Evaluation of the adult with acute weakness

Life-threatening central causes of unilateral weakness Ischemic stroke Intracerebral

hemorrhage Subarachnoid hemorrhage

Life-threatening and other serious causes of bilateral weakness Brainstem stroke

Lesions in the brainstem may produce ipsilateral cranial nerve and contralateral body
weakness. Clinical findings may include vertigo, depressed mental status, visual field
deficits, oculomotor abnormalities, and bulbar findings Spinal cord inflammation or
compression bilateral motor and sensory signs or symptoms that do not involve the
head. Motor deficits involve weakness, muscle spasticity, and hyperreflexia (although
hyporeflexia is often seen acutely); sensory findings involve a discrete level below
which sensation is absent or reduced. Urinary bladder function may be affected
resulting in either urinary retention or incontinence . trauma, infection (eg, epidural
abscess), neoplasm, hemorrhage, inflammation (eg, transverse myelitis), and
degenerative disorders. Peripheral nerve disease Guillain-Barr syndrome (GBS)
progressive, fairly symmetric muscle weakness, accompanied by absent or depressed
deep tendon reflexes. Patients usually present a few days to a week after onset, with
progressive weakness of the legs and arms (sometimes initially only in the legs).
numbness or paresthesias in the limbs. Weakness can vary from mild difficulty with
walking to nearly complete paralysis of all extremity, facial, respiratory, and bulbar
muscles Tick paralysis usually begins with paresthesias and a sense of fatigue and
weakness. Fever is characteristically absent. Despite patients' reports of paresthesias, the
sensory exam is typically normal. Most patients eventually develop an unsteady gait
that progresses to an ascending complete paralysis. Deep tendon reflexes are
characteristically absent. Respiratory paralysis and death can occur in severe cases.

Neuromuscular junction disease

Myasthenia gravis (MG) MG can produce weakness in any muscle group. Certain
presentations are more common: ocular symptoms (eg, ptosis, diplopia) ; bulbar
symptoms (eg, dysarthria, dysphagia, fatigable chewing) in 15 percent; and isolated
limb weakness in 5 percent. Myasthenic crisis occurs when respiratory and/or bulbar
muscle weakness produces acute respiratory distress. Organophosphate and carbamate
poisoning manifestations of cholinergic excess and include bradycardia, miosis,
lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, diarrhea,
diaphoresis, and generalized weakness. Botulism Patients with food-borne botulism
may have a prodrome of vomiting, abdominal pain, diarrhea, and dry mouth.
Symptoms of cranial nerve involvement then develop (eg, fixed pupillary dilation,
diplopia, nystagmus, ptosis, dysphagia, dysarthria), followed by descending muscle
weakness, which usually progresses from the trunk and upper extremities to the lower
extremities. Smooth muscle paralysis leads to urinary retention; diaphragmatic paralysis
can lead to respiratory distress requiring intubation.

Muscle disease

Alcoholic myopathy long-standing alcoholics, presents with muscle cramps,

tenderness, and swelling, and is a major cause of nontraumatic rhabdomyolysis.
Myositis Both dermatomyositis and polymyositis usually present with symmetric
proximal muscle weakness, which has often been worsening over several months.
Muscle pain and tenderness is present in up to half of cases.

Life-threatening medical causes with focal findings Metabolic conditions most often
cause generalized weakness without focal findings. However, exceptions exist, most
notably hypoglycemia and hypokalemic periodic paralysis. Periodic paralysis Severe
electrolyte abnormalities can cause generalized or focal muscle weakness. Hypo- or
hyperkalemia, hypo- or hypercalcemia, hypomagnesemia, or hypophosphatemia
Muscle weakness usually does not occur at potassium concentrations above 2.5 meq/L
if hypokalemia develops slowly, but significant weakness may occur with sudden
decreases. Weakness usually begins with the lower extremities, progresses to the trunk
and upper extremities, and can worsen to the point of paralysis. Patients with renal
dysfunction can develop hyperkalemia that manifests initially as weakness and may
deteriorate into a life-threatening arrhythmia if untreated.

Endocrine abnormalities, such as thyrotoxicosis, may also cause periodic paralysis.

