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 • Stupor
– Inability to sustain – Patient can be roused only
wakeful state w/out by vigorous + repeated
application of external stimuli
stimuli – Cannot be sustained
– Mental, speech, physical w/out repeated
activity reduced stimulation
– Pts shift positions – Responses to spoken
naturally; lids droop, commands (-) or curtailed
snoring, jaw & limb or slow & inadequate
muscles slack, limbs – Restless/stereotyped
relaxed  motor activity common
indistinguishable from light – When left unstimulated,
sleep pts quickly drift back to
– Sometimes slow arousal deep sleep-like state
elicited by speaking to pts – Eyes move outward
or apply tactile stimulus 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 Systemic causes  brain
deficiency of substrates globally affected, (x) signs that
needed for neuronal function localize dysfunction to a
(as with hypoglycemia or specific area of the brainstem
hypoxia). or cortex

Primary CNS causes 

Unilateral hemispheric disease
brainstem disorder, eg.:
 stroke, should not alone
hemorrhage or from bilateral
result in coma. Fx of the
cortical dysfunction.
brainstem &/or both
• Signs localizing to specific areas of CNS hemispheres must be impaired
dysfunction: hemiparesis or cranial
nerve abnormalities may be present. 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; • Fractures traverse carotid canals
– linear or stellate,  damage the carotid arteries
– open or closed. (dissection, pseudoaneurysm, or
• Basilar skull fractures require CT thrombosis)  given to cerebral
scanning bone-window settings for arteriography (CT angiography
identification. [CT-A] or catheter-based).
• Clinical signs of a basilar skull fracture: • Open or compound skull
– periorbital ecchymosis (raccoon fractures  direct
eyes), communication between the
scalp laceration & the cerebral
– retroauricular ecchymosis (Battle’s
surface, (dura may be torn)
sign),
• A linear vault fracture in
– CSF leakage from the nose
conscious patients >> likelihood
(rhinorrhea) or ear (otorrhea),
of intracranial hematoma ~400
– 7th & 8th nerve dysfunction (facial times.
paralysis and hearing loss),
may occur immediately or a few days after
the initial injury.
 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 Subdural Hematomas
• Uncommon, ~ 0.5% of patients brain • >> than epidural hematomas,
injuries & 9% of patients TBI comatose. – ~ 30% of patients with severe
• Hematomas biconvex or lenticular in shape brain injuries.
 push adherent dura away from the • Shearing of small surface or
inner table of the skull. bridging blood vessels of the
• >> located in temporal or temporoparietal cerebral cortex.
region • CT = conform to the contours of
• often result from tear of middle meningeal the brain.
artery  result of a fracture. • Brain damage underlying an
• Clots are classically arterial in origin; may acute subdural hematoma is
result from disruption of a major venous typically much more severe than
sinus or bleeding from a skull fracture. that associated with epidural
hematomas due to the presence
• A lucid interval between time of injury &
of concomitant parenchymal
neurologic deterioration = classic
injury.
presentation of an epidural hematoma.
 Epidural Hematoma
• The development of symptoms and tear develop more slowly, and clinical
signs of EDH is entirely dependent on manifestations may be delayed, with
how quickly the EDH is developing resultant delays in detection.
within the cranial vault. • A posterior fossa EDH is the result of
• Patients with an EDH often complain of direct occipital trauma resulting in a
a severe headache, sleepiness, skull fracture that disrupts a venous
dizziness, nausea, and vomiting. A sinus is the usual cause, and most
small EDH may remain asymptomatic, patients have external evidence of
but this is rare. occipital injury.
• If the EDH is rapidly detected and • Most patients become symptomatic
evacuated, the functional outcome is within 24 hours after injury, with
excellent. Because of their rapid complaints of headache, nausea,
formation, EDHs from arterial bleeding vomiting, and nuchal rigidity.
are usually detected within hours after • Most patients eventually have a
injury and often earlier in children. decreased LOC
• EDHs that develop from a dural sinus
 Subdural Hematoma
• SDHs classified by time of manif: • A chronic SDH may have initially been
• Acute SDHs are symptomatic within a small asymptomatic SDH that
24 hours after trauma. eventually expanded owing to a
• Patients with acute SDHs often have a combination of recurrent hemorrhage
decreased LOC. and escape of plasma into the
hematoma.
