Neurocrit Care

https://doi.org/10.1007/s12028-019-00834-0

ACUTE NON-TRAUMATIC WEAKNESS

Emergency Neurological Life Support: Acute

Non‑traumatic Weakness
Aimee M. Aysenne1* and Shahana Uddin2,3

© 2019 Neurocritical Care Society

Abstract
Acute non-traumatic weakness may be life-threatening if it involves the respiratory muscles or is associated with auto-
nomic dysfunction. Most patients presenting with acute muscle weakness have a worsening neurological disorder
that requires a rapid, systematic evaluation and detailed neurological examination to localize the disorder, create a
differential diagnosis, initiate treatment or stabilize the condition to prevent further deterioration and optimize out-
comes. Additionally, urgent neuroimaging and laboratory investigations are needed to confirm the diagnosis. Because
acute weakness is a common presenting sign of neurological emergencies, it was chosen as an Emergency Neuro-
logical Life Support protocol. For each diagnosis, key features of the history, examination, investigations and treatment
are outlined in the included tables or in the “Appendix”.
Keywords: Neuromuscular weakness, Acute weakness, Respiratory failure, Autonomic dysfunction

Introduction relevant features and considerations are included. Also in

The differential diagnoses of acute non-traumatic weak-
ness range from imminently life-threatening to slowly
progressive conditions. The approach to this presenta-
tion comprises synchronous resuscitation with relevant
examination and investigations to develop an individual-
ized treatment plan.
Time-sensitive diagnoses must be considered early to
ensure optimal patient outcomes with prompt initiation
of therapeutic interventions or transfer if necessary. A
detailed history and comprehensive neurological exami-
nation may help localize the disorder and narrow the
differential and relevant investigations can confirm the
diagnosis.
The first section of this article describes neurologi-
cal assessment and patterns to consider to help localize
the problem and guide the clinicians to a diagnosis. This
broad range of conditions is discussed in this chapter and
in the “Appendix”, where supporting tables outlining the
*Correspondence: aaysenne@tulane.edu
1
Department of Clinical Neurosciences, Tulane University, New Orleans,
LA, USA
Full list of author information is available at the end of the article
this section are specific pediatric considerations.
The second section describes the ENLS algorithm and
immediate management considerations including pri-
orities, practical steps and emergent investigations. This
section also expands on specific circumstances includ-
ing time critical conditions, nursing and prehospital
considerations.
Traumatic weakness and disorders of chronic weak-
ness are not discussed in this chapter. Also, this module
is meant to give a broad framework for the principles of
diagnosis and emergent management of acute non-trau-
matic weakness, which can be adapted to reflect global
and regional variations based on the local availability of
diagnostic tools and treatments.
Differential Diagnosis
A detailed history and comprehensive neurological exam-
ination are important but may not be practical in the pre-
hospital and immediate resuscitation period and may
be completed when the patient’s airway and ventilation
have been stabilized. However, at a minimum, obtain the
patient’s last known well time and perform a brief neuro-
logical examination to form a workable and realistic list
of differential diagnoses. If possible, asking the patient or
a witness the timeline of onset, where the person is weak,
if there are any sensory symptoms including numbness
or tingling, and any associated symptoms is helpful. For
children, a developmental and family history obtained
from the parents may help in early evaluation for the first
acute presentation of metabolic or neurodegenerative
disorder with muscle weakness.
Neurological Examination
Determining the pattern of weakness and associated
findings on clinical history and examination help to local-
ize the anatomical lesion. Each anatomical lesion has dif-
ferent disease processes that affect that location. Brain
lesions or global metabolic processes such as toxins may
affect consciousness. While the clinical examination may
be limited in confused or obtunded patients, it should be
possible to elicit certain features in all patients including
whether the deficit affects the face, arms, legs or a com-
bination; whether the deficit is unilateral or bilateral; the
presence or absence of reflexes; and whether there is a
gross sensory deficit. These findings will help determine
the anatomical region affected. Figure 1 and Table 1 dif-
ferentiate anatomic regions including the brain and spi-
nal cord, the anterior horn cell, the peripheral nerve,
neuromuscular junction (NMJ) and muscle.
Key elements of the neurological examination include
state of consciousness, language disturbances, cranial
nerve involvement, motor strength, tone, reflexes, sen-
sory, and coordination.
State of consciousness is easily assessed on every
patient based on his or her ability to interact with the
examiner. The Glasgow Coma Scale (GCS) and the FOUR
score formalize these findings and add a quantitative
measurement [1–3]. Formal language testing may be lim-
ited in an emergency situation but may include the abil-
ity to follow verbal commands, naming, repeating and
reading when the situation is more stabilized. The cranial
nerves control the movements of the face including the
eyes, mouth and swallowing. Having the patient follow
the examiner’s finger in an H pattern tests extraocular
eye movements. Asking the patient to smile, protrude the
tongue, and say “ah” while observing the movements of
the palate and uvula test the remaining cranial nerves. In
an intubated patient, an in-line suction catheter and oral
suction catheter can test cough and gag reflexes.
Interpretation of the motor examination should
account for the patient’s age, capacity to understand
commands and degree of cooperation. In infants, the
examination will rely primarily on observation. The apha-
sic patient with a stroke, migraine or encephalitis may
not understand the command. Grading of weakness in
myasthenia gravis is contingent on the degree of coop-
eration of the patient to provide their best effort.
Motor strength testing may be cursory in an acute
setting including lifting the arms and legs off the bed.
Pronation of the arms when held in an extended posi-
tion quickly denotes more distal than proximal mus-
cle weakness with a high degree of sensitivity. Detailed
motor strength testing of each muscle group will help
better localize the lesion. Establish whether the weak-
ness is symmetrical or asymmetrical, whether it is affect-
ing the proximal or distal extremities. Because weakness
can affect the muscles of ventilation, having the patient
attempt to count as high as possible on exhalation of a
single breath is a rapid assessment of strength of these
muscles. Forced vital capacity of 1.0 L is roughly equal to
counting from 1 to 10, and counting above 20 is normal
[4, 5].
Tone may be either increased or decreased (flaccid)
and is tested by passively moving the patient’s neck and
extremities. Reflexes are tested by rapidly tapping on the
tendon of a muscle to watch for response.
The sensory examination is most complete when test-
ing different modalities such as pain/temperature, light
touch, vibration and proprioception. In an emergency
situation, light touch and pain are most useful and can be
done quickly by running a soft material along the patient’s
skin or, if a greater degree of stimulation is required for
testing, pinching the patient can be used. Care must be
taken to not injure the skin by twisting or puncturing.
Coordination may be tested by asking the patient to
touch his or her nose, extend the arm, then touch the
examiner’s finger and by having the patient slide his or
her heel along the shin from the knee to the ankle and
back up to the knee. Gait is usually deferred in emer-
gency situations, as it may be unsafe to have the patient
stand while weak. Table 2 describes components of the
neurological exam.
During the neurological examination, it is important
to differentiate between an upper motor neuron (UMN)
and a lower motor neuron (LMN) lesion, although this
may be difficult in the acute setting. In well-established
UMN lesions (brain and spinal cord), hyperreflexia,
increased extremity tone and a positive Babinski sign
(great toe extension with lateral plantar stimulation) are
seen on examination. In comparison, LMN lesions (from
the anterior horn cells in the spinal cord to the mus-
cles) cause a flaccid, areflexic weakness and, with time,
atrophy and fasciculations (involuntary contractions or
twitching of muscle fibers). However, in the acute phase,
UMN lesions may mimic a LMN lesion: flaccid paralysis,
normal or reduced tone, and unreliable reflexes. There is
often not enough time for atrophy to be evident, and fas-
ciculations are rarely seen.
 Fig. 1 Localization along the neuroaxis

After performing a neurological examination, refer to ••  Hypoglycemia/hyperglycemia (Tables 10, 11 in

Table 1 and Fig. 1 to ascribe the appropriate anatomic “Appendix”) [9–11]
localization. ••  Postictal Todd’s paresis (Table 12 in “Appendix”) [12,
13]
••  Hemiplegic migraine (Table 13 in “Appendix”) [14,
Additional Patterns of Weakness
15]
Hemiparesis/Hemiplegia
••  Brown-Sequard syndrome (Table 14 in “Appendix”)
••  Acute stroke: ischemic, hemorrhagic, or subarachnoid [16, 17]
hemorrhage [6]
••  Intracranial mass (Table 9 in “Appendix”) [7, 8]
••  Meningitis/encephalitis
Table 1 Physical examination findings for each anatomic localization of weakness
Localization Pattern of weakness Sensory loss Reflexes Acute etiologies

