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 in-depth way, useful resources are listed at the end of the presentation.

Recognizing Encephalitis:Clinical Manifestations and Diagnosis

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.

Learning objectives

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

Photo credit: Dr. Julie Jacobson

• 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- history

• 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- physical exam

• 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.

Clinical case- laboratory testing

• 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

What is encephalitis?

Viral infections of the Central Nervous System (CNS) result in the following clinical syndromes:

Note: A single infection can affect multiple locations of the CNS, making clinical diagnosis difficult (i.e., meningomyeloencephalitis)

Clinical syndrome Part of CNS affected

Encephalitis Brain Parenchyma

Aseptic meningitis Meninges

Myelitis Spinal Cord

Neuritis Peripheral Nerves

• 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

How to distinguish encephalitis from viral meningitis

Encephalitis vs. meningitisEncephalitis

Viral Meningitis

Constitutional symptoms

Fever Yes Yes

Headache, nausea, vomiting, lethargy Yes Yes

Photophobia, neck stiffness No Yes

Neurologic dysfunction

Seizures Yes Minimal

Cranial nerve palsies, paralysis Yes No

Altered mental status (i.e. confusion, coma)

Yes Minimal

Inflammation of brain parenchyma secondary to infection is known as?

a. Meningitis

b. Encephalitis

c. Neuritis

d. Epilepsy

QUIZ

• 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

What causes encephalitis?

*Note: A large number of reported cases of encephalitis are due to an unspecified cause

• 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.

Arboviruses

Photo credit: Richard G. Weber

Note: Unclear whether Dengue virus causes true encephalitis syndrome

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.

• Bacteria— Tuberculosis, cat-scratch disease, Brucellosis,

typhoid fever• Spirochetes

— Leptospirosis, Syphilis, Lyme disease

• Fungi — Cryptococcosis, Histoplasmosis

• Other infections— Cerebral malaria, Toxoplasmosis, amoebiasis

Non-viral causes of encephalitis

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

QUIZ

• Young children or the elderly.

• Persons with HIV.

• Persons taking immunosuppressive drugs.

• Persons living in encephalitis endemic areas.

Who is at risk for encephalitis?

Anyone can get encephalitis. However, the following groups are at higher risk:

• 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 approach to 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!

Clinical manifestations of encephalitis

• 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)

Important signs of encephalitis to watch for in children

LethargySudden fever

Vomiting and diarrhea

Tremors or convulsions

Headache Change in consciousness

Irritability or restlessness

Common symptoms 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

Differential diagnosis of encephalitis

The following are common symptoms of encephalitis in children, EXCEPT

a. Seizures

b. Poor appetite

c. Bloody diarrhea

d. Fever

e. Lethargy

QUIZ

• 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.

General principles of history taking

When taking a history, it is important to remember the principles of good communication:

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):

• Fever?

• Vomiting or diarrhea?

• Food and fluid intake, urine output?

• Rash and location?

ROS (neurological):

• Headache?• Seizures?

—how many and how long—when was last seizure—shaking of entire body or part of body

• 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?

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

QUIZ

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)

3. Motor exam— Assess strength, tone of upper and lower extremities

– Compare sides— Abnormal movements or posturing?

4. Sensory system— Assess pain, vibration, temperature sensation

– Compare sides

2. Cranial nerves— Pupil reactivity, eye movements,

fundoscopic exam for papilledema, facial muscles

Testing facial nerve (VII)

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

Romberg Test

Source: http://medicine.tamu.edu/neuro/index.html

Tandem walking

Photo credit: Dr. Rao

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!

At completion of physical examination

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

QUIZ

Photo credit: Dr. Julie Jacobson

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*

Acute encephalitis syndrome (AES):

* 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.

• 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.

Surveillance for cases of encephalitis

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

QUIZ

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).

• 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

Relative contra-indications to lumbar puncture

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)

  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

66% < 40% Normal < 30%

Protein 5-40 mg/dl increased +/-increased increased

Culture negative positive negative +TB

Gram stain negative positive negative positive

C

CSF plasma : glucose ratio

Summary of typical CSF findings

General:• Blood count, differential• Glucose• Electrolytes• Culture

Specific:• Malaria smear• Serum anti-JEV IgM ELISA• Dengue serology

Laboratory tests on blood:

• Blood: liver enzymes, blood urea nitrogen, creatinine, ammonium, calcium, magnesium, blood gas

• Urine: analysis, culture

• Brain biopsy

Additional laboratory tests to consider

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

QUIZ

• 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.

Prognosis

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

QUIZ

• 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.

Important points to remember

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.htm

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.

References:

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