2. Objectives
• Review seizure pathophysiology
• Manage Status Epilepticus
• Be comfortable with anticonvulsant drugs and
adjuncts
• Use an anatomic approach to neuromuscular
weakness
• Manage emergent potentially life threatening
weakness
• Review and differentiate diagnosis and
management of select causes of weakness
3. Case 1
• 23 yo F brought to ED by friend confused,
lethargic but rousable
• Triage VS: HR 115 BP 118/80 RR 20 T 37.5 Sat
97%
• PMH: Migraines
• Nurse calls you to bedside as she is having
generalized tonic/clonic seizures
• How would you manage this patient?
6. Case 2
• 63 yo M homeless found down at shelter
• Unknown PMH/meds except EtOH abuse and
recent depression
• Appears dishevelled and mumbling at triage
• HR 112 BP 168/87 RR 20 T 37.1 Sat 96%
• ABCs intact
• Glucose 7.7 GCS 11-12
7. Examination
• H+N : no sign of trauma, vomitus around
mouth, neck supple
• Chest: decreased AE at bases
• CV: unremarkable
• Abdo: unremarkable
• Ext: erythematous skin lesion on arm
• Neuro exam: non focal
8. Investigations
• Bedside CXR: normal
• EKG: sinus tachycardia
• Nurse sends CBC, lytes, blood gas, tox screen
• Patient starts to seize
• Please outline your management
9. Labs
• Na 141 K 4.8 Cl 95
• pH 7.0 HCO3 9 pCO2 30
• Lactate 7
• Tox screen: negative
• Ethanol level : 20
• APAP and ASA levels negative
• Rest of labs are within normal limits
18. Status epilepticus
• Continuous seizures >5 min
• >2 discrete seizure without intervening
recovery of consciousness
• Can cause neuronal damage
• Can become refractory over time
• Underlying pathology determines M&M
19. Treatment goals
• Manage ABCs
– A: position, NPA, intubate
– B: 100% O2, prevent prologed
hypocapnia/acidosis, BMV may be impossible
– C: IV/IO access ASAP, monitoring may be
impossible
• Abort seizure (use IM/intranasal/buccal/rectal
routes prn)
• Treat underlying cause
20. Non convulsive status epilepticus
• Can occur after prolonged status epilepticus
or incomplete treatment
• Small amplitude twitching/jerking of eyes
• No visible motor activity with seizure activity
on EEG
• NCSE present in up to 9% hospitalized patients
with prolonged AMS
• Mortality 30% if seizing >1hour
25. The “cocktail” works well for:
Etiology
• Epilepsy, neurodegenerative
diseases, stroke, CNS
vasculitis
• Structural causes (trauma,
ICH, masses
• Infectious (HIV, meningitis,
encephalitis, parasites)
• Most toxic seizures and
withdrawal
Definitive Management
• Targeted therapies
(antiepileptics, tPA, steroids,
etc.), Neurology assessment
• CT, ICP management,
Neurosurgery
• LP, antibiotics, antivirals,
antimalarials/antifungals
• Supportive care,
decontamination, enhanced
elimination, antidote
26. Seizures persist: think outside the box
Etiology
• Hypoglycemia
• Hyponatremia (<120 mEq/l)
• Hypocalcemia (<1.9 mmol/l)
• Hypomagnesemia (<0.4
mmol/l)
• Eclampsia
• Na-Channel blockers intox
• INH intox
• Cholinergic (OP/nerve
agent) intox
Immediate management
• D50W (50ml IVP)
• 3% NS (100ml over 10min)
• CaCl 10% (10ml over 10min)
• MgSO4 (2g over 15 min)
• MgSO4 (4-6g over 15min)
• NaHCO3 (1-2 mEq/kg IVP)
• Pyridoxine (5g empiric, or
1g/kg, or 1:1 if known dose)
• Atropine (1g q5min) 2-PAM
(1-2g over 5-10min)
27.