Cerebral cortex, brain- Distal > proximal, extensors > flexors,
stem or spinal cord hemiparesis or single limb
Spinal cord Distal > proximal, extensors > flexors,
paraparesis, quadriparesis, rarely
hemiparesis
Anterior horn cell Proximal and distal, fasciculations are
prominent
Peripheral nerve In the distribution of the nerve, or
diffusely present as stocking/glove
weakness
Neuromuscular junction First in eye muscles, neck extensors,
pharynx, diaphragm, followed by more
generalized weakness
Muscle Proximal
May be present depending on whether
sensory tracts or cortex are involved
May be present depending on whether
sensory tracts are involved; loss of
sensation below a certain spinal level is
diagnostic
Absent
Variable
Absent
Absent
Elevated; however, reflexes may be
decreased initially but later increase
Elevated; however, reflexes may be
decreased initially but later increase
Decreased if muscle bulk is severely
decreased; increased in ALS
Absent or decreased
Normal, decreased if muscle is paralyzed
Normal unless muscle severely weak
Acute stroke: ischemic, hemorrhagic or
subarachnoid hemorrhage
Intracranial mass
Meningitis/encephalitis
Hypoglycemia/hyperglycemia
Postictal Todd’s paresis
Hemiplegic migraine
Transverse myelitis
Spinal cord infarction
Spinal cord compression: epidural abscess,
disc herniation, tumor
ALS, polio, West Nile Virus
Guillain–Barre syndrome
Vasculitic neuropathy
Toxin-induced
Nerve compression syndromes
Acute diabetic lumbosacral radiculoplexus
neuropathy
Myasthenia gravis, Lambert-Eaton myes-
thenic syndrome, botulism, tick bite,
organophosphate toxicity
Acute myopathy, Rhabdomyolysis, myositis
Table 2 Key assessments
Examination component Key maneuvers and findings

State of consciousness Interaction with examiner

Glasgow Coma Scale
FOUR score
Language Following verbal commands, naming, repeating and reading
Cranial nerves Follow the examiner’s finger in an H pattern
Ask the patient to smile
Protrude the tongue
Say “ah” while observing the movements of the palate and uvula
In an intubated patient, in-line suction catheter and oral suction catheter can test cough
and gag reflexes
Motor strength Lift the arms and legs
Pronation of the arms when held in an extended position
Detailed motor strength testing of each muscle group
Single-breath count for muscles of respiration
Tone Passively move the neck, arms and legs: may be either increased or decreased (flaccid)
Reflexes Rapidly tap on the tendon of a muscle
Sensory Different modalities include pain/temperature, light touch, vibration and proprioception
Pain and light touch in emergencies
Coordination Finger to nose to finger
Heel to shin