• Most patients with an SDH have a GCS
score less than 8. • At some point, a critical mass is
reached, and the chronic SDH
• A chronic SDH becomes symptomatic becomes symptomatic.
2 weeks or more after trauma.
• Clinical manifestations of posterior
• The signs and symptoms may be very SDH vary but usually include nausea,
subtle or nonspecific, but many vomiting, headache, and decreased
patients demonstrate unilateral LOC.
weakness or hemiparesis.
• Occasionally, CN palsies may be
• Patients with unilateral chronic SDH found, as well as nuchal rigidity,
have more frequent occurrence of cerebellar signs and symptoms, and
hemiparesis than those with bilateral papilledema
chronic SDH
 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 of the basal cisterns
ASAP after hemodynamic – A shift of >5 mm = indicative of
normalization. need for surgery to evacuate the
• Also should be repeated whenever blood clot or contusion causing the
there is a change in the patient’s shift.
clinical status and routinely within 24 • Caution in assessing patients w/ TBI
hours after injury for patients with a who are anti-coagulated or on
contusion or hematoma on the initial antiplatelet therapy.
scan. – INR should be obtained & a CT
• Findings of significance on CT images = should be performed expeditiously
scalp swelling & subgaleal hematomas in these patients when indicated.
at the region of impact. – Rapid normalization of
• Skull fractures = better with bone anticoagulation is the general rule.
windows, often apparent even on
soft-tissue windows.
• Crucial findings on CT= intracranial
hematoma, contusions, shift of the
midline (mass effect) and obliteration
 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 only in moderation and for as
• In most patients, normocarbia is limited a period as possible.
preferred. • In general, it is preferable to keep
• Hyperventilation  << PaCO2  the PaCO2 at ~35 mm Hg (4.7
causing cerebral vasoconstriction. kPa), the low end of the normal
• Aggressive prolonged range (35 mm Hg to 45 mm Hg).
hyperventilation  promote • Brief periods of hyperventilation
cerebral ischemia in injured brain (PaCO2 of 25 to 30 mm Hg [3.3 to
(causing severe cerebral 4.7 kPa]) may be necessary for
vasoconstriction)  impaired acute neurologic deterioration
cerebral perfusion. while other treatments are
– PaCO2 is allowed to fall < 30 mm initiated.
Hg (4.0 kPa). • Hyperventilation will lower ICP in a
– However, hypercarbia (PCO2 > 45 deteriorating patient with
mm Hg) will promote vasodilation expanding intracranial hematoma
and increase intracranial pressure, until emergent craniotomy can be
and thus it should be avoided. performed.
• Hyperventilation should be used
MANNITOL administering mannitol in a
• used to reduce elevated ICP. euvolemic patient = Acute
• Preparation most commonly neurologic deterioration:
used = 20% solution (20 g development of a dilated
mannitol/100 ml solution). pupil, hemiparesis, or loss of
consciousness while the
• Mannitol should not be given patient is being observed, is a
to patients with
– In this setting, a bolus of
hypotension, because mannitol (1 g/kg) should be
mannitol does not lower ICP given rapidly (over 5 minutes)
in hypovolemia & a potent and the patient transported
osmotic diuretic.  further immediately to the CT scanner
or directly to the operating
exacerbate hypotension &
room (if a causative surgical
cerebral ischemia. lesion is already identified)
• Strong indication for
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 generally used in the acute phase.
• Post-traumatic epilepsy (+) in: • For adults, the usual loading dose is 1
– ~5% of patients admitted to the hospital g of phenytoin IV
with closed head injuries – Rate (x) > 50 mg/min.
– 15% of individuals with severe head • The usual maintenance dose = 100
injuries.
mg/8 hours
• 3 main factors linked to a high – dose titrated to achieve therapeutic
incidence of late epilepsy are: serum levels.
