dr swapna - neocon2019 · dr swapna .l md(ped) ,dm (nenatology), assistant professor of neonatology...

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Dr Swapna .LMD(Ped) ,DM (Nenatology),

Assistant Professor of NeonatologyNiloufer Hospital, Hyderabad

AndConsultant Neonatologist

Soumya Childrens Hospital

Refractory Neonatal Seizurescase based discussion

Epidemiology

Causes of neonatal seizures

Causes of recurrent neonatal seizures

• HIE

• Cerebral dysgenesis

• Cerebral malformation

• Intra cranial bleed

• Neonatal stroke

Metabolic

• Pyridoxine dependency

• Pyridoxal phosphate dependency

• Folinic acid dependent seizures

• Biotinidase deficiency

• Molybdenum cofactor deficiency

• Sulfite oxidase deficiency

• GLUT1 deficiency

Major effects of recurrent neonatal seizures

• Increased susceptibility to later epilepsy

• Impaired cognitive function

• Developmental delay.

Case 1

• Preterm ,34weeks , 1.78 kg, male baby

• primi mother by LSCS

• Baby cried after tactile stimulation

• spontaneous preterm labour shifted to in view of respiratory distress

ANTENATAL HISTORY:

• 29 year old mother.

• Had regular antenatal check ups

• Antenatal TIFFA scans and dopplers are normal.

Examination

Wt: 1.78 kg

HC: 28 cm (<3rd percentile )

LENGTH – 42 cm

Axial hypotonia present.

Power is 4/5 in all the limbs

External genitalia: hypospadias present

At admission the baby has RD with SAS score of 4/10.

In nicu

• Baby started on CPAP. PEEP(6cm)

• Xray showed 7 space lung expansion

• Baby was weaned off from CPAP after 24 hours of life .

• At 23 hrs of life baby had 2 episodes of seizures loaded with Inj. Phenobabitone.

• GRBS normal, serum calcium – normal

Further course…

• At 42 hours of life the baby had 2 more episodes of seizures requiring phenobarbitonehalf loading and levetiracetam loading dose.

Further course…

• After 18 hours being seizure free, the baby had 2 more episodes of seizures requiring half loading levetiracetam, pyridoxine,biotin, folinic acid.

• S. electrolytes are within normal limits.

Investigations(in selected cases)

Neonatal -onset epilepsies (Familial & Genetic epilepsies)

– Clinical/ Whole exome sequencing

– Whole genome sequencing

– Targeted epileptic encephalopathy gene panels

– CSF Neurotransmitters

– Muscle biopsy (Respiratory enzyme assay)

– High resolution MRI Brain

Investigations

• S. electrolytes are within normal limits

• NSG- normal ventricle size with RI of 0.59.

• Septic work up negative

• CSF analysis-normal

• 2d echo- normal.

• TORCH profile - NEGATIVE

• MRI Brain was done

Normal / abnormal

MRI brain

MRI brain

• Decreased sulcation of brain with thick cortex and smooth surface with shallow sylvianfissures .

• Moderate dilatation of temporal horns and body of lateral ventricles

• Partial agenesis of corpus callosum noted with absent splenium.

• Features suggestive of lissencephaly.

EEG

• Diagnosis :

• X linked lissencephaly:

• Lissencephaly

• Agensis of corpus callosum

• Hypospadias

• Intractable seizures

• Acquired microcephaly

• Male phenotype

• We have send whole genome clinical exomsequencing for the baby to rule out genetic cause for lissencephaly.

• Counselled the parents about the baby’s condition

• The prognosis in such patients is poor. They show marked developmental delay. Most patients die before the age of 18 months.

