Acute encephalitis syndrome

AES

1. ACUTE ENCEPHALITIS SYNDROME- Case based discussion Dr.MANOJ PRABHAKAR Resident , Dept. of Paediatrics

2. CASE 5months old male, first born to a 2 nd degree consanguinous parents who was previously normal brought with c/o of fever for 5 days,followed by seizures during defervesence period.Multiple episodes of seizures in the form of stiffening of limbs before coming to hospital. At ER, Child was intubated in view of poor GCS and raised ICP precautions were taken . No hepatosplenomegaly or rash was present. Provisional diagnosis was acute CNS infection. Started on ceftriaxone,phenytoin,3% saline and other antiedema measures.

3. Case contd … CBC: Hb 11, TLC 6500 (N30L68)Platelet 2.5 lakhs Na 128,K4.5,Ca 8.7, Mg 2.5 LFT – Normal CSF – 3 cells(Lymphocytes) Protein – 34 mg, glucose 68 mg Gram stain, C/S – sterile

4. Case cont…. On day three of admission child had subtle seizures and lid twitching hence was loaded with phenobarbitone , leviteracetam and midazolam infusion. P yridoxine and folinic acid was added for refractory seizures. Day 4: MRI Brain with contrast /MRA & MRS Normal

5. CASE contd … Initial CSF study was normal . Dengue serology was sent on day 3 since encephalopathy occurred during defervescence period. Igm and Ig G reported as positive. But classical features of dengue were not present EEG showed epileptiform activity for which midazolam infusion was continued. S.Ammonia – Normal HIV- Non reactive

6. Contd.. Since child was refractory to supportive management and definite diagnosis could not be achieved ,suspecting autoimmune encephalitis- M ethylprednisolone was added. Possibilities kept at this point were 1.Infection triggered Encephalopathy ? Viral (FIRES) 2.Metabolic 3.Autoimmune encephalitis

7. CASE C ontd … By day 8 – GCS dropped. Pupils SRL. C hild had refractory raised ICP and subsequently pupils became dilated ,absent gag reflex and spontaneous triggers . O n 19.5.2017, baby went in for cardiac arrest. D eclared dead on 19.5.2017 at 11.30am Postmortem LP done CSF Dengue,HSV,JE and encephalitis panel – Negative DNA has been separated for genetic studies( Epileptic encephalopathy panel)

8. Final diagnosis: Refractory Raised intracranial pressure Epileptic encephalopathy ? Cause

9. What else could have been done Continuous EEG monitoring Continous ETCO2 monitoring

10. IMPORTANT DEFINITIONS 1) Encephalopath y : Encephalopathy describes a clinical syndrome of altered mental status, manifesting as reduced consciousness or altered behavior. 2 ) Encephalitis : Encephalitis means inflammation of the brain .

11. IMPORTANT DEFINITIONS 3) Acute Encephalitis Syndrome : A person of any age, at any time of year with the acute onset of fever and a change in mental status.

12. Etiological Agents Herpes simplex virus Dengue Virus Measles virus Mumps virus Chikungunya Varicella zoster virus Epstein-Barr virus Human immunodeficiency virus Rabies

13. Contd.. Bacterial Malaria 2.Metabolic : Reye syndrome and ther IEM 3.Autoimmune encephalitis 4.Poisoning

14. EVALUATION AND MANAGEMENT Step I : Rapid assessment and stabilization Step II : Clinical evaluation: History and Examination Step III : Investigation/Samples to be collected Step IV : Empirical Treatment Step V : Supportive care and treatment Step VI : Prevention/treatment of complications and rehabilitation

15. Step I: Rapid assessment and stabilization Establish and maintain airway Ventilation, Oxygenation Circulation Identify signs of cerebral herniation or raised ICP. Temperature: treat fever and hypothermia Treat ongoing seizures- Benzodiazepine, followed by phenytoin loading

16. Step II: Clinical evaluation: History and Examination There may be a prodrome of upper respiratory illness, flu-like illness or diarrhea. Altered behavior, cognition, personality changes, altered consciousness. History of recurrent episodes of encephalopathy. Family history of previous infant/child deaths. Recent history of travel