Acute hemiparesis is partial paralysis affecting only one
side of the body. Acute hemiplegia is complete paralysis
of one side of the body. Acute hemiparesis and hemiple-
gia are localized anatomically to the brain or the spinal
cord. If the brain is involved, muscles of the face includ-
ing movement of the eyes and the ability to speak and
swallow are included in the condition while they are
spared in processes of the spinal cord.
In the patient with acute onset hemiparesis or hemiple-
gia, stroke is the most important emergency etiology to
diagnose. See ENLS modules on stroke care (ENLS Acute
Ischemic Stroke, ENLS Intracranial Hemorrhage and
ENLS Subarachnoid Hemorrhage) for information about
treatment. While stroke is the most common, other dif-
ferential diagnoses must also be considered, as manage-
ment varies. The history and demographic of the patient
will narrow the diagnosis, and examination findings pro-
vide further clues. A blood glucose level and a non-con-
trast head computed-tomography (CT) scan are part of
the initial workup.
Quadriparesis/Paraparesis ± Sensory Level
••  Transverse myelitis (Table 15 in “Appendix”) [18–20]
••  Spinal cord compression
••  Acute West Nile virus associated paralysis
••  Spinal cord infarction (Table 16 in “Appendix”) [21]
••  Syrinx
••  Drug ingestion (nitrous oxide inhalation)
••  Generalized weakness: electrolyte and glucose abnor-
malities (Tables 9, 10, 17, 18, 19 in “Appendix”) [7–9,
22–28])
Quadriparesis/plegia is symmetrical weakness of all
four limbs. Paraparesis/plegia is a symmetrical weakness
of both lower limbs. Often, this is related to a spinal cord
dysfunction. See ENLS Spinal Cord Compression module.
The anterior horn of the spinal cord houses the con-
nection between the upper and lower motor neurons.
Conditions that affect these cells can cause examination
findings of both UMN and LMN and spare sensory neu-
rons. There is a limited number of disease processes that
affect this area: amyotrophic lateral sclerosis (ALS) or
“Lou-Gehrig’s disease”, enterovirus D68, polio, and West
Nile virus [29–34]. These are rare conditions and require
expert consultation where available. Only 29 cases of
polio have been reported worldwide in 2018 [35].
Proximal Weakness
••  Acute myopathy (Table 20 in “Appendix”) [36]
••  Myasthenia gravis (Table 21 in “Appendix”) [37–39]
••  Lambert-Eaton myasthenic syndrome (LEMS)
••  Botulism
••  Acute diabetic lumbosacral radiculoplexus neuropa-
thy (DLRN) (Table 22 in “Appendix”) [40–42]
Proximal weakness is weakness predominantly affect-
ing the axial muscles, deltoid and hip flexors. Acute prox-
imal weakness classically presents with difficulty rising
from a chair or brushing hair. Patients may have difficul-
ties flexing and extending their neck. The most common
cause is myopathy, followed by disorders of the neu-
romuscular junction such as myasthenia gravis, LEMS
and botulism. DLRN typically affects only the lower
extremities and may be the presenting feature of diabetes
mellitus [40–42].
A key clinical examination finding of myasthenia gravis
is fatigability causing increased weakness with use of the
muscle, while LEMS may gain strength with repeated
activation. Electromyography shows characteristic find-
ings in both conditions. Myasthenia gravis is much
more common than LEMS. This condition is caused by
anticholinergic antibodies in the neuromuscular junc-
tion and is typically treated with acetylcholine esterase
inhibitors, namely pyridostigmine and immunosuppres-
sion with steroids and other steroid sparing agents. Clini-
cal findings include ptosis, dysphagia and hoarseness in
addition to proximal muscle weakness. Patients may be
admitted with myasthenia crisis, which involve respira-
tory failure. In these cases, stop pyridostigmine as this
can increase secretions, worsening breathing and delay-
ing weaning of the ventilator if necessary. Increasing
immunosuppression including steroids or adding plasma
exchange or intravenous immunoglobulins are the main-
stay of treatment [38, 39, 43, 44]. Noninvasive mechani-
cal ventilation may be considered if the patient is able to
manage secretions and the time course suggests that the
crisis is rapidly reversible. If the patient requires intuba-
tion, an additional consideration is the choice of paralytic
agent [45]. Caution must be used to avoid medications
that worsen myasthenia gravis, most commonly beta-
blockers and antibiotics such as fluoroquinolones and
macrolides. LEMS is typically a paraneoplastic illness
related to an underlying lung cancer and has a worse
prognosis [46].
Botulism is a neurotoxin that acts at the neuromus-
cular junction to cause weakness. Clostridium bac-
teria create the toxin in specific conditions including
improperly canned foods and wounds from intravenous
drug use. Spores in honey can be gastrically absorbed in
infants under one year of age. Iatrogenic cases have been
reported. Symptoms usually start with the face and upper
extremities and spread downward. Pupils are classically
involved but may be spared. Respiratory failure may
occur. Diagnosis is made via stool sample while electro-
myography studies may help. Treatment is with support-
ive care and botulism antitoxin. Cases should be reported
to public health authorities as outbreaks are possible, and
as botulism may be a bioterrorism agent [47–49].
Tetanus is another toxin that affects the neuromuscu-
lar junction, but instead of weakness, causes sustained
contraction. The incidence has decreased worldwide due
to the availability of the tetanus vaccine. Patients may be
exposed via wounds. Electromyography findings confirm
the diagnosis and treatment is supportive [49].
Distal Weakness
••  Guillain–Barre syndrome (Table 23 in “Appendix”)
[50–58]
••  Vasculitic neuropathy (Table 24 in “Appendix”) [59,
60]
••  Toxin-induced peripheral neuropathy (Table 25 in
“Appendix”) [61]
••  Nerve compression syndromes [62, 63]
Distal weakness is weakness mainly affecting the hands,
wrists and feet. Patients have decreased grip strength and
drop objects or develop gait disturbance due to foot drop.
Weakness that is severe can affect muscles of respira-
tion and of the airway. Depending on the etiology, these
patients may progress to quadraparesis and have involve-
ment of the diaphragm. Peripheral neuropathies can pre-
sent with sensory symptoms if sensory nerves are also
involved. The pattern of weakness and history are of great
significance and often lead to the diagnosis. Of the many
types of peripheral neuropathy, autoimmune demyelina-
tion, vasculitic and toxin are most likely to induce acute
weakness.
Guillain–Barre syndrome, or acute inflammatory
polyneuropathy (AIPD), is the most common acutely
progressive peripheral neuropathy. History is often sig-
nificant for an upper respiratory or gastrointestinal infec-
tion or vaccination in the weeks preceding symptom
onset. Symptoms usually start in a stocking glove dis-
tribution and may progress rapidly to include the mus-
cles of respiration including the diaphragm and airway.
Intubation is paramount in these cases, and noninvasive
positive pressure ventilation should not be attempted.
Autonomic instability is common and should be carefully
monitored. Acute flaccid paralysis and areflexia or dimin-
ished reflexes are hallmark characteristics of the physical
examination. Diagnosis is made with lumbar puncture
showing increased protein without leukocytosis and is
augmented with electromyographic studies and spe-
cific antibody testing. A variety of underlying conditions
can cause or mimic Guillain–Barre syndrome including
Campylobacter jejuni infection, influenza vaccine, Lyme
disease, Chikungunya virus, Zika virus and the quadriva-
lent human papillomavirus vaccine [50–58].
Peripheral nerve syndromes can cause acute weak-
ness. Compression including compartment syndrome is
a common cause. Knowledge of the innervation of each
nerve is paramount to making the diagnosis. When more
than one peripheral nerve has been affected, this is called
mononeuropathy multiplex and is more commonly a vas-
culitic immune-mediated process. These conditions are
rarely neurological emergencies [62, 63].
Monoparesis
••  Acute stroke
••  Intracranial mass (Table 9 in “Appendix”)
••  Postictal Todd’s paresis (Table 12 in “Appendix”)
••  Nerve compression syndromes
••  Diabetic lumbosacral radiculoplexus neuropathy
(Table 22 in “Appendix”)
Monoparesis refers to paralysis of a single muscle, mus-
cle group or limb.
Acute paralysis involving a single limb may be caused
by a central or a peripheral lesion. Historical and exami-
nation factors may help to localize the lesion. For exam-
ple, sudden onset right arm weakness with an associated
dysphasia is most likely to result from a central lesion,
whereas wrist drop in the right hand, with hypoesthesia
on the back of the hand after falling asleep with the arm
over the back of a chair, results from a peripheral nerve
compression syndrome.
Generalized Weakness
Acute generalized weakness may occur due to acute
metabolic disorders including sepsis, electrolyte distur-
bances, anemia or endocrine disorders. Marked hyper-
glycemia may rarely present with an acute hemiplegia,
but the majority of electrolyte disorders result in sym-
metric involvement. Hypoglycemia must be excluded
early, but it should be noted that most of these patients
are confused or have a decreased level of consciousness
[9–11]. Other electrolyte causes that must be considered
include hyponatremia and hypernatremia (Table 17 in
“Appendix”), hypermagnesemia (Table 18 in “Appendix”)
and hypophosphatemia (Table 19 in “Appendix”) [22, 23,
25–28]. Thyroid function studies may be helpful. Specific
vitamin deficiencies can cause generalized weakness but
are usually not emergent. Central nervous system infec-
tion (meningitis, encephalitis, encephalomyelitis) may
cause weakness and is diagnosed with lumbar puncture.
See ENLS Meningitis and Encephalitis module. A pos-
tictal patient or a patient in status epilepticus can also
present with focal or generalized weakness. See ENLS
Status Epilepticus module. There is typically little confu-
sion about the diagnosis, but if there is no history avail-
able leading up to the presentation of a weak patient, the
diagnosis may be more elusive. Acute weakness is also
a prominent feature of certain organophosphate toxic-
ity and envenomations, though the latter is exceedingly
rare (see Tables 26 and 27 in “Appendix”) [64–68]. Finally,
specific drugs may cause acute weakness including slow
clearance of neuromuscular blocker given during intuba-
tion [69].
Unique Pediatric Considerations
The core principles of protecting the airway and clini-
cal localization apply equally to the evaluation and acute
stabilization of children with weakness. Important differ-
ences from the presentation and etiologies in adults will
be highlighted here and are summarized in Table 3.
In young children, symptoms may be variable, includ-
ing refusal to walk, restlessness, irritability, waking
repeatedly from sleep, wanting to frequently be held
or loss of milestones. As with adults, the presence or
absence of reflexes, signs of bulbar weakness or a sensory
level are critical elements of the physical examination.
In young children, it may be difficult to assess a sensory
level indicative of spinal cord localization. In children, the
inability to walk may be due to weakness, pain or ataxia,
and these distinctions can be a challenge to make in the
field or emergency department (ED). Expidited care with
an expert in pediatric neurology may be needed.
Common causes of acute non-traumatic weakness in
children include acute transverse myelitis, seizure, acute
demyelinating encephalomyelitis (ADEM), Guillain–
Barré syndrome (GBS), myasthenia gravis and migraine
[19, 57, 70]. While stroke in children is rare compared
to adults, this should be considered early in the differen-
tial diagnosis for all children with acute non-traumatic
weakness, especially those with established risk factors
including sickle cell anemia, congenital heart disease or
a prothrombotic disorder. When a vascular insult is con-
sidered in a previously healthy child, a vascular dissection
is more likely than spinal cord ischemic injury as anterior
spinal artery infarcts are rare in children [71].
Initial Management
The ENLS suggested algorithm for the initial manage-
ment of acute non-traumatic weakness is shown in Fig. 2,
and a summary checklist is outlined in Table 4.
When using the algorithm, begin with simultaneous
assessment of the history and physical. A team-based
approach is recommended as with any medical emer-
gency. Pertinent historical elements include the last
known well time and date, the anatomic region that is
weak, and assessment of the airway, breathing and cir-
culation (ABCs) of stabilization as well as a blood glu-
cose check. From there, use the neurologic examination
to assess whether the patient has global weakness or an
upper or lower motor neuron injury. Strength, tone and
reflexes are important examination maneuvers for this
distinction. Remember an upper motor neuron lesion can
mimic a lower motor neuron injury early in the process.
Next, localize the lesion to the brain, spinal cord, nerve,
neuromuscular junction or muscle based on pattern of
weakness. This may not be evident in the first few hours
of the emergency. Always circle back to assess airway and
muscles of respiration as the condition may change over
time. Laboratories should be sent as outlined in the algo-
rithm (Fig. 2) and checklist (Table 4). MRI or CT imaging
with and without contrast as renal function allows may
need to be emergently obtained. Depending on the likely
differential diagnosis and local healthcare systems, trans-
fer to an appropriate facility with the necessary imaging
modalities and/or relative medical expertise will need to
be considered at various points in this initial assessment.
The “Appendix” includes tables for various disease
states that may be used as a reference when considering
the patient’s diagnosis. Additional laboratories may need
to be sent depending on the suspected diagnosis. Finally,
it should be noted that healthcare providers must circle
back to the start of the algorithm as the patient’s ventila-
tion and neurological examination may have declined in
the interim requiring intubation.
Assessing Ventilation and the Need for Urgent Intubation
and Ventilatory Support
In cases of acute weakness, respiratory compromise is
either due to altered consciousness or weakness of the
muscles of respiration, including the oropharyngeal
muscles and diaphragm. See Table 5 for details. Assess-
ment of the patient’s ABCs, with appropriate resuscita-
tion measures, takes precedence over a comprehensive
neurological examination. If any adverse signs are pre-
sent, it is prudent to consider a team approach to patient
management akin to cardiac arrest teams or trauma
teams, which allows stabilization and assessment to be
carried out simultaneously by appropriate specialists. If
a team-based approach is not possible, then a system-
atic ABC approach should be followed. When there is
uncertainty regarding the respiratory status and rate of
deterioration, it is generally safer to consider elective
intubation and initiation of ventilatory support, particu-
larly if transfer to specialist center is likely. Alternatively,
the patient should be admitted to an area where support
can be implemented without delay, such as an intensive
care unit or high-dependency care wards. It is important
to perform and document at least a focused neurologi-
cal examination as the signs and symptoms may later be
masked by the use of drugs such as sedative and muscle
relaxants. If the patient is alert, protecting their airway
and respiratory failure is mainly due to diaphragmatic
and intercostal muscle weakness, a trial of noninvasive
ventilatory support (NIV) may be considered to augment
respiratory efforts, until the precipitating condition has
been treated and resolved. For example, a patient with a
myasthenia gravis crisis may recover quickly, but a quick
recovery is unlikely in a rapidly deteriorating patient with
Guillain–Barre syndrome or stroke, where it would be
preferred to proceed directly with intubation. Intubation

