Pemicu 4 KGD

A Dire Situation(s)
Muhammad Fahmi Rosyadi
405140220
Penurunan Kesadaran

LI 1
• Disorders of consciousness may be divided into processes; affect:
– Arousal:
• wakefulness and basic alerting.
• neurons responsible for these arousal functions reside in the reticular
activating system, a collection of neurons scattered through the
midbrain, pons, and medulla.
– content of consciousness
• neuronal structures responsible for the content of consciousness reside
in the cerebral cortex.
• self-awareness, language, reasoning, spatial relationship integration,
emotions, and the myriad complex integration processes that make us
human.
– OR combination of both.
• Dementia = failure of the content portions of consciousness with relatively
preserved alerting functions.
• Delirium = arousal system dysfunction with the content of consciousness
affected as well.
• Coma = failure of both arousal and content functions.
 States of Normal & Impaired consciousness
terminologies for describing sates of awareness &
responsiveness of patients
• Normal consciousness
– Awake
– Fully responsive to thought & perception
– Indicates by behavior & speech
– (+) attention to & interaction w/ immediate
surroundings
– May fluctuate to mild general inattentiveness but
latter circumstances can be brought back to state
of full alertness & fx
 – Mildest degree:
• Confusion • slight & overlooked
• Roughly oriented time & place,
– Inability to think w/ occasional irrelevant & slowness of
customary speed, thinking
clarity, coherence • Responses inconsistent, attention span
reduced, unable to stay to one topic
– Marked by degree of • Disoriented & easily distractable
inattentiveness & – Severe confused & inattentive
disorientation persons
– Implies degree of • Unable to do more than carry out
imperceptiveness & simplest commands
distractibility • Inconsistent & brief in sequence
“clouding of the • Speech limited to few words or phrases
• Appearance of unaware
sensorium”
• Disoriented in time & place
• Don’t grasp immediate situation
• Miss identify people or objects
• Illusions may lead to fear & agitation
• Degree of confusion varies from 1
time of day to another
• Tends to be least pronounced in
morning
• Increases as day wears on
• Peaking in early evening hours
“sundowning” = pts is fatigued,
environmental cues not as clear
Delirium
• Extreme state of confusion is
termed delirium
• Observed most often in alcoholics
(not exclusively)
• Vivid hallucinations
• Extreme agitation
• Trembling, startling
• Convulsion
• Overactivity of autonomic nervous
system
• Drowsiness
– Inability to sustain
wakeful state w/out
application of external
stimuli
– Mental, speech, physical
activity reduced
– Pts shift positions
naturally; lids droop,
snoring, jaw & limb
muscles slack, limbs
relaxed 
indistinguishable from light
sleep
– Sometimes slow arousal
elicited by speaking to pts
or apply tactile stimulus
• Stupor
– Patient can be roused only
by vigorous + repeated
stimuli
– Cannot be sustained
w/out repeated
stimulation
– Responses to spoken
commands (-) or curtailed
or slow & inadequate
– Restless/stereotyped
motor activity common
– When left unstimulated,
pts quickly drift back to
deep sleep-like state
– Eyes move outward
upward
 Coma
• A state of reduced alertness and responsiveness from which
the patient cannot be aroused.
• GCS is a widely used clinical scoring system for alterations in
consciousness.
– Advantages: simplicity of the scoring system and assessment of
separate verbal, motor, and eye opening functions.
– Disadvantages: lack of acknowledgment of hemiparesis or other focal
motor signs and lack of testing of higher cognitive functions.
• Another coma scale, FOUR (Full Outline of Un-
Responsiveness) score, has been used in ICU & has the
advantages of assessing simple brainstem functions &
respiratory patterns, eye and motor responses.
 Pathophysiology
Coma can result from
deficiency of substrates
needed for neuronal function
(as with hypoglycemia or
hypoxia).
Primary CNS causes 
brainstem disorder, eg.:
hemorrhage or from bilateral
cortical dysfunction.
• Signs localizing to specific areas of CNS
dysfunction: hemiparesis or cranial
nerve abnormalities may be present.
Systemic causes  brain
globally affected, (x) signs that
localize dysfunction to a
specific area of the brainstem
or cortex
Unilateral hemispheric disease
 stroke, should not alone
result in coma. Fx of the
brainstem &/or both
hemispheres must be impaired
for unresponsiveness to occur
 Herniation syndromes = models for alterations of consciousness, but their
mechanisms are unknown.
• Because midline shift without herniation, as demonstrated by neuroimaging,
seems to correlate with a decreased level of consciousness  Vascular
compression due to local cerebral edema or local increased ICP may be an
underlying mechanism for these syndromes

Uncal herniation syndrome: Central herniation syndrome

• Medial temporal lobe shifts  • progressive loss of consciousness,

compress the upper brainstem  • loss of brainstem reflexes,
progressive drowsiness  • Decorticate posturing,
unresponsiveness
• Irregular respiration.
• 3rd cranial nerve is compressed by
medial temporal lobe  Ipsilateral
pupil is sluggish  dilated &
nonreactive
• compression of descending motor
tracts in opposite cerebral
peduncle.  Hemiparesis develop
ipsilateral to the mass
• Diffuse increase in ICP  diffuse CNS dysfunction.
• Cerebral blood flow = constant at MAP of 50 - 100 mmHg due to
the process of cerebral autoregulation.
– MAPs other than this range, cerebral BF may be reduced  diffuse ischemia
may develop. (cerebral perfusion pressure = MAP – ICP).
– Uncontrolled >> ICP  cerebral perfusion pressure diminished as ICP
approaches the MAP  brain ischemia.
• Particularly in unresponsive patients + history of seizures 
possibility of ongoing non-convulsive seizures must be considered.
• Subtle status epilepticus or ictal coma may represent transformed
generalized convulsive status epilepticus.
• Electrical seizures may continue in the absence of clinical seizures.
• The clinical features of coma vary with both the
depth of coma & cause.
• For example:
– a patient in a coma with a hemispheric hemorrhage and
midline shift  << muscle tone on the side of the
hemiparesis. Eyes may conjugately deviate toward the
side of the hemorrhage.
– Expansion of the hemorrhage & surrounding edema, >>
ICP, or brainstem compression, unresponsiveness 
complete loss of motor tone & loss of the ocular findings
as well.
• A variety of abnormal breathing patterns may be seen in the
comatose patient.
– They offer little information in the acute setting.
• Pupillary findings, the results of other cranial nerve
evaluation, hemiparesis, & response to stimulation are all
part of the clinical picture that need assessment.
• These findings assign cause of coma into a probable general
category:
– Diffuse CNS dysfunction (toxic-metabolic coma)
– Focal CNS dysfunction (structural coma).
Further division:
• hemispheric (supratentorial)
• posterior fossa (infratentorial) coma
is often possible at the bedside
 Diffuse: Toxic-Metabolic Coma
• Many different toxic & metabolic conditions cause coma.
• Diffuse CNS dysfunction is reflected by: lack of focal physical
examination findings that point to a specific region of brain
dysfunction.
– If the patient demonstrates either spontaneous movements or
reflex posturing, the movements are symmetric without
evidence of hemiparesis.
– Muscle stretch reflexes, if present, are symmetric.
• Pupillary response is generally preserved in toxic-metabolic coma.
– Typically the pupils are small but reactive.
• If extraocular movements are present, they are symmetric.
• Exception: severe sedative poisoning as from barbiturates; the
pupils may be large, extraocular movements absent, muscles
flaccid, and the patient apneic  simulates the appearance of
brain death
 Focal: Coma from Supratentorial Lesions
• Coma caused by lesions of the hemispheres, or supratentorial masses =
progressive hemiparesis or asymmetric muscle tone & reflexes.
• The hemiparesis may be suspected with asymmetric responses to stimuli
or asymmetric extensor or flexor postures.
• Uncal herniation syndrome is an example of a supratentorial syndrome.
• Frequently, however, large acute supratentorial lesions are seen without
the features consistent with temporal lobe herniation.
• Coma without lateralizing signs  decreased cerebral perfusion
secondary to increased ICP.
• Reflex changes in BP & HR may be observed with >> ICP or brainstem
compression.
• Hypertension and bradycardia in a comatose patient may represent the
Cushing reflex from increased ICP
 Focal: Coma from Infratentorial Lesions
• Posterior fossa or infratentorial lesions comprise another
structural coma syndrome.
• An expanding lesion, e.g: cerebellar hemorrhage or
infarction, may cause abrupt coma, abnormal extensor
posturing, loss of pupillary reflexes, and loss of extraocular
movements.
• The anatomy of the posterior fossa leaves little room for
accommodating an expanding mass.
• Early brainstem compression + loss of brainstem reflexes may
develop rapidly.
• Another infratentorial cause of coma is pontine hemorrhage,
which may present with the unique signs of pinpoint-sized
pupils.
 Pseudocoma
• Psychogenic coma is occasionally encountered and may present a
perplexing clinical problem.
• Adequate history taking and observation of responses to stimulation
reveal findings that differ from those in the syndromes described in the
previous sections.
• Pupillary responses, extraocular movements, muscle tone, and reflexes
are shown to be intact on careful examination.
• Tests of particular value = responses to manual eye opening (there
should be little or no resistance in the truly unresponsive patient) and
extraocular movements.
• Specifically, if avoidance of gaze is consistently seen with the patient
always looking away from the examiner, or if nystagmus is demonstrated
with caloric vestibular testing, this is strong evidence for non-physiologic
or feigned unresponsiveness.
 Diagnosis
• Approach to the comatose patient = perform stabilization,
diagnosis, and treatment actions simultaneously.
• Examination, laboratory procedures, and neuroimaging
allow differentiation between structural and metabolic
causes of coma in almost all patients in the ED.
• History and physical examination findings allow that initial
assignment in many patients, but liberal use of CT scanning is
encouraged because exceptions to the tentative clinical
diagnosis are frequent.
• Address ABC immediately.
• Consider reversible causes of coma: hypoglycemia or opiate
overdose.
• Access all available historical sources (EMS personnel,
caregivers, family, witnesses, medical records, etc.) to aid in
diagnosis.
• The tempo of onset of the coma is of great diagnostic value.
• Abrupt coma = abrupt CNS failure
– possible causes: catastrophic stroke or seizures.
• A slowly progressive onset = suggest a progressive CNS lesion
– tumor or subdural hematoma.
– Metabolic causes, such as hyperglycemia, may also develop over
several days.
• Address general examination and measurement of vital signs
(including oxygen saturation and temperature) following
stabilization & resuscitation.
• General examination may reveal signs of trauma or suggest
other diagnostic possibilities for the unresponsiveness.
– E.g; a toxidrome may be present that suggests diagnosis and
treatment, e.g: opiate syndrome with hypoventilation and small
pupils.
• Neurologic testing deviates from the standard examination.
– Fine tests of weakness, such as testing for pronator drift of the
outstretched upper extremities, are not possible in the
unresponsive patient.
• However, asymmetric findings on examination of cranial nerves
through pupillary examination, assessment of corneal reflexes, and
testing of oculovestibular reflexes may suggest focal CNS lesions.
• Abnormal extensor or flexor postures are nonspecific for
localization or cause of coma but suggest profound CNS
dysfunction.
• Asymmetric muscle tone or reflexes raise the suspicion of a focal
lesion.
• The goal of rapidly determine if the CNS dysfunction is from diffuse
impairment of the brain or if signs point to a focal (and perhaps
surgically treatable) region of CNS dysfunction.
CT = neuroimaging procedure of choice.
• Acute hemorrhage is readily identified, as is midline
shift and mass lesions.
• Consider lumbar puncture if CT scan findings are
unremarkable and subarachnoid hemorrhage or
CNS infection is suspected.
• Suspect basilar artery thrombosis in a comatose
patient with “normal” results on head CT, in which
the only finding may be a hyperdense basilar artery.
– MRI or cerebral angiography is needed to make the
diagnosis of basilar artery thrombosis.
 Special Considerations
• If trauma is suspected  maintain stabilization of the cervical spine
during assessment.
• If protection of the airway is in doubt or the coma state is likely
prolonged, then protect the airway by intubating the patient.
• Patients who have had generalized seizures and remain unresponsive
may be in a continuing state of electrical seizures without corresponding
motor movements = non-convulsive status epilepticus or subtle status
epilepticus and can be described as electromechanical dissociation of the
brain and body.
• If the motor activity of the seizure stops and the patient does not awaken
within 30 minutes, then consider non-convulsive status epilepticus.
• Obtain neurologic consultation and electroencephalography
 Treatment
• Treatment of coma = identification of the cause of the brain failure and
initiation of specific therapy directed at the underlying cause.
• Attend to airway, ventilation, and circulation.
• Evaluate and treat for readily reversible causes of coma: hypoglycemia &
opioid toxicity
– Antidotes Rapid point-of-care glucose determination can identify the
need for dextrose.
– Although thiamine should be administered before glucose infusion in
patients with a suspected history of alcohol abuse or malnutrition,
thiamine is not necessary for all patients.
– Routine use of flumazenil in coma of unknown cause is not
recommended.
– Naloxone, the opiate antagonist, is useful in coma because typical
signs of opiate overdose may be absent.
Increased ICP
• If history, physical examination, or neuroimaging findings suggest
increased ICP, specific steps can reduce or ameliorate any further rise in
ICP.
• Any noxious stimulus, including “bucking” the ventilator, can increase ICP,
so use paralytic and sedative agents.
• A general recommendation is to keep the head elevated about 30
degrees and at midline to aid in venous drainage.
• Mannitol (0.5 to 1.0 gram/kg IV) can decrease intravascular volume and
brain water and may transiently reduce ICP.
• In cases of brain edema associated with tumor, dexamethasone, 10
milligrams IV, reduces edema over several hours.
• Hyperventilation with reduction of partial pressure of arterial carbon
dioxide can reduce cerebral blood volume and transiently lower ICP.
• Current recommendations are to avoid excessive hyperventilation (partial
pressure of arterial carbon dioxide ≤35 mm Hg) during the first 24 hours
after brain injury  Brief hyperventilation may be necessary for
refractory intracranial hypertension
 Disposition & Follow ups
• Patients with readily reversible causes of coma, such as
insulin-induced hypoglycemia, may be discharged if home
care and follow-up care are adequate and a clear cause for
the episode is suspected.
• Admit patients with persistent altered consciousness.
• Most institutions depend on emergency physicians to stabilize
the patient’s condition and correctly assign a tentative
diagnosis so that the patient may be admitted to the proper
specialty service.
• If the appropriate service is not available, then consider
transfer to another hospital after patient stabilization
Trauma Kepala