Life-threatening causes of generalized weakness Sepsis Acute coronary syndrome

Carbon monoxide (CO) poisoning Adrenal insufficiency Patients with chronic,
progressive adrenal insufficiency most often develop the following symptoms: chronic
malaise, lassitude, fatigue that is worsened by exertion and improved with bed rest,
weakness that is generalized (ie, not limited to particular muscle groups), anorexia

Other neurologic causes of acute weakness Multiple sclerosis (MS) Hemiplegic

migraine : unilateral motor and sensory symptomsPostictal (Todd's) paralysis
Generalized or complex partial seizures may be followed by a focal motor deficit that
can persist for hours, but typically resolves within 30 to 60 minutes, and is often related
to a structural abnormality of the brain

Other medical causes of generalized weakness Hypothyroidism fatigue, slow

movement and slow speech, cold intolerance, constipation, delayed relaxation of deep
tendon reflexes, and bradycardia. The second is accumulation of matrix
glycosaminoglycans in tissues, which can lead to coarse hair and skin, puffy facies,
enlargement of the tongue, and hoarseness. Infection Occult infection, particularly in
elderly patients, may manifest as malaise and generalized weakness Anemia
Dehydration or hypovolemia Presyncope Medications Many medications, in
isolation or combination, and illicit drugs can cause weakness. Common culprits include
beta blockers, diuretics, laxatives, chemotherapeutic agents, isoniazid, opioids, and
alcohol. Some agents may have direct toxic effects on muscle, including
glucocorticoids, statins, antimalarial drugs, antipsychotic drugs, colchicine,
antiretrovirals, alcohol, and cocaine. Rheumatologic disease Weakness is a common
feature of rheumatologic disease. As examples, fatigue is the most common complaint
in patients with systemic lupus erythematosus and a common complaint among those
with rheumatoid arthritis. Polymyalgia rheumatica, which can be associated with the
vision-threatening condition of temporal arteritis, can present with generalized
weakness and myalgias.

Elderly patients Occult infection, metabolic disorders, stroke, and medication related
problems are common causes of weakness in the elderly.
Defining weakness True weakness is the inability to perform a desired movement with
normal force because of a reduction in muscle strength. When a neurologic or
neuromuscular problem is suspected, an algorithmic approach based upon a thorough
history and examination facilitates neuroanatomic localization and exclusion of
potentially life-threatening and other serious illness The history should include a
distribution of weakness (eg, bilateral hands) and its manifestations (eg, difficulty with
fine motor tasks), the period over which symptoms developed, and clinical features
associated with the weakness (eg, aphasia, diplopia).

Unilateral weakness Are cortical signs present, such as aphasia, neglect, agnosia, or
apraxia? Is the face involved (eg, facial droop)?Is there a myotomal pattern to the
distribution of weakness? particular peripheral nerve?. A localized process (eg,
weakness and paresthesias limited to one or two fingers) suggests peripheral nerve
entrapment

Bilateral weakness Is mental status depressed?Which limbs are involved?Is

there sensory involvement? If so, is a sensory level deficit suggested?Is there bladder
involvement?Does weakness primarily involve proximal or distal muscles?Are there
bulbar signs (involving tongue, jaw, face, or larynx)?Does the degree of weakness
fluctuate?

A central nervous system (CNS) lesion causing bilateral weakness is usually

accompanied by diminished mental status, unless the lesion lies in the spinal cord. The
presence of bladder dysfunction or a sensory deficit below a discrete dermatomal level
suggests a myelopathy.The proximal motor weakness typically found early in the course
of a myopathy is suggested by difficulty walking up stairs or getting up from a chair, if
the lower limbs are involved, or difficulty with overhead activities (eg, combing hair), if
the upper extremities are involved.Symptoms associated with disease at the
neuromuscular junction include visual symptoms, particularly ptosis and diplopia, and
bulbar signs. Bulbar muscle weakness may manifest as nasal speech, coughing, or
lingual dysarthria. A fatiguing pattern to weakness, suggested by worsening with
repeated activity (eg, chewing), suggests myasthenia gravis.

Periodic paralysis due to imbalances in potassium regulation (or other electrolyte

abnormalities) is suggested by acute attacks of weakness lasting a few hours to a couple
of days that spontaneously resolve.

PHYSICAL EXAMINATION Motor neuron findings Recognition and distinction

between upper motor neuron (UMN) or lower motor neuron (LMN) signs is important
when determining the nature of a weakness syndrome .Signs of UMN disease include
spasticity (ie, increased muscle tone), hyperreflexia, and an extensor plantar response
(Babinski reflex). These findings are absent in pure peripheral disease. However,
hyporeflexia and flaccid paralysis may occur with acute central lesions, with
hyperreflexia and spasticity developing later. An example of UMN disease encountered
in the ED is the patient who presents with acute spinal cord transection from trauma.

