Transcript Recent Advances in Japanese Encephalitis Control

Instructions for users
• This slide presentation provides an overview
of the clinical manifestations and diagnosis of
encephalitis.
• Below many of the slides, there are notes to
explain the information in the slide.
• You should adapt the presentation for your
own use.
• If you want to present this topic in a more indepth way, useful resources are listed at the
end of the presentation.
Recognizing Encephalitis:
Clinical Manifestations and Diagnosis
Learning objectives
Participants will:
• Identify common causes of encephalitis.
• Take a complete history from a patient with
encephalitis.
• Conduct a thorough physical examination for a
patient with encephalitis.
• Know the steps to conduct a successful lumbar
puncture.
• Identify the appropriate laboratory investigations
for a patient presenting with encephalitis.
Clinical Case
Photo credit: Dr. Julie Jacobson
Raj is a 5-year-old previously healthy boy who is
brought in to his local health clinic by his mother
with complaints of fever, poor appetite, and
drowsiness.
—
What questions do you want to ask?
Clinical case- history
• The patient’s mother reports a 3 day history of not
eating and high fevers at night. He started
vomiting this morning and complained that his
“tummy” and head hurt.
• Patient is not taking any medications. No one else
is sick at home. Patient has received his routine
immunizations.
—
What are important parts of your physical
examination?
Clinical case- physical exam
• Vital Signs
—
Temperature: 39.0, Respiratory rate: 42, Heart rate:
150
• General: patient looks pale, clammy, and is lying
motionless in his mother’s lap
• Eyes, Ears, Throat: Left pupil slightly dilated, dry
lips
• Chest: tachypneic, clear
• Cardiac: capillary refill > 3 seconds, no Murmur
• Neurological: responsive only to painful stimuli,
decreased tone throughout, symmetric
hyperreflexia
—
What investigations would you do for this patient?
Clinical case- laboratory testing
• Lumbar puncture
—
Cerebrospinal fluid (CSF): 850 WBC’s (80%
Lymphocytes), glucose 80, protein 110
—
Anti-JEV IgM- pending
• Patient’s clinical presentation and findings on
CSF are more consistent with encephalitis than
meningitis. An IV is placed and Raj is started
on antibiotics and IV hydration. He becomes
more alert and responsive. His CSF is sent to
the state lab and comes back later positive for
Japanese encephalitis.
What is encephalitis?
• Encephalitis is an inflammation of the brain
tissue due to infection.
• Most often caused by viruses that pass into
blood stream and then into cerebral spinal fluid,
leading to destruction of neural cells and
inflammation of brain parenchyma.
— Primary
or acute encephalitis
• May also result from a viral-mediated
inflammatory response in the brain following an
acute, systemic infection.
— Secondary
or post-infectious encephalitis
Viral infections of the Central
Nervous System (CNS) result in
the following clinical syndromes:
Clinical syndrome
Part of CNS affected
Encephalitis
Brain Parenchyma
Aseptic meningitis
Meninges
Myelitis
Spinal Cord
Neuritis
Peripheral Nerves
Note: A single infection can affect multiple locations of the CNS, making clinical diagnosis
difficult (i.e., meningomyeloencephalitis)
How to distinguish encephalitis from
viral meningitis
• Unfortunately, the clinical syndromes and results
of routine laboratory tests are typically nonspecific
and often do not help distinguish encephalitis and
viral meningitis.
• Patients may have symptoms of both
parenchymal and meningeal processes.
— i.e.,
A patient with stiff neck and photophobia, though
classic signs of meningitis, could in fact also have
encephalitis! (called meningoencephalitis)
• It is important to recognize other infectious and
noninfectious causes, particularly those which are
treatable
Encephalitis vs. meningitis
Encephalitis
Viral
Meningitis
Fever
Yes
Yes
Headache, nausea, vomiting, lethargy
Yes
Yes
Photophobia, neck stiffness
No
Yes
Seizures
Yes
Minimal
Cranial nerve palsies, paralysis
Yes
No
Altered mental status (i.e. confusion,
coma)
Yes
Minimal
Constitutional symptoms
Neurologic dysfunction
QUIZ
Inflammation of brain parenchyma secondary to
infection is known as?
a. Meningitis
b. Encephalitis
c. Neuritis
d. Epilepsy
What causes encephalitis?