– seizures occurring within 1st week, • Diazepam or lorazepam is frequently
– an intracranial hematoma, used in addition to phenytoin until
– depressed skull fracture. the seizure stops.
• Acute seizures may be controlled • Control of continuous seizures may
with anticonvulsants, but early require general anesthesia.
anticonvulsant use does not change
• It is imperative that acute seizures be
long-term traumatic seizure outcome.
controlled as soon as possible,
– Anticonvulsants may also inhibit brain
recovery, so they should be used only because prolonged seizures (30 to 60
when absolutely necessary. minutes) may cause secondary brain
• Currently, phenytoin and injury.
fosphenytoin are the agents
 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 imaging.
• CT scanning of the head is strongly • Patients with a penetrating injury
recommended to evaluate patients involving the orbitofacial or pterional
with penetrating brain injury. regions should undergo angiography to
identify a traumatic intracranial
• Plain radiographs of the head can be
aneurysm or arteriovenous (AV)
helpful in assessing bullet trajectory
fistula.
and fragmentation, and the presence
of large foreign bodies and intracranial • When an aneurysm or AV fistula is
air. identified, surgical or endovascular
management is recommended.
• However, when CT is available, plain
radiographs are not essential. • MRI can play a role in evaluating
injuries from penetrating wooden or
• CT and/or conventional angiography is
other nonmagnetic objects.
recommended with any penetrating
brain injury, or when a trajectory • The presence on CT of large
passes through or near the skull base contusions, hematomas, or
or a major dural venous sinus. intraventricular hemorrhage is
associated with increased mortality,
• Substantial subarachnoid hemorrhage
especially when both hemispheres are
or delayed hematoma should also
involved.
prompt consideration of vascular
• 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 • Certain reversible conditions:
recovery of brain function. hypothermia or barbiturate coma,
• Following criteria should be satisfied for may mimic the appearance of brain
the diagnosis of brain death: death; therefore, this diagnosis
– GCS = 3 should be considered only after all
– Nonreactive pupils physiologic parameters are
– (x) brainstem reflexes (e.g., normalized & CNS fx is not
oculocephalic, corneal, and Doll’s potentially affected by medications.
eyes, and no gag reflex)
• The remarkable ability of children to
– (x) spontaneous ventilatory effort on
recover from seemingly devastating
formal apnea testing
brain injuries should be carefully
• Ancillary studies that may be used to
considered prior to diagnosing brain
confirm the diagnosis of brain death:
death in children.
– Electroencephalography: No activity
at high gain • If any doubt exists, especially in
– CBF studies: No CBF (e.g., isotope children, multiple serial exams
studies, Doppler studies, xenon CBF spaced several hours apart are useful
studies) in confirming the initial clinical
– Cerebral angiography 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 • The 2 CSF tests of greatest
interest = presence of
• Most authorities recommend CSF xanthochromia and RBC count.
analysis when a patient with
suspected SAH has a normal • Xanthochromia = yellow
head CT. appearance of the CSF due to the
enzymatic breakdown of blood
• Another advantage of LP is the  bilirubin.
ability to identify other causes of
– Any exposure of the CSF to light
headache (e.g: meningitis or prior to interpretation can
idiopathic intracranial increase the rate of bilirubin
hypertension) degradation, which decreases
• The disadvantages of LP: post-LP any xanthochromia present.
headache and inability to – Similarly, a delay in processing
perform the procedure in the the CSF specimen may result in
patient with coagulopathy or the development of
thrombocytopenia. 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
• Intracerebral hemorrhage
• RF for intracerebral hemorrhage:
– long-standing hypertension,
occurs >2 x more freq in
– arteriovenous malformations, blacks > whites  higher
– arterial aneurysm, prevalence of HTN in blacks.
– Anticoagulant therapy, • Anticoagulation w/ warfarin
– Use of sympathomimetic drugs = significant RF for
(particularly cocaine and
phenylpropanolamine), intracerebral hemorrhage
– intracranial tumors, – Risk of intracerebral
– amyloid angiopathy in the hemorrhage ~2x for each 0.5
elderly. increase in INR >4.5.
