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 NO GROWTH

ABG 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 hippocampi.

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: 226–30.

*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 newsyndrome presenting with multifocal, symmetric brain lesions. Journal ofNeurology, Neurosurgery and Psychiatry 1995;58:555-561

Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novelform of acute encephalopathy prevalent in Japan and Taiwan. Brain andDevelopment 1997; 19:81-92

San Millan B. Acute Necrotizing Encephalopathy of Childhood: Report of aSpanish Case. Pediatric Neurology 2007;37 (6):438.

Kim JH, et al. Acute Necrotizing Encephalopathy in Korean Infants andChildren: Imaging Findings and Diverse Clinical Outcome. Korean Journalof Radiology 2004;5:171-177

Kirton A. Acute Necrotizing Encephalopathy in Caucasian Children: TwoCases and Review of the Literature. J Child Neurol 2005;20:527-532

Centers for Disease Control and Prevention. Neurologic complicationsassociated with novel influenza A (H1N1) virus infection in childrenDallas, 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 theUnited States. Pediatr Infect Dis J 2004; 23:259–263.

Thank you