LMN disease include decreased muscle tone and hyporeflexia. The Babinski reflex is
absent. If weakness is bilateral and signs of LMN disease are present, consider are
neuropathies, myopathies, and disorders of the neuromuscular junction (NMJ).
Neuropathies tend to involve distal muscle groups, while myopathies more often
involve proximal muscles. Reflexes are decreased in neuropathies, but may be present,
decreased, or absent with myopathies. Myopathies may have associated myalgias but
sensory symptoms are generally absent. The most distinguishing feature of
neuromuscular junction disease is early involvement of the bulbar musculature (ie,
tongue, jaw, face, and larynx).

Strength testing Strength testing is central to the examination of the weak patient..
Hemiparesis suggests a hemispheric lesion; paraparesis suggests a spinal cord lesion.
Peripheral nerve disease, notably Guillain-Barr syndrome, can also cause paraparesis.
Proximal weakness suggests a myopathic process rather than a neuropathy. Assess
extraocular movements, eyelid strength, masseter muscle strength, facial expression,
and palatal movement.

Reflex testing Tendon jerks are graded using a standard scale, with zero
representing absence and four representing hyperactivity with clonus Lesions in one
cerebral hemisphere generally result in hyperreflexia of the affected side due to
disruption of the UMN. Interruption of the corticospinal tracts bilaterally generally
causes symmetrical hyperreflexia and extensor plantar responses (positive Babinski). A
spinal cord lesion is the most common cause of such findings, but in rare instances,
bilateral cerebral hemisphere damage or brainstem disease may be present.

Nerve root compression most often causes unilateral absence of a specific lower
extremity reflex. As an example, unilateral loss of the ankle jerk suggests a lesion at the
S1 nerve root.

Fatigability Fatigability describes normal strength during initial testing that

decreases significantly as testing continues. It is characteristic of myasthenia gravis.

Sensation testing Classically, a cortical lesion causes relatively mild hemisensory

loss, which affects touch and proprioception more than pain. The patient may simply
describe this as their arm or leg "feeling funny." A spinal cord lesion often affects
sensation bilaterally, with the upper level of the sensory loss defining the lesion level.In
contrast, cervical central cord lesions most commonly produce a "cape" sensory loss
over the shoulders affecting pain and temperature sensation, but spares vibration and
proprioception (so-called "dissociated" sensory loss). Lesions of the conus medullaris or
cauda equina produce loss of sensation in the perineum. When the lateral half of the
spinal cord is damaged (Brown-Sequard syndrome) proprioception and vibration are
lost ipsilateral to the lesion, while pain and temperature sensation are lost on the
contralateral side.

CT w/o contrast for acute hemorrhage, mass lesions, and cerebral edema. A head CT
with contrast is obtained if an intracranial tumor or certain infections (eg, toxoplasmic
encephalitis) Brainstem and cerebellar lesions are best seen with MRI

CSF analysis is indicated when Guillain-Barr syndrome (GBS), myelitis, or

demyelinating peripheral neuropathy is suspected. In GBS, the CSF often reveals an
elevated protein with a normal white blood cell count. With a myelitis, CSF analysis is
normal in approximately half of patients. In the other half, it may reveal an elevated
protein or moderate lymphocytosis, but the glucose concentration remains normal. A
process such as an inflammatory demyelinating peripheral neuropathy generally
demonstrates elevated CSF protein. A lymphocytic pleocytosis is often present if
disease is related to HIV.

Signs of respiratory distress in patients with neuromuscular weakness can include

Rapid, shallow breathing Poor respiratory effort; use of accessory muscles
Difficulty swallowing; inability to handle secretions Inability to lift head off bed
Weak, ineffective cough Weak or muffled voice Depressed mental status

When performing rapid sequence intubation (RSI), it is important in some settings to

avoid depolarizing neuromuscular blocking agents (eg, succinylcholine) and instead to
use a nondepolarizing neuromuscular blocking agent (eg, rocuronium) Evidence
suggests that neurologic injury markedly exaggerates the potassium release associated
with succinylcholine administration The risk of a hyperkalemic response is greatest
among particular patients with neuromuscular weakness, including the
following:Denervating injuries (eg, stroke, spinal cord injury) of greater than three
days duration Denervating diseases (eg, Guillain-Barr syndrome with symptoms over
three days, multiple sclerosis, amyotrophic lateral sclerosis, transverse myelitis with
symptoms over three days)Inherited myopathies (eg, Duchenne's muscular
dystrophy)Prolonged immobilization

Autonomic instability in the setting of neurologic weakness typically manifests initially

as a hypersympathetic state, heralded by sinus tachycardia [7]. Thereafter, fluctuation in
the heart rate and blood pressure occur.