Take home message

• Consider cerebral malformations

polymicrogyria, neuronal heterotopias, lissencephaly, holoprosencephaly, and hydranencephaly

intractable seizures

Dysmorphic facies

Microcephaly

No history of birth asphyxia / perinatal events

After ruling out metabolic causes

Case 2

• 2 days old female baby , term , birth weight – 2.9 kg

• Second in birth order , consanguinous parents • No history of birth asphyxia• Decreased feeding from first day of life • History of seizures , not controlled after

phenobarbitone, phenytoin and levitiracetam, pyridoxine, biotin,folinic acid

• On examination : had hypotonia and encephalopathy

• GRBS : normal,serum calcium – normal

• Serum electrolytes – normal

• Septic work up: negative

• Neurosonogram normal

• MRI brain - normal

• CSF analysis : normal

• TMS : elevated glycine levels

• Baby expired due to refractory seizures

• We got the results after the baby expired

• We have send new born screening filter paper card for mutational analysis

Case 3

• Term baby , 39 weeks , 3.1 kg, born to primimother

• Non consanguinous parents

• NVD

• Cried after one cycle of bag and mask ventilation

• Presented with seizures at 7 hours of life

• Myoclonic in type , multiple

• Treated with phenobarbitone, phenytoin, levipil, pyridoxine

• Investigations:

• GRBS : normal

• Serum calcium- normal

• Serum electrolytes – normal

• Septic work up negative

• Usg cranium – RI – normal

• Seizures controlled

• MRI brain – normal

• Baby discharged with gardinal.

• Baby readmitted with seizures on day 10 with refractory myoclonic seizures,

• Restarted on pyridoxine, seizures controlled

• Currently baby is on follow up 8 months on pyridoxine, and is seizure free.

Pyridoxine dependent seizures

• Diagnostic criteria:

• Seizures resistant to traditional antiepileptic therapy and cessation of clinical seizures with administration of parenteral or oral pyridoxine

• Complete seizure control on pyridoxine

• Recurrence of seizures upon pyridoxine withdrawl

• No clinical evidence of pyridoxine deficiency

• Acute: 100 to 200 mg of pyridoxine iv

• Maintanence : 30 mg/kg/day

Fourth case

• Term ( 38 weeks ), male, 3.44 kg

• primi mother by LSCS in view of non progression of labour was shifted to sowmya childrenshospital in view of respiratory distress

ANTENATAL HISTORY

• 25 year old mother.

• Had regular antenatal check ups

• All the trimesters uneventful

• Antenatal TIFFA scans and dopplers are normal.

Natal history

• Prolonged labour of 30 hours duration.2nd

stage being 3 hours.

• Vertex presentation

• Baby cried after tactile stimulation. APGAR 5& 9.

• H/o MSL+

Further course

• At admission the baby has RD with Downesscore of 5/10.

• Activity at admission good, tone normal, moros complete, Baby was started on CPAP. In v/o higher fio2 and PEEP requirements the baby is connected to mechanical ventilator on assist mode.

Further course

• At 7 hours of life, the baby had cyclical movements of all the limbs

• GRBS normal, i.v phenobarbitone loading dose was given.

• At 12 hours of admission the baby had 2 more episodes of seizures requiring phenobarbitonehalf loading and levetiracetam loading dose

Further course

• At 17 hours of life, baby developed two more episodes , treated with half loading levipil, pyridoxine, folinic acid, biotin.

• At 25 hours, baby developed two more epidoes, started on midazolam infusion

• Midazolam infusion tapered over next 48 hours and stopped

Investigation

• CBP: hb-17.7gm%,wbc:19900(46%,45%,01%,8%),plt1.73laks

• ABG: 7.252/48.9/68/-6/21.6/2.1• RBS:76mg/dl• Electrolytes: Na+ 135

k+ 3.6cl- 96

• S.calcium:8.2• S.magnesium 1.55

Day 2:

CRP 44mg/lit

B/C/S- no growth

Day 4:

• CSF analysis-normal

• PT-13.4 Sec,aPTT-54 sec, INR 1.2

• 2d echo-normal

MRI brain

• focal DWI hyperintensity in left temporal,parieto-occipital and high parietal cortical, subcortical regions with restriction of ADC-INFARCTS

• MRI brain:Focal DWI hyperintensity in left temporal,parieto-occipital and high parietal cortical, subcortical regions with restriction of ADC-INFARCTS

Cephalhematoma+

Take home message

• Consider metabolic causes

• Cerebral malformations

• Neonatal epilepsy syndrome