28. Case 3
• 68 yo F in ED feeling “weak and dizzy”
• Evaluated by previous MD
• Signed over to you as “probable viral illness,
exam and x-rays normal, cleared for discharge
if labs normal”
• Nurse relates CBC extended electrolytes, renal
and liver function are normal, except patient
unable to get up complaining of numbness in
legs
29. Exam
• ABCs intact
• VS: HR 78 BP 132/78 RR 15 Sat 99 T 36.9
• GCS 15 PERRLA
• Chest: unremarkable
• CV: unremarkable
• Abdo unremarkable
• Ext: no swelling tenderness or deformity
• Please outline your next steps in management
30. Case 4
• 42 yo M presents with weakness and diplopia
• PMH: unremarkable
• Meds: none
• Social: admits to occasional IVDU
• HR 80 BP 135/90 RR 15 Sat 98%
• A: intact
• B: good AE bilat
• C: well perfused
• GCS 15 Pupils 5mm bilat
31. Exam
• Neuro exam:
• CN: diplopia with EOM, dysconjugate gaze, mild
slurred speech, rest of CN normal
• Power: UE 3/5 LE 4/5
• Sensory normal
• Reflexes: diminished in UE, normal in LE
• Gait/cerebellar normal
• Rest of exam unremarkable
• Outline your management
43. Background
• Acute polyneuropathy due to immune-mediated
peripheral nerve myelin sheath destruction
• Associated with:
– viral or febrile illness
– campylobacter infection
– vaccination
• Symptoms:
– worst 2-4wk after onset,
– plateau for 2-4wk
– remit from wks-months
44. Clinical Features
• Viral illness -> ascending, symmetric weakness or
paralysis and loss of DTRs
• May progress to diaphragm resulting in need for
mechanical ventilation (33% of pts)
• Autonomic dysfunction occurs in 50% of pts
• Miller-Fisher Syndrome
– Associated w/ campylobacter infection
– More likely to be preceded by diarrhea than viral
prodrome
– Consists of ophthalmoplegia and ataxia
– Weakness is less severe but descending; disease course
milder than classic GBS
45. Diagnosis
• Required
– Progressive weakness of more than one limb
– Areflexia
• Suggestive
– Progression over days to weeks
– Recovery beginning 2—4 wk after cessation of progression
– Relative symmetry of symptoms
– Mild sensory signs and symptoms
– CN involvement (Bell's palsy, dysphagia, dysarthria, ophthalmoplegia)
– Autonomic dysfunction
– Absence of fever at onset
– Cytoalbuminologic dissociation of CSF (high protein (>45) and low
WBC count (<10))
– Typical findings on electromyogram and nerve conduction studies
46. Treatment
• Intubation indications:
– Vital capacity <15mL/kg
– PaO2 <70 mm Hg on room air
– Bulbar dysfunction (difficulty with breathing,
swallowing, or speech)
– Aspiration
• IVIG or plasmapheresis (provide equivalent
but not additive effects)
47. Disposition
• Indications for admission to ICU:
– Autonomic dysfunction
– Bulbar dysfunction
– FVC <20 mL/kg
– NIF <30 cm H2O
– Decrease of >30% of FVC or NIF
– Inability to ambulate
– Treatment with plasmapheresis
– Anticipated clinical course requiring mechanical
ventilation
49. Background
• Clostridium botulinum produces toxin that
blocks Ach release from presynaptic
membrane
• Cases due to:
– Improper canning
– Black-tar heroin use
– Wound infection (contaminated wounds, C-
section, tooth abscess, sinus infection)
• Symptoms begin 6-48hr after exposure
50. Clinical Features
• GI
– N/V, abdo cramps, diarrhea or constipation
– Not seen in pts who contract botulism from heroin or
contaminated wound
• Paralysis
– Descending, symmetric
– Cranial nerves and bublar muscles are affected first:
diplopia, dysarthria, dysphagia
• Will progress to respiratory depression if not treated
• Anticholinergic signs
– Urinary retention, dry skin/eyes, hyperthermia
• Dilated pupils (in contrast to pts w/ MG)
51. Infantile Botulism
• Background
– Due to consumption of botulinum spores (usually from
honey)
• Higher GI tract pH of infants makes them more susceptible
– Most cases occur in <1yr, 90% occur in <6m
• Clinical Features
– GI
• Constipation
• Poor feeding
– Lethargy
– Weak cry
– Floppy infant
52. Management
• Ventilatory support
– Consider intubation when FVC <30% predicted or
<15cc/kg
• Antitoxin/immune globulin
• Infant
– Supportive care only (no benefit from antitoxin or abx)
• Wound
– Antitoxin, wound irrigation & debridement, Pen G 10-
20 mil units/day
• Disposition
– ICU
54. Background
• Autoantibody degradation, dysfunction, and
blockade of acetylcholine receptor at the NMJ
• Thymus is abnormal in 75% of pts
– Thymectomy resolves or improves symptoms in
most pts, especially those with a thymoma
• No sensory, reflex, pupillary, or cerebellar
deficits
55. Myasthenic Crisis vs. Cholinergic Crisis
• Myasthenic Crisis
– Respiratory failure is feared complication
– Much more common
– Triggers:
• med non-compliance, infection, surgery, tapering of
immunosuppressants, meds (corticosteroids, thyroxine, BBs, CCBs,
Na-channel blockers, aminoglycosides, tetrayclines, clindamycin)
• Cholinergic Crisis
• Excessive anticholinesterase medication may cause weakness and
cholinergic symptoms
• Rarely seen w/ dose limitation of pyridostigmine <120mg q3hr
• If on usual dose of meds assume exacerbation due to MG even w/
cholinergic side effects
