newborn epilepsy

Case PresentationNewborn Seizures

To be presented by:me

Chief complaint

A 22-day-old girl with CC: seizures

History of presenting illness

•A full-term infant was noted to be stuporous and jittery and startled easily on DOL#1.

•On DOL#2, she developed repetitive twitching in the eyelids, face, and limbs

•loaded with phenobarbital once for clinical suspicion of seizures.

History of presenting illness co.

•EEG showed no evidence of seizure activity.

• She had some improvements until DOL#10.


•Investigations for infectious etiologies including blood, urine cultures and CSF analysis were unrevealing.

•CBC . N

•Blood sugar. N

•Electrolytes. N

•Brain imaging. Small Subdural hemorrhage


•On DOL#10 she had marked worsening of her neurologic status with excessive irritability and jitteriness.

•recurrent irregular lightening- like jerks

•She was reloaded with phenobarbital and started on maintenance phenobarbital.

of therapy.)

Usual Pediatric Dose for Seizures

Status Epilepticus:Loading dose IV:Neonatal:15 to 20 mg/kg by slow IV infusion over 30 minutesrepeat doses of 5 to 10 mg/kg every 15 to 20 minutes as needed (maximum total dose: 40 mg/kg).

Note: Additional respiratory support may be required, especially when maximizing loading dose.

Maintenance dose: Oral, IV: 3 to 4 mg/kg/day given once daily; maintenance dose usually starts 12 hours after loading dose;assess serum concentrations;increase to 5 mg/kg/day if needed (usually by second week


At DOL#20, she had recurrent episodes of body tightening with arms and legs pulled in tightly accompanied by loud grunts, eye blinking, gagging and jerking movements.

Abdominal distension and increased irritability were also noted


• Keppra was added with temporary improvement. She continued to get multiple boluses of Keppra, lorazepam and phenobarbital for persistent clinical seizures activities.

•She was subsequently started on a pentobarbital drip and intubated prior to transfer to SLCH on DOL#22

Keppra

•Keppra (levetiracetam) an anti-epileptic drug, also called an anticonvulsant.

•Keppra is used to treat partial onset seizures in adults and children who are at least 4 years old.

•Keppra is also used to treat tonic-clonic seizures in adults and children who are at least 6 years old, and myoclonic...

Pentobarbital•Pentobarbital is a barbiturate.

•Short acting.

•Block the high frequency sodium channels.

•Loading dose: 5 mg/kgMaintenance infusion: Initial: 1 mg/kg/hour, may increase up to 3 mg/kg/hour

•(usual range: 1 to 3 mg/kg/hour);

Past medical history

•Pregnancy was complicated by preterm contractions at 35 weeks.

•Infant female was born at 37 6/7 week EGA via vaginal delivery.

•44 yo G5P4 now 5 with unremarkable serologies.


•Apgars were 4, 6, 7 at 1, 5, 10 minutes.

• Delivery was spontaneous and with vacuum extraction.

• Nuchal cord x1 was noted.

Apgar score

Virginia Apgar invented the Apgar score in 1952 as a method to quickly summarize the health of newborn children.

The test is generally done at one and five minutes after birth, and may be repeated later if the score is and remains low.

Scores 7 and above are generally normal, 4 to 6 fairly low, and 3 and below are generally regarded as critically low.

Apgar Sign 2 1 0

Appearance(skin color)

Normal color all over (hands and feet are

pink)

Normal color (but hands and feet are

bluish)

Bluish-gray or pale all over

Pulse(heart rate)

Normal (above 100 beats per minute)

Below 100 beats per minute

Absent(no pulse)

Grimace("reflex irritability")

Pulls away, sneezes, coughs, or cries with

stimulation

Facial movement only (grimace) with

stimulation

Absent (no response to stimulation)

Activity(muscle tone)

Active, spontaneous movement

Arms and legs flexed with little movement

No movement, "floppy" tone

Respiration(breathing rate and

effort)

Normal rate and effort, good cry

Slow or irregular breathing, weak cry

Absent (no breathing)


•She received bag-mask ventilation for 30 seconds at birth.

Drug History

•Pentobarbital drip at 2 mg/kg/hour (phenobarbital and levetiracetam were on hold at the time of transfer).

•Mother did not received any drug during pregnancy.

Family History

•Her parents are from the same area of Pakistan and are otherwise not known to be related. They live in Paducah, Ky.

•No history of genetic disease.

•No history of sudden death.

•No history of epilepsy.

Physical examination

VS T36.9, HR 164, RR 23, BP 74/51. OFC: 36.7 cm. General:•Intubated and ventilated on SIMV.

•anterior fontanelle is open, soft and flat.

•No dysmorphic features. No head abnormalities

Physical examination co.

•Palate is intact.

•Heart: regular rate and rhythm.

•Lungs: clear bilaterally.

•Abdomen: benign.

•GU: normal Tanner I female genitalia.


•Pupils were equal, round and reactive to light from 2 to 1.5 mm bilaterally.

•Positive red reflex bilaterally.

•No eye spots.

•No Nystagmus.


• Did not open her eyes spontaneously.

•Did not startle to a loud clap or noise.

•did not have a vigorous cry

•Normal flexion of the extremities

•bilateral thumbs tightly clinched inside fists


• Moved all extremities asynchronously and with at least antigravity strength when stimulated

• little spontaneous movement without any form of stimulation.

•Responded to touch in all four extremities.

Deep tendon reflexes were symmetric and 3+ throughout in the biceps, brachial radialis, patellar and Achilles tendons.