LI 2
 Head injuries
• Among the most common • Primary goal of treatment for pts w/
types of trauma suspected TBI= prevent secondary brain
encountered in EDs injury.
• Many pts in severe brain • (+) adeq oxygenation & maintaining BP
injuries die before reaching that is sufficient to perfuse the brain =
a hospital = ~90% most important ways to limit secondary
• ~75% minor injuries, 15% brain damage  improve outcome
as moderate, 10% as • ABCDEs  identification of a mass lesion
severe. that requires surgical evacuation is critical
• Survivors of TBI are often  best achieved by CT scan of head.
left with neuropsychologic – should not delay patient transfer to a
impairments  disabilities trauma center that is capable of
affecting work & social immediate and definitive neurosurgical
activity. intervention.
• Triage of a patient with brain injury depends on the
severity of the injury & facilities
– For facilities without neurosurgical coverage, prearranged
transfer agreements with higher-level facilities should be in
place.
– Consultation with a neurosurgeon early in the course of
treatment is strongly recommended
• Head trauma may include:
• skull fractures
• intracranial lesions (contusions, hematomas, diffuse injuries,
resultant swelling (edema/hyperemia).
 Severity of
Injury
• GCS score =
objective clinical
measure of the
severity of brain
injury
• < 8 = coma or
severe brain injury.
• 9 - 12 are
categorized as
“moderate,”
• 13 - 15 are
designated as
“minor.”
 Skull Fractures
• Occur in cranial vault or skull base;
– linear or stellate,
– open or closed.
• Basilar skull fractures require CT
scanning bone-window settings for
identification.
• Clinical signs of a basilar skull fracture:
– periorbital ecchymosis (raccoon
eyes),
– retroauricular ecchymosis (Battle’s
sign),
– CSF leakage from the nose
(rhinorrhea) or ear (otorrhea),
– 7th & 8th nerve dysfunction (facial
paralysis and hearing loss),
may occur immediately or a few days after
the initial injury.
• Fractures traverse carotid canals
 damage the carotid arteries
(dissection, pseudoaneurysm, or
thrombosis)  given to cerebral
arteriography (CT angiography
[CT-A] or catheter-based).
• Open or compound skull
fractures  direct
communication between the
scalp laceration & the cerebral
surface, (dura may be torn)
• A linear vault fracture in
conscious patients >> likelihood
of intracranial hematoma ~400
times.
 Diffuse Brain Injuries
• Mild concussions: CT scan of the head is normal  severe hypoxic
ischemic injuries.
• Concussion: transient, non-focal neurologic disturbance: loss of
consciousness.
• Severe diffuse injuries: hypoxic, ischemic insult to the brain due to
prolonged shock or apnea occurring immediately after the trauma.
• CT scan may initially appear normal, or the brain may appear
diffusely swollen, with loss of the normal gray-white distinction.
• Diffuse pattern in high-velocity impact or deceleration injuries 
multiple punctate hemorrhages throughout the cerebral
hemispheres ( >> seen in the border between the gray matter and
white matter)
• “shearing injuries,”/diffuse axonal injury (DAI) = clinical syndrome
of severe brain injury + variable  poor outcome.
 Focal Brain injuries:
Epidural Hematomas
• Uncommon, ~ 0.5% of patients brain
injuries & 9% of patients TBI comatose.
• Hematomas biconvex or lenticular in shape
 push adherent dura away from the
inner table of the skull.
• >> located in temporal or temporoparietal
region
• often result from tear of middle meningeal
artery  result of a fracture.
• Clots are classically arterial in origin; may
result from disruption of a major venous
sinus or bleeding from a skull fracture.
• A lucid interval between time of injury &
neurologic deterioration = classic
presentation of an epidural hematoma.
Subdural Hematomas
• >> than epidural hematomas,
– ~ 30% of patients with severe
brain injuries.
• Shearing of small surface or
bridging blood vessels of the
cerebral cortex.
• CT = conform to the contours of
the brain.
• Brain damage underlying an
acute subdural hematoma is
typically much more severe than
that associated with epidural
hematomas due to the presence
of concomitant parenchymal
injury.
 Epidural Hematoma
• The development of symptoms and
signs of EDH is entirely dependent on
how quickly the EDH is developing
within the cranial vault.
• Patients with an EDH often complain of
a severe headache, sleepiness,
dizziness, nausea, and vomiting. A
small EDH may remain asymptomatic,
but this is rare.
• If the EDH is rapidly detected and
evacuated, the functional outcome is
excellent. Because of their rapid
formation, EDHs from arterial bleeding
are usually detected within hours after •
injury and often earlier in children.
• EDHs that develop from a dural sinus
tear develop more slowly, and clinical
manifestations may be delayed, with
resultant delays in detection.
• A posterior fossa EDH is the result of
direct occipital trauma resulting in a
skull fracture that disrupts a venous
sinus is the usual cause, and most
patients have external evidence of
occipital injury.
• Most patients become symptomatic
within 24 hours after injury, with
complaints of headache, nausea,
vomiting, and nuchal rigidity.
Most patients eventually have a
decreased LOC
 Subdural Hematoma
• SDHs classified by time of manif:
• Acute SDHs are symptomatic within
24 hours after trauma.
• Patients with acute SDHs often have a
decreased LOC.
• Most patients with an SDH have a GCS
score less than 8.
• A chronic SDH becomes symptomatic
2 weeks or more after trauma.
• The signs and symptoms may be very
subtle or nonspecific, but many
patients demonstrate unilateral
weakness or hemiparesis.
• Patients with unilateral chronic SDH
have more frequent occurrence of
hemiparesis than those with bilateral
chronic SDH
• A chronic SDH may have initially been
a small asymptomatic SDH that
eventually expanded owing to a
combination of recurrent hemorrhage
and escape of plasma into the
hematoma.
• At some point, a critical mass is
reached, and the chronic SDH
becomes symptomatic.
• Clinical manifestations of posterior
SDH vary but usually include nausea,
vomiting, headache, and decreased
LOC.
• Occasionally, CN palsies may be
found, as well as nuchal rigidity,
cerebellar signs and symptoms, and
papilledema
 Contusions & Intracerebral
Hematomas
• Fairly common (~20% - 30% of severe brain injuries).
• >> in frontal & temporal lobes
– may occur in any part of the brain.
• Contusions (hrs - days)  form intra cerebral hematoma or a
coalescent contusion + enough mass effect  require
immediate surgical evacuation.
– repeat CT scanning to evaluate for changes in the pattern of injury
w/in 24 hrs of initial scan.
• ~20% of patients presenting with contusions on initial CT scan
of the head.
 Management of
Minor Brain Injury
(GCS 13-15)
Most patients with minor brain injury
make uneventful recoveries.
~3% have unexpected deterioration,
potentially resulting in severe neurologic
dysfunction unless the decline in mental
status is detected early
• The secondary survey = particularly important in evaluating patients with MTBI.
• Note:
– mechanism of injury
– particular attention to any loss of consciousness:
• length of time the patient was unresponsive,
• any seizure activity,
• subsequent level of alertness.
– Determine the duration of amnesia = before (retrograde) and after (antegrade) the
traumatic incident.
• Serial examination and documentation of the GCS score is important in all
patients with a GCS score <15.
• CT scanning is the preferred method of imaging
 Management of
Moderate Brain
Injury (GCS 9-12)
• ~ 15% in the ED
• Still are able to follow simple
commands, but usually are
confused or somnolent & can
have focal neurologic deficits:
hemiparesis.
• ~ 10% to 20% pts deteriorate &
lapse into coma  serial
neurologic examinations are
critical in the treatment of these
patients.
 Management of Severe Brain Injury (GCS 3-8)

• ~ 10% of patients with brain injury in ED

• Patients who have sustained a severe brain injury are unable to follow simple commands, even after
cardiopulmonary stabilization.
– Although this definition includes a wide spectrum of brain injury, it identifies the patients who are at greatest risk
of suffering significant morbidity and mortality.
• “wait and see” approach  disastrous!
• Prompt diagnosis & treatment = extremely important.
• Do not delay patient transfer to obtain a CT scan.
 Primary Survey & Resuscitation
• Brain injury often is adversely affected by
secondary insults.
• Mortality rate for patients w/ severe brain injury
+ hypotension on admission is >> 2x patients w/
(x) hypotension.
• (+) of hypoxia in addition to hypoTN  >>
relative risk of mortality 75%.
• Therefore, it is imperative that cardiopulmonary
stabilization be achieved rapidly in patients with
severe brain injury.
 PRIORITIES FOR INITIAL EVALUATION & TRIAGE
OF PATIENTS W/ SEVERE BRAIN INJURIES
1. All comatose patients + brain injuries should undergo resuscitation
(ABCDEs) on arrival in ED.
2. As soon as the BP is normalized  neurologic exam performed
(GCS & pupillary reaction).
– If the BP cannot be normalized, neurologic examination is still performed,
and the hypotension recorded.
3. If patient’s SBP (X) brought up to >100 mm Hg, priority = establish
cause of hypotension w/ neurosurgical evaluation taking second
priority.
– Patient undergoes a diagnostic peritoneal lavage (DPL) or ultrasound in the
ED and may need to go directly to the operating room (OR) for a laparotomy.
– CT scans of the head are obtained after the laparotomy.
– If there is clinical evidence of an intracranial mass, diagnostic burr holes or
craniotomy may be undertaken in the OR while the celiotomy is being
performed.
4. If SBP >100 mm Hg after resuscitation & patient
has clinical evidence of a possible intracranial mass
(unequal pupils, asymmetric results on motor
exam), 1st priority = CT head scan.
– A DPL or FAST exam may be performed in the ED, CT
area, or OR, but the patient’s neurologic evaluation or
treatment should not be delayed.
5. In borderline cases—e.g: SBP temporarily corrected
 slowly decrease; every effort should be made to
get a head CT prior to taking the patient to the OR
for a laparotomy or thoracotomy.
– Such cases call for sound clinical judgment and
cooperation between the trauma surgeon and
neurosurgeon.
 Airway & Breathing
• Transient respiratory arrest and hypoxia are common with severe brain
injury and may cause secondary brain injury.
• Early endotracheal intubation should be performed in comatose patients.
• The patient should be ventilated with 100% oxygen until blood gas
measurements are obtained, after which appropriate adjustments to the
fraction of inspired oxygen (FIO2) are made.
• Pulse oximetry is a useful adjunct, and oxygen saturations of >98% are
desirable.
• Ventilation parameters are set to maintain a PCO2 of ~35 mm Hg.
• Hyperventilation (PCO2 <32 mm Hg) should be used cautiously in patients
with severe brain injury and only when acute neurologic deterioration
has occurred.
Circulation
• Hypotension usually is not due to the brain Neurologic Exam (Disability)
injury itself, • As soon as the patient’s
– except in terminal stages when medullary cardiopulmonary status is managed, a
failure supervenes or there is a rapid and directed (focused) neurologic
concomitant spinal cord injury. examination is performed.
• It consists primarily of determining the
• Intracranial hemorrhage cannot cause
GCS score, pupillary light response, and
hemorrhagic shock.
focal neurological deficit.
• Euvolemia should be established ASAP if the • It is important to recognize confounding
patient is hypotensive = blood products, whole issues in the evaluation of TBI: presence
blood, isotonic fluids of drugs, alcohol, intoxicants, and other
• It must be emphasized that the neurologic injuries.
examination of patients with hypotension is – Do not overlook a severe brain injury
unreliable. because the patient is also intoxicated.
– Patients with hypotension who are
unresponsive to any form of stimulation
may recover and substantially improve
soon after normal blood pressure is
restored.
• The primary source of the hypotension must
be urgently sought and treated.
• The postictal state after a traumatic seizure will typically
worsen the patient’s responsiveness for minutes or hours.
• In a comatose patient, motor responses may be elicited by
pinching the trapezius muscle or with nail-bed or
supraorbital ridge pressure.
• If a patient demonstrates variable responses to stimulation,
the best motor response elicited is a more accurate
prognostic indicator than the worst response.
• Testing for doll’s eye movements (oculocephalic), the caloric
test with ice water (oculovestibular), and testing of corneal
responses are deferred to a neurosurgeon.
– Doll’s eye testing should never be attempted until a cervical spine
injury has been ruled out.
• It is important to obtain the GCS score and to perform a
pupillary examination prior to sedating or paralyzing the
patient, because knowledge of the patient’s clinical condition
is important for determining subsequent treatment.
• Long-acting paralytic and sedating agents should not be used
during the primary survey.
• Sedation should be avoided except when a patient’s agitated
state could place him or her at risk.
• The shortest-acting agents available are recommended when
pharmacologic paralysis or brief sedation is necessary for safe
endotracheal intubation or obtaining good quality diagnostic
studies.
 Secondary Survey
• Serial examinations (e.g., GCS score, lateralization, and
pupillary reaction) should be performed to detect neurologic
deterioration as early as possible.
• A well-known early sign of temporal lobe (uncal) herniation =
dilation of pupil & loss of pupillary response to light.
• Direct trauma to eye = potential cause of abN pupillary
response & may make pupil evaluation difficult.
• However, in the setting of brain trauma, brain injury should be
considered first.
 Diagnostic Procedures
• A head CT scan must be obtained
ASAP after hemodynamic
normalization.
• Also should be repeated whenever
there is a change in the patient’s
clinical status and routinely within 24 •
hours after injury for patients with a
contusion or hematoma on the initial
scan.
• Findings of significance on CT images =
scalp swelling & subgaleal hematomas
at the region of impact.
• Skull fractures = better with bone
windows, often apparent even on
soft-tissue windows.
• Crucial findings on CT= intracranial
hematoma, contusions, shift of the
midline (mass effect) and obliteration
of the basal cisterns
– A shift of >5 mm = indicative of
need for surgery to evacuate the
blood clot or contusion causing the
shift.
Caution in assessing patients w/ TBI
who are anti-coagulated or on
antiplatelet therapy.
– INR should be obtained & a CT
should be performed expeditiously
in these patients when indicated.
– Rapid normalization of
anticoagulation is the general rule.
 Medical Therapies for Brain Injury
• The primary aim of intensive care protocols is to prevent
secondary damage to an already injured brain.
• The basic principle is that if injured neural tissue is provided
an optimal milieu in which to recover, it may recover and
regain normal function.
• Medical therapies for brain injury:
– intravenous fluids,
– temporary hyperventilation,
– mannitol,
– hypertonic saline,
– barbiturates,
– anticonvulsants.
INTRAVENOUS FLUIDS
• IV fluids, blood, blood products should be administered as
required to resuscitate the patient and maintain
normovolemia.
– Hypovolemia in these patients is harmful.
– Care should also be taken not to overload the patient with fluids.
– Furthermore, the use of glucose-containing fluids may result in
hyperglycemia, which has been shown to be harmful to the injured
brain.
– Therefore, it is recommended Ringer’s lactate solution or normal
saline be used for resuscitation.
• Serum sodium levels need to be very carefully monitored in
patients with head injuries = Hyponatremia is associated with
brain edema and should be prevented.
HYPERVENTILATION
• In most patients, normocarbia is
preferred.
• Hyperventilation  << PaCO2 
causing cerebral vasoconstriction.
• Aggressive prolonged
hyperventilation  promote
cerebral ischemia in injured brain
(causing severe cerebral
vasoconstriction)  impaired
cerebral perfusion.
– PaCO2 is allowed to fall < 30 mm
Hg (4.0 kPa).
– However, hypercarbia (PCO2 > 45
mm Hg) will promote vasodilation
and increase intracranial pressure,
and thus it should be avoided.
• Hyperventilation should be used
only in moderation and for as
limited a period as possible.
• In general, it is preferable to keep
the PaCO2 at ~35 mm Hg (4.7
kPa), the low end of the normal
range (35 mm Hg to 45 mm Hg).
• Brief periods of hyperventilation
(PaCO2 of 25 to 30 mm Hg [3.3 to
4.7 kPa]) may be necessary for
acute neurologic deterioration
while other treatments are
initiated.
• Hyperventilation will lower ICP in a
deteriorating patient with
expanding intracranial hematoma
until emergent craniotomy can be
performed.
MANNITOL
• used to reduce elevated ICP.
• Preparation most commonly
used = 20% solution (20 g
mannitol/100 ml solution).
• Mannitol should not be given
to patients with
hypotension, because
mannitol does not lower ICP
in hypovolemia & a potent
osmotic diuretic.  further
exacerbate hypotension &
cerebral ischemia.
• Strong indication for
administering mannitol in a
euvolemic patient = Acute
neurologic deterioration:
development of a dilated
pupil, hemiparesis, or loss of
consciousness while the
patient is being observed, is a
– In this setting, a bolus of
mannitol (1 g/kg) should be
given rapidly (over 5 minutes)
and the patient transported
immediately to the CT scanner
or directly to the operating
room (if a causative surgical
lesion is already identified)
HYPERTONIC SALINE
• reduce elevated ICP.
• [ ] of 3% - 23.4% are used, and this may be the
preferable agent to use in patients with
hypotension, as it does not act as a diuretic.
• However, there is no difference between
mannitol and hypertonic saline in lowering
ICP, and neither will adequately lower ICP in
hypovolemic patients.
BARBITURATES
• Barbiturates are effective in reducing ICP refractory to other
measures.
• They should not be used in the presence of hypotension or
hypovolemia.
• Furthermore, hypotension often results from their use.
• Therefore, barbiturates are not indicated in the acute
resuscitative phase.
• The long T ½ of most barbiturates will also prolong the time
to brain death determination, a consideration in patients
with devastating and likely non survivable injury
ANTICONVULSANTS
• Post-traumatic epilepsy (+) in:
– ~5% of patients admitted to the hospital
with closed head injuries
– 15% of individuals with severe head
injuries.
• 3 main factors linked to a high
incidence of late epilepsy are:
– seizures occurring within 1st week,
– an intracranial hematoma,
– depressed skull fracture.
• Acute seizures may be controlled
with anticonvulsants, but early
anticonvulsant use does not change
long-term traumatic seizure outcome.
– Anticonvulsants may also inhibit brain
recovery, so they should be used only
when absolutely necessary.
• Currently, phenytoin and
fosphenytoin are the agents
generally used in the acute phase.
• For adults, the usual loading dose is 1
g of phenytoin IV
– Rate (x) > 50 mg/min.
• The usual maintenance dose = 100
mg/8 hours
– dose titrated to achieve therapeutic
serum levels.
• Diazepam or lorazepam is frequently
used in addition to phenytoin until
the seizure stops.
• Control of continuous seizures may
require general anesthesia.
• It is imperative that acute seizures be
controlled as soon as possible,
because prolonged seizures (30 to 60
minutes) may cause secondary brain
injury.
 Pitfalls
• It is important to monitor the ICP if active ICP management is being
undertaken.
– E.g: mannitol may have a significant rebound effect on ICP, additional
therapies may be indicated if ongoing management is required.
• It is important to remember that seizures are not controlled with muscle
relaxants.
• Prolonged seizures in a patient whose muscles are relaxed
pharmacologically can still be devastating to brain function, and may go
undiagnosed and untreated if tonic-clonic muscle contractions are
masked by a neuromuscular blocker such as vecuronium or
succinylcholine.
• In a patient with a witnessed seizure, make sure appropriate antiseizure
therapy is being initiated and that the seizure is under control before
initiating neuromuscular blockade if at all possible.
 Surgical management
SCALP WOUNDS
• It is important to clean and inspect the wound thoroughly before suturing.
• The most common cause of infected scalp wounds = inadequate cleansing and
debridement.
– Blood loss from scalp wounds may be extensive, especially in children
• Scalp hemorrhage usually can be controlled by applying direct pressure and
cauterizing or ligating large vessels  sutures, clips, or staples may then be
applied.
• Carefully inspect wound under direct vision for signs of a skull fracture or foreign
material.
• CSF leakage indicates associated dural tear.
• A neurosurgeon should be consulted in all cases of open or depressed skull
fractures.
• Not infrequently, a subgaleal collection of blood can feel like a skull fracture.
– In such cases, the presence of a fracture can be confirmed or excluded by
plain x-ray examination of the region and/or a CT scan.
DEPRESSED SKULL FRACTURES
• Generally, a depressed skull fracture needs operative
elevation if:
– the degree of depression is > thickness of the adjacent skull,
– if it is open & grossly contaminated.
• Less significant depressed fractures can often be managed
with closure of the overlying scalp laceration, if present.
• A CT scan is valuable in identifying the degree of depression,
but more importantly in excluding the presence of an
intracranial hematoma or contusion.
PENETRATING BRAIN INJURIES
• CT scanning of the head is strongly
recommended to evaluate patients
with penetrating brain injury.
• Plain radiographs of the head can be
helpful in assessing bullet trajectory
and fragmentation, and the presence
of large foreign bodies and intracranial •
air.
• However, when CT is available, plain
radiographs are not essential.
• CT and/or conventional angiography is
recommended with any penetrating
brain injury, or when a trajectory
passes through or near the skull base
or a major dural venous sinus.
• Substantial subarachnoid hemorrhage
or delayed hematoma should also
prompt consideration of vascular
imaging.
• Patients with a penetrating injury
involving the orbitofacial or pterional
regions should undergo angiography to
identify a traumatic intracranial
aneurysm or arteriovenous (AV)
fistula.
When an aneurysm or AV fistula is
identified, surgical or endovascular
management is recommended.
• MRI can play a role in evaluating
injuries from penetrating wooden or
other nonmagnetic objects.
• The presence on CT of large
contusions, hematomas, or
intraventricular hemorrhage is
associated with increased mortality,
especially when both hemispheres are
involved.
• Prophylactic broad-spectrum Abs = appropriate for patients w/
penetrating brain injury.
• Early ICP monitoring is recommended when:
– unable to assess the neurologic examination accurately,
– the need to evacuate a mass lesion is unclear,
– imaging studies suggest elevated ICP.
• It is appropriate to treat small bullet entrance wounds to the head
with local wound care and closure in patients whose scalp is not
devitalized and who have no major intracranial pathology.
• Objects that penetrate intracranial compartment or infra-temporal
fossa & remain partially exteriorized (e.g., arrows, knives,
screwdrivers) must be left in place until possible vascular injury
evaluated & definitive neurosurgical management established.
– Disturbing or removing penetrating objects prematurely can
lead to fatal vascular injury or intracranial hemorrhage
 Prognosis
• All patients should be treated aggressively
pending consultation with a neurosurgeon.
• This is particularly true of children, who have
a remarkable ability to recover from
seemingly devastating injuries.
 Brain death
• Dx of brain death  no possibility for
recovery of brain function.
• Following criteria should be satisfied for
the diagnosis of brain death:
– GCS = 3
– Nonreactive pupils
– (x) brainstem reflexes (e.g.,
oculocephalic, corneal, and Doll’s
eyes, and no gag reflex)
– (x) spontaneous ventilatory effort on
formal apnea testing
• Ancillary studies that may be used to
confirm the diagnosis of brain death:
– Electroencephalography: No activity
at high gain
– CBF studies: No CBF (e.g., isotope
studies, Doppler studies, xenon CBF
studies)
– Cerebral angiography
• Certain reversible conditions:
hypothermia or barbiturate coma,
may mimic the appearance of brain
death; therefore, this diagnosis
should be considered only after all
physiologic parameters are
normalized & CNS fx is not
potentially affected by medications.
• The remarkable ability of children to
recover from seemingly devastating
brain injuries should be carefully
considered prior to diagnosing brain
death in children.
• If any doubt exists, especially in
children, multiple serial exams
spaced several hours apart are useful
in confirming the initial clinical
impression.
 Subarachnoid Hemorrhage &
Intracerebral Hemorrhage
• The leakage of blood into the subarachnoid space, most often due to a
ruptured intracranial aneurysm.
• The classic presentation = sudden, severe headache.
• Intracerebral hemorrhage, or hemorrhagic stroke, typically presents as an
acute neurologic deficit, often + headache.
• ~75% of subarachnoid hemorrhages are caused by a ruptured aneurysm.
• ~20%, a cause is not identified.
• Remaining causes are related to a variety of miscellaneous conditions:
arteriovenous malformations, sympathomimetic drugs, etc (less common)
• ~20% of patients w/ 1 aneurysm will have an additional aneurysm 
identification of initial aneurysm important.
• 2% of family members of patients with subarachnoid hemorrhage will
develop the same disease.
• This risk rises with increasing number of family members
involved or with a family history of adult polycystic kidney
disease.
• Hypertension and smoking increase the risk
 Clinical Features
• Classically present to the ED w/ severe headache of acute
onset (termed a “thunderclap” headache) that reaches
maximal intensity within minutes.
• Typically, the headache persists for several days, but may
resolve in a shorter period.
– Subarachnoid hemorrhage is diagnosed in 11% - 25% of patients who
present to the ED with a thunderclap headache.
• Even if a patient is not experiencing the “worst ever”
headache, a headache that is different in intensity or quality
from past headaches raises concern for subarachnoid
hemorrhage
• Headaches associated with loss of consciousness, seizure, diplopia
or other neurologic signs, or nuchal rigidity also require clinical
investigation.
• Less frequently, patients may present with nausea and vomiting,
altered mental status, photophobia, or symptoms suggestive of
ischemic stroke.
• ~20% of patients develop their symptoms while engaged in
activities that cause increased blood pressure (exercise, sexual
intercourse, or defecation)
• Isolated, uncomplicated true syncope without head trauma,
headache, seizure, neurologic deficits, nuchal rigidity, or other
symptoms of subarachnoid hemorrhage does not require
evaluation for subarachnoid hemorrhage.
• In the absence of blunt trauma, subhyaloid retinal hemorrhage is
pathognomonic of subarachnoid hemorrhage but is not commonly
seen
 Diagnosis
• Patients with subarachnoid hemorrhage who are misdiagnosed at their
initial ED visit have worse outcomes than those who are diagnosed early.
• Misdiagnosis due to: normal mental status (present in ~1/2 patients w/
SAH) and smaller size of hemorrhage
• Complications of missed diagnosis: repeat hemorrhage and obstructive
hydrocephalus.
• Symptomatic improvement following analgesics does not exclude life-
threatening causes of headache.
Imaging
• Initial diagnostic modality of choice when SAH is
suspected is a non-contrast CT of the head
• Sensitivity of CT in diagnosing SAH = highest shortly
after symptoms begin (98%) within 6 - 12 hours of
the onset of symptoms.
• Sensitivity decreases to ~ 91% - 93% at 24 hours and
continues to decline rapidly thereafter, reaching 50%
at 1 week.