Table 3 Pediatric considerations

History
Assess risk factors including known history of migraine, epilepsy, myasthenia gravis, GBS
Assess vascular risk factors for known diagnosis of sickle cell disease; congenital heart disease; prothrombotic disorder
Presence of recent illness (possible post-infectious demyelinating disorder)
Assess rate of onset of symptoms; transverse myelitis may be fulminant in onset in children
Examination
Priority on assessment of bulbar weakness and protection of the airway
Identify presence or absence of deep tendon reflexes
Observe for signs of pain or ataxia which may mimic weakness in infants
Sensory examination is often unreliable in children
Look for signs of muscle or limb pain
Acute empiric treatment
If reflexes are present, consider transverse myelitis, ADEM, Todd’s paralysis, myasthenia gravis or stroke (significantly less common in children)
If reflexes are diminished or absent, consider early GBS or transverse myelitis with spinal shock
Protect airway and start intravenous fluids until imaging or lumbar puncture performed
Treatment for confirmed transverse myelitis or ADEM (methylprednisolone) Myasthenia or GBS (IVIG or plasma exchange) are similar to adults
Diagnostic studies
For the patient with history and examination suspicious for stroke, obtain MRI with diffusion imaging
For the patient with signs of muscle pain, obtain creatine kinase to evaluate for myositis
For the patient with diminished or absent reflexes obtain MRI of spine:
If the history and imaging are consistent with transverse myelitis, lumbar puncture can be performed electively
If the MRI is not diagnostic, obtain lumbar puncture to evaluate for GBS or transverse myelitis
 Fig. 2 ENLS acute non-traumatic weakness protocol

Table 4 Acute weakness checklist for the first hour

Checklist

☐ Assess and manage airway, breathing, and circulation

☐ Characterize the weakness by neurological exam
☐ Localize the lesion to create a differential diagnosis of the causes of weakness
☐ Initial labs: Glucose, electrolytes, Ca, Mg, PO4, BUN/Cr, LFTs, PT, PTT, CBC, and ABG
☐ Special Labs: TFTs, CPK or CK, ESR, parathyroid hormone, GGT​
☐ Relevant MRI and CT imaging

should always be performed by trained and skilled per-
sonnel. It is prudent to remember that hypoxemia and
hypercapnia occur late with neuromuscular respiratory
failure, and ventilation should be assessed frequently for
increased weakness or signs of distress.
Table 6 outlines factors to consider when deciding on
whether to intubate a patient with acute weakness [4, 5].
No single parameter independently predicts the need for
intubation; rather, the constellation of signs and symp-
toms with a temporal trend should be evaluated. Certain
salient points that are specific to intubation of patients
presenting with acute weakness are listed in Table 7 [45,
69]. Also, see the ENLS Airway, Ventilation, and Sedation
protocol.
Table 5 Causes of respiratory compromise

Pathophysiology
Oropharyngeal weakness: poor cough reflex leads to aspiration
Airway failure (airway collapse)
The diaphragm is responsible for approximately two-thirds of ventilatory effort
Examination
Consider oropharyngeal weakness with increased secretions
Assessing diaphragmatic weakness with formal pulmonary function tests may be valuable, as gas exchange abnormalities (hypoxia and hypercarbia)
may be a late marker of functional respiratory deterioration
Consider bedside pulmonary function tests (vital capacity, maximal inspiratory and expiratory pressure/force) to quantify neuromuscular respiratory
insufficiency
Continue to regularly assess the patient as his or her clinical condition may deteriorate rapidly

Table 6 Factors to consider in the intubation decision a GCS score or FOUR score and a prehospital stroke scale
score such as the Los Angeles Prehospital Stroke Screen,
General Cincinatti Prehospital Stroke Scale or VAN screening [1–
Decreased level of consciousness 3, 6, 72–74]. Determine when the patient was last known
Increasing generalized muscle weakness
Dysphagia to be normal (date and time) as it is extremely important
Dysphonia for diagnostic and treatment purposes. If toxin exposure
Dyspnea on exertion and at rest is suspected, document the type and location of the expo-
Subjective sure. Remove exposures if possible. Always assess a blood
Rapid shallow breathing sugar level and treat hypoglycemia.
Tachycardia
Weak cough Prompt recognition of a stroke should activate a ‘stroke
Interrupted speech (gasping for air) call/system’ for expedited ED care and/or expert neuro-
Use of accessory muscles logical opinion. It is helpful to know hospitals that are
Abdominal paradoxical breathing
Orthopnea certified in stroke care such as Primary or Comprehen-
Weakness of trapezius and neck muscles: inability to lift head from bed sive Stroke Centers in the USA. More detailed guidance
Inability to perform single-breath count: count from 1 to 20 in single for the initial and prehospital ischemic stroke assessment
exhalation (FVC 1.0 L is roughly equal to counting from 1 to 10)
Cough after swallowing may be found in the ENLS Acute Ischemic Stroke module.
Objective Regardless of diagnosis, the first steps should be per-
Decreased level of consciousness (have a lower threshold to control the formed urgently, if possible involving a team of providers
airway if patient requires transfer or movement to unmonitored areas) to allow simultaneous assessment, stabilization and ini-
Hypoxemia tiation of emergency interventions.
Vital capacity < 1 L or 20 mL/kg, or 50% decrease in VC in a day
Maximum inspiratory pressure > − 30 cm H ­ 2O
Maximum expiratory pressure < 40 cm H ­ 2O Step 1 ABC: airway/breathing/circulation including
Hypercarbia (a late finding) blood glucose.
FVC forced vital capacity, VC vital capacity Step 2 History: onset and progression of symptoms,
when was the patient last known well.
Step 3 Focused neurological examination to establish
Prehospital Considerations affected anatomical region.
In any patient presenting with weakness, it is imperative
to consider early whether: Nursing Considerations
Nurses are an integral component of assessment and
1. Is this a localized issue unlikely to affect respiratory treatment of any patient including those with acute non-
muscles or have cardiovascular effects (autonomic traumatic weakness. Nursing responsibilities vary region-
function)? ally with roles defined by national standards and cultural
2. Is this a rapidly progressive disorder? norms. Nursing education should include content aimed
3. Is this a time-sensitive diagnosis? at developing neurological assessment skills and history
taking to effectively utilize nurses as team members. As
The diagnosis may not be immediately apparent—but part of the initial assessment, nurses may help to obtain
there are indicators in the history and examination which history, start IV access, draw laboratories and administer
should ring alarm bells and mandate urgent evaluation, initial medications. Importantly in a patient who is weak,
extreme vigilance and close monitoring. As allowed, obtain nurses are relied upon as the people who most frequently
assess changes in clinical status. In some situations, this
Table 7 Special considerations for intubation

Special considerations for intubation

Rapid sequence induction/intubation is advised
Avoid use of succinylcholine if there is evidence of underlying progressive neuromuscular disease (e.g., Guillain–Barre, chronic muscular weakness, or
prolonged immobility)
Consider sedation only or 1.0–1.4 mg/kg rocuronium as an alternative
Succinylcholine will be relatively ineffective to achieve muscle relaxation in myasthenia gravis. Either a higher dose (approximately 2.5 times standard
dose) of succinylcholine can be used or half-dose of non-depolarizing agents (rocuronium 0.5–0.6 mg/kg)
Consider noninvasive ventilation as a temporizing measure in a neurologically stable patient, while the diagnosis is established or with a known neuro-
muscular condition expected to have rapid resolution (e.g., myasthenia gravis exacerbation)
Prepare atropine/glycopyrrolate, fluids and vasopressors (risk of associated autonomic instability)
See the ENLS Airway, Ventilation and Sedation protocol for additional information

improving or decompensating, and if the treatments pro-

Table 8 Acute weakness communication with assessment
and referral vided have improved the condition.

Acute weakness communication with assessment and referral Transportation

☐ Salient history and examination findings
☐ Airway status and any respiratory issues
☐ Relevant labs and imaging (if done)
☐ Cause of weakness if known; differential diagnosis if not known
☐ Treatments provided
☐ Trajectory of disease process
may be continuous, every few minutes, or every hour.
Patients must be in an area of the hospital that allows
for intensive monitoring in the dynamic phase of illness.
When neurological changes are detected by a nurse, the
provider should notify other team members who can
help determine next steps in management. If there is new
acute weakness on a patient who was otherwise neuro-
logically well, consider activation of a stroke alert.
Communication
Healthcare providers should follow a checklist of items
(Table 8) to communicate their initial assessment of the
patient with acute non-traumatic weakness to the admit-
ting hospital staff or consultant. Provide the patient’s age,
history of present illness and neurological examination
findings. Include information on the patient’s airway and
respiratory status (i.e., respiratory rates, oxygen satura-
tion); ABG results; note any “Ds”: dysarthria, dysphagia,
dysphonia and dyspnea; provide pulmonary function test
results (vital capacity, maximal inspiratory and expiratory
pressures); progression and trajectory of changes; if intu-
bated, list the ventilator settings; and chest X-ray results.
Sign out abnormal laboratories provide imaging results
and inform what diagnostic tests are still pending comple-
tion. If known, provide the etiology of the acute weakness
and, when not known, a list of potential considerations.
Summarize any treatments provided or planned. Note
the trajectory of disease process indicating if the patient is
When moving patients with acute weakness, it is impor-
tant to remember proper positioning of neck and extrem-
ities, as the patient may unable to position him or herself
in a safe and comfortable manner. Head of bed should
be elevated to 30 degrees to avoid aspiration. Continued
assessments throughout the patient’s acute period cannot
be overstated, even during transport. Providers should be
aware of any additional equipment that may be necessary
during transport. This includes monitor equipment for
heart rate with telemetry if possible, blood pressure, and
oxygenation as variability of autonomic and respiratory
status can occur. If the patient has been shown to have
unstable vital signs, medications may be needed during
transport to continue to stabilize the patient. The patient
should have access to supplemental oxygen as needed
and potentially more advanced airway equipment if the
situation requires. All team members should be made
aware prior to the transport of an unstable patient.
Clinical pearls
• Team-based approach to the patient with acute non-traumatic weak-
ness is best.
• Use the neurological examination to help localize the lesion.
• A differential diagnosis can be generated based on localization.
• Respiratory failure may occur with an acutely weak patient.
• Frequent assessments are needed early in the disease course as the
patient’s condition is evolving.
• Autonomic instability may occur.
Author details
1
Department of Clinical Neurosciences, Tulane University, New Orleans, LA,
USA. 2 Department of Critical Care Medicine, King’s College Hospital, London,
UK. 3 King’s Health Partners Academic Health Sciences Centre, London, UK.
Acknowledgements
The authors are grateful for the contributions and insight provided by the fol-
lowing reviewers: Christina Watford, BSN, RN, CCRN; Joshua N. Goldstein, MD,
PhD; Christopher M. Ruzas, MD; Natalie Gofman, Pharm.D., BCPS, BCCCP; Christi Conflict of interest
DeLemos, MSN, CNRN, ACNP-BC. None.