Bilateral ankle clonus for 3-4 beats.


•Normal Moro response.

•Normal Grasp response.

•Bit on finger tip but did not suck.

•(ventral suspension)(vertical suspension) Signs of hypotonic.


•No skin manifestation.

•Sacral examination normal .


•Clinical impression: 22-day-old female infant with intractable seizures

Causes of seizures.

• Metabolic• Hypoglycemia• Hypocalcemia• Hypomagnesemia• Hyponatremia• Hypernatremia• Maternal drug use – leading to withdrawal• Inborn errors of metabolilsm

(hyperammonemia, pyridoxine-responsive, hyperglycinemia)

• Cerebrovascular• Hypoxic Ischemic Encephalopathy• Arterial and Venous stroke• Intracerebral hemorrhage• Intraventricular hemorrhage• Subdural hemorrhage• Subarachnoid hemorrhage• Brain tumers

• Infection– Bacterial infection– Viral meningitis– Fetal infections– TORCH infections

• Developmental– Cortical dysplasia– Schizencephaly– Double cortex– Lissencephaly

• Other– Genetic disorders ( ARX, etc)– Benign familial convulsions– Early myoclonic convulsions– Ohtahara syndrome– Zellweger syndrome– Pyridoxine deficiency– neurocutaneous syndrome– trauma

Course: While the patient and the EEG were recorded (Video EEG), excessive discontinuity and epileptiform activity were seen. Emergence of status epilepticus after discontinuation of pentobarbital.

Diagnosis

Dramatic elimination of the clinical seizures and flattening of the EEG when pyridoxine 100 mgm given intravenously.

epilepsy pyridoxine dependent (EPD).

Special studies:

•DNA analysis showed two mutations in the antiquitin gene (ALDH7A1).

•alpha-aminoadipic semialdehyde dehydrogenase (AASA) deficiency.

•accumulation of α-aminoadipic semialdehyde, piperideine-6-carboxylate, •and pipecolic acid with a secondary defi ciency in pyridoxal-5-phosphate (active •form of vitamin B6).

Hospital course:

• Pyridoxine 50 mg twice daily was initiated and she remained seizure free the remainder of her admission.

Hospital course:

•She was discharged home on DOL#32 with a nearly normal neurological exam, on pyridoxine PO twice daily and phenobarbital.• •Phenobarbital was discontinued at the Neurology follow-up visit 3 months later. Exam at that time was remarkable for only axial hypotonia. Development was age appropriate.

Pyridoxine-Dependent Epilepsy


•Epilepsy, pyridoxine-dependent (EPD; PDS) is an autosomal recessive disorder.

•incidence between 1:400,000 and 1:750,000.


• Patients with PDS typically present with seizures activities within hours after birth that are refractory to typical anti-epileptics.

• Affected infants may also exhibit intrauterine seizures.

• Seizure types vary, including myoclonic, atonic, partial, generalized and infantile spasms.


•PDS also can be associated with hyper-alertness, irritability.

•abnormal cry, excessive startle response, abdominal distension, vomiting and respiratory distress.


•Clinical diagnosis of PDS can be made with rapid resolution of seizure activity with administration of pyridoxine.


•The pathophysiology of PDS is not fully understood.

•mutations in the ALDH7A1 gene. The enzyme that is deficient is α-aminoadipic semialdehyde dehydrogenase (antiquitin). A deficiency results in the accumulation of α-aminoadipic semialdehyde, piperideine-6-carboxylate, and pipecolic acid with a secondary deficiency in pyridoxal-5-phosphate (active form of vitamin B6).

Elevation of plasma pipecolic acid and urinary and CSF α-aminoadipic semialdehyde act as diagnostic markers.


•Pyridoxal-5-phosphate is an essential cofactor in neurotransmitter synthesis (especially GABA) and amino acid metabolism. (especially lysine)


•The treatment for pyridoxine-dependent epilepsy is lifelong supplementation with pyridoxine.

•the majority of patients all antiepileptic drugs can be withdrawn and seizure control continued with daily pyridoxine monotherapy in pharmacologic doses.

•Infants who do not respond to pyridoxine should have a trial of pyridoxal-5-phosphate.

•Lysine restriction was well tolerated with good compliance; no adverse events were reported.


•Untreated seizures may also be associated with intraventricular hemorrhage and/or subarachnoid hemorrhage, white matter changes and hydrocephalus.

•The developmental outcome of patients with pyridoxine varies, with most patients experiencing some degree of cognitive impairment, particularly expressive language and learning difficulties.


•Patients with a history of intrauterine seizures carry the worst outcome.

• Women who previous gave birth to a child with PDS are recommended to receive pyridoxine supplementation in the final half of subsequent pregnancies.

References …

•http://www.stlouischildrens.org/health-care-professionals/publications/doctors-digest/februarymarch-2011/case-study-newborn-seizures

•http://www.ncbi.nlm.nih.gov/pubmed/23022070

•http://www.ncbi.nlm.nih.gov/books/NBK1486/

•http://www.animatedimages.org/cat-libraries-1316.htm

http://www.stlouischildrens.org/health-care-professionals/publications/doctors-digest/februarymarch-2011/case-study-newborn-seizures

http://www.stlouischildrens.org/health-care-professionals/publications/doctors-digest/februarymarch-2011/case-study-newborn-seizures

http://www.ncbi.nlm.nih.gov/pubmed/23022070

http://www.ncbi.nlm.nih.gov/books/NBK1486/

http://www.animatedimages.org/cat-libraries-1316.htm

newborn epilepsy

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