– Current smoking & increased – Intracerebral hemorrhage
freq of smoking also >> risk of occurs in ~3% - 9% patients
intracerebral hemorrhage treated with tissue
• but etiology of this increased risk has plasminogen activator for
not been as well defined as in
ischemic stroke 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 extremities are extended, and the
simultaneous activation of the entire patient falls to the ground  tonic
cerebral cortex, phase subsides, there is increasing
– perhaps caused by an electrical coarse trembling  symmetric,
discharge originating deep in the rhythmic (clonic) jerking of the trunk
brain and spreading outward. and extremities.
• The attacks begin with abrupt loss of – Patients are often apneic during
consciousness. this period and may be cyanotic.
– Loss of consciousness may be the – They often urinate and may vomit.
only clinical manifestation of the • As the attack ends, the patient is left
seizure (as in absence attacks), or flaccid and unconscious, often with
there may be a variety of motor deep, rapid breathing.
manifestations (e.g., tonic • Typical attacks last from 60 to 90
posturing, clonic jerking of the seconds;
body and extremities). • Consciousness returns gradually, and
• Generalized tonic-clonic seizures (grand postictal confusion, myalgias, and
mal) = most familiar & dramatic of fatigue may persist for several hours or
generalized seizures. more.
• In a typical attack, patient suddenly
• Absence seizures (petit mal) are very • Patients and witnesses may be
brief, generally lasting only a few unaware that anything has
seconds. happened.
• Patients suddenly develop altered • Classic absence seizures occur in
consciousness but no change in school-age children and are often
postural tone. attributed by parents or teachers to
• They appear confused, detached, or daydreaming or inattention.
withdrawn, and current activity • The attacks can occur as frequently
ceases. as 100 or more times daily and may
• They may stare or have twitching of result in poor school performance.
the eyelids. • They usually resolve as the child
• They may not respond to voice or to matures.
other stimulation and may exhibit • Similar attacks in adults are more
involuntary movements or lose likely to be minor complex partial
continence. seizures and should not be termed
• The attack ceases abruptly, and the absence.
patients typically resume previous • The distinction is important because
activity without postictal symptoms. the causes and treatment of the two
seizures are different.
 Partial (focal) Seizures
• Partial seizures are due to electrical discharge from the clinical features
discharges beginning in a localized at the onset of the attack.
region of the cerebral cortex. • For example, unilateral tonic or
• The discharge may remain localized clonic movements limited to one
or may spread to involve nearby extremity suggest a focus in the
cortical regions or the entire motor cortex, whereas visual
cortex. symptoms suggest an occipital
• Focal seizures are more likely to be focus.
secondary to a localized structural • Bizarre olfactory or gustatory
lesion of the brain. hallucinations suggest a focus in the
• In simple partial focal seizures, the medial temporal lobe.
seizure remains localized, and • Such sensory phenomena, known
consciousness and mentation are as auras, are often the initial
not affected. symptoms of attacks that then
• It is possible to deduce the likely become more widespread, termed
location of the initial cortical secondary generalization.
• COMPLEX PARTIAL SEIZURES = repeating short phrases.
focal seizures in which consciousness • Visceral symptoms: sensation of
or mentation is affected. “butterflies” rising up from the
• They are often caused by a focal epigastrium.
discharge originating in the temporal • Hallucinations may be olfactory,
lobe and are sometimes referred to as gustatory, visual, or auditory.
temporal lobe seizures. • There may be complex distortions of
• Complex partial seizures are visual perception, time, and memory.
commonly misdiagnosed as • Affective symptoms: intense
psychiatric problems because sensations of fear, paranoia,
symptoms can be so bizarre. depression, elation, or ecstasy.
• Symptoms: • Because such seizures result in
– automatisms, visceral symptoms, alterations of thinking and behavior,
hallucinations, memory they were previously referred to as
disturbances, distorted psychomotor seizures, but to avoid
perception, and affective any confusion with psychiatric illness,
disorders. the term complex partial seizure is
preferred.