Author contributions
All authors contributed to drafting and/or revising the manuscript. Appendix
Tables 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,
Source of Support
None. 23, 24, 25, 26, and 27.

Table 9 Intracranial mass [7, 8]

History
Hemiparesis is uncommon with brain tumors
Other symptoms of brain tumors vary widely from headaches, seizures, nausea, ataxia and cognitive dysfunction
Focal neurological deficits may present late and follow a predictable pattern based on structural disease
Manifestations may be subtle, particularly in the early stages
As with other UMN lesions, weakness is generally more pronounced in flexors of lower extremities than in extensors and more pronounced in extensors
than flexors in upper extremities
Transient weakness may represent a postictal state, as in postictal Todd’s paresis
Fever, headache and focal neurological deficit is characteristic of a brain abscess
Examination
Detailed neurological examination may help localize the lesion and create a list of differential diagnoses
Investigations
CT head with and without contrast to identify tumor, exclude other diagnoses, look for associated hemorrhage and assess for bone or vascular involve-
ment
MRI with and without contrast usually required
Consider functional MRI, perfusion MRI, PET and SPECT imaging, depending on the situation
Management
Involve neurological clinicians
Peritumoral vasogenic edema responds to glucocorticoids (dexamethasone IV 10 mg stat then 4 mg IV every 6 h)
Corticosteroid use should be avoided prior to biopsy or surgery if either a primary CNS lymphoma or infectious process is part of the differential diag-
nosis
Manage raised ICP in the standard stepwise approach
If there is evidence of intra-tumoral hemorrhage, correct any coagulopathy and control BP
Brain abscesses require targeted anti-microbial treatment and sometimes drainage

Table 10 Hypoglycemia (serum glucose < 3 mmol/l; < 50 mg/dl) [9]

History
Diabetes
Insulin regimen
Oral hypoglycemics
Alcohol
Sepsis
Liver disease
Any cause of hypocortisolemia
Examination
Generalized nonspecific weakness
Many forms of focal neurological deficit possible including re-expression of previous lesions
Tremor, palpitations, anxiety, sweating, hunger and paresthesia
Dysphoria
Seizures
Decreased consciousness
Investigations
Blood glucose level (more accurate from venous or arterial blood rather than capillary and measured in a blood gas analyzer)
CT head
Treatment
20 mL IV 50% dextrose
Repeat if necessary
Oral carbohydrate if patient safe to swallow
Alternatively, 1 mg glucagon IM or IV
Table 11 Hyperglycemia [10, 11]

History
History of diabetes
Possible precipitating events (e.g., infection, ischemia, surgery, critical illness)
Diabetic regimen and compliance
Neurological symptoms primarily occur when plasma osmolality is greater than 320 mOsm/kg
Neurological symptoms may include hemiparesis, focal motor deficits, decreased consciousness and seizures
Diabetic ketoacidosis (DKA) usually evolves rapidly, over a 24-h period
Symptoms of hyperosmolar hyperglycemia syndrome (HHS) develop gradually with polyuria, polydipsia and weight loss for several days before presen-
tation
Examination
Level of consciousness may be reduced
Detailed neurological examination may reveal focal motor and sensory deficits including aphasia, hyperreflexia, hemianopia and brainstem dysfunction
Other findings associated with HHS include evidence of volume depletion
Patients with DKA may present with hyperventilation and abdominal pain
Investigations
Serum glucose
Plasma osmolality
Serum electrolytes (with anion gap), urea and creatinine
Complete blood count with differential
Urinalysis, and urine ketones by dipstick
Serum ketones (if urine ketones are present)
Blood gas (if urine ketones or anion gap are present)
Electrocardiogram
CT head to exclude other causes
Treatment
Fluid replacement to correct hypovolemia and hyperosmolality
Insulin infusion
Close electrolyte monitoring with potassium, magnesium and phosphate replacement
Treat precipitant (e.g., sepsis)

Table 12 Postictal Todd’s Paresis [12, 13] Table 13 Hemiplegic migraine [14, 15]

History History
Follows seizure Typical hemiplegic migraine attacks start in the first or second decade of
More common when seizures prolonged (status epilepticus) life and include gradually progressing visual, sensory, motor, aphasic
Can last seconds, but often has a duration of hours and often basilar-type symptoms, accompanied by headaches
Examination Most patients also have attacks of migraine with typical aura without
weakness
Weakness always present, but wide variation in location, severity, dura- Aura may consist of a fully reversible motor weakness
tion, tone reflexes and sensory involvement The weakness may resolve before the headache starts or may persist for
Investigations days
To exclude other forms of weakness May be preceded by a prodrome of affective symptoms 24–48 h prior to
the migraine
Treatment May be accompanied by ipsilateral numbness or tingling, with or without
Supportive a speech disturbance
Examination
Neurological examination assessing for other causes of hemiplegia
The short-time course and full reversibility of deficit are key components
Investigations
Diagnosis of exclusion
CT or MRI to exclude other etiologies
Treatment
Early neurologist involvement
Anti-emetics, nonsteroidal anti-inflammatory drugs and non-narcotic
pain relievers
Triptans and ergotamine preparations are contraindicated because of
their potential vasoconstrictive effects
There is no evidence for antiplatelet agents
Table 14 Brown-Sequard syndrome [16, 17]
History
Sudden onset hemiplegia with contralateral loss of pain and temperature
Incomplete hemisection causing Brown-Sequard syndrome plus other
signs and symptoms is more common than the classical form
Non-traumatic causes include
Extramedullary spinal neoplasm
Herniated cervical intervertebral disc
Transverse myelitis
Examination
Ipsilateral weakness
Ipsilateral loss of proprioception and vibratory sensation
Contralateral loss of pain and temperature sensation
Investigations
MRI
CT myelography if MRI contraindicated
Treatment
Spinal precautions if from traumatic injury
Surgery with spinal cord decompression
See ENLS Spinal Cord Compression and ENLS Traumatic Spinal Injury
Protocols
Table 15 Transverse myelitis [18–20]
History
The development of isolated spinal cord dysfunction over hours or days
in patients in whom there is no evidence of a compressive lesion
Segmental spinal cord injury caused by acute inflammation, usually
thoracic cord
50% have preceding infection, often viral
Can occur in multiple sclerosis or neuromyelitis optica
Symptoms usually develop over hours
Present with weakness and sensory disturbance below the level of the
lesion
Back pain with bladder and bowel dysfunction is common
Examination
Evidence of myelopathy, with weakness and sensory symptoms that cor-
respond to a specific level
Increased or decreased sensation may be present
Investigations
MRI is diagnostic; however, negative MRI does not exclude diagnosis
Treatment
Many patients are treated with IV methylprednisolone, IVIG or plasma
exchange
Table 16 Spinal cord infarction [21]
History
Acute quadraparesis or paraparesis with a sensory level corresponding
with level of cord infarct
No historical suspicion of trauma or infection
60% of patients present with pain that localizes to the level of injury
May be associated with aortic surgery or procedures
Risk factors: female sex, atrial fibrillation with no anticoagulation, hyper-
tension, hypercholesterolemia, type II diabetes, smoking, hypercoagu-
lable states
Examination
Anterior spinal artery syndrome is most common: loss of motor function
and pain/temperature sensation, with relative sparing of propriocep-
tion and vibratory sense below the level of lesion
Initially presents with a flaccid paralysis and loss of deep tendon reflexes
Usually bilateral weakness, occasionally unilateral
Posterior spinal artery syndrome: loss of proprioception and vibratory
sense below the level of the injury and total anesthesia at the level of
injury; weakness usually mild/transient
Other variants possible
Investigations
MRI is diagnostic, showing an ischemic lesion defined as a well-demar-
cated T2-weighted hyperintensity matching an arterial territory of the
cord
Spinal angiogram recommended if vascular malformation suggested
from MRI
Other investigations are as for ischemic stroke, i.e., prothrombotic and
vasculitis screen, toxicology screen, echocardiography, duplex ultra-
sonography of the cervical arteries, chest X-ray, electrocardiography,
24-h Holter electrocardiography
Treatment
Supportive treatment only
Corticosteroids are currently not recommended, as the current literature
indicates minimal benefits outweighed by the risks of this treatment
Consider antiplatelet agents in patients with underlying vascular risk
factors or comorbid vascular disease to prevent more secondary
atherothrombotic events
Table 17 Hyponatremia, hypernatremia [22–26]
History
Hyponatremia: diuretic overdose, hypervolemia, CHF, cirrhosis, SIADH,
cerebral salt wasting and water intoxication
Hypernatremia: dehydration, pituitary insufficiency, iatrogenic sodium
supplementation
Lethargy and confusion are most common neurologic manifestations
At either extreme in serum sodium concentration, seizures and coma
may occur
Examination
Depressed level of consciousness or delirium
Investigations
Serum sodium levels
Treatment
Hyponatremia: fluid restriction, stop diuretics, avoid rapid correction of
serum sodium
Hypernatremia: IV fluids if hypovolemic, hypotonic solutions prefer-
able, avoid rapid correction to normal, if urine specific gravity is low
consider pituitary insufficiency and administer DDAVP
Table 18 Hypermagnesemia [25]

