficulty with standing from a seated position or
ascending stairs points to an etiology resulting in a proximal muscle weakness. Inquire
about any medications, such as diuretics, that may cause pertinent electrolyte distur-
bances, with particular emphasis on newly started, changed, or discontinued
medications.
Ask:
1. Where is the weakness (note unilateral vs bilateral involvement)?
2. When did this start?
3. Is the weakness persistent or intermittent or is there some consistent pattern?
4. What activities make the weakness more noticeable?
5. What other symptoms accompany the weakness?
Physical Features
The clinician’s first duty is to assess for emergent or urgent conditions necessitating
timely action. For patients with a suspected neurologic cause, respiratory status is
particularly at risk given the propensity for altered mental status or diaphragmatic or
accessory respiratory muscle weakness. Note that tachypnea often presents sooner
than, and may herald other signs of, impending respiratory failure.3
Look for:
1. Abnormal or poor mentation
2. Difficulty with speech or weak voice
3. Drooling or other indication of difficulty handling secretions
4. Inability to lift head off the bed
5. Weak, rapid, or shallow breaths or use of accessory muscles
If rapid sequence intubation is deemed necessary, consider avoiding depolarizing
neuromuscular blocking agents such as succinylcholine. These agents carry the risk
of potentially fatal hyperkalemia in those with neurologic disease by amplifying the
succinylcholine-related cellular potassium release.4,5 For most relevant conditions,
this response occurs in those with symptoms or illness for 3 or more days. Succinyl-
choline is considered safe in myasthenia gravis, although it should be noted that the
emergency physician may not always be certain of the etiology at the time rapid
sequence intubation is performed. Nondepolarizing agents such as rocuronium and
vecuronium may be preferable in such suspected or unknown cases. On a related
note, there may also be some degree of autonomic dysfunction or instability
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Approach to Acute Weakness 175
secondary to the suspected or known neurologic process that requires some support
or resuscitation until the underlying issue can be identified and managed.
In the absence of emergent or critical findings, a more thorough neurologic exami-
nation can be illuminating. This process includes an assessment of the cranial nerves,
reflex testing, sensory and motor examinations, coordination, and gait. Any one or
combination of these components may be key in narrowing the differential and guiding
testing, as well as determining any necessary emergent interventions.
The localization of the culprit lesion as an upper versus lower motor neuron (UMN
and LMN, respectively) can be made partly or even completely on the basis of the
physical examination. Hyperreflexia, increased muscle tone (spasticity), and a positive
or present Babinski sign (the extensor plantar response resulting in a fanning of the
toes) indicate UMN involvement. Decreased or absent reflexes and/or muscle tone
and an absent Babinski reflex indicate LMN involvement. Note that, in early UMN dis-
ease, there may initially be hyporeflexia and decreased muscle tone before the more
characteristic spasticity and hyperreflexia develop. These distinctions, coupled with
pertinent anatomy, can be helpful in the emergency department. For example, recall
that in the adult the spinal cord terminates at L1. Below this point is the cauda equina,
at which point an insult would result in an LMN-patterned examination. A patient pre-
senting with bilateral leg weakness, hyperreflexia, and a positive Babinski sign
(consistent with a UMN-level lesion) would thus be extremely unlikely to have a lesion
at L1 or lower. Consequently, limiting this patient’s imaging to an MRI lumbar spine,
presumably to identify cauda equina syndrome, would not reveal the etiology. We pro-
vide an overview of a localization paradigm as Fig. 1.
Strength testing may seem an obvious cornerstone of the physical examination in
the acutely weak patient, but its yield is greater when looking for patterns that can nar-
row the differential diagnosis. The first indication of a pattern may be found in the pa-
tient’s history, as alluded to elsewhere in this article, look to corroborate this on
examination if possible. If the complaints or examination reveal some hemiparesis,
consider a central lesion in the brain. Paraplegia is more likely secondary to a spinal
cord lesion. Proximal muscle weakness suggests a myopathy. Oculomotor and/or
bulbar dysfunction or weakness point to a neuromuscular junction problem such as
myasthenia gravis. Fatigability—diminishing strength with repeated normal use or
testing of the muscle—is also highly suspicious for neuromuscular junction disease.
