Instructions for users

1. 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.

2. Recognizing Encephalitis:Clinical Manifestations and Diagnosis

3. 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.

4. Clinical Case 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? Photo credit: Dr. JulieJacobson

5. 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?

6. 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?

7. 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.

8. 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

9. 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)

10. 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

11. Encephalitis vs. meningitis

12. QUIZ Inflammation of brain parenchyma secondary to infection is known as? • Meningitis • Encephalitis • Neuritis • Epilepsy

13. 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

14. 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

15. 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.

16. 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.

17. 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

18. QUIZ Which of the following is NOT a common cause of encephalitis? • Arbovirus infection • Herpes virus infection • Tuberculosis infection • Vitamin A deficiency

19. 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.

20. 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.

21. 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!

22. 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)

23. Lethargy Sudden fever Headache Change in consciousness Irritability orrestlessness Vomiting and diarrhea Tremors or convulsions Common symptoms of encephalitis

24. 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

25. QUIZ The following are common symptoms of encephalitis in children, EXCEPT • Seizures • Poor appetite • Bloody diarrhea • Fever • Lethargy

26. 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.

27. 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)

28. 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?

29. 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?

30. Example of History (2)

31. 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?

32. QUIZ True or False. It is okay to skip the history if a family comes in and does not speak your native language. • True • False

33. 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.

34. 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

35. 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?

36. 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?

37. 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.

38. The neurologic exam • 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?

39. The neurologic exam (2) • Cranial nerves • Pupil reactivity, eye movements, fundoscopic exam for papilledema, facial muscles • Motor exam • Assess strength, tone of upper and lower extremities • Compare sides • Abnormal movements or posturing? • Sensory system • Assess pain, vibration, temperature sensation • Compare sides Testing facial nerve (VII)

40. The neurologic exam (3) • Deep tendon reflexes • 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

41. 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!

42. QUIZ Which of the following abnormalities in the neurological exam can be seen in a patient with encephalitis? • Decreased level of alertness • Abnormal movements of the lips • Paralysis of left arm • Abnormal finger-to-nose test • All of the above Photo credit: Dr. JulieJacobson

43. 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.

44. 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.

45. QUIZ Which of the following is NOT part of the WHO case definition for acute encephalitis syndrome? • Fever • Change in mental status • Diffuse rash • New onset seizure

46. 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)

47. 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.

48. Steps in performing a lumbar puncture • Obtain informed consent. • Gather materials. • Position patient. • Administer local anesthetic. • Insert needle with sterile technique. • Measure opening pressure. • Collect cerebrospinal fluid (CSF).

49. 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

50. 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)