• Common automatisms : lip smacking,
fiddling with clothing or buttons, or
• 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 – clonic extremity motions that are
– often associated with a conversion alternating rather than symmetric.
disorder, panic disorder, psychosis, • Incontinence and injury are
impulse control disorder, uncommon, and there is usually no
Munchausen syndrome, or postictal confusion.
malingering. • Patients will often stop the seizure-like
• Suspect the diagnosis of activity on command.
pseudoseizures when seizures occur in • Accurate diagnosis of pseudoseizures
response to emotional upset or only may require prolonged EEG or video
occur with witnesses present. monitoring to demonstrate normal EEG
• These attacks are often bizarre and activity during an attack.
highly variable. • The lack of a lactic acidosis or elevated
• Patients often are able to protect prolactin level drawn within 10 to 15
themselves from noxious stimuli minutes of the cessation of seizure-like
during the attack. activity makes true seizures much less
• Characteristic movements: likely
– side-to-side head thrashing,
– rhythmic pelvic thrusting,
Hyperventilation syndrome
• Can be misdiagnosed as a seizure disorder. Movement disorders:
• A careful history will reveal the gradual • such as dystonia, chorea, myoclonic jerks,
onset of the attacks with shortness of tremors, or tics, may occur in a variety of
breath, anxiety, and perioral numbness. neurologic conditions.
• Such attacks may progress to involuntary • Consciousness is always preserved during
spasm (especially carpopedal) of the these movements, and the patient can
extremities and even loss of often temporarily suppress the
consciousness, although postictal movements.
symptoms are rare.
• Asking the patient to hyperventilate often
reproduces the episodes.

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 studies, a follow-up contrast-
with a first-ever seizure or a change enhanced CT or MRI is often needed.
in established seizure patterns to • Obtain other radiographic studies as
evaluate for a structural lesion. indicated by the clinical presentation
– A non-contrast CT is an to avoid missing injuries acquired as a
appropriate screening tool. result of the seizure.
• Obtain a CT scan if there is any – Obtain radiographs of the cervical
concern for an acute intracranial spine if there is suspicion of head
process or neck trauma.
– based on history, comorbidities, – Chest radiographs may reveal
or findings on physical primary or metastatic tumors or
examination. aspiration.
• Concern for an acute intracranial – Shoulder radiographs may help
process is an important indication for rule out posterior dislocations.
obtaining CT imaging, even if there is Special examinations, such as
a coexistent metabolic process. cerebral angiography, are rarely
• Because many important processes: part of the ED evaluation.
tumors or vascular anomalies, may
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 should be readily available.
SEIZURES • It is not necessary or recommended
to give IV anticonvulsant
• Typically, little is required during the
medications during the course of an
course of an active seizure other
uncomplicated seizure  Most
than supportive & protective
seizures will self-resolve within
measures.
5 minutes.
• If possible, turn the patient to the
• Any unnecessary sedation at this
side  reduce the risk of aspiration.
point will complicate the evaluation
• It is usually not necessary or even and result in a prolonged decrease
possible to ventilate a patient in level of consciousness.
effectively during a seizure, but once
• Seizures that fail to abate after 5
the attack subsides, clear the
minutes  status epilepticus and
airway.
require more aggressive medical
– Suction and airway adjuncts 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 PREGNANCY
• Mass lesions, encephalopathy, herpes • Most seizures in pregnancy are not first-
zoster, toxoplasmosis, Cryptococcus, time seizures, and initial evaluation is
neurosyphilis, and meningitis are all generally as discussed earlier, with the
seen more frequently in this population addition of an obstetric evaluation to
and can all provoke seizure activity. determine gestational age and fetal well-
• Perform an extensive investigation for being.
the cause of the seizure. • When a woman >20 weeks of gestation
• If no space-occupying lesion is identified develops seizures in the setting of
on non-contrast head CT scan & there is hypertension, edema, and proteinuria,
no evidence of increased intracranial the condition is defined as eclampsia.
pressure, perform a lumbar puncture to • Magnesium sulfate has long been used to
exclude CNS infection. treat eclampsia with good results.