Important neurologic diagnoses to consider in the weak patient with respiratory distress
or hemodynamic instability include:Ischemic or hemorrhagic stroke CNS
infectionSpinal cord injury (including compression) or inflammation Guillain-Barr
syndrome Myasthenic crisis (

Important causes of generalized weakness to consider in the patient with respiratory

distress or hemodynamic instability include:Sepsis (Acute cardiovascular disease
(eg, coronary syndrome, decompensated heart failure)Intoxication or poisoning
Severe electrolyte abnormalities (eg, hypokalemia, hyperkalemia) Endocrine crisis
(eg, diabetic ketoacidosis, hypoadrenal (Addisonian) crisis, myxedema coma,
thyrotoxicosis)

Left-sided neglect is a cortically mediated deficit that usually occurs in right

hemispheric strokes. The centers controlling conjugate gaze are located in each frontal
lobe. If one center is damaged, the unopposed action of the other causes the eyes to
deviate toward the side of the lesion and away from the hemiplegia.

Lacunar and basal ganglia lesions Lesions in the subcortical cerebral hemisphere,
namely deep hemorrhages due to hypertension and ischemic lacunar strokes, can cause
weakness. Importantly, cortical deficits are absent .Lacunar infarcts are small, deep
cerebral infarcts due almost exclusively to disease of the perforating arterioles. They
account for about one quarter of strokes or with nonischemic lesions, including
hemorrhage and tumor.

Brainstem processes Weakness syndromes referable to the brainstem may present

with "crossed" findings (ipsilateral cranial nerve weakness and contralateral
hemiparesis) due to lesions involving cranial nerve nuclei or their tracts and the
corticospinal tract before its decussation. However, this is often not the case. As an
example, a lacunar stroke in the pons can appear indistinguishable clinically
(hemiparesis, ataxia) from a lacunar stroke affecting the internal capsule.

Brown-Sequard syndrome Most myelopathies present with bilateral weakness, even

if the distribution is patchy. The main exception is Brown-Sequard syndrome. In this
syndrome, involvement of either lateral hemisection of the spinal cord results in
ipsilateral hemiplegia or monoplegia, ipsilateral loss of vibration and proprioception,
and contralateral loss of pain and temperature below the level of the lesion. Brown-
Sequard syndrome is typically caused by penetrating trauma

Radiculopathies Spinal nerve roots mark the beginning of the peripheral nervous
system. Radiculopathies are any disease or condition affecting the spinal nerve roots.
These syndromes typically present as pain in a dermatomal distribution. Weakness in a
myotomal distribution can occur but is less common [16]. Most spinal nerve
compression syndromes usually involve either the cervical or lumbosacral region

Plexopathies The best way to diagnose a plexopathy (eg, brachial plexopathy,

thoracic outlet syndrome, lumbar plexopathy) is to identify a motor and sensory deficit
in a limb that involves more than one spinal or peripheral nerve. Lower motor neuron
(LMN) signs are more prominent than sensory findings. Causes include trauma,
radiation therapy, and malignancy [

Peripheral nerve injuries Peripheral nerve injuries typically involve neurapraxias,

implying a temporary insult to the nerve that resolves when compression is relieved.
The most common sites for such neurapraxias are narrow passageways in which the
nerve moves during flexion and extension of the neighboring joint. Carpal tunnel
syndrome is a classic example.)

The "locked-in syndrome" is a devastating central process that causes quadriparesis and
mutism, but leaves consciousness intact .In this syndrome, a ventral pontine lesion
causes quadriplegia, facial weakness, lateral gaze weakness, and dysarthria. Vertical
gaze and eyelid opening are preserved. In the ED it is critical to distinguish between a
comatose patient and one with locked-in syndrome, who may be a candidate for
reperfusion therapy to recanalize a basilar artery occlusion

Myelopathies Nontraumatic myelopathies (diseases of the spinal cord) typically

present with bilateral extremity weakness and sensory deficits. Leg weakness is the
most common symptom, but arm weakness can occur when the cervical spinal cord is
involved. Bowel and bladder symptoms may be present due to interruption of the
descending upper motor neuron pathways, which control the urinary and rectal
sphincters [25]. Impotence or priapism may occur. Disturbances in autonomic function,
such as loss of sweating, trophic skin changes, loss of temperature control, and
vasomotor instability, can occur below the level of the lesion. . Without a history of
trauma, acute disruptions suggest vascular pathology; subacute or chronic development
of symptoms suggests an inflammatory lesion. Myelopathies generally present with
some signs of upper motor neuron (UMN) disease. However, the traumatic and vascular
processes that cause myelopathy often produce a flaccid areflexic paralysis initially.
Over several hours to days, the motor findings become characteristic of an UMN
paralysis, with hyperreflexia and bilateral extensor plantar responses (positive Babinski
test). Discrete dermatomal sensory loss may not be obvious on examination..

