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 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.

Thank you