17. Etiological Clues Pallor : Cerebral malaria, or IC bleed Icterus : Leptospirosis , hepatic encephalopathy, or cerebral malaria. Skin rashes : dengue, measles, varicella , rickettsial diseases Petechiae : dengue and viral hemorrhagic fevers Parotid swelling and orchitis : Mumps

18. Examination GCS Pupillary size, shape, symmetry and response to light provide valuable clues to brainstem and third nerve dysfunction. Special attention should be given to posturing because it often signals a brainstem herniation syndrome. Fundus examination must be performed to look for papilledema and retinal hemorrhages.

19. Step III : Investigation Basic investigations : CBC, RFT, Electrolytes, LFT, Blood Culture, CXR Lumbar puncture : In Patients who are hemodynamically stable, and no features of raised intracranial pressure . CSF analysis is an important investigation in children with AES (Should include full viral panel) Neuroimaging : May give valuable information such as presence of bleed, cerebral edema etc MRI should be obtained, as soon as the patient is stable.

20. Investigation Other microbiological investigations: These samples include urine, throat swab, nasopharyngeal aspirate, swab from vesicles or rash, if present. Unexplained encephalopathy with fever and rash : Weil- Felix test, rickettsial serology Unexplained encephalitis : HIV testing

21. Investigation Other tests EEG is not routinely needed . It must be performed in children with unexplained altered s ensorium to look for suspected non-convulsive status epilepticus. Metabolic. Autoimmune encephalitis panel.

22. Step IV: Empirical Treatment Must be started if CSF cannot be done/report will take time and patient sick. Ceftriaxone {100mg/kg/day} • Acyclovir (use in all suspected sporadic viral encephalitis) 3mt – 12yr : 500mg/m2 Q8H > 12yr : 100mg/kg Q8H

23. Step V: Supportive care and treatment ( a) Maintenance intravenous fluids : Isotonic fluids are preferred ( b) Management of raised intracranial pressure: Head elevation, Minimal disturbance, Normothermia , Hyperventilation,

24. Supportive care and treatment ( c) Maintain euglycemia ( d) Treatment and prevention of seizures: ( Lorazepam 0.1 mg/kg, diazepam 0.3 mg/kg, or midazolam 0.1 mg/kg) ( e) Other drugs : Corticosteroids ( f) Other measures: Acid-base and electrolyte abnormalities should be corrected.

25. Step VI: Prevention/treatment of complications and rehabilitation Physiotherapy, posture change, Prevent bed sores and exposure keratitis . • Complications: aspiration pneumonia , nosocomial infections, coagulation disturbances • Nutrition: early feeding • Psychological support to patient and family

26. PREVENTIVE STRATEGIES ( i ) Surveillance for cases of AES; ( ii) Vector control; (iii) Reduction in man-vector contact; ( iv) Vaccination

27. ACUTE ENCEPHALOPATHY IN CHILDREN WITH INBORN ERRORS OF METABOLISM Acute encephalopathy is a common and potentially medical emergency in patients with inborn errors of metabolism. In young children with unexplained altered s ensorium , especially with pre-morbid developmental delay, investigations for inborn errors of metabolism plasma must be carried out.

28. Contd.. Lactate, ketones . Serum ammonia , Blood tandem mass spectroscopy , Urine gas chromatography mass spectroscopy

29. Autoimmune Encephalitis In older children, the possibility of autoimmune disorders such as SLE (anti-nuclear antibodies, anti- ds -DNA antibodies ), Hashimoto encephalopathy ( anti-TPO antibodies ), and Anti-NMDA receptor and Anti-VKGC antibody-mediated encephalitis may be considered.

30. In this case infectious etiology has been reasonably worked up and ruled out. M etabolic & autoimmune encephalitis was not completely worked up. Also there is a subgroup of disorders which can have infantile epileptic encephalopathy which can cause refractory raised ICP.

31. Take home message Early stabilization and institution of non-specific supportive measures is the cornerstone of management. Investigations are aimed at recognition of etiological agent for specific therapeutic and control measures.

32. THANKYOU