Polyneuropathy Polyneuropathies (eg, Guillain-Barr syndrome) manifest both

motor and sensory symptoms, unlike myopathies and NMJ disorders. Weakness is due
to the large number of nerves involved. Distal power is reduced most dramatically.
Deep tendon reflexes are characteristically diminished and vibratory sense is invariably
lost distally. Paresthesias often herald the weakness from a peripheral neuropathy

Neuromuscular junction processes The most common presenting signs of disease at

the neuromuscular junction (NMJ) are ocular (ptosis, diplopia) and bulbar abnormalities
(dysarthria, dysphagia). Limb weakness, when it occurs, tends to involve the upper
extremities Myasthenia gravis (MG) is a common example and diagnosis is
straightforward in a patient with ocular, bulbar, and limb weakness that fluctuates
throughout the day and improves with rest.)

Myopathies Myopathies result from disease within the myocyte (eg, muscular
dystrophy) or as a manifestation of a systemic disorder (eg, metabolic or inflammatory
polymyopathies). Sensory abnormalities are usually absent in patients with generalized
myopathies, while myalgias may occur in those with inflammatory myopathies.
Weakness typically begins in the proximal muscles and extends distally thereafter. Deep
tendon reflexes are often maintained until severe weakness develops. Myotonic
muscular dystrophy type 1 presents with distal muscle involvement. Myotonic muscular
dystrophy type 2 (ie, proximal myotonic dystrophy) most often presents with weakness
in the muscles of the hip girdle.
ifferential diagnosis of acute weakness organized anatomically
Central
Stroke
Space occupying/structural lesion
Cerebrum Postictal (Todd) paralysis
Multiple sclerosis
Other inflammatory conditions
Subcortex/brainstem Stroke
Spinal cord Acute transverse myelitis
 Spinal cord infarct
Spinal epidural or subdural hemorrhage
Central intervertebral disc herniation
Tumors (metastatic or primary)
Multiple sclerosis
Peripheral
Intervertebral disc herniation
Epidural abscess
Spinal nerve root Tumors
Leptomeningeal metastases

Guillain-Barr syndrome
Diabetic
Ciguatoxin (ciguatera poisoning)
Saxitoxin (paralytic shellfish poisoning)
Polyneuropathies Tetrodotoxin poisoning (pufferfish poisoning)
Porphyria
Lead or other heavy metal poisoning
Alcohol or drug induced

Brachial
Plexopathies Lumbar

Nerve compression syndromes

Peripheral neuropathies

Myasthenia Gravis
Lambert-Eaton myasthenic syndrome
Botulism
NMJ Disorder
Organophosphate poisoning
Tick paralysis

Electrolyte induced
Inflammatory (polymyositis)
Myopathy Alcohol or drug-induced
Muscular dystrophy
Endocrine related
Nonphysiologic/noncategorical
Conversion disorder
Chronic fatigue syndrome (CFS, also known as systemic exertion intolerance disease [SEID])
Anxiety disorders
Fibromyalgia
Malingering
Classic lacunar syndromes
Positive
Lacunar syndrome Location Clinical findings
predictive value
Pure motor Internal capsule, corona radiata, Unilateral paralysis of face, arm and leg, no sensory
52-85 percent
hemiparesis basal pons, medial medulla signs, dysarthria and dysphagia may be present
Thalamus, pontine tegmentum, Unilateral numbness of face, arm and leg without
Pure sensory syndrome 95-100 percent
corona radiata motor deficit
Internal capsule-corona radiata, basal
Ataxic hemiparesis Unilateral weakness and limb ataxia 59-95 percent
pons, thalamus
Sensorimotor Thalamocapsular, maybe basal pons Hemiparesis or hemiplegia of face, arm and leg with
51-87 percent
syndrome or lateral medulla ipsilateral sensory impairment
Dysarthria-clumsy Basal pons, internal capsule, corona Unilateral facial weakness, dysarthria and dysphagia, About 96
hand syndrome radiata with mild hand weakness and clumsiness percent