• If no explanation for seizures is found, • In eclamptic women, magnesium sulfate
then obtain a contrast-enhanced head infusion compared to diazepam and
CT or MRI. 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
Liver disease
Hepatic coma  elevation of
blood NH3 to 5-6 x (N)  coma impair hepatocellular detoxifying mechanism or
portosystemic shunting of venous blood
• As complication of cirrhosis,
portosystemic shunting, ammonia & toxins accumulate in blood
chronic active hepatitis, or
fulminant hepatic necrosis diffuse to brain
(following viral hepatitis)
• Alcoholism = most common cerebral ssx
underlying disorder
Cilinical findings:
• Syndrome may be chronic
• Ssx of encephalopathy may precede
progressive or acute (onset) systemic ssx: nausea, anorexia, weight
• Latter case  GI hemorrhage loss
(freq precipitating cause) • Recent GI bleeding, consume high-prot
foods, use of sedatives or diuretics,
systemic infx = clue to cause of clinical
decompensation
Lange. Clinical neurology 7th edition
• PF:
– Systemic signs of liver disease • Treatment
– Cognitive disturbances: somnolence, – Restrict dietary proteins
agitation, coma – Reverse electrolyte disturbances
– Occular reflex usually brisk & hyperglycemia
– Nystagmus; tonic downward ocular deviation – Discont.drugs causing
& disconjugate eye movement seen decompensation
– Most helpful neuro sign of metabolic – AB, Frozen fresh plasma or vit K
disturbance (not restricted to liver) = – Oral/rectal + lactulose 20-30 g 3-
ASTERIXIS (flapping tremor of outstretched 4x/d decreases colonic pH
dorsiflexed hands or feet from impaired ammoia abs.
postural control)
– Neomycin 1-3g PO 4x/d reduce
– Other: seizures, tremors, spasticity, rigidity, ammonia forming bacteria in
posturing colon
• Lab – Benzodiazepine rec antagonist
– Bilirubin, transaminase, ammonia, PT/PTT, flumazenil
respi alkalosis – Orthotopic liver transplant req
– Most specific CSF abnormalitis = elevated some cases
glutamine – Prognosis: correlates w/ severity
– EEF: diffuse slow triphasic waves of hepatocellular >> neuro dysfx

Lange. Clinical neurology 7th edition

 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
• EEG
• Uremia  accumulation of
– Slow triphasic or parozysmal
dialzyable small molecular toxins
spikes or sharp waves
(phenolic derivatives of Aromatic
AA) • Acute management:
• Renal failure (esp acute onset or – Hydration
rapid progressive)  – Protein
encephalopathy or coma + – Salt restriction
hyperventilation & prominent • Long-term management:
motor manifestation
– Reverse cause (e.g urinary tract
– Tremor, asterixis, myoclonus, obstruction)
tetany – Dialysis, kidney transplant
• Lab:
• Dialysis itself can produce
– Abnr elevated serum urea
encephalopathy (dialysis
nitrogen, creatinine, K+,
met.acidosis disequilibrium syndrome)
result from hypoosmolarity
– Use briefer period of dialysis at
reduced rate of BF
Lange. Clinical neurology 7th edition
 Pulmonary encephalopathy
• Impairment of • Exam: papilledema,
consciousness + pulmo asterixis, myoclonus,
insufficiency  hypercapnia confusional state or coma
• Pts w/ lung disease or • Tendon reflexes decreased,
brainstem or neuro pyramidal signs may
disorders affect respi fx  present
encephalopathy related to – plantar extension and
hypoventilation hyperreflexia
• SSx: • Seizure occasional
– Headache, confusion, • ABG = respi acidosis
somnolence
• Th/ ventilatory support to
decrease hypercapnia to
maintain adeq oxygenation
Lange. Clinical neurology 7th edition
 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 • Asterixis, myoclonus, and tremor
preceding coma = important clues that
• other processes that affect the brain
suggest metabolic disease.