• Viruses (most common)
—
More than 100 different viruses can cause acute
encephalitis
—
Seasonal and geographic distribution can help narrow
differential diagnosis
—
Examples of common viruses:
–
Arboviruses
–
Enteroviruses
–
Mumps, Varicella
–
Herpes simplex virus
–
Influenza
–
Rabies
*Note: A large number of reported cases of encephalitis are due to an
unspecified cause
Arboviruses
•
Arboviruses or “arthropod-borne viruses” are
the primary cause of encephalitis in many
countries.
•
Arthropods that transmit the viruses include
mosquitoes and ticks.
•
Common arboviruses include Japanese
encephalitis, West Nile, and Dengue viruses.
Note: Unclear whether Dengue virus causes true
encephalitis syndrome
Photo credit: Richard G. Weber
Japanese Encephalitis (JE)
• Most important global cause of arboviral encephalitis
with > 50,000 cases and 15,000 deaths reported each
year.
• Only about 1 in 250 JE infections result in symptomatic
illness.
• Primarily affects children 1 to 15 years of age.
• Incubation period is 5 to 14 days.
• If unrecognized, mortality is up to 30%
with half of survivors sustain severe
neurological sequelae.
Clinical approach to JE
• JE classically presents as an acute encephalitis
syndrome.
—
Fever, impaired mental status, seizures, flaccid
paralysis
• From a clinical perspective, encephalitis due to
JE is indistinguishable from encephalitis caused
by other agents.
• Therefore, this presentation will focus on
recognizing acute encephalitis in general.
Non-viral causes of encephalitis
• Bacteria
—
Tuberculosis, cat-scratch disease, Brucellosis,
typhoid fever
• Spirochetes
— Leptospirosis, Syphilis, Lyme disease
• Fungi
— Cryptococcosis, Histoplasmosis
• Other infections
— Cerebral malaria, Toxoplasmosis, amoebiasis
QUIZ
Which of the following is NOT a common cause of
encephalitis?
a. Arbovirus infection
b. Herpes virus infection
c. Tuberculosis infection
d. Vitamin A deficiency
Who is at risk for encephalitis?
Anyone can get encephalitis. However, the
following groups are at higher risk:
• Young children or the elderly.
• Persons with HIV.
• Persons taking immunosuppressive drugs.
• Persons living in encephalitis endemic areas.
Clinical approach to encephalitis
•
Understanding clinical manifestations.
•
Considering differential diagnosis.
•
Taking a good history.
•
Performing a physical exam.
•
Identifying treatable vs. untreatable causes.
•
Reporting suspected cases for disease
surveillance.
Clinical manifestations of encephalitis
• The clinical presentation of encephalitis is
generally nonspecific:
—
Fever, headache, vomiting, occasionally accompanied
by seizures, mental status changes, and/or focal
neurologic deficits
• Any patient presenting with fever and an
abnormal neurologic exam should be evaluated
closely for encephalitis!
Important signs of encephalitis to
watch for in children
•
Vomiting
•
Body stiffness
•
Constant crying that may become worse when
the child is picked up
•
Full or bulging fontanel (the soft spot on the top
of the head)
Common symptoms of encephalitis
Sudden fever
Headache
Lethargy
Change in
consciousness
Irritability or
restlessness
Tremors or
convulsions
Vomiting and
diarrhea
Differential diagnosis of encephalitis
• Bacterial infection
• Other infections
—
—
•
•
•
•
•
Meningitis, tuberculosis, brain abscess
Cerebral malaria, Rickettsial, spirochetal,
toxoplasmosis
Intracranial hemorrhage or tumor
Trauma
Toxic ingestion
Hypoglycemia
Guillain-Barre syndrome
QUIZ
The following are common symptoms of
encephalitis in children, EXCEPT
a. Seizures
b. Poor appetite
c. Bloody diarrhea
d. Fever
e. Lethargy
General principles of history taking
When taking a history, it is important to
remember the principles of good
communication:
• Be respectful.
