PHOTO

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