History
Typically follows excessive magnesium administration in context of renal impairment
More likely when supranormal magnesium levels targeted (e.g., in management of pre-eclampsia)
Lethargy and confusion are most common neurologic manifestations
As concentrations rise, generalized weakness develops, which progresses to involve muscles of respiration resulting in respiratory failure
Examination
Hyporeflexia: early loss of deep tendon reflexes often precedes other signs
Flaccid quadraparesis involving all muscle groups
Lethargy, confusion
Investigations
Serum magnesium levels
Treatment
Cease magnesium administration
IV calcium gluconate or chloride if symptoms severe
IV fluids
Consider dialysis

Table 19 Hypophosphatemia [27, 28]

History
Hypophosphatemia may occur with
Intracellular shift: re-feeding syndrome, respiratory alkalosis, diabetic ketoacidosis, rapidly growing malignancies, osmotic diuresis, certain drugs includ-
ing diuretics, malabsorption, renal tubular acidosis
Increased urinary excretion: primary or secondary hyperparathyroidism, osmotic diuresis (e.g., hyperosmolar hyperglycemic syndrome), diuretics, renal
tubular acidosis, transplanted kidneys, congenital defects or Fanconi syndrome
Decreased intestinal absorption: diarrhea, malabsorption syndromes, phosphate binders (e.g., aluminum hydroxide)
Decreased dietary intake: anorexia nervosa or chronic alcoholism
Hypothermia
Weakness may present as a painful proximal myopathy
Other neurological symptoms may include changes in mental function, seizures and neuropathies
Other features may include arrhythmias, skeletal muscle weakness, respiratory failure, rhabdomyolysis, leukocyte dysfunction, sepsis and sudden death
Examination
Proximal muscle weakness is common, though any muscle group may be involved, alone or in combination, ranging from ophthalmoplegia to proxi-
mal myopathy to dysphagia or ileus
Muscle pain is common
Weakness may be so profound as to mimic Guillain–Barre syndrome [70]
Confusion, seizures and coma may occur
Impaired cardiac contractility may occur, leading to generalized signs of myocardial depression
Investigations
Serum phosphate
Hypomagnesemia is commonly associated
Hypercalcemia if hyperparathyroidism
Urea, creatinine, other electrolytes
Rhabdomyolysis screen
Treatment
Correct precipitant
Replace total body phosphate with careful IV sodium or potassium phosphate
Table 20 Acute myopathy [36] Table 21 Myasthenia gravis [37–39]

History History
Typically present with symmetric proximal muscle weakness, malaise and History of myasthenia gravis (but may have not been diagnosed)
fatigue Acute decompensation may be spontaneous or precipitated by infection,
No sensory complaints except occasional myalgia surgery or tapering of immunosuppression
Metabolic causes: periodic paralyses, hypo- and hyperkalemia, hypophos- Drugs may precipitate symptoms, including certain antibiotics, beta-
phatemia blockers and magnesium
Inflammatory causes: rhabdomyolysis, polymyositis, dermatomyositis, Excessive treatment with cholinesterase inhibitors may paradoxically
infectious causes cause weakness and increased secretions worsening respiration acutely
Toxic etiologies: alcohol, corticosteroids, statins, retroviral agents, colchi- A myasthenic crisis refers specifically to worsening symptoms causing
cine, cocaine, heroin potential respiratory failure
Endocrine causes: Addison’s disease, Cushing’s disease, hypo- or hyper- Examination
thyroidism, hyperparathyroidis
85% of patients have involvement of the eyelids and extraocular muscles,
Examination resulting in ptosis and/or diplopia
Symmetric proximal muscle weakness Weak, flaccid facial muscles
No sensory disturbance other than myalgia Nasal speech with impaired bulbar reflexes
Fever may be present in rhabdomyolysis, polymyositis, and infectious Neck and proximal limb weakness may occur
causes Respiratory failure occurs in 1%
Other findings specifically associated with associated endocrinopathies Respiratory examination may reveal evidence of aspirated secretions or
may be present infection
Investigations Investigations
CK with isoenzymes (may not correlate with clinical condition) Ice pack test (e.g., ice on affected eyelid improves ptosis)
Electrolytes, calcium, magnesium ACh receptor antibodies if diagnosis uncertain, present in 85% of cases;
Serum urea, creatinine and electrolytes anti-MuSK is present in the majority of those without anti-ACh antibod-
Complete blood count ies
Erythrocyte sedimentation rate Pulmonary function tests
Aspartate aminotransferase Consider arterial blood gas
Urinalysis: myoglobinuria Consider CT chest (thymoma may affect breathing)
Specific workup for individual endocrinopathies Treatment
Consider EMG, nerve conduction velocity testing and muscle biopsy
For acute decompensation, admit to ICU
Treatment Frequent forced vital capacity measurement
Remove or treat any precipitant If respiratory involvement, withdraw anticholinesterase medications
Safely correct electrolyte abnormalities Plasmapheresis or IVIG
Vigorous hydration for rhabdomyolysis High dose steroids (e.g., 80 mg prednisolone)
Consider other immunosuppressants
Table 22 Diabetic lumbosacral radiculoplexus neuropathy [40–42]

History
Diabetes mellitus with proximal weakness in the quadriceps, hip adductors and iliopsoas muscles
Asymmetrical pain in the hip, buttock or thigh
Often occurs in conjunction with significant recent weight loss
Associated with poor glycemic control
Patients without distal symmetrical polyneuropathy most often have sudden, unilateral onset
Occasionally the initial presenting feature of diabetes mellitus
Examination
Proximal lower limb muscle weakness and wasting
Minimal sensory loss is observed
Knee-jerk reflex is absent, with commonly preserved ankle jerks
Ankle jerks may also be absent, with underlying distal symmetrical polyneuropathy
Investigations
Fasting blood glucose and Hb A1c
Imaging of lumbosacral spine to exclude other causes
EMG and nerve conduction studies
Treatment
Optimize glycemic control
Physical and occupational therapy

Table 23 Guillain–Barre syndrome [50–58]

History
Usually follows 2–4 weeks after mild respiratory or gastrointestinal illness
Typically symmetrical ascending paralysis
10% present with upper limb or facial weakness
Respiratory failure occurs in approximately 10% and oculomotor weakness in 15%
Limb paresthesia is common (80%)
Dysautonomia occurs in 70%
Examination
Absent deep tendon reflexes
Signs of respiratory failure
In acute motor axonal neuropathy variant, sensation is preserved and occasionally deep tendon reflexes
Acute motor and sensory axonal neuropathy has more sensory symptoms
Other rarer variants exist
Investigations
CSF analysis: elevated protein, normal cell count
Electromyography
Nerve conduction studies
Glycolipid antibodies may be associated with different subtypes
Treatment
Supportive care
Plasma exchange and IVIG are equivalent in efficacy, and both improve outcome. Choice depends on local availability, patient preference, risk factors
and contraindications
Corticosteroids have no benefit and may worsen the condition
Table 24 Vasculitic neuropathy [59, 60] Table 26 Organophosphate toxicity [64–66]