• Use familiar words and phrases and avoid
technical language.
• Be patient - parents under stress may not
remember well.
• Find a translator if language is a barrier.
Steps in Conducting Patient history
• Chief complaint (CC)
• History of present illness (HPI)
• Review of systems (ROS)
• Past medical history (PMH), family history (FH),
social history (SH)
Important questions to ask a
patient presenting with symptoms
of encephalitis
• Any symptoms of a viral prodrome?
—
Upper respiratory infection symptoms, cough,
malaise, decreased oral intake, diarrhea, nausea,
vomiting?
• Any recent exposures?
—
Ill contacts, travel history, occupation, pets, tick or
mosquito bites?
• Perform a thorough neurological review of
systems (ROS)
—
Headache, photophobia, stiff neck, poor sleep,
change in mental status, irritability, convulsions?
Example of History
• CC:
—
What brings you to medical attention?
• HPI:
—
When did you become sick?
—
What were the first symptoms and how have they
evolved?
Example of History (2)
ROS (general):
ROS (neurological):
• Fever?
• Headache?
• Seizures?
• Vomiting or
diarrhea?
• Food and fluid
intake, urine
output?
—how
many and how long
—when was last seizure
—shaking of entire body or part of body
•
•
• Rash and location? •
•
Unable to arouse?
Irritable?
Abnormal facial or eye movements?
Tremors or abnormal body
movements?
• Unable to walk or talk?
Example of History (3)
• PMH:
—
—
—
—
—
Preexisting health problems?
History of abnormal chest X-ray?
Current medications?
Allergies?
Immunization status?
– In particular JE, measles, mumps, Hib
• FH/SH:
—
—
—
Any household members recently ill?
Any recent animal bites, exposure to toxins?
Any travel within the previous 2 weeks?
QUIZ
True or False. It is okay to skip the history if a
family comes in and does not speak your native
language.
a. True
b. False
Physical examination of a patient
with suspected encephalitis
• Assess ABC’s (airway, breathing, and circulation).
• Rule out Cushings triad:
—
Hypertension + bradycardia + irregular respirations
—
This is a medical emergency! (indicates increased
intracranial pressure and impending cerebral
herniation)
• Perform thorough neurological exam.
Emergency signs/Reasons for referral
• Respiratory distress
—
Obstructed breathing OR central cyanosis OR severe
respiratory distress
• Shock
—
Cold hands with capillary refill > 3 seconds; weak, rapid pulse
• Severe dehydration
—
Diarrhea plus two of these:
– Lethargy
– Sunken eyes
– Very slow skin pinch
• Coma or convulsions
Child with convulsions
Overview of physical exam (1)
• Vital signs:
—
Temperature, heart rate, respiratory rate, blood pressure,
weight
• General appearance:
—
Drowsy, severe wasting, edema?
• Skin:
—
—
—
Turgor, capillary refill, palmar pallor
Rash: petechiae, vesicles, bruising?
Diffuse adenopathy?
Overview of physical exam (2)
• Head, eyes, ears, nose and throat:
—
pupils equal and reactive, corneal clouding, neck stiffness?
• Heart:
—
gallop rhythm, slow heart rate?
• Chest:
—
rales, crackles, signs of pneumonia, respiratory distress?
• Abdomen:
—
enlargement of liver or spleen?
The neurological exam
Remember:
The neurological exam in an encephalitis patient is
part of the general physical examination. Thus, the
neurologic exam should always be preceded by and
interpreted in the context of a more general
examination.
The neurologic exam
1. Mental status
—
Level of alertness:
– AVPU scale for rapid assessment: Alert / Responds to
voice / Reacts to pain / Unconscious
– Glasgow Coma Scale or other coma scale
—
Orientation, memory, speech, etc.
