Febrile encephalopathy

1. FEBRILE ENCEPHALOPATHY D KALPANA Addl. Professor of Pediatric Neurology, Medical College, Thiruvananthapuram

2. overview Definition of terms Differential diagnosis Points from history/epidemiology Investigations Supportive management Specific management Autoimmune encephalitis

3. DEFINITION

4. ENCEPHALITIS

5. AES=acute encephalitis syndrome Clinically, a case of Acute Encephalitis Syndrome (AES) is defined as a person of any age, at any time of year with the acute onset of fever and at least one of: a) change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk); b) New onset of seizures (excluding simple febrile seizures. ( A simple febrile seizure is defined as a seizure that occurs in a child aged 6 months to less than 6 years old, whose only finding is fever and a single generalized convulsion lasting less than 15 minutes, and who recovers consciousness within 60 minutes of the seizure) Bull World Health Organ 2008, 86(3):178-186.

6. DIFFERENTIAL DIAGNOSIS INFECTIONS DEMYELINATION - ADEM AUTOIMMUNE ENCEPHALITIS DRUGS/TOXINS COLLAGEN VASCULAR DISORDERS SEIZURES –NON CONVULSIVE STATUS METABOLIC ICSOL

7. Infectious causes Viral encephalitis Herpes simplex type 1. type2 Varicella zoster HHV6 Epstein Barr virus Arboviruses – JE,West Nile,Dengue , Chikun gunya , Rhabdoviruses -rabies Orthomyxo –H1N1 Paramyxo –measles HIV

8. Infectious causes Bacterial Meningitis Brain abscess Sepsis associated encephalopathy Leptospirosis Typhoid M. tuberculosis Rickettsial (scrub typhus) Parasitic Cerebral malaria Toxoplasma

9. GENERAL CLINICAL FEATURES Features of infection Evidence of CNS involvement Features of raised intracranial tension Signs and symptoms of meningeal irritation

10. Differentiating points

11. history

12. Abnormal behaviour /psychosis HSV Limbic encephalitis NCSE Meningeal signs MENINGITIS ADEM meningoencephalitis Opisthotonic posture Choreoathetosis JE,autoimmune Asymmetric signs and symptoms Encephalitis TBM ADEM Ataxia ADEM VZV Entero virus Lower cranial nerve palsies TBM VASCULITIS Brainstem encephalitis JE,west nile Papilloedema ICSOL Hydrocephalus –TBM Hypertensive encephalopathy Visual loss Optic neuritis Hypertensive encephalopathy

13. OTHER USEFUL SIGNS

14. management

15. identify

16. NEUROLOGICAL INVESTIGATIONS

17. LUMBAR PUNCTURE CONTRAINDICATIONS IMAGING BEFORE LP IN RAISED ICT EMPIRICAL ANTIBIOTICS +ACYCLOVIR IF DELAY OF SEVERAL HRS IS EXPECTED

18. LUMBAR PUNCTURE NOTE THE OPENING PRESSURE CELLS GRAM STAIN,CULTURE PROTEIN SUGAR VIROLOGICAL STUDIES – PCR,IgM TBPCR LACTATE

19. Pcr IN CSF Take at least 5 ml of CSF Be sure that it is not mixed with blood Sensitivity and specificity are relatively good Can be negative very early in HSV and after 10 days of treatment Never stop Acyclovir before repeating once more after 72hrs – if clinical history, EEG and imaging are suggestive Serum/CSF Ig M antibodies useful in JE Paired samples – 4 fold rise in titre

20. imaging MRI is preferable to CT scan- CTis advised in unstable patients, delirious children who cannot be kept still for 30 min

21. JE

22. RABIES

23. EEG Diffuse slowing suggests encephalopathic process PLEDS in HSE Triphasic waves in metabolic encephalopathy Non convulsive status epilepticus