History History
May be part of systemic vasculitis or a non-systemic vasculitic neuropathy Insecticide exposure (e.g., malathion, parathion, diazinon, fenthion,
Asymmetric or multifocal painful sensorimotor neuropathy is most com- dichlorvos, chlorpyrifos, ethion)
mon presentation Nerve gas exposure (e.g., sarin, VX, soman, tabun)
May present as mononeuritis multiplex or a sensorimotor neuropathy, Ophthalmic agents (e.g., echothiophate, isoflurophate)
which may or may not be symmetric Anti-helminthics (trichlorfon)
Typically sensory symptoms of pain, burning or paresthesias precede Examination
weakness of muscles supplied by the affected nerve
Sensory symptoms virtually always present Fasciculations with paralysis
Constitutional symptoms, including weight loss, anorexia, fatigue, arthral- Bronchospasm, bradycardia, miosis, lacrimation, salivation, bronchorrhea,
gia, myalgia, and fevers occur in approximately two-thirds of patients urination, emesis and diarrhea
At 48–72 h, neck flexion weakness, decreased deep tendon reflexes,
Examination cranial nerve abnormalities, proximal muscle weakness and respiratory
Detailed neurological examination reveals a flaccid asymmetric paresis insufficiency may develop
with sensory abnormalities in variable distributions At 1–3 weeks, ascending flaccid paralysis may develop (delayed neuropa-
Lower limbs are more commonly involved than upper limbs thy)
Distal involvement is more frequent than proximal Investigations
Cranial nerve involvement occurs in 8% of patients, typically involving
the facial nerve RBC acetyl cholinesterase (if available) for severity and to guide oxime
Proximal symmetric polyneuropathy is least frequent presentation therapy
Investigations Treatment
Vasculitic screen, including erythrocyte sedimentation rate, anti-nuclear Remove contaminated clothes
antibodies, extractable nuclear antigens, rheumatoid factor, anti- 100% oxygen
neutrophil cytoplasmic antibodies, hepatic enzymes, renal function Intubation (no succinylcholine)
tests, serum complement serum immunoelectrophoresis (or immuno- Atropine 2–3 mg IV stat, then double the dose every five minutes until
fixation) and quantitative immunoglobulins, cryoglobulins, Hepatitis B bronchospasm and secretions are controlled; an infusion may be
antigen and antibody, Hepatitis C antigen and CBC (anemia) required, and glycopyrrolate is an alternative
Nerve conduction studies and EMG If pralidoxime is considered, it must be used in conjunction with atropine.
Nerve and muscle biopsy A response to atropine should be established before pralidoxime is
administered
Treatment Loading dose: 2 g over 15 min
Consider combination therapy with steroids and cyclophosphamide in Maintenance dose: 500 mg/h as a continuous infusion
liaison with treating neurologist Consider benzodiazepines for the prevention and treatment of seizures
Manage neuropathic pain with agents such as pregabalin, gabapentin,
amitriptyline, nortriptyline or carbamazepine

Table 25 Toxin-induced peripheral neuropathy [61]

