acute necrotizing encaphelomylitis

1. PRESENTER
DR TANUJ VERMA

2.  MANJULA 4 years old girl from ANDRA
PRADESH addmited in Pediatric casualty with
Cough and cold 4 days
Fever 2 days
Altered behaviour and sensorium 1 day.
 1st
born to nonconsanguineous parents
 Birth history was uneventful
 Developmental milestones were normal.

3.  no h/o headache vomiting ,ear discharge,
exanthems , dog bite, recent immunization ,
recent travel or bleeding manifestations

4.  No significant past medical history
 No home medications
 No prior surgeries

5.  She had status epilepticus and was loaded
with phenytoin, Leviteracetam, and
valproate.
 GCS worsened to 5/15, so she was intubated
and shifted to PICU.
 She was started on Midazolam infusion,
meningitic doses of Cefotaxime, Acyclovir
and Neuroprotective measures.

6.  PICU ADMISSION GCS 6T/15
 SEVERE NEUROLOGICAL COMPROMISE
 IN ABSENSE OF NEUROMAUSCULAR BLOCKAGE MO
SPONTENOUS MOVEMENTS WITH MINIMAL WITHDRAWL TO
PAIN
 COUGH GAG AND CORNEAL REFLEX ABSENT
 B/L PUPIL CONSTRICTED AND REACTING TO LIGHT
 NO FACIAL WEAKNESS AND TONE DECRESED IN ALL FOUR
LIMBS
 B/L PLANTER EXTENSOR , DTR DEPRESSED
 NO NECK RIGIDITY AND KERNIG/ BRUDZENKY ANSENT

7. ACUTE MENINGOENCEPHALITIS WITH
STATUS EPILEPTICUS

8. HB 13.2%
WBC 13000
DLC N87 / L4
CRP 6.7
BLOOD CULTURE NO GROWTH
URINE CULTURE NO GROWTH
ABG 7.18 / 73 / 87 / 27.3 / -1.2 / 1.4

9. CT shows hypodensities involving bilateral thalamic and midbrain, mild
prominence of ventricles

11.  VIRAL MENINGOENCAPHLITIS
 IEM
 ACUTE NECROTIZING MENINGOENCPHLITIS
(Genetic/ infection associated/ metabolic)

12. • MRI with contrast
• Etiology work up: blood lactate, ammonia,
acylcarnitine profile, TMS to Clinical
Pharmcological lab, H1N1 screening,
biotinidase assay, serum aminoacids, urine
organic acids
• BBVS screen
• Genetic studies: RNBP gene mutation
• Supportive measures
• HLA DRB1*1401, HLA BRB3*0202, HLA
DQB1*05052

13. T2 FLAIR hyperintensities involving bilateral symmetrical swelling, haemorrhagic
areas and restricted diffusion of thalami. Hyperintensity, swelling and restricted
diffusion of posterior putamen, caudate head, hippocampi,pons,dentate
nucleus and fornices with haemorrhagic areas in pons and hippocampi.

15. ESR 30
ANA NEGATIVE
DS DNA 19 IU/ML ( < 100 IU/ML)
S AMMONIA 80mcg%
S LACTATE 1 mmol/l
SE AMINO ACIDS NORMAL
S FREE
ACYLCARNITINE
NORMAL
S TOTAL
CARNITINE
NORMAL
URINE ORGANIC
ACIDS
NOT DETECTED
URINE OROTIC
ACIDS
NORMAL LEVELS

16. GLUCOSE 52 mg/dl
PROTEIN 152mg/dl
CELLS TLC 5 / CC
CELLS DLC P 60%/ L 40%
LACTATE 1.1 mmol/l
CSF CULTURE NO GROWTH
CSF ACYLCARNITINE NORMAL
CSF TOTAL
ACYLCARNITINE
NORMAL
CSF MULTIPLEX PCR
CMV
NEGATIVE
CSF ENTEROVIRUS NEGATIVE
CSF HHV 6 NEGATIVE
CSF JAP- B NEGATIVE

17. diffuse slowing with no
epileptiform activity

18. H1N1 POSITIVE

19. ACUTE NECROTIZING ENCEPHALOPATHY OF
CHILDHOOD (ANEC)

20.  Now not a first reported case of acute
necrotizing encaphlopathy but among
few with H1N1
 1st
reported in japan by Mizuguzi in 1995
 Report on 13 consecutive cases and 28
previous cases

21. • Acute encephalopathy following viral disease, with seizure and
deterioration of consciousness.
• Absence of CSF pleocytosis. CSF protein is commonly increased.
• Neuroimaging findings of symmetric, multifocal brain lesions
involving the bilateral thalami, upper brain stem tegmentum,
periventricular white matter, internal capsule, putamen and
cerebellum.
• Elevation of serum aminotransferase level to a variable degree. No
increase in blood ammonia.
• Exclusion of any resembling disease.
Journal of Neurology, Neurosurgery, and Psychiatry 1995;58:555-561

22.  Clinico-radiological diagnosis
 Etiology: Mostly associated with Influenza A
and B virus, parainfluenza virus, Mycoplasma,
Herpes simplex virus and Human herpes virus-6.