For suspected SAH, a negative head CT is typically

followed by Lumbar puncture

• CT angiography (CTA) and MRI/MRA are options

after a negative head CT, when these studies are
clinically appropriate and available.
– The probability of excluding a subarachnoid hemorrhage
following CT/CTA is about 99.4%.
• Important consequences of this dx pathway:
– the detection of incidental aneurysms, as opposed to clinically
significant bleeds, with the background incidence of aneurysms in the
population (2% to 6%) exceeding that of the morbidity and mortality
associated with subarachnoid hemorrhages.
• The major disadvantage of CT/CTA is ionizing radiation.
• The usefulness of MRI is limited
• A negative MRI result would still need to be followed by an
LP.
• The major disadvantages of MRI/MRA at this time are:
availability, time to perform the examination, cost.
Lumbar Puncture
• Most authorities recommend CSF
analysis when a patient with
suspected SAH has a normal
head CT.
• Another advantage of LP is the
ability to identify other causes of
headache (e.g: meningitis or
idiopathic intracranial
hypertension)
• The disadvantages of LP: post-LP
headache and inability to
perform the procedure in the
patient with coagulopathy or
thrombocytopenia.
• The 2 CSF tests of greatest
interest = presence of
xanthochromia and RBC count.
• Xanthochromia = yellow
appearance of the CSF due to the
enzymatic breakdown of blood
 bilirubin.
– Any exposure of the CSF to light
prior to interpretation can
increase the rate of bilirubin
degradation, which decreases
any xanthochromia present.
– Similarly, a delay in processing
the CSF specimen may result in
the development of
xanthochromia following a
traumatic LP.
• (N) head CT, (x) xanthochromia, 0 or few RBCs (<5 RBCs/L) in
CSF help reliably exclude SAH
• (N) CT result w/ +ve xanthochromia or >> RBC count 
considered dx of SAH.
• Subarachnoid Hemorrhage Grading Scales: Hunt and Hess
scale & World Federation of Neurosurgical Societies scale
• A higher grade on either scale indicates a higher likelihood of
poor outcome.
 Treatment
• Medical management of SAH patient in ED should
occur in a monitored critical care area & should
target prevention of complications.
• Check GCS & pupillary responses regularly; < 1 GCS
point = indicate onset of complications.
• Intracerebral & extracerebral complications of SAH:
– Re-bleeding, vasospasm, cerebral infarction, cerebral
edema, hydrocephalus, intracranial hypertension, fluid
status & electrolyte abN, respiratory failure, myocardial
dysfunction, thromboembolism, sepsis.
• The risk of rebleeding >>> in 1st 24 hours and can be
reduced by adequate BP control;
– ideal target blood pressure and antihypertensive agent
remain unclear.
– If known, maintain the patient’s pre-hemorrhage blood
pressure; otherwise, a MAP of <140 mm Hg is a
reasonable target while avoiding hypotension.
• Because BP may fluctuate through the course of the
disease, a titratable IV antihypertensive is preferred =
Labetalol and nicardipine are most often used
• Avoid nitroprusside and nitroglycerin  >> cerebral
B.Vol & ICP
• Pain medications & antiemetics = important role in
maintaining the alert patient’s comfort and BP
• Vasospasm; most common 2 days - 3 weeks after SAH
• A modest protective benefit is w/ administration of
nimodipine, 60 milligrams PO @4 hours, and this
therapy should be initiated within 96 hours of
symptom onset
– unless contraindicated due to allergy, nonfunctioning GI
tract, or hepatic disease.
• Delayed cerebral ischemia assc w/ hypothermia,
hyperthermia, hyperglycemia  Prevent these
conditions w/ appropriate use of warming or cooling
blankets, antipyretics, or insulin when indicated.
• ~5% - 20% of patients w/ SAH have at least one
seizure.
– Consideration of seizure prophylaxis
 Disposition & Follow up
• Admit all patients diagnosed with SAH to an ICU in
consultation w/ a neurosurgeon.
• In the absence of another indication for admission, patients
who have normal findings on head CT & CSF analysis w/in 2
weeks of occurrence of initial symptoms may be safely
discharged from the ED.
• Consider consultation with a neurosurgeon for patients who
present >2 weeks after the sudden onset of a severe
headache  suspicion for SAH if the initial workup yields
normal findings.
 Intracerebral Hemorrhage
• Spontaneous intracerebral hemorrhage causes 8% - 11% of all
acute strokes & 2x > subarachnoid hemorrhage.
• Like subarachnoid hemorrhage, intracerebral hemorrhage
carries a high morbidity and mortality.
• There has been no recent change in mortality after
intracerebral hemorrhage.
• This may be because the >> use of anticoagulation for atrial
fibrillation to prevent ischemic stroke  poorer outcomes in
those patients taking anticoagulants who develop
intracerebral hemorrhage
 Pathophysiology
• RF for intracerebral hemorrhage:
– long-standing hypertension,
– arteriovenous malformations,
– arterial aneurysm,
– Anticoagulant therapy,
– Use of sympathomimetic drugs
(particularly cocaine and
phenylpropanolamine),
– intracranial tumors,
– amyloid angiopathy in the
elderly.
– Current smoking & increased
freq of smoking also >> risk of
intracerebral hemorrhage
• but etiology of this increased risk has
not been as well defined as in
ischemic stroke
• Intracerebral hemorrhage
occurs >2 x more freq in
blacks > whites  higher
prevalence of HTN in blacks.
• Anticoagulation w/ warfarin
= significant RF for
intracerebral hemorrhage
– Risk of intracerebral
hemorrhage ~2x for each 0.5
increase in INR >4.5.
– Intracerebral hemorrhage
occurs in ~3% - 9% patients
treated with tissue
plasminogen activator for
acute ischemic stroke.
 Clinical Features
• Intracerebral hemorrhage may be • Cerebellar hemorrhage 
clinically indistinguishable from dizziness, vomiting, marked
cerebral infarction, subarachnoid truncal ataxia, gaze palsies,
hemorrhage, & ischemic stroke.
depressed level of consciousness.
• In intracerebral hemorrhage,
headache, nausea, vomiting often
• Patients with cerebellar
precede neurologic deficit, and in hemorrhage are more likely to
contrast to subarachnoid have rapidly progressive
hemorrhage, the headache onset is symptoms and may require more
usually more insidious. aggressive intervention > other
• In hypertensive intracerebral forms of intracerebral
hemorrhage, bleeding is usually hemorrhage.
localized to the putamen, thalamus,
pons, or cerebellum (in decreasing
order of frequency), and clinical
examination findings may be
relatable to those areas.
 Diagnosis & Imaging
• DD = SAH
• The history, rapidity of progression of symptoms, and other clinical
features may suggest that intracerebral hemorrhage is more likely than
subarachnoid hemorrhage or ischemic stroke, but these features are not
adequate alone to make a clinical diagnosis.
• CT & MRI each have areas of superiority in evaluating a patient for
intracerebral hemorrhage.
– CT = optimal for demonstrating hemorrhage extension into ventricles
• Widespread availability of CT makes a non-contrast CT the initial
study of choice in most EDs
• The addition of contrast may allow identification of masses or
aneurysms.
– MRI = superior for demonstrating underlying structural lesions.
Either modality is considered acceptable as the initial study for
diagnosing intracerebral hemorrhage.
• Cerebral angiography = useful in selected patients in stable
condition who do not require urgent surgery, particularly
those in whom no obvious cause of bleeding is identified and
<45 years of age w/out hypertension.
• Additional tests should be performed to exclude coexisting
pathology or facilitate surgery, if necessary:
– complete blood count,
– electrolyte levels,
– creatinine level,
– glucose level,
– electrocardiogram,
– chest radiograph,
– coagulation studies,
– Blood type and screen.
– A urine pregnancy test and screen for drugs of abuse should be
performed as appropriate
 Treatment
• Treatment of patients with intracerebral hemorrhage should
occur in a monitored critical-care area with appropriate
urgency.
• Patients with cerebellar hemorrhage are at particularly high
risk of rapid deterioration and may require rapid intervention.
• Maintain close attention to the patient’s airway, monitoring
of neurologic status, management of hyperthermia with
antipyretics, administration of antiepileptic medications if
seizures occur, aggressive management of hyperglycemia
(>160 milligrams/dL), blood pressure management, and
reversal of coagulopathy (if present).
• Management of elevated
intracranial pressure should
include raising the head of the
bed 30 degrees and providing
appropriate analgesia and
sedation.
• If more aggressive reduction of
intracranial pressure is required—
such as administration of osmotic
diuretics or intubation with
neuromuscular blockade and
mild hyperventilation—invasive
intracranial pressure monitoring
is generally indicated.
Kejang