History
Many drugs and industrial chemicals may cause distal axonopathy
Drugs include alcohol, amiodarone, chloramphenicol, disulfiram, isonia-
zid, lithium, metronidazole, nitrofurantoin, nitrous oxide, thalidomide,
vincristine and thallium. Dose, duration of exposure and host factors
affect outcome
Presentation is often with pain, paresthesia, and hypoesthesia in the feet
and distal weakness and gait disturbance
Autonomic dysfunction may be present
Examination
Sensory changes in glove and stocking distribution
Distal weakness that progresses proximally
Hyporeflexia, symmetrical loss of ankle jerks first
May be evidence of CNS involvement
Investigations
EMG
Nerve conduction study
Serum levels for suspected toxin
Consider nerve and muscle biopsies
Treatment
Prevent ongoing exposure
Supportive care
Table 27 Envenomation [67, 68]
History
Snake bite
Scorpion sting (C. exilicauda and C. suffusus)
Funnel web spider and widow spiders
Marine envenomation (mainly Australia):
Stonefish
Blue-ringed octopus
Ingestion of puffer fish (prepared as delicacy in Japan: fugu)
Examination
Snake bites
Cardiovascular: hypotension, shock, arrest
Neurological: paralysis- ptosis, diplopia, bulbar palsy, dysarthria; progres-
sion to respiratory muscle paralysis; desaturation is a late sign
Coagulopathy: decreased GCS due to intracranial hemorrhage, bleeding
from bite site, ecchymoses, bleeding gums, hemarthroses
Rhabdomyolysis: tender muscles
Bite site: bleeding and necrosis; do not remove the pressure immobiliza-
tion bandage to examine the bite site
Scorpion sting
Cranial nerve and somatic skeletal neuromuscular dysfunction, with pain
and parasthesia
Spider bites
Latrodectism is related to neurotoxins present in the venom of widow
spiders. Most cases present with headache, lethargy, irritability, myalgia,
tremor, fasciculation or ataxia
Loxoscelism is caused by envenoming by spiders of the family Sicariidae.
It may present with a stroke due to a severe coagulopathy
Funnel spider (Australia) envenomation stimulates neurotransmitter
release, resulting in sensory disturbances and muscle paralysis
Blue-ringed octopus and puffer fish envenomation
Descending symmetrical flaccid paralysis with clear sensorium, nausea
and vomiting, blurred vision, ataxia, respiratory failure; symptoms
delayed if ingested
Stonefish envenomation
Weakness in the affected limb, severe pain, shock
Investigations
All envenomations: serial pulmonary function tests if descending paraly-
sis; other investigations as clinically indicated
Snake bite: CBC, EUC, LFTs, CK, whole blood clotting time, coagulation
screen, D-dimer, fibrinogen levels, urinalysis for blood (myoglobin),
head CT if decreased GCS; if envenomation suspected on the basis of
clinical findings and pathology, use venom detection kit for bite swab
and urine to determine appropriate anti-venom
Treatment
Pressure immobilization bandage
Immediate transport to a hospital
Anti-venom, preferably specific
Correction of hemostatic disorder
Supportive care with early intubation for paralysis
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
References
* Important papers
** Landmark papers
1. Kasprowicz M, Burzynska M, Melcer T, Kubler A. A comparison of the full
outline of unresponsiveness (FOUR) score and Glasgow Coma Score
(GCS) in predictive modelling in traumatic brain injury. Br J Neurosurg.
2016;30(2):211–20.
2. Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The
Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol.
2014;13(8):844–54.
3. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland
RL. Validation of a new coma scale: the FOUR score. Ann Neurol.
2005;58(4):585–93.
4. Mehta S. Neuromuscular disease causing acute respiratory failure. Respir
Care. 2006;51(9):1016–21 (discussion 1021–1023).
5. Lawn ND, et al. Anticipating mechanical ventilation in Guillain-Barre
syndrome. Arch Neurol. 2001;58(6):893–8.
6. *Teleb MS, et al. Stroke vision, aphasia, neglect (VAN) assessment-a
novel emergent large vessel occlusion screening tool: pilot study and
comparison with current clinical severity indices. J Neurointerv Surg.
2017;9(2):122–6. Strokes are by far the most common cause of non-trau-
matic weakness in adults. VAN is the most recently described screening tool
for large vessel strokes and is helpful in the first assessments of patients.
7. DeAngelis LM. Brain tumors. N Engl J Med. 2001;344(2):114–23.
8. Muzumdar D, Jhawar S, Goel A. Brain abscess: an overview. Int J Surg.
2011;9(2):136–44.
9. DeRosa MA, Cryer PE. Hypoglycemia and the sympathoadrenal system:
neurogenic symptoms are largely the result of sympathetic neural,
rather than adrenomedullary, activation. Am J Physiol Endocrinol Metab.
2004;287(1):E32–41.
10. Guisado R, Arieff AI. Neurologic manifestations of diabetic comas:
correlation with biochemical alterations in the brain. Metabolism.
1975;24(5):665–79.
11. Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes.
Diabetes Care. 2009;32(7):1335–43.
12. Gallmetzer P, et al. Postictal paresis in focal epilepsies–incidence,
duration, and causes: a video-EEG monitoring study. Neurology.
2004;62(12):2160–4.
13. Rolak LA, et al. Clinical features of Todd’s post-epileptic paralysis. J Neurol
Neurosurg Psychiatry. 1992;55(1):63–4.
14. Olesen J, Steiner TJ. The international classification of headache disorders.
Cephalalgia. 2004;24(Suppl 1):9–160.
15. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine:
pathophysiological mechanisms, clinical characteristics, diagnosis, and
management. Lancet Neurol. 2011;10(5):457–70.
16. Sayer FT, et al. Brown-Sequard syndrome produced by C3–C4 cervical
disc herniation: a case report and review of the literature. Spine (Phila Pa
1976). 2008;33(9):E279–82.
17. Antich PA, et al. High cervical disc herniation and Brown-Sequard
syndrome. A case report and review of the literature. J Bone Joint Surg Br.
1999;81(3):462–3.
18. Brinar VV, et al. The differential diagnosis of acute transverse myelitis. Clin
Neurol Neurosurg. 2006;108(3):278–83.
19. Chen L, et al. Prognostic indicators of acute transverse myelitis in 39
children. Pediatr Neurol. 2013;49(6):397–400.
20. Pidcock FS, et al. Acute transverse myelitis in childhood: center-based
analysis of 47 cases. Neurology. 2007;68(18):1474–80.
21. Novy J, et al. Spinal cord ischemia: clinical and imaging patterns, patho-
genesis, and outcomes in 27 patients. Arch Neurol. 2006;63(8):1113–20.
22. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ.
2006;332(7543):702–5.
23. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med.
2000;342(20):1493–9.
24. Schrier RW, Bansal S. Diagnosis and management of hyponatremia in
acute illness. Curr Opin Crit Care. 2008;14(6):627–34.
25. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol
Clin. 2002;20(1):227–39, vii.
26. Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for
controlled correction. Am J Kidney Dis. 2010;56(4):774–9.
27. Ravid M, Robson M. Proximal myopathy caused by latrogenic phosphate
depletion. JAMA. 1976;236(12):1380–1.
28. Sebastian S, Clarence D, Newson C. Severe hypophosphataemia mimick-
ing Guillain–Barre syndrome. Anaesthesia. 2008;63(8):873–5.
29. Kiernan MC, et al. Amyotrophic lateral sclerosis. Lancet.
2011;377(9769):942–55.
30. Racaniello VR. One hundred years of poliovirus pathogenesis. Virology.
2006;344(1):9–16.
31. Marx A, Glass JD, Sutter RW. Differential diagnosis of acute flaccid
paralysis and its role in poliomyelitis surveillance. Epidemiol Rev.
2000;22(2):298–316.
32. Maloney JA, et al. MRI findings in children with acute flaccid paralysis and
cranial nerve dysfunction occurring during the 2014 enterovirus D68
outbreak. AJNR Am J Neuroradiol. 2015;36(2):245–50.
33. Messacar K, et al. A cluster of acute flaccid paralysis and cranial nerve
dysfunction temporally associated with an outbreak of enterovirus D68 in
children in Colorado, USA. Lancet. 2015;385(9978):1662–71.
34. Kramer R, Lina B, Shetty J. Acute flaccid myelitis caused by enterovirus
D68: case definitions for use in clinical practice. Eur J Paediatr Neurol.
2019;23(2):235–9.
35. WHO 10 facts on polio eradication. 2017 [cited 2019 8/1/2019]. https​://
www.who.int/featu​res/factf​i les/polio​/en/.
36. Kuncl RW. Agents and mechanisms of toxic myopathy. Curr Opin Neurol.
2009;22(5):506–15.
37. Grob D, et al. Lifetime course of myasthenia gravis. Muscle Nerve.
2008;37(2):141–9.
38. Meriggioli MN, Sanders DB. Advances in the diagnosis of neuromuscular
junction disorders. Am J Phys Med Rehabil. 2005;84(8):627–38.
39. Roper J, et al. Myasthenia Gravis and Crisis: evaluation and management
in the emergency department. J Emerg Med. 2017;53(6):843–53.
40. Barohn RJ, et al. The Bruns-Garland syndrome (diabetic amyotrophy).
Revisited 100 years later. Arch Neurol. 1991;48(11):1130–5.
41. Tracy JA, Dyck PJ. The spectrum of diabetic neuropathies. Phys Med
Rehabil Clin N Am. 2008;19(1):1–26, v.
42. Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med.
2001;344(22):1688–700.
43. *Evoli A. Myasthenia gravis: new developments in research and treat-
ment. Curr Opin Neurol. 2017;30(5):464–70. This update describes the
unique pathophysiology, diagnosis and treatment of a cause of non-trau-
matic weakness that can result in severe consequences including neuromus-
cular respiratory failure.
44. Gilhus NE. Myasthenia and the neuromuscular junction. Curr Opin Neu-
rol. 2012;25(5):523–9.
45. Abel M, Eisenkraft JB. Anesthetic implications of myasthenia gravis. Mt
Sinai J Med. 2002;69(1–2):31–7.
46. Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton
myasthenic syndrome. Cochrane Database Syst Rev. 2011;2:Cd003279.
47. Long SS. Infant botulism. Pediatr Infect Dis J. 2001;20(7):707–9.
48. Chalk CH, et al. Medical treatment for botulism. Cochrane Database Syst
Rev. 2019;4:Cd008123.
49. *Berkowitz AL. Tetanus, botulism, and diphtheria. Continuum (Minneap
Minn). 2018;24((5, Neuroinfectious Disease)):1459–88. This review article
gives prospective of neurologic conditions that are rare in higher resource
settings but endemic elsewhere in the world.
50. Ropper AH. The Guillain-Barre syndrome. N Engl J Med.
1992;326(17):1130–6.
51. Seneviratne U. Guillain-Barre syndrome. Postgrad Med J.
2000;76(902):774–82.
52. Meena AK, Khadilkar SV, Murthy JM. Treatment guidelines for Guillain-
Barre syndrome. Ann Indian Acad Neurol. 2011;14(Suppl 1):S73–81.
53. Alshekhlee A, et al. Guillain-Barre syndrome: incidence and mortality rates
in US hospitals. Neurology. 2008;70(18):1608–13.
54. Ropper AH, Victor M. Influenza vaccination and the Guillain-Barre syn-
drome. N Engl J Med. 1998;339(25):1845–6.
55. *Pritchard J, et al. Pharmacological treatment other than corticosteroids,
intravenous immunoglobulin and plasma exchange for Guillain-Barre
syndrome. Cochrane Database Syst Rev. 2016;11:Cd008630. Guillain–Barre
is one of the more common causes of non-traumatic weakness from periph-
eral neuropathies; this provides a review of the latest evidence for treatment.
56. Wachira VK, Peixoto HM, de Oliveira MRF. Systematic review of factors
associated with the development of Guillain-Barre syndrome 2007–2017:
what has changed? Trop Med Int Health. 2019;24(2):132–42.
57. Zuccoli G, et al. Redefining the Guillain-Barre spectrum in children: neu-
roimaging findings of cranial nerve involvement. AJNR Am J Neuroradiol.
2011;32(4):639–42.
58. Ropper AH. Further regional variants of acute immune polyneuropathy.
Bifacial weakness or sixth nerve paresis with paresthesias, lumbar polyra-
diculopathy, and ataxia with pharyngeal-cervical-brachial weakness. Arch
Neurol. 1994;51(7):671–5.
59. Davies L, et al. Vasculitis confined to peripheral nerves. Brain. 1996;119(Pt
5):1441–8.
60. Mathew L, et al. Treatment of vasculitic peripheral neuropathy: a retro-
spective analysis of outcome. QJM. 2007;100(1):41–51.
61. *London Z, Albers JW. Toxic neuropathies associated with pharmaceutic
and industrial agents. Neurol Clin. 2007;25(1):257–76. A review of causes of
non-traumatic weakness from exposures, many of which are highly treatable
when identified.
62. Neal S, Fields KB. Peripheral nerve entrapment and injury in the upper
extremity. Am Fam Physician. 2010;81(2):147–55.
63. Fox IK, Mackinnon SE. Adult peripheral nerve disorders: nerve entrap-
ment, repair, transfer, and brachial plexus disorders. Plast Reconstr Surg.
2011;127(5):105e–18e.
64. Eddleston M, et al. Management of acute organophosphorus pesticide
poisoning. Lancet. 2008;371(9612):597–607.
65. Roberts DM, Aaron CK. Management of acute organophosphorus pesti-
cide poisoning. BMJ. 2007;334(7594):629–34.
66. Aitio A et al. WHO-UNEP sound management of pesticides and diagnosis
and treatment of pesticide poisoning. 2006. [cited 2019 7/31/2019]. https​
://www.who.int/ipcs/asses​sment​/publi​c_healt​h/Sound​Manag​ement​Pesti​
cides​_Resou​rceTo​ol.pdf.
67. Warrell DA. Snake bite. Lancet. 2010;375(9708):77–88.
68. White J. Venomous animals: clinical toxinology. Exs. 2010;100:233–91.
69. Orebaugh SL. Succinylcholine: adverse effects and alternatives in emer-
gency medicine. Am J Emerg Med. 1999;17(7):715–21.
70. Wolf VL, Lupo PJ, Lotze TE. Pediatric acute transverse myelitis overview
and differential diagnosis. J Child Neurol. 2012;27(11):1426–36.
71. Bernard TJ, et al. Emergence of the primary pediatric stroke
center: impact of the thrombolysis in pediatric stroke trial. Stroke.
2014;45(7):2018–23.
72. Kidwell CS, Starkman S, Eckstein M, Weems K, Saver JL. Identifying stroke
in the field. Prospective validation of the Los Angeles prehospital stroke
screen (LAPSS). Stroke. 2000;31(1):71–6.
73. Zhelev Z, Walker G, Henschke N, Fridhandler J, Yip S. Prehospital stroke
scales as screening tools for early identification of stroke and transient
ischemic attack. Cochrane Database Syst Rev. 2019;4:Cd011427.
74. Maddali A, Razack FA, Cattamanchi S, Ramakrishnan TV. Validation
of the cincinnati prehospital stroke scale. J Emerg Trauma Shock.
2018;11(2):111–4.