Laboratory Tests, Imaging, and Adjuncts
For patients who are ill appearing, presenting with generalized weakness (as opposed
to discrete and localized complaints), or are suspected or known to have a potentially
dangerous diagnosis, we expect initial diagnostics to be broad screening examina-
tions. These include:
Complete blood count: anemia or signs of infection
Serum electrolyte panel: hypoglycemia, electrolyte derangements including potas-
sium, sodium, and calcium
Electrocardiogram: acute coronary syndrome or abnormalities secondary to elec-
trolyte disturbances
Urinalysis
Blood and urine cultures
Arterial or Venous blood gas
For patients in whom a more narrowed differential may be considered, intentional
use of some less common testing may be helpful. A lumbar puncture with cerebral spi-
nal fluid collection is emergently indicated in cases of suspected bacterial meningitis,
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176 Khamees & Meurer
Fig. 1. Approach to undifferentiated weakness in the emergency department. MS, multiple
sclerosis. (Modified from Asimos, Andrew, Birnbaumer, Diane, et al. Weakness: A Systematic
Approach to Acute, Non-traumatic, Neurologic And Neuromuscular Causes. Emerg. med.
pract.. 2002;4(12):1-26; with permission.)
particularly because treatment diminishes returns on microbial cultures. Cerebral spi-
nal fluid analysis can be revealing in cases of Guillain–Barre syndrome, myelitis, and
demyelinating peripheral neuropathy, although conditions these may not necessarily
require an emergent lumbar puncture in the emergency department. In case of sus-
pected myopathy and subsequent muscle damage, serum creatinine phosphokinase
may be elevated.
The most frequently utilized neuroradiography in the emergency department is a
computed tomography. Computed tomography imaging of the head without contrast
can reveal intracranial hemorrhage, mass lesions, cerebral edema, and midline shift.
Head computed tomography scans with contrast are often more illustrative of mass
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Approach to Acute Weakness 177
lesions and other malignancy-related processes, cerebral enhancing lesions which
may be due to infectious causes such as abscess, neurocysticercosis, toxoplasma,
or noninfectious etiologies such as demyelination or subacute infarct.6
MRI of the brain may be used to assess for acute ischemic stroke, because small
and early infarcts may not be identified on computed tomography imaging for several
days.7 MRI of the spinal cord should be obtained in the emergency department for
emergent cord and nerve root problems, such as compression, abscess, or transverse
myelitis; less time-critical diagnoses such as multiple sclerosis may also be identified
via MRI.
Tests of respiratory muscle strength, particularly vital capacity and maximal inspi-
ratory pressure, can be performed in the emergency department to identify those
with impending respiratory failure. The vital capacity is the maximal amount of air
expired after maximal inhalation. The maximal inspiratory pressure (MIP), also known
as the negative inspiratory force, indicates diaphragmatic strength, or lack thereof.
Normal ranges for the MIP vary widely based on patient sex and age and is generally
lower in women and the elderly.7,8 The data from such tests are best used in
conjunction with the clinical appearance and other information and singular mea-
surements may be less helpful than trending these over time. Certainly these are
not necessary before intubation if clear respiratory distress or failure exists on clin-
ical examination. In less apparent cases, these may help with decisions regarding
elective intubation; a common example of this occurs in myasthenic crisis.9,10 In
such an instance, acceptable cutoff values have been proposed as follows: a vital
capacity of less than 15 to 20 mL/kg and MIP between 0 and –30 cmH2O.11 Reliance
on the MIP should be weighed carefully as it relates to elective intubation; there is
good negative predictive value (a normal MIP reliably excludes significant respiratory
muscle weakness) but poor positive predictive value (a low MIP cannot confirm res-
piratory muscle weakness).12
Differential Diagnosis
Although outside the scope of this article, recall that a generalized malaise,
compared with a true neuromuscular weakness, can and often results from such
non-neurologic causes such as sepsis, dehydration, or anemia. Assuming a true
neurologic disorder exists, begin by determining if the patient requires any immedi-
ate interventions such as intubation, or has any known chronic neurologic condition;
if so, consider if this may be the most likely culprit compared with a new, additional
condition (see Considerations for Those with Known Chronic Conditions elsewhere
in this article).
If the patient is well-appearing and without any previously diagnosed relevant con-
dition, a more methodical approach may be used. Assuming an objective weakness
exists on examination, determine if the weakness is unilateral or bilateral. If bilateral
with decreased or altered mental status, consider a significant cerebral event such
as mass lesions or stroke. If bilateral with normal or baseline mental status, next deter-
mine if UMN or LMN signs are present on examination. Signs of UMN disease with
weakness in all 4 extremities (quadriparesis), usually with some sensory level deficit,
is concerning for cervical myelopathy. If the weakness is found to be in the bilateral
lower extremities (paraparesis) instead of all 4, consider a thoracic or lumbar myelop-
athy. Signs of LMN disease with bilateral weakness should prompt suspicion of acute
polyneuropathy or Guillain–Barre syndrome.
For patients who present with bilateral weakness but without obvious UMN or LMN
signs, differentiate between extremity weakness and oculomotor and bulbar weak-
ness on examination. The former, when more proximally localized, is consistent with
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178 Khamees & Meurer
a myopathy. The latter is most commonly associated with neuromuscular junction dis-
orders such as myasthenia gravis.
For patients with unilateral weakness, the approach may be comparatively simpler.