LI 3
 Seizure
• An episode of abnormal neurologic function caused by inappropriate
electrical discharge of brain neurons.
– Neuronal electrical discharge, in its most simple form, can be thought
of as the homeostasis of glutaminergic (excitatory) and γ-
aminobutyric acid (inhibitory) activity.
• Epilepsy
– Clinical condition in which an individual is subject to recurrent
seizures.
– It implies a fixed, more excitatory condition of the brain with a lower
seizure threshold.
– The term epileptic does not refer to an individual with recurrent
seizures caused by reversible conditions
• alcohol withdrawal, toxins, hypoglycemia, or other metabolic
derangements.
• Primary, or idiopathic, seizures
– those in which no evident cause can be identified.
• Secondary, or symptomatic, seizures
– Consequence of an identifiable neurologic condition, such
as a mass lesion, previous head injury, or stroke.
• Electrical stimulation of the brain, convulsant
potentiating drugs, profound metabolic disturbances,
or a sharp blow to the head all may cause reactive
seizures in otherwise normal individuals.
• Reactive seizures are generally self-limited, and a
reactive seizure is not considered to be a seizure
disorder or epilepsy
Further definitions of seizures based on clinical factors:
• Provoked seizure = acute precipitating event within 7
days of the insult;
• Unprovoked seizure = no acute precipitating factor or
may result from a very remote incident;
• Status epilepticus = seizure activity for ≥5 minutes or
two or more seizures without regaining
consciousness between seizures;
• Refractory status epilepticus = persistent seizure
activity despite the IV administration of adequate
amounts of two antiepileptic agents.
The International League Against Epilepsy recommends dividing seizures
into two major groups: generalized seizures and partial seizures
 Generalized Seizures
• Thought to be caused by a nearly
simultaneous activation of the entire
cerebral cortex,
– perhaps caused by an electrical
discharge originating deep in the
brain and spreading outward.
• The attacks begin with abrupt loss of
consciousness.
– Loss of consciousness may be the
only clinical manifestation of the •
seizure (as in absence attacks), or
there may be a variety of motor
manifestations (e.g., tonic
posturing, clonic jerking of the
body and extremities).
• Generalized tonic-clonic seizures (grand
mal) = most familiar & dramatic of
generalized seizures.
• In a typical attack, patient suddenly
extremities are extended, and the
patient falls to the ground  tonic
phase subsides, there is increasing
coarse trembling  symmetric,
rhythmic (clonic) jerking of the trunk
and extremities.
– Patients are often apneic during
this period and may be cyanotic.
– They often urinate and may vomit.
As the attack ends, the patient is left
flaccid and unconscious, often with
deep, rapid breathing.
• Typical attacks last from 60 to 90
seconds;
• Consciousness returns gradually, and
postictal confusion, myalgias, and
fatigue may persist for several hours or
more.
• Absence seizures (petit mal) are very
brief, generally lasting only a few
seconds.
• Patients suddenly develop altered
consciousness but no change in
postural tone.
• They appear confused, detached, or
withdrawn, and current activity
ceases.
• They may stare or have twitching of
the eyelids.
• They may not respond to voice or to
other stimulation and may exhibit
involuntary movements or lose
continence.
• The attack ceases abruptly, and the
patients typically resume previous
activity without postictal symptoms.
• Patients and witnesses may be
unaware that anything has
happened.
• Classic absence seizures occur in
school-age children and are often
attributed by parents or teachers to
daydreaming or inattention.
• The attacks can occur as frequently
as 100 or more times daily and may
result in poor school performance.
• They usually resolve as the child
matures.
• Similar attacks in adults are more
likely to be minor complex partial
seizures and should not be termed
absence.
• The distinction is important because
the causes and treatment of the two
seizures are different.
 Partial (focal) Seizures
• Partial seizures are due to electrical
discharges beginning in a localized
region of the cerebral cortex.
• The discharge may remain localized
or may spread to involve nearby
cortical regions or the entire
cortex.
• Focal seizures are more likely to be
secondary to a localized structural •
lesion of the brain.
• In simple partial focal seizures, the
seizure remains localized, and
consciousness and mentation are
not affected.
• It is possible to deduce the likely
location of the initial cortical
discharge from the clinical features
at the onset of the attack.
• For example, unilateral tonic or
clonic movements limited to one
extremity suggest a focus in the
motor cortex, whereas visual
symptoms suggest an occipital
focus.
Bizarre olfactory or gustatory
hallucinations suggest a focus in the
medial temporal lobe.
• Such sensory phenomena, known
as auras, are often the initial
symptoms of attacks that then
become more widespread, termed
secondary generalization.
• COMPLEX PARTIAL SEIZURES =
focal seizures in which consciousness •
or mentation is affected.
• They are often caused by a focal
discharge originating in the temporal •
lobe and are sometimes referred to as
temporal lobe seizures.
• Complex partial seizures are
commonly misdiagnosed as
psychiatric problems because
symptoms can be so bizarre.
• Symptoms:
– automatisms, visceral symptoms,
hallucinations, memory
disturbances, distorted
perception, and affective
disorders.
• Common automatisms : lip smacking,
fiddling with clothing or buttons, or
repeating short phrases.
Visceral symptoms: sensation of
“butterflies” rising up from the
epigastrium.
Hallucinations may be olfactory,
gustatory, visual, or auditory.
• There may be complex distortions of
visual perception, time, and memory.
• Affective symptoms: intense
sensations of fear, paranoia,
depression, elation, or ecstasy.
• Because such seizures result in
alterations of thinking and behavior,
they were previously referred to as
psychomotor seizures, but to avoid
any confusion with psychiatric illness,
the term complex partial seizure is
preferred.
• As noted, a focal seizure may spread to
involve both hemispheres, mimicking a
typical generalized seizure.
– For the purpose of classification, diagnosis, and
treatment, such attacks are still regarded as focal
seizures.
– In some patients, the discharge may spread so
rapidly that no focal symptoms are evident, and
the correct diagnosis may depend entirely on
demonstration of the focal discharge on an EEG
recording.
 Clinical Features
• Patient presents after the event  1st step = determine whether episode
was truly a seizure.
• Obtain a careful history of the details of the attack from the patient and
any bystanders who witnessed the attack.
• Inquire about physical description of the attack, because witnesses may
mislabel the activity and mistake non-seizure activity as a seizure.
• Important avenues of inquiry:
– presence of a preceding aura,
– abrupt or gradual onset,
– progression of motor activity,
– loss of bowel or bladder control,
– presence of oral injury,
– whether the activity was localized or generalized and symmetric or
unilateral.
• Ask about the duration of the episode and determine the presence of
postictal confusion or lethargy.
• Next, determine the clinical context of the episode.
– If the patient is a known epileptic, clarify the baseline
seizure pattern.
– If the attack is consistent with the previous seizure
pattern, identify precipitating factors of the current
seizure.
• Common precipitating factors:
– missed doses of antiepileptic medications;
– recent alterations in medication: dosage change or
conversion from brand name;
– sleep deprivation;
– increased strenuous activity;
– infection;
– electrolyte disturbance;
– alcohol or substance use or withdrawal.
• If there is no previous history of seizures, a more detailed inquiry
is needed.
• Symptoms:
– unexplained injuries, nocturnal tongue biting, or enuresis
suggest previous unwitnessed or unrecognized seizures.
• Ask about a history of recent or remote head injury.
• Ask about any previous similar episodes that may be suspect as
seizures.
• Persistent, severe, or sudden headache suggests intracranial
pathology.
• Pregnancy or recent delivery raises the possibility of eclampsia.
• A history of metabolic or electrolyte abnormalities,
– hypoxia, systemic illness (especially cancer), coagulopathy or anticoagulation,
exposure to industrial or environmental toxins, drug ingestion or withdrawal,
and alcohol use may point to predisposing factors
 Physical Exam
• Immediately obtain a complete set of vital signs & a point-of-care
glucose determination.
• In the post-seizure setting: focus the initial exam on checking for injuries,
especially to the head or spine, as a result of the seizure itself.
• A posterior shoulder dislocation is an injury that is easy to overlook.
• Lacerations of the tongue and mouth, dental fracture, and pulmonary
aspiration are also frequent sequelae.
• Perform a directed, complete neurologic examination and subsequent
serial examinations.
• Follow the patient’s level of consciousness and mentation closely to avoid
missing nonconvulsant status epilepticus
• A transient focal deficit (usually unilateral) following a simple or complex
focal seizure is referred to as Todd’s paralysis and should resolve within
48 hours.
 Diagnosis
• Clinical features distinguish seizures from other non-seizure attacks:
– Abrupt onset & termination.
• Some focal seizures are preceded by auras that can last 20 - 30
seconds, but most attacks begin abruptly.
• Attacks reported to develop over several minutes or longer should be
regarded with suspicion.
• Most seizures last only 1 - 2 minutes,
– unless the patient is in status epilepticus.
• Lack of recall.
– Except for simple partial seizures, patients usually cannot recall the
details of an attack.
• Purposeless movements or behavior during the attack.
• Most seizures followed by a period of postictal confusion and lethargy.
– except for simple absence attacks or simple partial seizures, are
 DD
Syncope
• Many episodic disturbances of
Usually presents w/
neurologic function may be mistaken
prodromal symptoms:
for seizures (seizure mimics). A
lightheadedness,
complete review of these conditions
diaphoresis, nausea,
is too lengthy for inclusion here, but
“tunnel vision.”
several important entities are
But cardiac syncope may
mentioned
occur suddenly without
any prodromal warning.
Syncope may be
associated with injury,
incontinence, or even
brief tonic-clonic
activity.
Recovery is usually
rapid, with no postictal-
like symptoms.
 Pseudoseizures
• Psychogenic in origin
– often associated with a conversion
disorder, panic disorder, psychosis, •
impulse control disorder,
Munchausen syndrome, or
malingering.
• Suspect the diagnosis of
pseudoseizures when seizures occur in •
response to emotional upset or only
occur with witnesses present.
• These attacks are often bizarre and
highly variable.
• Patients often are able to protect
themselves from noxious stimuli
during the attack.
• Characteristic movements:
– side-to-side head thrashing,
– rhythmic pelvic thrusting,
– clonic extremity motions that are
alternating rather than symmetric.
Incontinence and injury are
uncommon, and there is usually no
postictal confusion.
• Patients will often stop the seizure-like
activity on command.
Accurate diagnosis of pseudoseizures
may require prolonged EEG or video
monitoring to demonstrate normal EEG
activity during an attack.
• The lack of a lactic acidosis or elevated
prolactin level drawn within 10 to 15
minutes of the cessation of seizure-like
activity makes true seizures much less
likely
Hyperventilation syndrome
• Can be misdiagnosed as a seizure disorder.
• A careful history will reveal the gradual
onset of the attacks with shortness of
breath, anxiety, and perioral numbness.
• Such attacks may progress to involuntary
spasm (especially carpopedal) of the
extremities and even loss of
consciousness, although postictal
symptoms are rare.
• Asking the patient to hyperventilate often
reproduces the episodes.
Movement disorders:
• such as dystonia, chorea, myoclonic jerks,
tremors, or tics, may occur in a variety of
neurologic conditions.
• Consciousness is always preserved during
these movements, and the patient can
often temporarily suppress the
movements.

Migraine headaches
• may be preceded by an aura similar to that seen in some partial
seizures.
• The most common migraine aura = scintillating scotoma.
• Migraine headaches may also be accompanied by focal neurologic
symptoms, such as homonymous hemianopsia or hemiparesis.
• However, active movement disorders are inconsistent with migraine.
 Lab Test
• Individualize the use of laboratory studies.
• In a patient with a well-documented seizure disorder who has had a single
unprovoked seizure, the only tests that may be needed are a glucose level and
pertinent anticonvulsant medication levels.
• In the case of an adult with a first seizure or unclear seizure history, more
extensive studies are usually needed and depend on the clinical context.
• Obtain serum glucose, basic metabolic panel, lactate, calcium, magnesium, a
pregnancy test, and toxicology studies.
• Consider assays for anticonvulsant drug levels.
• A seizure may result in a lactate driven, wide anion gap metabolic acidosis.
• Most lactate abnormalities will clear within 30 minutes.
• The prolactin level may also be elevated for a brief period (15 to 60 minutes)
immediately after a seizure.
• These tests can prove helpful in distinguishing true seizures from a
pseudoseizure.
• Interpret the results of anticonvulsant levels with caution.
• If the patient history is limited, a positive serum assay for anticonvulsant
drugs suggests (but does not prove) the presence of a chronic seizure
disorder.
• The usual therapeutic and toxic levels indicated in laboratory reports are
helpful only as rough guides.
• The therapeutic level of a drug is the level that provides adequate seizure
control without unacceptable side effects.
• A marked change in previously stable drug levels may indicate
noncompliance, a change in medication, malabsorption of a drug, or
ingestion of a potentiating or competing drug.
• A very low serum anticonvulsant drug level suggests noncompliance with
medication and is the most common cause of a breakthrough seizure.
 Imaging
• CT scan of head in ED for patients
with a first-ever seizure or a change
in established seizure patterns to
evaluate for a structural lesion.
– A non-contrast CT is an
appropriate screening tool.
• Obtain a CT scan if there is any
concern for an acute intracranial
process
– based on history, comorbidities,
or findings on physical
examination.
• Concern for an acute intracranial
process is an important indication for
obtaining CT imaging, even if there is
a coexistent metabolic process.
• Because many important processes:
tumors or vascular anomalies, may
studies, a follow-up contrast-
enhanced CT or MRI is often needed.
• Obtain other radiographic studies as
indicated by the clinical presentation
to avoid missing injuries acquired as a
result of the seizure.
– Obtain radiographs of the cervical
spine if there is suspicion of head
or neck trauma.
– Chest radiographs may reveal
primary or metastatic tumors or
aspiration.
– Shoulder radiographs may help
rule out posterior dislocations.
Special examinations, such as
cerebral angiography, are rarely
part of the ED evaluation.
LUMBAR PUNCTURE ELECTROENCEPHALOGRAPHY
• Lumbar puncture in • Although EEG is very helpful, it is often
the setting of an not readily available in most EDs.
acute seizure is • Emergent EEG can be considered in the
evaluation of:
indicated if the
– Patient with persistent, unexplained
patient is febrile or altered mental status to evaluate for
immunocompromise nonconvulsive status epilepticus,
d or if subarachnoid – subtle status epilepticus,
hemorrhage is – paroxysmal attack when a seizure is
suspected and the suspected,
noncontrast head CT – ongoing status epilepticus after
is normal. chemical paralysis for intubation.
• Patients in whom an emergent EEG is
warranted typically require neurologic
consultation & admission to a critical
care setting.
Treatment: Uncomplicated Seizures
PATIENTS WITH ACTIVE
SEIZURES
• Typically, little is required during the
course of an active seizure other
than supportive & protective
measures.
• If possible, turn the patient to the
side  reduce the risk of aspiration.
• It is usually not necessary or even
possible to ventilate a patient
effectively during a seizure, but once
the attack subsides, clear the
airway.
– Suction and airway adjuncts
should be readily available.
• It is not necessary or recommended
to give IV anticonvulsant
medications during the course of an
uncomplicated seizure  Most
seizures will self-resolve within
5 minutes.
• Any unnecessary sedation at this
point will complicate the evaluation
and result in a prolonged decrease
in level of consciousness.
• Seizures that fail to abate after 5
minutes  status epilepticus and
require more aggressive medical
interventions
PATIENTS WITH A HISTORY OF SEIZURES
• Identify and correct potential precipitants that may lower the seizure
threshold. Many seizures occur because of failure to take anticonvulsant
medication as prescribed.
• Some anticonvulsants have very short serum T ½ , and missing even a
single dose may result in a sharp drop in serum levels.
• If anticonvulsant levels are very low, supplemental doses are
appropriate, and the regular regimen can be restarted or adjusted.
• A loading dose is also frequently provided. Without a loading dose, the
patient may not achieve anticonvulsant effects for days to weeks  risk
for subsequent seizures.
• Because there are no data comparing parenteral versus oral replacement,
this issue is left to the discretion of the medical provider and should be
based on knowledge of pharmacology.
– For example, the oral loading dose of phenytoin is 20 milligrams/kg given in
three divided doses every 2 to 4 hours, a time frame not acceptable for a
typical ED stay, so the IV route is needed to achieve the proper loading dose.
• In the known or suspected noncompliant patient, obtain a
serum anticonvulsant level before administering a
supplemental or loading dose to avoid drug toxicity.
• If anticonvulsant levels are adequate and the patient has had
a single attack, specific treatment may not be needed if the
seizure pattern and frequency fall within the expected range
for the patient.
• If anticonvulsant levels are not locally available (e.g.,
levetiracetam or lacosamide), and there is a missed dose or
noncompliance, give the usual dose in the ED before
discharge.
• Even well-controlled patients may have occasional breakthrough
seizures.
• Attempt to identify any precipitants or conditions that have
lowered the seizure threshold.
• If none is found, a change or adjustment of medication may be
needed and should be made in consultation with the patient’s
primary care physician or neurologist.
• If the maintenance dose is increased, ensure follow-up within 1 to
3 days.
• There are no specific guidelines for the duration of ED observation
in the situation of an individual with a prior history of seizures.
• Some clinicians discharge patients with seizures resulting from
nontherapeutic anticonvulsant levels after administration of a
loading dose of an anticonvulsant if vital signs are normal and the
mental status has returned to baseline. Ideally, discharge patients
with a reliable family member or friend and with medical follow-up
arranged, as above.
PATIENTS WITH A FIRST UNPROVOKED SEIZURE
• Guidelines do not recommend hospital admission or initiation of
anticonvulsant therapy in the patient with a first unprovoked seizure, as
long as the patient has returned to neurologic baseline.
• The most important predictors of seizure recurrence are: underlying
cause of the seizure and the results of the EEG.
– The decision to begin outpatient treatment with antiepileptics
depends on the risk of recurrent seizures weighed against the risk–
benefit ratio of anticonvulsant therapy.
• In general, patients with a first unprovoked seizure who have a normal
neurologic examination, no acute or chronic medical comorbidities,
normal diagnostic testing (non-contrast head CT, normal mental status)
can safely be discharged from the ED.
– Initiation of antiepileptic medication may be deferred to the
outpatient setting where further studies, including an EEG and MRI,
can be performed.
• Consider consultation and/or admission for patients who do not meet the
above criteria
PATIENTS WITH PROVOKED (SECONDARY) SEIZURES
• Due to an identifiable underlying condition often require
admission and should generally be treated to minimize
seizure recurrence.
• The ideal initial antiepileptic regimen is a single-drug therapy
that controls seizures with minimum toxicity  If treatment
is initiated, drug selection is based on the type of seizure and
should be done in consultation with a neurologist.
• Antiepileptic agents: valproate, lamotrigine, topiramate,
levetiracetam, and oxcarbazepine  options for adults with
new-onset seizures.
• Instruct discharged patients to take precautions to minimize
the risks for injury from further seizures:
– Swimming, working with hazardous tools or machines, and
working at heights should be prohibited.
 Special populations
HUMAN IMMUNODEFICIENCY VIRUS
• Mass lesions, encephalopathy, herpes
zoster, toxoplasmosis, Cryptococcus,
neurosyphilis, and meningitis are all
seen more frequently in this population
and can all provoke seizure activity.
• Perform an extensive investigation for
the cause of the seizure.
• If no space-occupying lesion is identified
on non-contrast head CT scan & there is
no evidence of increased intracranial
pressure, perform a lumbar puncture to
exclude CNS infection.
• If no explanation for seizures is found,
then obtain a contrast-enhanced head
CT or MRI.
PREGNANCY
• Most seizures in pregnancy are not first-
time seizures, and initial evaluation is
generally as discussed earlier, with the
addition of an obstetric evaluation to
determine gestational age and fetal well-
being.
• When a woman >20 weeks of gestation
develops seizures in the setting of
hypertension, edema, and proteinuria,
the condition is defined as eclampsia.
• Magnesium sulfate has long been used to
treat eclampsia with good results.
• In eclamptic women, magnesium sulfate
infusion compared to diazepam and
phenytoin resulted in a >50% reduction
in recurrence of seizures and a lower
incidence of pneumonia, intensive care
unit admission, and assisted ventilation.
 Hypertensive Encephalopathy
• Sudden increase in BP (+/- preexisting chronic HTN) 
encephalopathy & headache (dev over period of sev hrs to days
• Vomiting, visual disturbances, focal neurologic deficits, focal or
generalized seizures can occur
• BP >250/150 mmHg usually req to precipitate the syndr in pts
w/ chronic HTN
• Prev normotensive pts may be affected at lower pressures
• Coexisting renal failure increase risk of HE
• Cerebrovasc spam, impaired autoregulation of cerebral BF,
intravasc coagulation = proposed as cause of neurossx
• small infacts & petechial hemorrhage  affect brainstem most
prominently + other subcortical gray & white matter regions