24. NCSE Should be suspected in confusion, stupor, unarousable coma Subtle features like eye blinking, nystagmus , perioral twitching, automatisms may be seen May follow convulsive seizures EEG is the only diagnostic clue Response to diazepam can be demonstrated in simultaneous EEG recording Generalised /complex partial

25. General management Maintain Normothermia Normoglycemia Normal electrolyte balance Normotension Management of raised ICT minimal stimulation Head end elevation Avoid hypotonic fluids 3% saline Mannitol 20% solution hyperventilation

26. Supportive management Management of seizures/status epilepticus Identify SIADH and manage Rapid correction of hyponatremia may lead to central pontine myelinolysis

27. Symptomatic Abnormal /psychotic behaviour – haloperidol+ phenergan Choreoathetosis – dopa blockers Dystonia - tetrabenezine , anticholinergics , muscle relaxants

28. Specific treatment HSE –ACYCLOVIR I/V 10 mg/kg/dose 8 hrly x 14 -21 days. (500 mg/m 2 )Neonates 20 mg/kg/dose Oral acyclovir has very low bioavailability Oral valacyclovir can be used Very costly Empirical acyclovir Repeat LP after 72 hrs if initial PCR is negative – and stop Acyclovir after that. Other drugs effective - foscarnet

29. Specific drugs Varicella zoster – acyclovir HHV 6 - foscarnet + gancyclovir CMV – gancyclovir H1N1- oseltamivir Rickettsia – doxycycline Mycoplasma – azithromycin Leptospira – penicillin Bacterial meningitis – ceftriaxone + vancomycin ADEM – steroids, IVIG Autoimmune encephalitis - immunosuppressants

30. Limitations in management Even in best centres a definite diagnosis of encephalitis is reached only in 42% of cases ( Granerod et al) ADEM in 21% 1% autoimmune encephalitis 37% no definite diagnoses Undiagnosed viral infections Autoimmune causes Unidentified metabolic causes

31. Sepsis associated encephalopathy Poorly understood CNS condition Manifests lethargy –delirium Pathogenesis bacterial invasion of brain endotoxins derangement of neurotransmitter and amino acid and microvascular changes Prognosis---serious May be seen in patient with 1. mechnical ventilation 2.critical ill patient in micu (sedatives, neuromuscular blocking agents, dyselectrolytemia,hepatic failure may contribute)

32. HIV ENCEPHALOPATHY MANIFESTATION MAY BE HIV VIRUS ITSELF OR ITS NEUROLOGICAL COMPLICATION D/T OPPORTUNISTIC INFECTION LIKE 1. CNS tuberculosis 2. cytomegalo virus encephalitis 3. toxoplasmosis 4. cryptococcal meningitis 5.syphilis 6.tumours (primary CNS lymphoma )or drug related complications

33. MALARIA ENCEPHALOPATHY The potentially fatal complication of falciparum malaria ( most important cause of unarousable coma in febrile patients in endemic area ) SUSCEPTIBILITY - childrens - pregnant women - non – immune adults 20 % all severe falciparum malaria requires ICU admission

34. malaria Selective cytoadherence and sequestration of parasitized RBC’S in cerebral venules and toxin release at schizont rupture are possible pathological mechanism Systemic complications like hypoglycemia may contribute to development of coma Diagnosis – PS for MP Treatment – artesunate is better than quinine

35. AUTOIMMUNE ENCEPHALITIS often presents with fever behavioural abnormalities psychosis movement disorders seizures/status May be paraneoplastic – teratoma ovary in young females Often no tumour is identified Antibodies to NMDA ,VGKC receptors Treatment – IVIG, plasmapheresis

36. FIRES AERRPS DEESC ???

37. CONCLUSIONS A variety of infective and non infective conditions in children can present as acute febrile encephalopathy Stabilisation of patient and supportive management helps a lot in reducing morbidity and mortality Identification of specific etiology helps in institution of specific therapy Awareness of Autoimmune encephalitis is important – another treatable cause like ADEM In a significant proportion of cases aetiology is yet to be identified

38. Thank You