• Edrophonium (Tensilon) test to distinguish the two is controversial
– Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm
– Treatment: Atropine
56. Clinical Features
• Fatigable symptoms: worsen with repetitive use / as
the day progresses
– Ice Pack Test- 2 min should improve symptoms temporarily
(usually ptosis; high specificity)
• Muscle weakness
– Proximal extremities
– Neck extensors
– Facial/bulbar muscles (dysphagia, dysarthria, dysphonia)
• Ocular weakness
– Ptosis
– Diplopia
– CN III, IV, or VI weakness
57. Treatment
• Always evaluate FVC, NIF, ability to handle secretions
• Meds
– Pyridostigmine
• If pt's usual dose has been missed the next dose is usually doubled
• PO route: 60-90mg q4hr
• IV route: 1/30th of the PO dose (2-3mg) by slow IV infusion
– Neostigmine
• 0.5mg IV
• Intubation
– If possible avoid depolarizing AND non-depolarizing agents
• If pt requires paralysis use non-depolarizing agent at smaller dose
• If must use depolarizing agents, will need higher doses
• Plasmapherisis
• IVIG
59. Background
• Autoantibodies against Ca-channels of axon
nerve terminals responsible for ACh release
• Epidemiology
– Predominantly a disease a/w older men w/ history
of cigarette smoking and lung cancer
• 50% of pts have concurrent small-cell lung cancer
– Syndrome can precede detection of malignancy by
several years
60. Clinical Features
• Fluctuating symmetric weakness and fatigue, esp of
proximal leg muscles
• Improvement in strength with sustained or repeated
exercise (in contrast to MG)
– Lambert sign: handshake strength increases over several
seconds
• Myalgias
• Muscle stiffness (especially in hip and shoulders)
• Paresthesias
• Metallic taste
• Autonomic symptoms (dry mouth, impotence)
• Eye movements are unaffected
• Sensory examination normal
61. Treatment
• Supportive (progression to respiratory or
bulbar failure is rare)
• Acetylcholinesterase inhibitors (e.g.
pyridostigmine) can improve symptoms
• Disposition
– Admission required when infectious complications
occur or when severe disability requires inpatient
immunotherapy
63. • Background
– Caused by neurotoxin produced by certain ticks in
the US and Australia
– Most cases reported in children
• Clinical Features
– Symptoms begin 2-6d after attachment of tick
• Ataxia -> symmetric ascending flaccid paralysis w/ loss
of DTRs
– Presentation can be identical to Guillain-Barre
including progression to resp paralysis
– Unlike GBS, may have ocular signs (e.g. fixed and dilated
pupils)
64. • Diagnosis
– Sensory abnormalities and elevation of CSF
protein level do not occur
– Progression and resolution of sx (w/ tick removal)
is faster than in Guillain-Barre
• Treatment
– Remove tick as quickly as possible with tweezers
– Supportive care (resolves on its own)
66. Background
• Inflammatory disorder that involves a
complete transverse section of the spinal cord
– Results from viral infection, postvaccination or as
part of MS, SLE, or cancer
• May present exactly like a compressive lesion
of the spinal cord
67. Clinical Features
• May progress over days-weeks
• Neck or back pain + neuro complaints:
– Bilateral motor, sensory, and autonomic
disturbances
– Fecal/urinary retention and incontinence
68. Diagnosis & Management
• Neurologic findings that are c/w epidural
compression but normal MRI
• Must rule-out compressive lesion of the cord
• MRI
– May show cord swelling
• LP
– Lymphocytosis, elevated protein
• Admit for corticosteroids and plasma
exchange
70. Background
• CNS myelin destruction causes variable motor,
sensory, visual and cerebellar dysfunction
• Types
– Relapsing/remitting (most common)
• Relapse (days-months) followed by remission
– Secondary progressive
• Relapses and partial recoveries occur, but disability doesn't
fade away between cycles
– Primary progressive
• Symptoms progress slowly and steadily without remission
– Progressive relapsing
• Similar to primary progressive but with superimposed flares
71. Clinical Features
• Classic pt has multiple presentations for neuro symptoms of
different areas of pathology
– Pt often has resolution of the earlier symptoms
• Symptoms worsen w/ increases in body temperature
• Muscle/sensory signs:
– Lower extremity weakness usually worse than upper extremity
– Upper motor neuron signs:
• Hyperreflexia
• Positive Babinski
– Decrease in proprioception / pain/temp sensation
– Lhermitte sign
• Electric shock sensation radiating down back into arms/egs from neck
flexion
72. Clinical Features
• Optic neuritis
– Initial sign in 30% of pts
– Vision loss (usually unilateral) often preceded by retrobulbar
pain
– Blurred vision
– Nystagus
– Diplopia
– Internuclear ophthalmoplegia
• Abnormal eye adduction bilaterally and horizontal nystagmus
• Dysautonomia
– Urinary retention (increased risk of UTI/pyelo)
– Constipation or incontinence
– Sexual dysfunction (males)
73. Diagnosis
• MRI
– Multiple lesions in supratentorial white matter,
paraventricular area, spinal cord
• CSF
– Elevated protein and gamma-globulin (increased
oligoclonal bands)
74. Management
• Treatment
– Fever must be reduced to minimize weakness assoc