Lange. Clinical neurology 7th edition

 Treatment
• Clinical findings • Agents of choice for BP reduction in hypertensive
– Most useful confirming dx: encephalopathy = labetalol & nicardipine
ophthalmoscopy – they produce an even decrease in resistance
• Retinal arteriolar across vascular beds in different organ systems.
spasm • In contrast, NO donors (nitroglycerin and
• Papilledema, retinal nitroprusside), although widely used for this
hemorrhage, exudates indication, have a differential effect on the cerebral
(+) and systemic circulations  relative increase in
– Lumbar puncture = cerebral BP and a shunt effect to the peripheral
normal or elevated CSF circulation.
pressure & prots – This serves to decrease cerebral blood flow and
• Prevention may produce a greater than anticipated
– Early th/ of reduction in cerebral perfusion  increasing the
uncomplicated HTN & risk of ischemia in watershed areas of the brain
prompt recognition of • This may be worsened by the relative
elevated BP (e.g acute increase in intracranial pressure known to
glomerulonephritis,
occur with sodium nitroprusside therapy.
eclampsia)

Lange. Clinical neurology 7th edition

 CNS Infections
• Regardless of etiology, most patients with CNS
infection have similar clinical manifestations.
• Common symptoms: headache, nausea, vomiting,
anorexia, restlessness, altered state of consciousness,
and irritability; most of these symptoms are
nonspecific.
• Common signs of CNS infection, in addition to fever:
photophobia, neck pain and rigidity, obtundation,
stupor, coma, seizures, and focal neurologic deficits.
• The severity and constellation of signs are determined
by the specific pathogen, the host, and the area of the
CNS affected.
 tet
• Infection of the CNS may be diffuse or focal.
• Meningitis and encephalitis are examples of diffuse
infection.
• Meningitis implies primary involvement of the meninges
• Encephalitis indicates brain parenchymal involvement.
• Because these anatomic boundaries are often not distinct,
many patients have evidence of both meningeal and
parenchymal involvement and should be considered to
have meningoencephalitis.
• Brain abscess is the best example of a focal infection of the
CNS.
– The neurologic expression of this infection is determined by the
site and extent of the abscess(es)
• The diagnosis of diffuse CNS infections depends on
examination of cerebrospinal fluid (CSF) obtained by lumbar
puncture (LP).
• Noninfectious
illnesses can cause
generalized
inflammation of the
CNS. Relative to
infections, these
disorders are
uncommon and
include malignancy,
collagen vascular
syndromes, and
exposure to toxins
 Clinical Manifestation
• The onset of acute meningitis has 2 predominant patterns.
• The more dramatic, less common presentation:
– sudden onset with rapidly progressive manifestations of shock,
purpura, disseminated intravascular coagulation (DIC), and reduced
levels of consciousness often resulting in progression to coma or death
within 24 hr.
• More often:
– preceded by several days of fever accompanied by upper respiratory
tract or gastrointestinal symptoms, followed by nonspecific signs of
CNS infection such as increasing lethargy and irritability.
 S&S
• Nonspecific findings: fever, anorexia and poor feeding,
headache, symptoms of upper respiratory tract infection,
myalgias, arthralgias, tachycardia, hypotension, and various
cutaneous signs, such as petechiae, purpura, or an
erythematous macular rash.
• Meningeal irritation: nuchal rigidity, back pain, Kernig sign
(flexion of the hip 90 degrees with subsequent pain with
extension of the leg), Brudzinski sign (involuntary flexion of
the knees and hips after passive flexion of the neck while
supine).
– In some children, particularly in those younger than 12-18 mo, Kernig
and Brudzinski signs are not consistently present
• Fever, headache, and nuchal rigidity are present in only 40%
of adults with bacterial meningitis.
• Increased ICP is suggested by:
– Headache, emesis, bulging fontanel or diastasis (widening) of the
sutures, oculomotor (anisocoria, ptosis) or abducens nerve paralysis,
hypertension with bradycardia, apnea or hyperventilation, decorticate
or decerebrate posturing, stupor, coma, or signs of herniation.
– Papilledema is uncommon in uncomplicated meningitis and should
suggest a more chronic process: e.g: presence of an intracranial
abscess, subdural empyema, or occlusion of a dural venous sinus.
– Focal neurologic signs usually are due to vascular occlusion.
– Cranial neuropathies of the ocular, oculomotor, abducens, facial, and
auditory nerves may also be due to focal inflammation.
– Overall, about 10-20% of children with bacterial meningitis have focal
neurologic signs.
• Seizures
– (focal or generalized) due to cerebritis, infarction, or electrolyte
disturbances occur in 20-30% of patients with meningitis. Seizures that
occur on presentation or within the 1st 4 days of onset are usually of
no prognostic significance. Seizures that persist after the 4th day of
illness and those that are difficult to treat may be associated with a
poor prognosis.
• Alterations of mental status
– common among patients with meningitis and may be due to increased
ICP, cerebritis, or hypotension; manifestations: irritability, lethargy,
stupor, obtundation, and coma.
– Comatose patients have a poor prognosis. Additional manifestations of
meningitis include photophobia and tache cerebrale (elicited by
stroking the skin with a blunt object and observing a raised red streak
within 30-60 sec)
https://clinicalgate.com/infections-of-the-central-nervous-system/
Clinical Neurology. Lange. 7th edition
Clinical Neurology. Lange. 7th edition
Clinical Neurology. Lange. 7th edition
Clinical Neurology. Lange. 7th edition
Clinical Neurology. Lange. 7th edition
 Treatment of Tuberculous meningitis
• Started ASAP
• Don’t withheld while waiting for culture results PROGNOSIS
• Decision to treat based on CSF findings • Even +
• Lymphocytic pleocytosis & decreased glucose = appropriate
suggestive even when Acid fast bacili smear (-)
th/; ~1/3 pts
w/ TB
• Early chemotherapeutic intervention in acute meningitis
tuberculous meningitis improves the patient’s
prognosis.
succumb
• A strong clinical suggestion of this disease is an • Coma at time
adequate indication to begin antituberculous of
therapy. presentation
• A standard treatment regimen: isoniazid, rifampin, = poor
pyrazinamide, and ethambutol or streptomycin. prognosis
• Corticosteroids have also been shown to decrease predictor
secondary complications.

Lange. Clinical neurology 7th edition

 Treatment of Viral infections
• Except for herpes simplex encephalitis, no specific therapy
for viral meningitis and encephalitis is available.
– Most effective = acyclovir 10-15 mg/kg IV every 8 hrs 14-21 days
– Complication: erythema at infusion site, GI disturbances, headache,
skin rash, tremor, seizures, encephalopathy or coma
– Th/ ASAP
• Headache and fever can be treated with acetaminophen, but
aspirin should be avoided, especially in children and young
adults (association with Reye syndrome)
• Seizures usually respond to phenytoin or phenobarbital.
• Supportive measures in comatose patients = mechanical
ventilation and IV or NGT feeding.

Clinical Neurology. Lange. 7th edition

 Fungal Meningitis
hematogenous invade meninges
spread from parameningeal (commonly
Fungi lungs, heart, GI, sites (orbits, mucormycosis,
genitourinary paranasal sinuses) aspergillosis &
tract, skin actinomycosis)
• Lab findings • Treatment & prognosis
– Urine should be examined for Candida – Amphotericin B most common
– CXR = hilar lymphadenopathy, patchy or – Nephrotoxicity is common (force
miliary infiltrates, cavitation or pleural interruption of th/ for 2-5 days)
effusion
– CT or MRI = intracerebral mass lession
– Newer lipid based formulations: Ampo B
assc w/ cryptococcus or others; a lipid complex/cholesteryl sulfate,
contiguous infx source in orbit or liposomal ampho B = less nephrotoxic
paranasal sinuses or hydrocephalus – Coccidioides meningitis or not respond
– Fluid clear but viscous (cryptococci) to IV th/ = intrathecal ampho B often
– Aspergillus = PMN pleocytosis added
– Micros w/ india ink = infecting organism – 0,1 mg test dose diluted in 10 ml CSF (+/-
– Mucormycosis = nasal mucosa biopsy corticosteroids)  increased to 0,25 –
essential 0,5 mg every other day
– Mortality rates remain high in fungal
menignitis
Lange. Clinical neurology 7th edition
 Encephalopathy
• Term for any diffuse disease of the brain that alters brain fx &
structure
• May be caused by:
– infectious agents, metabolic, or mitochondrial dsyfx, brain tumor or
increase pressure in skull, prolonged exposure to toxic elements,
chronic progressive trauma, poor nutrition, lack O2 or BF to brain
• Hallmark = altered mental state
• Depending on type & severity; common neuro ssx:
– Progressive loss of memory & cognitive ability
– Subtle personality changes, inability to concentrate
– Lethargy & progressive loss of consciousness
– Other neuro ssx: myoclonus, nystagmus, tremor, muscle atrophy
+ weakness, dementia, seizures, loss ability to swallow or speak
Encephalopathy. American College of Physicians.
https://www.mnhospitals.org/Portals/0/Documents/patientsafety/Delirium/ACP%20Encephalopathy%20Coding%20Article.pdf
 Categories of encephalopathy
Acute Chronic
• Acute/subacute global, fxal alteration • Chronic mental status
of mental status due to systemic alteration: slowly progressive
factors • Result from permanent,
• Reversible when abnr corrected, irreversible, structural
return to baseline mental status changes w/in brain itself
• Further identified: • Examples:
– Toxic – Anoxic brain injury
• Medications, drugs, chemicals – Chronic traumatic
encephalopathy
– Metabolic – Heavy metals
• Metabolic disturbances – HIV-related
– Toxic-metabolic – Hereditary enz def
• Causes: acute organ failure (hepatic – etc
& renal; alcohol; dehydration;
electrolyte imbalace; fever; HTN; Acute intra-cranial processes
hypoxemia; drugs; infx (sepsis); (stroke/traumatic lesions) should not be
meds; toxic chem; Wernicke classified as acute encephalopathy but
considered as alteration of consciousness or
(thiamine def)
concussion
Encephalopathy. American College of Physicians.
https://www.mnhospitals.org/Portals/0/Documents/patientsafety/Delirium/ACP%20Encephalopathy%20Coding%20Article.pdf
 Hepatic Encephalopathy
Hepatic coma  elevation of
blood NH3 to 5-6 x (N)  coma
• As complication of cirrhosis,
portosystemic shunting,
chronic active hepatitis, or
fulminant hepatic necrosis
(following viral hepatitis)
• Alcoholism = most common
underlying disorder
• Syndrome may be chronic
progressive or acute (onset)
• Latter case  GI hemorrhage
(freq precipitating cause)
Lange. Clinical neurology 7th edition
Liver disease
impair hepatocellular detoxifying mechanism or
portosystemic shunting of venous blood
ammonia & toxins accumulate in blood
diffuse to brain
cerebral ssx
Cilinical findings:
• Ssx of encephalopathy may precede
systemic ssx: nausea, anorexia, weight
loss
• Recent GI bleeding, consume high-prot
foods, use of sedatives or diuretics,
systemic infx = clue to cause of clinical
decompensation
• PF:
– Systemic signs of liver disease
– Cognitive disturbances: somnolence,
agitation, coma
– Occular reflex usually brisk
– Nystagmus; tonic downward ocular deviation
& disconjugate eye movement seen
– Most helpful neuro sign of metabolic
disturbance (not restricted to liver) =
ASTERIXIS (flapping tremor of outstretched
dorsiflexed hands or feet from impaired
postural control)
– Other: seizures, tremors, spasticity, rigidity,
posturing
• Lab
– Bilirubin, transaminase, ammonia, PT/PTT,
respi alkalosis
– Most specific CSF abnormalitis = elevated
glutamine
– EEF: diffuse slow triphasic waves
Lange. Clinical neurology 7th edition
• Treatment
– Restrict dietary proteins
– Reverse electrolyte disturbances
& hyperglycemia
– Discont.drugs causing
decompensation
– AB, Frozen fresh plasma or vit K
– Oral/rectal + lactulose 20-30 g 3-
4x/d decreases colonic pH
ammoia abs.
– Neomycin 1-3g PO 4x/d reduce
ammonia forming bacteria in
colon
– Benzodiazepine rec antagonist
flumazenil
– Orthotopic liver transplant req
some cases
– Prognosis: correlates w/ severity
of hepatocellular >> neuro dysfx
 Hypertensive Encephalopathy
• Sudden increase in BP (+/- preexisting chronic HTN) 
encephalopathy & headache (dev over period of sev hrs to days
• Vomiting, visual disturbances, focal neurologic deficits, focal or
generalized seizures can occur
• BP >250/150 mmHg usually req to precipitate the syndr in pts
w/ chronic HTN
• Prev normotensive pts may be affected at lower pressures
• Coexisting renal failure increase risk of HE
• Cerebrovasc spam, impaired autoregulation of cerebral BF,
intravasc coagulation = proposed as cause of neurossx
• small infacts & petechial hemorrhage  affect brainstem most
prominently + other subcortical gray & white matter regions