—
Irritability, aphasia?
The neurologic exam (2)
2. Cranial nerves
—
Pupil reactivity, eye movements,
fundoscopic exam for papilledema,
facial muscles
3. Motor exam
Testing facial nerve (VII)
—
Assess strength, tone of upper and lower extremities
– Compare sides
—
Abnormal movements or posturing?
4. Sensory system
—
Assess pain, vibration, temperature sensation
– Compare sides
The neurologic exam (3)
5. Deep tendon reflexes
6. Coordination and Gait
—
Finger-to-nose test, Romberg test
—
Tandem (heel to toe) walking
Source: http://medicine.tamu.edu/neuro
Tandem walking
Romberg Test
Photo credit: Dr. Rao
Source: http://medicine.tamu.edu/neuro/index.html
At completion of physical examination
Based on symptoms and signs:
•
Provide an initial assessment.
•
Determine which laboratory tests are required.
•
Develop a care plan.
•
Communicate the information with the parents or
caregiver.
•
Report suspected case of encephalitis to local
health authorities!
QUIZ
Which of the following abnormalities in the
neurological exam can be seen in a patient with
encephalitis?
a. Decreased level of alertness
b. Abnormal movements of the lips
c. Paralysis of left arm
d. Abnormal finger-to-nose test
e. All of the above
Photo credit: Dr. Julie Jacobson
Acute encephalitis syndrome (AES):
For surveillance purposes, WHO defines a case of
acute encephalitis by:
—
An acute febrile illness, AND
—
A change in mental status (such as confusion,
disorientation, inability to talk, coma) AND/OR
—
New onset seizures, excluding simple febrile seizures*
* Simple febrile seizure: a single seizure lasting < 15 minutes with recovery of
consciousness within 60 minutes, in a child aged 6 months to 5 years.
Surveillance for cases of encephalitis
• For surveillance purposes, JE is also commonly
reported under the heading of “acute
encephalitis”.
• In WHO’s guidelines for JE surveillance,
syndromic surveillance for JE is recommended.
This means all cases of acute encephalitis
syndrome (AES) should be reported.
• Laboratory confirmation of suspected cases is
done where feasible.
QUIZ
Which of the following is NOT part of the WHO
case definition for acute encephalitis syndrome?
a.
Fever
b.
Change in mental status
c.
Diffuse rash
d.
New onset seizure
Laboratory studies of suspected
encephalitis
• Lumbar puncture
—
CSF analysis and culture
• Blood, urine, secretion cultures
• Serum and CSF antibody testing
• Neurodiagnostic testing
—
Magnetic resonance imaging (MRI) or Computed
Tomography (CT) scan
—
Electroencephalogram (EEG)
Importance of performing a Lumbar
Puncture (LP) in a patient with suspected
encephalitis
•
Collection and testing of spinal fluid are standard
management for any patient with suspected CNS
infection to direct treatment (e.g., if CSF profile
suggests bacterial infection).
• An LP should be performed by a skilled
healthcare provider.
• For detailed review of LP procedure and
technique, see separate presentation.
Steps in performing a lumbar puncture
1. Obtain informed consent.
2. Gather materials.
3. Position patient.
4. Administer local anesthetic.
5. Insert needle with sterile technique.
6. Measure opening pressure.
7. Collect cerebrospinal fluid (CSF).
Relative contra-indications to lumbar
puncture
• Evidence of a space-occupying lesion such as
a tumor or brain abscess.
• Signs of increased intracranial pressure.
– Unequal pupils, elevated blood pressure, slow heart
rate, irregular breathing, posturing
• Cardiopulmonary instability.
• Soft tissue infection at puncture site.
• Significant, uncontrolled bleeding disorder.
