download form this link https://mohmmed-ink.blogspot.com/2020/11/new-born-epilepsy-case-study.html pyridoxine dependent seizures. case study. rare case. Newborn epilepsy.

2. Chief complaint
A 22-day-old girl with CC: seizures

4. 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.

5. History of presenting illness co.
•EEG showed no evidence of seizure activity.
• She had some improvements until DOL#10.

6. History of presenting illness co.
•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

7. History of presenting illness co.
•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.

8. of therapy).
Usual Pediatric Dose for Seizures
Status Epilepticus:
Loading dose IV:
Neonatal:15 to 20 mg/kg by slow IV infusion over 30 minutes
repeat 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

9. History of presenting illness co.
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

10. History of presenting illness co.
• 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

11. 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...

12. Pentobarbital
•Pentobarbital is a barbiturate.
•Short acting.
•Block the high frequency sodium channels.
•Loading dose: 5 mg/kg
Maintenance infusion: Initial: 1 mg/kg/hour,
may increase up to 3 mg/kg/hour
•(usual range: 1 to 3 mg/kg/hour);

13. 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.

14. Past medical history
•Apgars were 4, 6, 7 at 1, 5, 10 minutes.
• Delivery was spontaneous and with vacuum
extraction.
• Nuchal cord x1 was noted.

15. 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)

16. Past medical history
•She received bag-mask ventilation for 30
seconds at birth.

17. 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.

18. 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.

19. 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

20. Physical examination co.
•Palate is intact.
•Heart: regular rate and rhythm.
•Lungs: clear bilaterally.
•Abdomen: benign.
•GU: normal Tanner I female genitalia.

21. Physical examination co.
•Pupils were equal, round and reactive to light
from 2 to 1.5 mm bilaterally.
•Positive red reflex bilaterally.
•No eye spots.
•No Nystagmus.

22. Physical examination co.
• 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

23. Physical examination co.
• 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.

24. Deep tendon reflexes were symmetric and 3+
throughout in the biceps, brachial radialis,
patellar and Achilles tendons.
Bilateral ankle clonus for 3-4 beats.
Physical examination co.

25. •Normal Moro response.
•Normal Grasp response.
•Bit on finger tip but did not suck.
•(ventral suspension)(vertical suspension)
Signs of hypotonic.
Physical examination co.

26. •No skin manifestation.
•Sacral examination normal .
Physical examination co.

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

28. 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

29. 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).

30. 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).

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

32. 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.

33. Pyridoxine-Dependent
Epilepsy

34. Pyridoxine-Dependent Epilepsy
•Epilepsy, pyridoxine-dependent (EPD; PDS) is an
autosomal recessive disorder.
•incidence between 1:400,000 and 1:750,000.

35. Pyridoxine-Dependent Epilepsy
• 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.

36. Pyridoxine-Dependent Epilepsy
•PDS also can be associated with hyper-alertness,
irritability.
•abnormal cry, excessive startle response, abdominal
distension, vomiting and respiratory distress.

37. Pyridoxine-Dependent Epilepsy
•Clinical diagnosis of PDS can be made with rapid
resolution of seizure activity with administration of
pyridoxine.

38. Pyridoxine-Dependent Epilepsy
•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.

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

40. Pyridoxine-Dependent Epilepsy
•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.

41. Pyridoxine-Dependent Epilepsy
•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.

42. Pyridoxine-Dependent Epilepsy
•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.

43. 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