Lange. Clinical neurology 7th edition

 Treatment
• Clinical findings • Agents of choice for BP reduction in hypertensive
– Most useful confirming dx: encephalopathy = labetalol & nicardipine
ophthalmoscopy – they produce an even decrease in resistance
• Retinal arteriolar across vascular beds in different organ systems.
spasm • In contrast, NO donors (nitroglycerin and
• Papilledema, retinal nitroprusside), although widely used for this
hemorrhage, exudates indication, have a differential effect on the cerebral
(+) and systemic circulations  relative increase in
– Lumbar puncture = cerebral BP and a shunt effect to the peripheral
normal or elevated CSF circulation.
pressure & prots – This serves to decrease cerebral blood flow and
• Prevention may produce a greater than anticipated
– Early th/ of reduction in cerebral perfusion  increasing the
uncomplicated HTN & risk of ischemia in watershed areas of the brain
prompt recognition of • This may be worsened by the relative
elevated BP (e.g acute increase in intracranial pressure known to
glomerulonephritis,
occur with sodium nitroprusside therapy.
eclampsia)

Lange. Clinical neurology 7th edition

 Renal - Uremia
• Uremia  accumulation of
dialzyable small molecular toxins
(phenolic derivatives of Aromatic
AA)
• Renal failure (esp acute onset or
rapid progressive) 
encephalopathy or coma +
hyperventilation & prominent
motor manifestation
– Tremor, asterixis, myoclonus,
tetany
• Lab:
– Abnr elevated serum urea
nitrogen, creatinine, K+,
met.acidosis
Lange. Clinical neurology 7th edition
• EEG
– Slow triphasic or parozysmal
spikes or sharp waves
• Acute management:
– Hydration
– Protein
– Salt restriction
• Long-term management:
– Reverse cause (e.g urinary tract
obstruction)
– Dialysis, kidney transplant
• Dialysis itself can produce
encephalopathy (dialysis
disequilibrium syndrome)
result from hypoosmolarity
– Use briefer period of dialysis at
reduced rate of BF
 Pulmonary encephalopathy
• Impairment of
consciousness + pulmo
insufficiency  hypercapnia
• Pts w/ lung disease or
brainstem or neuro
disorders affect respi fx 
encephalopathy related to
hypoventilation
• SSx:
– Headache, confusion,
somnolence
Lange. Clinical neurology 7th edition
• Exam: papilledema,
asterixis, myoclonus,
confusional state or coma
• Tendon reflexes decreased,
pyramidal signs may
present
– plantar extension and
hyperreflexia
• Seizure occasional
• ABG = respi acidosis
• Th/ ventilatory support to
decrease hypercapnia to
maintain adeq oxygenation
 Wernicke Encephalopathy
• Complication of chronic alcoholism • Clinical findings
• Occurs in other disorders assc w/ – TRIAD: OPHTHALMOPLEGIA, ATAXIA,
malnutrition CONFUSIONAL STATE
• Caused by def of thiamin (B1) – Most common ocular abnr: nystagmus,
• Pathologic features: abducens (VI) nerve palsy, horizontal-
– Neuronal loss vertical gaze palsy
– Demyelination – Ataxia gait
– Gliosis in periventricular gray – Global confusion + prominent disorder
matter of immediate recall & recent memory
– Prolif of small BV & petechial – Absent ankle jerks
hemorrhages may be seen – Ypothermia & hypotension may occur
• Areas most commonly involved: do to hypothalamic involvement
– Medial thalamus, mammilary – Pupillary abnr: mild anisocoria, sluggish
bodies, periaqueductal gray reaction to light
matter, cerebellar vermis, – Periph blood smear: macrocytic anemia
oculomotor, abducens, vestibular – MRI: atrophy of mammillary bodies
nuclei
Lange. Clinical neurology 7th edition
 • Treatment • Prognosis
– Prompt adm of thiamine – + th/  ocular abnr
– Initial dose 100 mg IV begin to improve w/in 1
(before or +dextrose) day & ataxia & confusion
avoid precipitating or w/in 1 week
exacerbating disorder – Ophthalmoplegia,
– Parenteral thiamine vertical nystagmus,
cont.for sev days acute confusion
– Maintenance req for reversible w/in 1 mo
thiamine ~1mg/d (throu – Major long term
diet) although abs compliation = Korsakoff
impaired in alcoholics syndrome (amnestic
syndr)

Lange. Clinical neurology 7th edition

 Diffuse Encephalopathies/metabolic coma
• Hypoglycemia and drug intoxication
• other processes that affect the brain
diffusely:
– meningitis, subarachnoid
hemorrhage, and seizures.
• The clinical presentation is distinct
from that of a mass lesion.
• There are usually no focal signs:
– hemiparesis, hemisensory loss, or
aphasia
– no sudden loss of consciousness
• Except in some cases of subarachnoid
hemorrhage
• History reveals a period of progressive
somnolence or toxic delirium followed
by gradual descent into a stuporous
and finally comatose state
Lange. Clinical neurology 7th edition
• Asterixis, myoclonus, and tremor
preceding coma = important clues that
suggest metabolic disease.
• Symmetric decorticate or decerebrate
posturing can be seen with hepatic,
uremic, anoxic, hypoglycemic, or sedative-
drug–induced coma.
• Reactive pupils in the presence of
otherwise impaired brainstem function is
the hallmark of metabolic encephalopathy
• The few metabolic causes of coma that
also impair pupillary reflexes:
– massive barbiturate overdose with
apnea and hypotension,
– acute anoxia,
– marked hypothermia,
– anticholinergic poisoning (large
pupils)
– opioid overdose (pinpoint pupils).
 Metabolic encephalopathy (+ widespread
anatomic damage to hemispheres)
• BF may stay near normal
• Metabolism greatly reduced
• Coma arises from seizures (met & BF greatly
increase)
• Extremes of body temperature >410C or below
300C also induce coma through nonspecific
effect on met activity of neurons

Adams & Victors Principles of Neurology

Kejang Demam

LI 4
 Febrile Seizure
• Seizures that occur between the age of 6 - 60 mo w/ temperature
>= 380C; not a result of CNS infection or any metabolic imbalance,
occur in the absence of a history of prior afebrile seizures.

complex febrile Febrile status

simple febrile seizure
seizure epilepticus

• primary generalized, • more prolonged • febrile seizure lasting

• usually tonic- (>15 min), focal, >30 min.
clonic, attack • and/or recurs within
associated with 24 hr.
fever
• lasting maximum of
15 min
• not recurrent within
a 24-hour period.

Nelson Textbook of Pediatrics 2011

 • ~ 2% - 5% neurologically healthy infants & children experience
at least 1 simple febrile seizure.
– Simple FS (x) >> risk of mortality even though they are concerning to
the parents.
• Complex febrile seizures may have ~2-fold long-term increase
in mortality
– as compared to general population over subsequent 2 yr, probably
secondary to coexisting pathology.
• (x) long-term adverse effects of having ≥1 simple febrile
seizures.
– Recurrent simple febrile seizures (x) damage the brain.
– (X) increase in incidence of abnormalities of behavior, scholastic
performance, neurocognitive function, or attention.
• Children who develop later epilepsy might experience such difficulties.

Nelson Textbook of Pediatrics 2011

• Febrile seizures recur in:
– ~ 30% of those experiencing a first episode,
– ~ 50% after 2 or more episodes,
– 50% of infants <1 yr old at febrile seizure onset.
• Several factors affect recurrence risk:

• (x) risk factors carries a

recurrence risk of about 12%;
• 1 risk factor, 25-50%;
• 2 risk factors, 50-59%;
• 3 or more, 73-100%.

Nelson Textbook of Pediatrics 2011

• Although ~15% of children with epilepsy have had
febrile seizures, only 2-7% of children who
experience febrile seizures proceed to develop
epilepsy later in life.
• There are several predictors of epilepsy after febrile
seizures

Nelson Textbook of Pediatrics 2011

 Genetics
• The genetic contribution to incidence of febrile seizures is
manifested by a positive family history for febrile seizures.
• In many families the disorder is inherited as an autosomal
dominant trait, and multiple single genes causing the disorder
have been identified.
• Identified single genes: FEB 1, 2, 3, 4, 5, 6, & 7 genes on
chromosomes 8q13-q21, 19p13.3, 2q24, 5q14-q15, 6q22-24,
18p11.2, and 21q22.
• Only the function of FEB 2 is known: it is a sodium channel
gene, SCN1A.

Nelson Textbook of Pediatrics 2011

Figure 586-1 Management of febrile seizures.(Modified from Mikati MA, Rahi A: Febrile
seizures: from molecular biology to clinical practice, Neurosciences 10:14–22, 2004.)
 • Each child who presents with a febrile seizure
requires a detailed history and a thorough
general and neurologic examination 
cornerstones of the evaluation.
• Febrile seizures often occur in the context of:
– otitis media, roseola and human herpesvirus 6
(HHV6) infection, shigella, or similar infections,
making the evaluation more demanding.
– Several investigations need to be considered.

Nelson Textbook of Pediatrics 2011

 Lumbar Puncture
• Recommended <12 mo of age after
their 1st febrile seizure (rule out
meningitis)
– Esp important if child has received
prior ABs (mask clinical symptoms of
the meningitis)
– (+) identified source of fever: e.g.
otitis media, does not eliminate
possibility of meningitis.
• Seizures = major sign of meningitis in
13-15% of children presenting with
this disease; 30-35% of such children
have no other meningeal signs.
• According to the American Academy
of Pediatrics (AAP) practice
parameter, it is strongly
recommended in infants <1 yr of age
because other signs of the infection
might not be present.
Nelson Textbook of Pediatrics 2011
• 12 - 18 mo of age should also be
considered for lumbar puncture
 clinical symptoms of
meningitis may be subtle in this
age group.
– For the well-appearing child after a
febrile seizure, the yield of lumbar
puncture is very low.
• >18 mo of age, a lumbar
puncture is indicated in the
presence of clinical signs and
symptoms of meningitis (e.g.,
neck stiffness, Kernig sign,
Brudzinski sign) or if the history
and/or physical examination
otherwise suggest intracranial
infection.
 Electroencephalogram
• If the child is presenting with his or
her first simple febrile seizure and is
otherwise neurologically healthy, an
EEG need not normally be
performed as part of the
evaluation.
– An EEG would not predict the
future recurrence of febrile
seizures or epilepsy even if the
result is abnormal.
– Spikes during drowsiness are
often seen in children with
febrile seizures, esp >4 yr old 
do not predict later epilepsy.
– EEGs performed within 2 wk of
a febrile seizure often have
nonspecific slowing, usually
posteriorly.
Nelson Textbook of Pediatrics 2011
• Thus, in many cases, if an EEG is
indicated, it is delayed until or
repeated after >2 wk have passed.
EEG should therefore generally be
restricted to special cases in which
epilepsy is highly suspected, and it
should be used to delineate the type
of epilepsy rather than to predict its
occurrence.
• If an EEG is done, it should be
performed for at least 30 min in
wakefulness and in sleep according to
international guidelines  avoid
misinterpretation and drawing of
erroneous conclusions.
• If pts does not recover immediately
from a seizure  EEG can help
distinguish between: ongoing seizure
activity & prolonged postictal period
sometimes termed a nonepileptic
twilight state (NETS).
Blood Studies
• Blood studies (serum electrolytes,
calcium, phosphorus, magnesium, and
complete blood count [CBC]) = not
routinely recommended in work-up of
a child with 1st simple febrile seizure. • The work-up of children with complex
• Blood glucose = determined only in
children w/ prolonged postictal
obtundation or poor oral intake
(prolonged fasting).
• Serum electrolyte values may be
abnormal in children after a febrile
seizure, but this should be suggested
by precipitating or predisposing
conditions elicited in the history and
reflected in abnormalities of the
physical examination.
• If clinically indicated (e.g., in a history
or physical examination suggesting
dehydration) these tests are indicated.
Nelson Textbook of Pediatrics 2011
Neuroimaging
• According to the AAP practice
parameter, a CT or MRI is not
recommended in evaluating the child
after a first simple febrile seizure.
febrile seizures needs to be
individualized:
– EEG and neuroimaging, particularly if
the child is neurologically abnormal.
• Patients with febrile status epilepticus
have been reported to have swelling of
their hippocampus acutely and
subsequent long-term hippocampal
atrophy.
– These patients may be candidates for
neuroimaging, because they may be at
risk for later temporal lobe epilepsy.
 Treatment
• In general: antiepileptic therapy, continuous or intermittent,
is not recommended for children with one or more simple
febrile seizures.
• Parents should be counseled about the relative risks of
recurrence of febrile seizures and recurrence of epilepsy,
educated on how to handle a seizure acutely, and given
emotional support.
• If the seizure lasts for >5 min  acute th/ with diazepam,
lorazepam, or midazolam is needed

Nelson Textbook of Pediatrics 2011

 Bila setelah pemberian
diazepam rektal kejang belum
berhenti,
dapat diulang lagi dengan cara
dan dosis yang sama dengan
interval waktu 5 menit.

setelah 2 kali pemberian diazepam

rektal masih tetap kejang,
dianjurkan ke rumah sakit. Di
rumah sakit dapat diberikan
diazepam intravena dengan dosis
0,3-0,5 mg/kg.

Bila kejang telah berhenti,

pemberian obat
selanjutnya tergantung
dari jenis kejang demam
apakah kejang demam
sederhana
Konsensus Penatalaksanaan Kejang Demam IDAI 2006 atau kompleks dan faktor
http://www.idai.or.id/wp-content/uploads/2013/02/Kejang-Demam-Neurology-2012.pdf risikonya.