w/ elevated temperature
– Abx for UTI/pyelo
– High-dose steroid therapy for relapses
• Disposition
– Hospitalization indicated for:
• Any disease exacerbation a/w significant morbidity
• IV abx or steroid therapy required
• Depression and significant risk of suicide
76. Background
• Progressive muscle atrophy/weakness due to
degeneration of upper and lower motor
neurons
• Patients will rarely present to the ED
undiagnosed
• Likely related to mutated superoxide
dismutase (SOD1) gene
77. Clinical Features
• Acute respiratory failure
– Predicted by FVC <25 mL/kg or 50% decrease from
normal
• Aspiration pneumonia
• Trauma related to extremity weakness
Seizures are very common presenting complaint to the ED
Know how to differentiate seizures from syncope and pseudoseizures
Understanding the basics here gives insight into how the therapies work
Clinically it is easy to recognize this
Important to ask if witnessed generalized seizures began as focal ones
Any neuron is potentially a focus of seizure activity depending on this balance. Seizure thresholds can be modified by temperature, injury, changes in nutrient or oxygen supply, metabolic disturbances, toxins etc.
This graphic shows which channels, neurotransmitters and receptors are involved on the excitatory side.
A large proportion of anticonvulsants blocking recruitment and propagation by acting on the voltage-gated Na-Channel
Most of these drugs are used in preventative and maintenance therapy
Many other anti-convulsants work on potentiating inhibition
These are more often used in aborting seizures
It is important to know this well in EM because treatment is time dependent and life threatening
Often you are in the resuscitation room and must think on your feet and not make mistakes
Aborting the seizure is often the key to being able to assess and manage the ABCs
Can be subtle and missed. Must have high index of suspicion to look for it.
Many sources/institutions have slightly different recipes but most resemble this
*Use of Keppra as an abortive agent is relatively novel, 3 small size open label RCTs (1 adult and 2 pediatric) show benefit of 20mg/kg over 15 min
But large RCT is needed before it becomes standard of care
Know this table well because it summarizes adult and pediatric doses and potential side effects of most commonly used anticonvulsants in a resuscitation scenario (i.e. when you shouldn’t be wasting time looking stuff up)
Memorizing Rosen’s exhaustive list of etiologies of status, however, is more akin to medieval forms of torture
While many things can cause seizures, there are relatively fewer therapeutic interventions for seizures
It is easier to think of the causes in relation to what can be done about them
Besides the cocktail, there is a short list of other acute interventions that may abort refractory seizures
We’ll switch gears
Weakness is a VERY common and often vague complaint in the ED
While the vast majority of these complaints are non-focal generalized non-neuromuscular weakness, for which there are a myriad causes, once in a while there will be true neuromuscular weakness
The differential for this is also unfortunately quite wide and it is useful to try quickly to categorize symptoms into anatomic components of the neuromuscular chain as shown
Lesions in each area exhibit specific patterns and clusters of signs and symptoms that are important to recognize
Complaints of neuromuscular weakness require more detailed neurological evaluation
At the minimum these 5 areas of questioning and examination should allow broad categorization
Once you have localized the lesions, the list of cannot miss emergent diagnoses is relatively small, and while there are long lists of other potential pathologies, their evaluation and final diagnosis is often not made in the ED
Bear in mind some conditions have overlapping symptoms (e.g. MS and ALS)
We will focus on conditions you are likely not to be taught in the context of other sessions (e.g. Stroke, trauma, toxicology, connective tissue diseases)
Of the remaining conditions (which occur relatively rarely) the most common and potentially acutely life threatening are Guillain Barre Syndrome, Mysathenia Gravis and Botulism
*Tick paralysis is acutely life threatening but rare
Rosen has an additional approach to peripheral nerve disorders that is symptom pattern based and can be useful sometimes but the problem is the 7 categories which I find particularly confusing
It’s a little easier if you know some of the more common conditions in each category but if you look at all the causes it is actually quite overwhelming. Each category has a wide differential including many rare and esoteric diagnoses as well as several others that cannot be confirmed in the ED.
One thing that is common to the 3 major Emergent causes of neuromuscular weakness is that they all require evaluation of the airway using conventional approaches as well as blood gas monitoring and spirometry, and in cases of known or highly suspected GBS, MG or botulism, this evaluation should be done first.