PRESENTER

DR TANUJ VERMA

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.

no h/o headache vomiting ,ear discharge,

exanthems , dog bite, recent immunization ,
recent travel or bleeding manifestations

No significant past medical history

No home medications
No prior surgeries

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.

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

ACUTE MENINGOENCEPHALITIS WITH

STATUS EPILEPTICUS

HB

13.2%

WBC

13000

DLC

N87 / L4

CRP

6.7

BLOOD CULTURE NO GROWTH

URINE CULTURE
ABG

NO GROWTH
7.18 / 73 / 87 / 27.3 / -1.2 / 1.4

CT shows hypodensities involving bilateral thalamic

and midbrain, mild prominence of ventricles

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

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

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

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

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

diffuse slowing with no

epileptiform activity

H1N1 POSITIVE

ACUTE NECROTIZING ENCEPHALOPATHY OF

CHILDHOOD (ANEC)

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

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

Clinico-radiological diagnosis

Etiology: Mostly associated with Influenza A

and B virus, parainfluenza virus, Mycoplasma,
Herpes simplex virus and Human herpes virus-6.

Journal of Neurology, Neurosurgery, and

Psychiatry 1995;

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

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.

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: 22630.
*Gika AD. Recurrent acute necrotizing encephalopathy following Influenza A
in a genetically predisposed family. Dev Med Child Neurol 2010; 52: 99
102.

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

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.

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.

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: 773778.
Weitkamp JH, Spring MD, Brogan T, Moses H, Block KC, Wright PF.
Influenza A virusassociated acute necrotizing encephalopathy in the
United States. Pediatr Infect Dis J 2004; 23:259263.

Thank you