23. Journal of Neurology, Neurosurgery, and Psychiatry 1995;

24. A. Clinical differential diagnosis: toxic shock syndrome,
hemolytic uremic syndrome, Reye syndrome, hemorrhagic
shock and encephalopathy syndrome, and heat stroke.
B. Radiological (or pathological) differential diagnosis:
Leigh encephalopathy, glutaric acidemia, methyl malronic
aciduria, infantile bilateral strial necrosis, Wernicke
encephalopathy, carbon monoxide poisoning, acute
disseminated encephalomyelitis, acute hemorrhagic
leukoencephalitis, arterial or venous infarct, severer
hypoxic or traumatic injury.
Journal of Neurology, Neurosurgery, and
Psychiatry 1995;58:555-561

25. • Not clear.
• But postulated rapid development of intracranial
cytokine formation which causes blood brain
barrier damage in particular regions of brain
resulting in localized edema, congestion and
hemorrhage, without any signs of direct viral invasion
or post infectious demyelination.
Sugaya N. Influenza associated encephalopathy in Japan: pathogenesis and treatment.
Pediatr Intl 2000; 42: 215-218.

26.  RANBP2 gene mutation*: recurrent episodes
of ANEC and can present as Autosommal
Dominant with incomplete penetrance.
* Neilson DE. Autosomal dominant acute necrotizing encephalopathy.
Neurology 2003; 61: 226–30.
*Gika AD. Recurrent acute necrotizing encephalopathy following Influenza
A in a genetically predisposed family. Dev Med Child Neurol 2010; 52: 99–
102.

27.  Male to female 1:1
 Peak incidence age 6-18 months
 90% of cases have antecedent infection with
fever, URI symptoms, GI symptoms
 Onset of symptoms occur 0.5-3 days
following antecedent infection
 Rapidly progressing encephalopathy

28.  Refractory status epilepticus
 25% of ANE patients die, and up to 25% of
ANE survivors develop substantial neurologic
sequelae.
 The presence of hemorrhage and localized
tissue loss on MRI may suggest a poor
prognosis.

29. • Supportive: Neuroprotective measures and
anticonvulsants
• Antiviral agents/Antibiotics
• *Steroids: Anecdotal reports showed that
administration of steroid within 24 hours after the
onset was related to better outcome of children with
ANEC without brainstem lesions.
• IVIG?
*Okumura A. Outcome of acute necrotizing encephalopathy in relation to
treatment with corticosteroids and gammaglobulin. Brain Dev 2008; May 2.

33.  Mizuguchi M. Acute necrotising encephalopathy of childhood: a new
syndrome presenting with multifocal, symmetric brain lesions. Journal of
Neurology, Neurosurgery and Psychiatry 1995;58:555-561
 Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel
form of acute encephalopathy prevalent in Japan and Taiwan. Brain and
Development 1997; 19:81-92
 San Millan B. Acute Necrotizing Encephalopathy of Childhood: Report of a
Spanish Case. Pediatric Neurology 2007;37 (6):438.
 Kim JH, et al. Acute Necrotizing Encephalopathy in Korean Infants and
Children: Imaging Findings and Diverse Clinical Outcome. Korean Journal
of Radiology 2004;5:171-177
 Kirton A. Acute Necrotizing Encephalopathy in Caucasian Children: Two
Cases and Review of the Literature. J Child Neurol 2005;20:527-532
 Centers for Disease Control and Prevention. Neurologic complications
associated with novel influenza A (H1N1) virus infection in children
Dallas, Texas, May 2009. MMWR Morb Mortal Wkly Rep 2009; 58: 773–778.
 Weitkamp JH, Spring MD, Brogan T, Moses H, Block KC, Wright PF.
Influenza A virus–associated acute necrotizing encephalopathy in the
United States. Pediatr Infect Dis J 2004; 23:259–263.

34. Thank you