diffusely:
• Symmetric decorticate or decerebrate
– meningitis, subarachnoid
posturing can be seen with hepatic,
hemorrhage, and seizures.
uremic, anoxic, hypoglycemic, or sedative-
• The clinical presentation is distinct drug–induced coma.
from that of a mass lesion. • Reactive pupils in the presence of
• There are usually no focal signs: otherwise impaired brainstem function is
– hemiparesis, hemisensory loss, or the hallmark of metabolic encephalopathy
aphasia • The few metabolic causes of coma that
– no sudden loss of consciousness also impair pupillary reflexes:
• Except in some cases of subarachnoid – massive barbiturate overdose with
hemorrhage apnea and hypotension,
• History reveals a period of progressive – acute anoxia,
somnolence or toxic delirium followed – marked hypothermia,
by gradual descent into a stuporous – anticholinergic poisoning (large
and finally comatose state pupils)
– opioid overdose (pinpoint pupils).
Lange. Clinical neurology 7th edition
 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 • 12 - 18 mo of age should also be
• Recommended <12 mo of age after considered for lumbar puncture
their 1st febrile seizure (rule out  clinical symptoms of
meningitis) meningitis may be subtle in this
– Esp important if child has received age group.
prior ABs (mask clinical symptoms of – For the well-appearing child after a
the meningitis) febrile seizure, the yield of lumbar
– (+) identified source of fever: e.g. puncture is very low.
otitis media, does not eliminate • >18 mo of age, a lumbar
possibility of meningitis.
puncture is indicated in the
• Seizures = major sign of meningitis in
presence of clinical signs and
13-15% of children presenting with
this disease; 30-35% of such children symptoms of meningitis (e.g.,
have no other meningeal signs. neck stiffness, Kernig sign,
• According to the American Academy Brudzinski sign) or if the history
of Pediatrics (AAP) practice and/or physical examination
parameter, it is strongly otherwise suggest intracranial
recommended in infants <1 yr of age infection.
because other signs of the infection
might not be present.

Nelson Textbook of Pediatrics 2011

 Electroencephalogram • Thus, in many cases, if an EEG is
indicated, it is delayed until or
• If the child is presenting with his or repeated after >2 wk have passed.
her first simple febrile seizure and is EEG should therefore generally be
otherwise neurologically healthy, an restricted to special cases in which
EEG need not normally be epilepsy is highly suspected, and it
performed as part of the should be used to delineate the type
evaluation. of epilepsy rather than to predict its
– An EEG would not predict the occurrence.
future recurrence of febrile • If an EEG is done, it should be
seizures or epilepsy even if the performed for at least 30 min in
result is abnormal. wakefulness and in sleep according to
international guidelines  avoid
– Spikes during drowsiness are
misinterpretation and drawing of
often seen in children with
erroneous conclusions.
febrile seizures, esp >4 yr old 
• If pts does not recover immediately
do not predict later epilepsy.
from a seizure  EEG can help
– EEGs performed within 2 wk of distinguish between: ongoing seizure
a febrile seizure often have activity & prolonged postictal period
nonspecific slowing, usually sometimes termed a nonepileptic
posteriorly. twilight state (NETS).
Nelson Textbook of Pediatrics 2011
Blood Studies Neuroimaging
• Blood studies (serum electrolytes, • According to the AAP practice
calcium, phosphorus, magnesium, and parameter, a CT or MRI is not
complete blood count [CBC]) = not recommended in evaluating the child
routinely recommended in work-up of after a first simple febrile seizure.
a child with 1st simple febrile seizure. • The work-up of children with complex
• Blood glucose = determined only in febrile seizures needs to be
children w/ prolonged postictal individualized:
obtundation or poor oral intake – EEG and neuroimaging, particularly if
(prolonged fasting). the child is neurologically abnormal.