*See note
Laboratory tests on CSF
• Cell count, differential
• Glucose
• Protein
• Gram stain
• India ink preparation
• Stain for acid-fast bacilli
• Viral, bacterial, and fungal cultures
• Anti-JEV IgM ELISA
• JEV RT-PCR (if available)
Summary of typical CSF findings
Normal
Bacterial
Viral
TB
Cells
0-5 WBC/mm3
>1000/mm3
<1000/mm3
25-500/mm3
Polymorphs
0
predominate
early
+/- increased
Lymphocytes
5
late
predominate
increased
Glucose
40-80 mg/dl
decreased
normal
decreased
CSF plasma :
glucose ratio
66%
< 40%
Normal
< 30%
Protein
5-40 mg/dl
increased
+/-increased
increased
Culture
negative
positive
negative
+TB
Gram stain
negative
positive
negative
positive
Laboratory tests on blood:
General:
•
•
•
•
Blood count, differential
Glucose
Electrolytes
Culture
Specific:
• Malaria smear
• Serum anti-JEV IgM ELISA
• Dengue serology
Additional laboratory tests to
consider
• Blood: liver enzymes, blood urea nitrogen,
creatinine, ammonium, calcium, magnesium,
blood gas
• Urine: analysis, culture
• Brain biopsy
QUIZ
Why is it important to perform a lumbar puncture
on all suspected cases of encephalitis?
a. To get practice in the technique of performing a
lumbar puncture
b. To inject life-saving medications into the spinal
fluid
c. To identify treatable from non-treatable causes
of encephalitis (i.e. bacterial infections)
d. A lumbar puncture should not be performed on
patients with encephalitis
Prognosis
• Depends on cause and severity of illness and
patient’s age.
• Mild cases recover in 2 to 4 weeks with supportive
care.
• Severe encephalitis can lead to numerous
complications.
—
Hearing and/or speech loss, blindness, permanent
brain and nerve damage, behavioral changes,
cognitive disabilities, lack of muscle control, seizures,
memory loss.
QUIZ
Which of the following are possible complications
of encephalitis infection?
a. Paralysis
b. Hearing loss
c. Seizure disorder
d. Decreased intelligence
e. All of the above
Important points to remember
• Acute encephalitis is a medical emergency.
• Any patient presenting with fever and impaired
mental status or neurological exam should be
evaluated for encephalitis.
• The diagnosis of encephalitis is clinical.
—
Don’t forget the value of a good history and physical
exam.
• All suspected cases of encephalitis should be
reported to local authorities.
References:
Gutierrez, KM, Prober, CG. Encephalitis: identifying the specific cause is key to effective
management. Postgraduate Medicine. 1998;103(3):123-125, 129-130, 140-143.
Huang, C, Chatterjee, NK, Grady, LJ. Diagnosis of viral infections of the central nervous
system. New England Journal of Medicine. 1999;340(6):483-484.
Kabilan L, Rajendran R, et al. Japanese encephalitis in India: An overview. Indian Journal of
Pediatrics. 2004;71:609-615.
Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases.
Philadelphia: Churchill Livingstone; 2000.
National Institute of Neurological Disorders and Strokes (NINDS). Encephalitis and
meningitis [fact sheet]. Bethesda: National Institute of Health; 2004. Available at:
http://www.ninds.nih.gov/disorders/encephalitis_meningitis/detail_encephalitis_meningitis.ht
m
Roos KL. Encephalitis. Neurologic Clinics. 1999;17(4):813-33.
Solomon, T, Dung, NM, Kneen, R, et al. Seizures and raised intracranial pressure in
Vietnamese patients with Japanese encephalitis. Brain. 2002; 125:1084-1093.
U.S. Centers for Disease Control and Prevention (CDC). Japanese encephalitis [fact sheet].
Fort Collins: CDC; 2004. Available at: http://www.cdc.gov/ncidod/dvbid/jencephalitis
Whitley, RJ. Viral encephalitis. New England Journal of Medicine. 1990;323(4):242-250.
Acknowledgements
Please include the following acknowledgement
if you use this slide set:
This slide set was adapted from a slide set
prepared by PATH’s Japanese Encephalitis
Project.
For information: www.JEproject.org