Neonatal Seizure
• Neonates do not have a
fully developed neurologic
system, and seizures in this
age group can be subtle, are
more likely to be focal, and
often carry a poor
prognosis.
• Seizures occur in 1.4% of
full-term infants and 20% of
premature infants.
Tintinalli’s Emergency Medicine. 8th edition
• Identifying seizure activity in
the neonate and distinguishing
it from normal newborn
myoclonus and jitters can be
challenging.
• Subtle focal movements or
stereotyped activities (e.g., lip
smacking, eye deviation, or
bicycling) may represent
seizure activity; neonates less
often have generalized tonic-
clonic seizures
• Apparent life-threatening
events with pallor or cyanosis
and a change in muscle tone
may be a manifestation of
seizure activity.
 • A birth and maternal history may identify risks for
congenital or neonatal infection (e.g., herpes simplex
virus, cytomegalovirus, or group B streptococci) or
potential withdrawal from maternal narcotics.
• Complications with labor and delivery may suggest birth
asphyxia with subsequent seizures.
• Regardless of the history or presence of fever, neonates
with witnessed seizures require extensive evaluation.
• Obtain cultures of blood, urine, and cerebrospinal fluid
and test for herpes simplex virus and begin empiric
parenteral antibiotics and acyclovir.
• Toxicologic evaluation may provide the physician with
evidence of withdrawal or overdose of abused
substances.
Tintinalli’s Emergency Medicine. 8th edition
 • Neonates with seizures are more likely to have electrolyte
abnormalities than older children: calcium and glucose
should be measured.
• Consider head CT for concerns of non-accidental trauma,
intracranial hemorrhage, infarction, or mass (even without
external signs of injury).
• Finally, if inborn errors of metabolism are suspected, obtain
serum levels of lactate and ammonia, as well as serum
amino acids and urine organic acids
• All neonates with witnessed seizure require admission to the
hospital.
• Treat the actively seizing neonate with benzodiazepines as
with older children; consider phenobarbital for second-line
therapy.
• Identify and treat hypoglycemia and electrolyte
abnormalities.
Tintinalli’s Emergency Medicine. 8th edition
 Malaria
• A protozoan disease transmitted by the bite of the Anopheles mosquito
• It is a leading cause of morbidity and mortality in many tropical areas of
the world, especially in Africa.
• ~55% of the world’s population is exposed to the infection, which exerts
its toll mainly on the young and the pregnant.
• In an area of intense transmission, most malaria infections occur in
children, who gradually acquire a considerable degree of immunity.
– In such areas, a high percentage of children may have asymptomatic parasitemia
(malaria infection), and illness due to malaria (malaria disease) is commonly mild and
only occasionally severe or life threatening.
– Nevertheless, the absolute burden of mortality is large because nearly all children are
infected. Adults in such areas rarely develop severe or fatal disease.
–
 Clinical Manifestation
UNCOMPLICATED MALARIA
• Clinical hallmark of malaria = fever, + prodrome of malaise, myalgia,
headache, chills.
– In some patients, chest pain, cough, abdominal pain, or arthralgias may be prominent.
• Early symptoms are nonspecific, can easily be confused with a viral
syndrome (influenza or hepatitis) or with bacterial sepsis
• In a non-immune individual, illness usually progresses to  chills, + high-
grade fever + nausea, orthostatic dizziness, extreme weakness  Sev
hours  fever abates  diaphoresis & becomes exhausted.
• If the infection is untreated  paroxysms of malaria—chills and fever
followed by diaphoresis—may over time begin to occur at nearly regular
intervals that correspond to the length of the asexual erythrocytic cycles
• The classic paroxysms of malaria are often lacking in malaria due to P.
falciparum or those receiving chemoprophylaxis.
– Physical examination are also not specific for malaria.
• Most patients appear acutely ill with high fever, tachycardia,
tachypnea.
• Splenomegaly & abdominal tenderness are common. The liver may or
may not be enlarged.
• Clinical signs that point to a diagnosis other than (or in addition to)
malaria: lymphadenopathy & maculopapular or petechial skin rash.
• In children growing up in a malarious area, attributing an illness to
malaria is particularly difficult because many children carry parasites
without being unwell and because symptoms and signs of both mild
and severe malaria are nonspecific  In these circumstances, the
higher the parasite density in the peripheral blood, the greater is the
likelihood that malaria is the cause of the illness.
SEVERE (COMPLICATED) MALARIA
• when it includes 1 or more: syndromes in the context of a
plasmodial infection, usually due to P. falciparum:
– coma with or without seizures (“cerebral malaria”),
– prostration,
– severe anemia,
– acidosis,
– hypoglycemia,
– acute renal failure,
– acute respiratory distress syndrome,
– pulmonary edema,
– jaundice,
– intravascular hemolysis,
– shock,
– disseminated intravascular coagulation.
• Complications of malaria can develop rapidly in
untreated P. falciparum infection or may supervene
early in the course of treatment.
• Occasionally, 1 or more complications may
constitute the presenting illness, when correct
diagnosis may be both difficult and critically
important.
• A patient with severe malaria is at risk of dying even
with optimal case management.
– Case fatality rates range between 5% and 30% in patients
receiving treatment for severe malaria according to the
complications present and their intensity.
• When cerebral malaria is suspected,
meningitis or encephalitis must be either
excluded or treated, and the clinician must
decide whether a lumbar puncture is safe.
• At lumbar puncture, the opening pressure is
usually raised in children and normal in adults.
• The fluid is normal in appearance and on
routine tests.
• In children in P. falciparum–endemic areas,
asymptomatic parasitemia is common, so it is
difficult to be sure that an illness is due to
malaria.
• In a child with coma & parasitemia, the
presence of a recently identified retinopathy
greatly strengthens confidence that malaria is
the cause of the syndrome.
• Among those who recover from cerebral
malaria, up to 1 in 5 children and up to 1 in 20
adults may be left with, or may later develop,
neurologic sequelae.
• Infections caused by any species of Plasmodium 
hemolysis, some degree of anemia, splenic enlargement, and,
occasionally, splenic rupture.
• The very young, the elderly, and pregnant women are at
greatest risk of developing complications when infected with
P. falciparum.
• Additional risk factors for severe malaria:
– immunocompromised state, asplenia, failure to take appropriate
chemoprophylaxis, refusal of or delay in seeking medical care, and late
or erroneous diagnosis.
 Diagnosis
• The diagnosis of malaria rests on a
history of potential exposure in a
malarious area, clinical symptoms,
signs, and competent microscopic
examination of well-prepared thick
and thin blood films
• Diagnosis based on clinical features
alone has very low specificity and
results in overtreatment.
3 major questions to be answered by the
blood smear are as follows:
(1) Is there evidence of malaria?
(2) If so, what is the density of
parasitemia (correlates with prognosis)?
(3) What species of malaria is responsible
for the infection and, in particular, is P.
falciparum present?
 – Clues to the diagnosis of P. falciparum infection:
• presence of small ring forms w/ double-chromatin dots within the
erythrocyte,
• multiple infected rings in individual RBC
• a paucity (usually absence) of mature trophozoites and schizonts on
smear,
• infected erythrocytes that are not enlarged and that have cytoplasm
w/out basophilic stippling.
– In some (but not all) cases, gametocytes may be seen; in P. falciparum
infection, these have a diagnostic crescent shape (banana shape).
• Parasite densities >4% of erythrocytes are rare in malaria due to non-
falciparum species.
– Obtain smears daily to assess the efficacy of drug treatment.
• P. knowlesi is usually misdiagnosed as the less aggressive P. malariae, because
the two are identical under light microscopy and require polymerase chain
reaction for differentiation. Any patient coming from Asia with a high parasite
burden resembling P. malariae should be assumed to be harboring P. knowlesi
THICK BLOOD FILM
• Place a small drop of blood (5 μL) on
a microscope slide, spread it evenly
to a diameter of ~1 cm, allow it to
dry, and then stain, without initial
fixation, with Fields or Giemsa stain.
• Record the result as the number of
parasites seen per oil-immersion
field (for an approximate indication
of density) or per 200 white cell
nuclei counted (a more accurate
density of parasites can then be
calculated once the WBC count is
known).
• A thick blood film contains several
layers of red cells (which are lysed by
the staining procedure), allowing
parasitemias down to ~40/μL to be
detected by an expert microscopist.
THIN BLOOD FILM
• A standard hematologic blood smear
(fixed with methanol and stained with
Giemsa) allows a single sheet of intact
red cells to be scrutinized for the
percentage of red cells parasitized
– number of parasites per microliter can
be calculated when the red cell count is
known.
• Because the red cells are not destroyed,
a thin film allows both parasite and red
cell morphology to be examined,
enabling more confident identification
of the species of plasmodium.
• A thin film may fail to detect a
parasitemia with a density below
~1000/μL, but it is more useful than a
thick film for counting very heavy
infections
• A long and careful search for parasites is necessary before a
film is declared “negative.”
• In early infection, especially infection due to P. falciparum, in
which mature-stage parasitized erythrocytes are sequestered
from the bloodstream, parasitemia may be undetectable
even in a competently read thick blood film.
• In highly suspicious cases, failure to detect parasitemia is not
an indication to withhold therapy.
• If parasites are not seen in the stained thin smear, a thick
smear must be done.
• If parasites are not seen on the first thick film, obtain repeat
thick smears at least twice daily for as long as malaria
remains a suspected diagnosis or until the patient is better.
• The first smear is positive in >90% of cases
ADDITIONAL DIAGNOSTIC TECHNIQUES
• Newer techniques for rapid diagnosis and speciation include
quantitative buffy coat fluorescent microscopy and rapid
diagnostic tests (dipstick bedside tests) to detect parasite
antigens (BinaxNOW®, ParaSight-F®) or to detect the parasite
enzyme lactate dehydrogenase (OptiMal).
• Sensitivity of rapid tests is excellent for P. falciparum malaria
with high parasitemia levels,
– but poor for non-falciparum malaria, and sensitively drops with lower
parasitemia levels.
• Polymerase chain reaction–based techniques to detect
parasite DNA are more sensitive than microscopy and are
valuable for research studies but are rarely available for
routine clinical purposes.
ADDITIONAL LABORATORY STUDIES
• Nonspecific laboratory features of malaria =
– normochromic normocytic anemia with findings suggestive of hemolysis,
– a normal or mildly depressed total leukocyte count,
– thrombocytopenia,
– elevated erythrocyte sedimentation rate,
– mild abnormalities in liver and renal functions,
– Biologic false-positive Venereal Disease Research
• Laboratory test.
– In severe P. falciparum malaria, there may be:
• hypoglycemia,
• severe anemia,
• hyperlactatemia,
• electrolyte disturbances, or
• evidence of acute renal failure, or
• disseminated intravascular coagulation.
 Treatment
• Admit patient to hospital because severe disease can develop
rapidly even after the start of specific therapy.
• Give analgesia if required (e.g: acetaminophen 500 mg @6hrs PO)
& oral fluids.
• Patient can take and retain drugs by mouth  begin a full course
of oral antimalarial drugs without delay
• Artemisinin-containing combination therapies = drugs of choice
by WHO
• If a dose is vomited, the dose may be repeated; if it is vomited
again, switch to parenteral therapy as for severe disease until
able to resume treatment by mouth.
• Maintain regular checks for the development of any
complications
• Check blood daily for parasite density and for Hb []
• When stable, the patient may be discharged to complete the
course of oral drugs at home; stress the importance of
completing the course and of reporting back with any
recurrence of symptoms.
• WHO does not recommend chloroquine for the treatment of
P. falciparum malaria due to changing resistance patterns
and the superiority of artemisinin-containing combination
therapies
• CDC & Prevention recommend chloroquine for P. falciparum
malaria imported from areas of low chloroquine resistance
– Central America west of the Panama Canal, Haiti, the Dominican
Republic, and parts of the Middle East.
• Patients with P. vivax or P. ovale malaria require additional
treatment to eradicate hypnozoites from the liver.
• This treatment can be given after full recovery from the initial
illness; the most common agent used is primaquine phosphate.
• Adult dose = 30 mg of base/ day; 14 days.
• First check the patient for G6PD deficiency (glucose-6-phosphate
dehydrogenase–deficient persons are at risk of hemolysis when
treated with primaquine; an alternative management of relapsing
malarias is chloroquine base 300 mg weekly for 6 months).
• Treatment with primaquine is not needed in patients with P.
falciparum or P. malariae malaria because there are no dormant
asexual forms in the liver. P. vivax or P. ovale infections that have
been acquired by needlestick accident, blood transfusion, or
transplacental infection do not need treatment with primaquine
for the same reason.
SEVERE (COMPLICATED) MALARIA
• Severe malaria is usually due to
P. falciparum,
– occasionally, it is due to P.
vivax or P. knowlesi.
• The patients should be admitted
to an appropriate level of
intensive care.
• Both supportive and specific
antimalarial therapies are urgent
and critical to the patient’s
survival.
• Monitor the patient frequently;
new complications may develop
after the start of treatment.
SUPPORTIVE MANAGEMENT
• Initial resuscitation:
– O2 for hypoxia,
– fluid replacement, IV glucose for
hypoglycemia,
– blood transfusion for severe anemia or
DIC,
– occasionally intubation for severe
respiratory distress or suspected raised
ICP with altered mental status.
– Additional treatments for septic shock
may be necessary
• Monitor to identify and treat
seizures, hyperpyrexia, ARDS, or
acute renal failure.
• Culture blood samples for bacterial
infections, and give immediate
parenteral antibiotics  bacterial
co-infection cannot be ruled out by
clinical assessment initially.
SPECIFIC ANTIMALARIAL CHEMOTHERAPY
• Initiate parenteral therapy with an efficacious antimalarial drug
without delay; continue parenteral route at least 24 hrs;
– thereafter, as soon as the patient is well enough to take drugs by mouth,
switch to a complete course of the best available oral therapy
• If patient remains unable to take oral therapy, chosen parenteral
therapy should be continued for a maximum of 7 days.
• Do not delay treatment while awaiting laboratory confirmation,
because initial smear for P. falciparum may be negative, even on
microscopy of a thick blood film, in a non-immune individual.
• An unstable patient (abN vital signs, severe anemia, renal failure,
pulmonary edema, acute respiratory distress syndrome,
disseminated intravascular coagulation, acidosis, jaundice,
hemoglobinuria, or seizures) + clinical or travel history suggesting
malaria should be started on artesunate (if available) or quinidine
gluconate until a diagnosis of malaria can be ruled out.
• IV artesunate = drug of choice for severe malaria (World Health
Organization)
• Artesunate is rapidly effective and extremely potent against all
erythrocyte stages.
• It does not cause cardiac toxicity or hypoglycemia.
• It is effective and is superior to IV quinine in both adults and
children.
RATES OF PARASITE CLEARANCE • In a patient treated with quinidine
• With correct treatment, the or quinine, the density of asexual
parasite load in the peripheral parasites may be unchanged or
blood should decrease rapidly even increased after 24 hours of
during the first few days. therapy, but this is rarely the case
• This decrease is significantly faster in a person treated with an
with artemisinin drugs than with artemisinin therapy.
all other therapies  artemisinin • Asexual forms of the parasite
drugs kill early-stage as well as should not be detectable within 5
late-stage parasites. days of the start of any effective
• With artemisinin treatment, the treatment course.
parasite count usually decreases • Gametocytes, the sexual forms,
significantly within the first 12 which do not cause disease in the
hours, human host, may persist for
– whereas with other drugs, this steep several weeks after treatment and
decrease may take 24 to 48 hours. do not indicate treatment failure.
PREGNANCY
• Among non-immune adults, pregnant are at greater risk of
developing severe disease than others.
• Pregnant women = particular risk of anemia, hypoglycemia,
and, especially in the third stage of labor, fluid overload.
• Artemisinin drugs are probably safe in pregnancy but are still
subject to restriction in the first trimester.
• Quinidine and quinine can be used in pregnancy but carry a
greater risk of causing hypoglycemia (stimulation of insulin
secretion from hypertrophied pancreatic β-cells)
PREVENTION
• Reducing transmission through widespread use of long-lasting insecticide-
impregnated bed nets and programs of indoor residual spraying with
insecticides.
• Between dusk & dawn, travelers should remain in well-screened areas,
use insecticide-impregnated mosquito nets, and wear longsleeved, light-
colored clothing.
– Nets impregnated with long-lasting insecticides are very effective, although resistance of
mosquitoes to insecticides is an increasing concern.
• An insect repellent containing N,N-diethyl-m-toluamide (DEET) in [] s no
> 35% should be applied to exposed skin.
• Anyone requiring advice for the prophylaxis appropriate for travel to a
particular area should attend a travel clinic
– Failure to take appropriate chemoprophylaxis is a significant risk factor
for fatal infection.
– Even with the rigorous use of antimosquito measures and
chemoprophylaxis, malaria can be contracted or can recur.
 Tetanus
• Acute, spastic paralytic illness (called lockjaw)
• Caused by the neurotoxin produced by Clostridium tetani,
– motile, Gram-positive, spore-forming obligate anaerobe whose natural
habitat worldwide is soil, dust, and the alimentary tracts of various animals.
– C. tetani forms spores terminally, producing a drumstick or tennis racket
appearance microscopically.
• Tetanus spores can survive boiling but not autoclaving, whereas the vegetative cells are killed
by antibiotics, heat, and standard disinfectants.
• Unlike many clostridia, C. tetani is not a tissue-invasive organism and
instead causes illness through the effects of a single toxin, tetanospasmin
(tetanus toxin)
– Tetanospasmin is 2nd most poisonous substance known, surpassed in potency
only by botulinum toxin.
– Human lethal dose of tetanus toxin is estimated to be 10−5 mg/kg.
• Tetanus occurs worldwide and is endemic in ~ 90
developing countries
• The most common form:
– neonatal (or umbilical) tetanus
• kills ~ 300,000 infants each year, ~80% of deaths in 12 tropical
Asian and African countries.
• It occurs in infants whose mothers are not immunized.
– In addition, an estimated 15,000-30,000 unimmunized
women worldwide die each year of maternal tetanus,
which results from postpartum, postabortal, or
postsurgical wound infection with C. tetani.
• Most non-neonatal cases of tetanus are associated with a traumatic
injury, often a penetrating wound inflicted by a dirty object: nail, splinter,
fragment of glass, or unsterile injection.
– Tetanus occurring after illicit drug injection is becoming more common.
– Also occurs after use of contaminated suture material and after IM injection
of medicines, most notably quinine for chloroquine-resistant falciparum
malaria.
– may also occur in association with animal bites,
– abscesses (including dental abscesses),
– ear and other body piercing,
– chronic skin ulceration, burns,
– compound fractures,
– frostbite, gangrene,
– intestinal surgery,
– ritual scarification,
– infected insect bites
– female circumcision.
• Rare cases have no history of trauma.
 Introduced
vegetative
spores produce tetanus plasmid carries
bacterial cell
germinate; toxin the toxin gene
death & lysis
multiply

undergoes
enters motor retrograde
toxin binds at
Toxin is released nerve by axonal transport
NMJ
endocytosis to the cytoplasm
of α-motoneuron

blocks (N)
enters adjacent inhibition of
spinal inhibitory antagonistic affected muscles
toxin exits interneurons,
muscles on sustain maximal
motoneuron in prevents release of
neurotransmitters which voluntary contraction &
the spinal cord
glycine & γ- coordinated cannot relax.
aminobutyric acids movement
depends