• Serum electrolyte values may be • Patients with febrile status epilepticus
abnormal in children after a febrile have been reported to have swelling of
seizure, but this should be suggested their hippocampus acutely and
by precipitating or predisposing subsequent long-term hippocampal
conditions elicited in the history and atrophy.
reflected in abnormalities of the – These patients may be candidates for
physical examination. neuroimaging, because they may be at
risk for later temporal lobe epilepsy.
• If clinically indicated (e.g., in a history
or physical examination suggesting
dehydration) these tests are indicated.
Nelson Textbook of Pediatrics 2011
 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.
 • Identifying seizure activity in
Neonatal Seizure the neonate and distinguishing
it from normal newborn
myoclonus and jitters can be
• Neonates do not have a challenging.
fully developed neurologic • Subtle focal movements or
system, and seizures in this stereotyped activities (e.g., lip
age group can be subtle, are smacking, eye deviation, or
more likely to be focal, and bicycling) may represent
often carry a poor seizure activity; neonates less
prognosis. often have generalized tonic-
clonic seizures
• Seizures occur in 1.4% of
• Apparent life-threatening
full-term infants and 20% of events with pallor or cyanosis
premature infants. and a change in muscle tone
may be a manifestation of
seizure activity.

Tintinalli’s Emergency Medicine. 8th edition

 • 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 THIN BLOOD FILM
• Place a small drop of blood (5 μL) on • A standard hematologic blood smear
a microscope slide, spread it evenly (fixed with methanol and stained with
to a diameter of ~1 cm, allow it to Giemsa) allows a single sheet of intact
dry, and then stain, without initial red cells to be scrutinized for the
fixation, with Fields or Giemsa stain. percentage of red cells parasitized
• Record the result as the number of – number of parasites per microliter can
parasites seen per oil-immersion be calculated when the red cell count is
field (for an approximate indication known.
of density) or per 200 white cell • Because the red cells are not destroyed,
nuclei counted (a more accurate a thin film allows both parasite and red
density of parasites can then be cell morphology to be examined,
calculated once the WBC count is enabling more confident identification
known). of the species of plasmodium.
• A thick blood film contains several • A thin film may fail to detect a
layers of red cells (which are lysed by parasitemia with a density below
the staining procedure), allowing ~1000/μL, but it is more useful than a
parasitemias down to ~40/μL to be thick film for counting very heavy
detected by an expert microscopist. 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 SUPPORTIVE MANAGEMENT
• Severe malaria is usually due to • Initial resuscitation:
P. falciparum, – O2 for hypoxia,
– fluid replacement, IV glucose for
– occasionally, it is due to P. hypoglycemia,
vivax or P. knowlesi. – blood transfusion for severe anemia or
DIC,
• The patients should be admitted – occasionally intubation for severe
to an appropriate level of respiratory distress or suspected raised
intensive care. ICP with altered mental status.
– Additional treatments for septic shock
• Both supportive and specific may be necessary
antimalarial therapies are urgent • Monitor to identify and treat
and critical to the patient’s seizures, hyperpyrexia, ARDS, or
survival. acute renal failure.
• Monitor the patient frequently; • Culture blood samples for bacterial
new complications may develop infections, and give immediate
after the start of treatment. 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.
 DD
• Fully developed, generalized • Although strychnine poisoning may
tetanus cannot be mistaken for any result in tonic muscle spasms and
other disease. generalized seizure activity, it
• However, trismus may result from seldom produces trismus, and unlike
parapharyngeal, retropharyngeal, or in tetanus, general relaxation
dental abscesses or, rarely, from usually occurs between spasms.
acute encephalitis involving the • Hypocalcemia may produce tetany
brainstem. that is characterized by laryngeal
• Either rabies or tetanus may follow and carpopedal spasms, but trismus
an animal bite, and rabies may is absent.
manifest as trismus with seizures. • Occasionally, epileptic seizures,
– Rabies may be distinguished from narcotic withdrawal, or other drug
tetanus by hydrophobia, marked reactions may suggest tetanus.
dysphagia, predominantly clonic
seizures, and pleocytosis
 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)