Central lesions may result in a variety of examination signs such as cranial nerve def-
icits (brainstem), motor and ataxic hemiparesis (lacunae), or aphasia, apraxia, hemine-
glect, or other visual deficits (cortex). For patients with a history of epilepsy, postictal
paralysis (Todd’s paralysis) is a consideration, particularly if the onset of unilateral
weakness was sudden and unwitnessed. Note that postictal paralysis can present
bilaterally and/or with speech or vision deficits.
If none of these are present on examination, look for a peripheral lesion in form of a
peripheral nerve entrapment such as carpal tunnel syndrome, a plexopathy such as a
brachial plexus injury, or a radiculopathy which would be expected to follow a clear
myotomal distribution.
Remember that multiple sclerosis can present variably across patients and so may
not fit an algorithmic approach well. Generally, there is variable presentation of motor,
sensory, visual, and cerebellar deficits, but the duration of symptoms, pattern (relaps-
ing–remitting, progressive, and a variations of these), location of the deficit, and other
factors may all differ greatly. Frequently, patients report a subacute period of other or
similar deficits, relative to the acute presentation, that have self-resolved.
Certain toxins may induce generalized weakness. Botulism toxin in adults can
distinctively manifest as bilateral cranial neuropathies, with progression to flaccid pa-
ralysis. Carbon monoxide poisoning may present with weakness and other vague
symptoms when early, and is another potential consideration. Other neurotoxins
such as sarin or VX typically have a more dramatic presentation with seizures and
altered mental status.
Considerations for Those with Known Chronic Conditions
Patients with known neurologic conditions may present with an acute exacerbation of
the condition, or a complication of such. In these cases, assess for some triggering
event such as infection, recently started or discontinued medications, new dosages
of current medications, pregnancy, recent childbirth, trauma, or uncontrolled comor-
bid diseases that may impact a neuromuscular condition. The redemonstration of
once-resolved or worsening of persistent deficits from a prior stroke secondary to a
new pneumonia is a common example.
Flares of myasthenia gravis may be characterized by increasing weakness,
dysphagia, dyspnea, and other signs and symptoms of ocular and bulbar weakness.
Exacerbations range from the very mild to the severe myasthenic crisis, with potential
for neuromuscular respiratory failure. Consider additional workup if there is evidence
of sensory, reflex, pupillary, or cerebellar deficits; these symptoms are not expected in
myasthenia gravis.
Patients with multiple sclerosis often present with an exacerbation similar to those
experienced in the past, and although these symptoms may be relatively consistent
for any given patient, flares are likely to vary markedly between patients. Carefully
consider additional workup for patients whose symptoms do not match prior flares,
or are accompanied by a change in mental status.
A history of Guillain–Barre syndrome is important to note in patients presenting with
new or continuing weakness. The Guillain–Barre syndrome variant chronic inflamma-
tory demyelinating polyneuropathy may persist or progress from an initial diagnosis of
Guillain–Barre syndrome (specifically acute inflammatory demyelinating polyneurop-
athy, the most common form of Guillain–Barre syndrome), or present as a series of
relapses.
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Approach to Acute Weakness 179
SUMMARY
The chief complaint of weakness can be difficult to address in the emergency depart-
ment, but may be the only clue to one of many life-threatening diagnoses. Always start
with the identification of those in critical condition who may require intubation or other
immediate interventions upon assessment. Carefully gather a history and detailed
neurologic examination where possible, with an emphasis on differentiating factors
discussed in this article, such as the distribution and quality of the weakness. These
findings may be more revealing than imaging and laboratory testing, but certainly
they may contribute significantly. Remember there exists a spectrum of patient pre-
sentations such that you will encounter those with known neurologic disorders in an
acute exacerbation, as well as those whose weakness is both significant and uniden-
tifiable in origin in the emergency department.
CLINICAL CARE POINTS
Carefully differentiate between true neuromuscular weakness and the more com-
mon generalized malaise in the patient presenting with weakness because this
markedly impacts the differential.
Assess for critically ill or emergent conditions, with special attention to the respi-
ratory status.
For those critically ill or with consistent clinical presentations, consider the poten-
tially life-threatening diagnoses of ischemic or hemorrhagic stroke, myasthenia
gravis, Guillain–Barré syndrome, cord compression, and infection such as bac-
terial meningitis or epidural abscess.
If pursuing rapid sequence intubation, consider a nondepolarizing agent such as
rocuronium or vecuronium instead of the depolarizing neuromuscular blocking
agent succinylcholine, which may cause respiratory arrest owing to severe hy-
perkalemia in the neurologically ill or injured.
A targeted but detail-oriented history and physical are key in shaping and nar-
rowing the differential; pay attention to that which differentiates unilateral versus
bilateral weakness and UMN from LMN, and note signs of central versus periph-
eral nervous system involvement.
Exercise caution when using the vital capacity and/or MIP to determine the need
for intubation in patients with potential or known respiratory muscle weakness.
DISCLOSURE
The authors of this article have no conflicts of interest to disclose.
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