Because C. tetani is not an invasive organism, its toxin-producing vegetative cells remain where
introduced into the wound, which may display local inflammatory changes and a mixed bacterial
flora.
• Tetanus is most often generalized but may also be localized.
• The incubation period ~2-14 days
– but may be as long as months after injury.
• In generalized tetanus, the presenting symptom in ~1/2 of cases is trismus
(masseter muscle spasm, or lockjaw).
• Headache, restlessness, irritability = early symptoms,
– often followed by stiffness, difficulty chewing, dysphagia, neck muscle spasm.
• So-called sardonic smile of tetanus (risus sardonicus) results from
intractable spasms of facial & buccal muscles.
• When the paralysis extends to abdominal, lumbar, hip, and thigh
muscles, the patient may assume an arched posture of extreme
hyperextension of the body, or opisthotonos
– head and the heels bent backward and the body bowed forward with only the
back of the head and the heels touching the supporting surface.
• Opisthotonos = equilibrium position; results from unrelenting total
contraction of opposing muscles, all of which display the typical
board-like rigidity of tetanus.
• Laryngeal and respiratory muscle spasm  airway obstruction &
asphyxiation.
• Because tetanus toxin does not affect sensory nerves or cortical
function, the patient unfortunately remains conscious, in extreme
pain, and in fearful anticipation of the next tetanic seizure.
• The seizures are characterized: sudden, severe tonic contractions
of the muscles, with fist clenching, flexion, and adduction of the
arms and hyperextension of the legs.
• W/out th  seizures range from a few seconds to a few minutes in
length with intervening respite periods  as illness progresses,
spasms become sustained & exhausting.
• The smallest disturbance by sight, sound, or touch may
trigger a tetanic spasm.
• Dysuria & urinary retention  bladder sphincter spasm;
forced defecation may occur.
• Fever, occasionally as high as 40°C (104°F), is common
because of the substantial metabolic energy consumed by
spastic muscles.
• Notable autonomic effects: tachycardia, dysrhythmias, labile
hypertension, diaphoresis, & cutaneous vasoconstriction.
• Tetanic paralysis usually becomes more severe in the 1st wk
after onset, stabilizes in the 2nd wk, and ameliorates
gradually over the ensuing 1-4 wk.
 Neonatal Tetanus
• Infantile form of generalized tetanus, typically manifests
within 3-12 days of birth as: progressive difficulty in feeding
(sucking and swallowing), associated hunger, crying.
• Paralysis or diminished movement, stiffness and rigidity to
the touch, and spasms, with or without opisthotonos, are
characteristic.
• The umbilical stump may hold remnants of dirt, dung, clotted
blood, or serum, or it may appear relatively benign.
• Localized tetanus  painful spasms of the muscles
adjacent to the wound site and may precede
generalized tetanus.
• Cephalic tetanus is a rare form of localizaed tetanus
involving the bulbar musculature that occurs with
wounds or foreign bodies in the head, nostrils, or
face.
– It also occurs in association with chronic otitis media.
– characterized by: retracted eyelids, deviated gaze, trismus,
risus sardonicus, and spastic paralysis of the tongue and
pharyngeal musculature.
• The typical setting is an unimmunized patient (and/or mother)
who was injured or born within the preceding 2 wk, who presents
with trismus, other rigid muscles, and a clear sensorium.
• Results of routine laboratory studies are usually normal.
• A peripheral leukocytosis may result from a secondary bacterial
infection of the wound or may be stress induced from the
sustained tetanic spasms.
• The CSF is normal, although the intense muscle contractions may
raise intracranial pressure.
• Neither the electroencephalogram nor the electromyogram shows
a characteristic pattern.
• C. tetani is not always visible on Gram stain of wound material and
is isolated in only approximately 30% of cases.

• Fully developed, generalized
tetanus cannot be mistaken for any
other disease.
• However, trismus may result from
parapharyngeal, retropharyngeal, or
dental abscesses or, rarely, from
acute encephalitis involving the
brainstem.
• Either rabies or tetanus may follow
an animal bite, and rabies may
manifest as trismus with seizures.
– Rabies may be distinguished from
tetanus by hydrophobia, marked
dysphagia, predominantly clonic
seizures, and pleocytosis
DD
• Although strychnine poisoning may
result in tonic muscle spasms and
generalized seizure activity, it
seldom produces trismus, and unlike
in tetanus, general relaxation
usually occurs between spasms.
• Hypocalcemia may produce tetany
that is characterized by laryngeal
and carpopedal spasms, but trismus
is absent.
• Occasionally, epileptic seizures,
narcotic withdrawal, or other drug
reactions may suggest tetanus.
 Treatment
• Management of tetanus requires:
– Eradication of C. tetani
– Wound environment conducive to its anaerobic multiplication,
• Surgical wound excision and debridement are often needed to
remove the foreign body or devitalized tissue that created
anaerobic growth conditions.
• Surgery should be performed promptly after administration of
human tetanus immunoglobulin (TIG) and antibiotics.
• Excision of the umbilical stump in the neonate with tetanus is no
longer recommended.
– neutralization of all accessible tetanus toxin,
– control of seizures and respiration,
– palliation,
– provision of meticulous supportive care,
– prevention of recurrences.
• Tetanus toxin cannot be neutralized by TIG after it has begun
its axonal ascent to the spinal cord.
• TIG should be given ASAP so as to neutralize toxin that
diffuses from the wound  circulation before toxin can bind
at distant muscle groups.
– The optimal dose of TIG has not been determined.
• A single IM injection of 500 units of TIG = sufficient to
neutralize systemic tetanus toxin
– but total doses as high as 3,000-6,000 units are also recommended.
• If TIG is unavailable, use of Human IV Ig may be necessary.
• IVIg contains 4-90 units/ mL of TIG;
– the optimal dosage of intravenous immunoglobulin for treating tetanus is not
known, and its use is not approved for this indication.
• Another alternative is equine- or bovine-derived
tetanus antitoxin (TAT).
– Usual dose = 50,000-100,000 units,
• half given IM and half IV, but as little as 10,000 units may be
sufficient.
– ~15% of patients given the usual dose of TAT experience
serum sickness.
– When TAT is used, it is essential to check for possible
sensitivity to horse serum; desensitization may be
needed.
• The human-derived Ig are much preferred because of
their longer T ½ (30 days) & virtual absence of allergic
& serum sickness adverse effects.
• Penicillin G (100,000 units/kg/day divided every 4-6
hr IV for 10-14 days) remains the antibiotic of choice
because of its effective clostridiocidal action and its
diffusibility, which is an important consideration
because blood flow to injured tissue may be
compromised.
• Metronidazole (500 mg every 8 hr IV for adults)
appears to be equally effective.
• Erythromycin and tetracycline (for persons >8 yr of
age) are alternatives for penicillin-allergic patients.
• All patients with generalized tetanus need muscle relaxants.
• Diazepam  relaxation and seizure control.
– Initial dose = 0.1-0.2 mg/kg @3-6 hr IV is subsequently titrated to control the
tetanic spasms, after which the effective dose is sustained for 2-6 wk before a
tapered withdrawal.
• Magnesium sulfate, other benzodiazepines (midazolam), chlorpromazine,
dantrolene, and baclofen are also used.
• Intrathecal baclofen produces such complete muscle relaxation that
apnea often ensues; like most other agents listed, baclofen should be
used only in an ICU setting
• The highest survival rates in generalized tetanus are achieved with
neuromuscular blocking agents: vecuronium & pancuronium  produce
a general flaccid paralysis; then managed by mechanical ventilation.
• Autonomic instability is regulated with standard α- or β- (or both)
blocking agents; morphine has also proved useful.
The seizures & severe, sustained rigid paralysis of tetanus predispose
the patient to many complications.
• Aspiration of secretions & pneumonia may have begun before the first medical
attention was received.
• Maintaining airway patency often mandates endotracheal intubation &
mechanical ventilation w/ their attendant hazards: pneumothorax &
mediastinal emphysema.
• The seizures may result in lacerations of the mouth or tongue, in intramuscular
hematomas or rhabdomyolysis with myoglobinuria and renal failure, or in long
bone or spinal fractures.
• Venous thrombosis, pulmonary embolism, gastric ulceration with or without
hemorrhage, paralytic ileus, and decubitus ulceration are constant hazards.
• Excessive use of muscle relaxants, which are an integral part of care, may
produce iatrogenic apnea.
• Cardiac arrhythmias; asystole, unstable BP, and labile temperature regulation
reflect disordered autonomic nervous system control that may be aggravated
by inattention to maintenance of intravascular volume needs
 Prevention
• Tetanus is an entirely preventable disease.
• A serum antibody titer of ≥0.01 units/mL = protective.
• Active immunization should begin in early infancy + diphtheria toxoid–
tetanus toxoid–acellular pertussis (DTaP) vaccine at 2, 4, 6 and 15-18 mo
of age + boosters at 4-6 yr (DTaP) & 11-12 yr (Tdap) of age & at 10 yr
intervals thereafter throughout adult life with tetanus and reduced
diphtheria toxoid (Td).
• Immunization of women with tetanus toxoid prevents neonatal tetanus,
and pregnant women should receive 1 dose of reduced diphtheria and
pertussis toxoids (Tdap) during each pregnancy, preferably at 27-36 wk
gestation.
• Arthus reactions (type III hypersensitivity reactions), a localized vasculitis
associated with deposition of immune complexes and activation of
complement, are reported rarely after tetanus vaccination.
Stroke and cerebrovascular disease are caused by some
disturbance of the cerebral vessels in almost all cases.
2 major types: ischemic and hemorrhagic.
• Ischemic stroke = most common variety (80% - 85% of all stroke)
– hemorrhagic stroke accounts for the remainder.
• Process leading to HS mostly due to lost affect integrity of the vessel wall in some
way.
• Ischemic stroke can undergo secondary hemorrhagic transformation;
• Cerebral hemorrhage (particularly a subarachnoid hemorrhage [SAH])
can cause a secondary ischemic stroke via vasospasm.
• Ischemic stroke occurs = blood vessel in or around the brain becomes
occluded or has a high-grade stenosis that reduces the perfusion of distal
cerebral tissue.
– On rare occasions, venous thrombosis can occlude a cerebral vein and
lead to ischemic + hemorrhagic strokes (venous infarction).
• It is not uncommon for there to be some overlap, such as an ICH also
causing some degree of SAH and/or an intraventricular hemorrhage. SAH
can produce some elements of an ICH if the aneurysmal rupture directs
blood into the brain parenchyma.
G.S. Silva et al. Causes of Ischemic Stroke
https://clinicalgate.com/clinical-presentation-and-diagnosis-of-cerebrovascular-disease/
 TIA
• Defined as “a transient episode of neurological
dysfunction caused by focal brain, spinal cord, or
retinal ischemia, without acute infarction.”
• This tissue-based definition recognizes that although
TIA symptoms typically last less than 1 to 2 hours,
– duration of symptoms is an unreliable discriminator
between TIA and infarction.
– A TIA should be viewed as analogous to unstable angina—
that is, an ominous harbinger of a potential future
vascular event.
In contrast to TIA, acute ischemic stroke implies a persistent focal neurologic deficit,
which may be improving, stable, or worsening (stroke in evolution or progressing
stroke) when the patient is seen.
• Some data suggest that 50% of these subsequent events
occur within 2 days after presentation to the ED.
• Published risk factors associated with increased risk for
subsequent stroke:
– hypertension,
– diabetes mellitus,
– symptom duration of ≥10 minutes,
– weakness,
– speech impairment.
• A study of admitted patients found increased risk with:
– male sex,
– age ≥65 years,
– hyperlipidemia, and
– dysarthria
• View TIAs as ominous
signs of cerebral vascular
disease indicating a high
risk of stroke in the near
future.
• In 2007, the ABCD2
scoring system was
intended to replace two
previous scoring scales
(California score and
ABCD score)

Johnston et al137 initially reported a 2-day risk of subsequent stroke as:

1% (ABCD2 score 0 to 3),
4.1% (score 4 to 5),
8.1% (score 6 to 7).
The 7-day risk of stroke was
1.2% (ABCD2 score 0 to 3),
5.9% (score 4 to 5),
11.7% (score 6 to 7).
Treatment
Antiplatelet Agents
• After TIA, the use of aspirin to prevent vascular
events is historically well accepted.
• Current practice:
– Dipyridamole plus aspirin (reasonable as a first
choice),
– Clopidogrel,
– Aspirin alone.
The selection of a particular antiplatelet regimen is a
multifactorial decision based on comorbid conditions,
bleeding risk, prior drug use, and cost.
Anticoagulation
• Adjusted-dose oral anticoagulation warfarin = historical therapy of choice
for stroke prevention in patients w/ non-valvular atrial fibrillation & TIA;
• The risk of recurrent stroke in the presence of atrial fibrillation without
anticoagulation is low, probably <5% over the next 48 hours; moreover,
the risk of hemorrhagic transformation of an acute stroke is also greatest
in the first 48 hours.
– Consequently, in the setting of acute atrial fibrillation,
anticoagulation therapy typically should not be started in the ED but
should be initiated in the inpatient setting.
• Multiple studies have demonstrated that, although unfractionated
heparin may help prevent recurrent stoke, its potential benefits are
outweighed by the increased risk of intracranial hemorrhage.
– Therefore, the use of unfractionated heparin, low-molecular-weight
heparin, or heparinoids for emergent treatment of a specific stroke
subtype or TIA cannot be recommended based on available evidence,
even in the presence of atrial fibrillation
Status Epilepticus

LI 5
 • Status epilepticus can occur in
patients with a history of seizures
or can be a first epileptic event.
• The most common causes of status
epilepticus:
– subtherapeutic antiepileptic levels;
– preexisting neurologic conditions, e.g:
• prior CNS infection, trauma,
hemorrhage, or stroke; acute stroke;
anoxia or hypoxia;
– metabolic abnormalities;
– alcohol or drug intoxication or
withdrawal.

Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 8th edition

 SE
• A single seizure ≥5 minutes in length or
• >=2 seizures without recovery of consciousness
between seizures.
• > 5 minutes, seizures are:
– less likely to spontaneously terminate,
– less likely to be controlled with antiepileptic drugs,
– more likely to cause neuronal damage.
• A neurologic emergency, and treatment should be
initiated in all patients with continuous seizure
activity lasting more than 5 minutes.
 dramatic changes occur hypotension, hypoxia, Neurotoxic amino acids

> 20 minutes
As seizures > 5-minute mark

> 2 hours of seizure activity

at the cellular level: metabolic acidosis, & Ca2+ released into
<< expression & hyperthermia, cells  permanent
internalization of γ- hypoglycemia are neuronal necrosis &
aminobutyric acid present. apoptosis.
receptors + >> (+) cardiac
expression of glutamine dysrhythmias,
& N-methyl-d-aspartate rhabdomyolysis,
receptors  greatly pulmonary edema can
diminished seizure develop.
threshold.
Blood–brain barrier
compromised  CNS
penetration of K+ &
albumin,  hyper-
excitatory CNS
chemicals.

Hyperexcitatory milieu makes standard antiseizure therapies <<<

effective in seizure termination.
• In non-convulsive status epilepticus, the patient is comatose
or has fluctuating abnormal mental status or confusion, but
no overt seizure activity is present.
• The diagnosis is challenging and is typically made by EEG.
• Findings suggestive of nonconvulsive status epilepticus:
– prolonged postictal period after a generalized seizure;
– subtle motor signs such as twitching, blinking, and eye
deviation;
– fluctuating alterations in mental status; or
– unexplained stupor & confusion in the elderly.
• Epilepsia partialis continua = focal tonic-clonic seizure
activity with normal alertness; >>> affects the distal leg or
arm.
 Refractory SE
• Defined as SE that has failed to respond to therapy, usually
with at least 2 (although some have specified 3) medications.
Whether there should be a minimum duration has not been
agreed upon, as authors have variably cited 30-min, usually
60-min, or 2-hr durations.
• New-onset refractory status epilepticus (NORSE) has been
identified as a distinct entity that can be caused by almost any
of the causes of status epilepticus in a patient without prior
epilepsy. It also is often of unknown etiology, presumed to be
encephalitic or postencephalitic, can last several weeks or
longer, and often has a poor prognosis

(Nelson Textbook of Pediatrics, 19th Edition)

Treatment
(Nelson Textbook of Pediatrics, 19th Edition)