1141031-高雄地區第515次小兒科聯合病例討論會-高醫大附設中和紀念醫院兒科.pdf

高雄地區第515次小兒科聯合病例討論會

1. 高雄地區兒科聯合病例討論會
王晨華醫師
高雄醫學大學附設醫院小兒神經科
2025-10-31

2. Patient profile
•Age: 8 months old
•Gender: female
•Body length: 69cm (25
th
-50
th
percentile)
•Body weight: 7.6kg (25
th
percentile)
•Head circumference: 44.5cm (50-75
th
percentile)
Chief complaint
•Seizure attack was noted since 8-month-2-day
old

3. Age
7m12d
7m25d
8m2d
8m12d
Fell down from sofa
Seizure attack 1-2 times per day, duration: 5-10+mins
5-6 times/day
Seizure pattern: epileptic spasm(most common),
Focal seizure with or without impaired awareness
Admission
COVID-19 infection, fever subsided spontaneously 3
days later
Developmental regression

4. Past history
•No underlying diseaseBirth history
•Term, via NSD (normal spontaneous delivery)
•Newborn screening: normal
•Prenatal examination: normal

5. Developmental history
•Gross motor: roll over, supine to prone at 5
m/o, now still cannot prone to supine, cannot
sit alone, cannot creep/crawl
•Fine motor: Entire hand grasp
•Speech: coos without babbles before
7months, seldom made sounds now

6. PE/NE
•Consciousness: alert
•I: smell: not test
•II: visual acuity: not test,
visual fields: not test
•III,IV,VI: pupils: 3/3mm. light
reflex: (+/+).
• EOM: free
• 0 0 0 0
• 0--+---+--0 0--+---+--0
• 0 0 0 0
•Ptosis: nil
•Nystagmus: nil
•V: facial sensation: not test
•VII: no facial palsy
•VIII: hearing: not test
•IX, X: uvula position: central
position. gag reflex:(+/+).
•XI: sternocleidomastoid &
trapezius: not test
•XII: tongue deviation(-)

7. PE/NE
•Spontaneous antigravity movement over
extremities(+)
•DTR: bilateral 2+
•Head lag(+)
•Heel to ear(+)
•Scarf signs(+)
•Nohypopigmentation over skin
•Heart sound: no murmur

8. Impression
•Infantile epileptic spasms syndrome Differential diagnosis
•Structural cause
•Metabolic cause
•Infection/inflammation
•Genetic cause

9. Plan
•Structural cause
–Brain MRI, EEG•Metabolic cause
–Biochemistry data, metabolite survey•Infection/inflammation
–CSF analysis, culture, filmarray, IgG index,
monoclonal band
•Genetic cause
–Whole exome sequencing

13. CSF analysis
•Cell counts:1/uL
–RBC:0/uL
–Neu:0%;lymph:100%•Protein: 16.3mg/dL
•Glucose: 57mg/dL(CSF/Serum: 61.3%)
•Lactate: 1.03 m mol/L
•IgG index: 0.46
•Monoclonal band: negative

15. Diagnosis
•West syndrome with unknown cause
–Epileptic spasms
–Hypsarrhythmia
–Developmental regression

16. Treatment
•Steroid protocol, according to Pediatric
Epilepsy Research Consortium
•Prednisolone
•1-14day 10mg 4 times daily (8/7-8/21)
•15-19day 10mg 3 times daily (8/21-8/25)
•20-24day 10mg 2 times daily (8/26-8/30)
•25-29days 10mg daily (8/31-9/4)

17. Final diagnosis
•STXBP1 encephalopathy
•West syndrome

18. Current condition
•Ketogenic dietseems seizure free clinically
recently
•Increased interaction with parents and toys
•Smiles responsively
•Still can’t sit alone
•Prone to supine sometimes

19. •Discussion

20. Outline
•Infantile epileptic spasms syndrome (IESS)
•Treatment options and efficacy comparison
•STXBP1 encephalopathy

21. Impact factor: 5.6

22. Infantile epileptic spasms syndrome
(IESS)
•IESSis a term proposed to encompass both
West syndrome as well as infants presenting
with epileptic spasms who do not fulfil all the
criteria for West syndrome
•West syndrome
–Epileptic spasms
–Hypsarrhythmia
–Developmental stagnation or regression
Epilepsia. 2022 Jun;63(6):1349-1397.

23. Infantile epileptic spasms syndrome
(IESS)
•Importance of early diagnosis and therapy
because shorter lag time to treatment is
associated with a better outcome
Epilepsia. 2022 Jun;63(6):1349-1397.

24. Epidemiology
•Incidence: 30/100 000 live born infants
•higher incidence in males
Epilepsia. 2022 Jun;63(6):1349-1397.

25. Clinical manifestation
•Onset of epileptic spasms between 1 and 24
(peak 3 and 12) months of age
•Infants may have no antecedent history, or the
antecedent history may reflect the underlying
cause
–In some cases, infants with EIDEE or other early
onset epilepsies (usually with focal seizures) may
evolve to have clinical and EEG features of IESS
after 3–4 months of age
Epilepsia. 2022 Jun;63(6):1349-1397.

26. Clinical manifestation
•Prior to the onset of IESS the development can
be normal, but there is often a history of
preceding clear or suspected abnormal
development.
•Developmental slowing, arrest, or regression
is seen with the onset of spasms, although it
may not be apparent very early in the course
Epilepsia. 2022 Jun;63(6):1349-1397.

27. Course of illness
•IESS frequently evolves to other epilepsy types or
syndromes, especially Lennox-Gastautsyndrome, or
drug-resistant focal epilepsies
•Developmentally, many infants are left with poor
developmental outcome, regardless of seizure
outcome. The severity of developmental delay relates
predominantly to etiology and promptness of
treatment.
•Prognosis is more favorable for infants with preceding
normal development, no known cause, and prompt
initiation of syndrome-specific treatment
Epilepsia. 2022 Jun;63(6):1349-1397.

28. Seizure semiology
•Epileptic spasms are mandatory for the
diagnosis
–brief tonic contractions of axial muscles, each
typically lasting <3 s, which may be flexor,
extensor, or mixed.
–cluster, often over a period of minutes
–Often seen on awakening
–may be symmetric or asymmetric
Epilepsia. 2022 Jun;63(6):1349-1397.

29. Seizure semiology
•Focal seizures may also be seen
–particularly in structural etiology
•tuberous sclerosis
•Focal cortical dysplasia
Epilepsia. 2022 Jun;63(6):1349-1397.

30. EEG-interictal
Epilepsia. 2022 Jun;63(6):1349-1397.

31. EEG-ictal
Epilepsia. 2022 Jun;63(6):1349-1397.

32. Neuroimaging
•Structural etiologytreatment decision
making
•Brain MRI is abnormal in one half to two
thirds of children with IESS
•Early imaging should be repeated after 2 years
of age
Epilepsia. 2022 Jun;63(6):1349-1397.

33. Genetics
•Genetic studies should be considered if
–no etiology is found after clinical examination and MRI
–patients with structural brain disorders known to be
associated with a genetic basis•A genetic etiology can be defined in up to 41% of
cases
–Trisomy 21, ARX, CDKL5, STXBP1, IQSEC2, TSC1, TSC2,
and many others.
•A range of chromosomal abnormalities and copy
number variants have been associated with IESS
Epilepsia. 2022 Jun;63(6):1349-1397.

34. Metabolic and other lab studies
•Metabolic etiologies are a rare but important
cause of IESS
•Metabolic testing should be considered if an
etiology is not found
•Pyridoxine dependency should be considered
Epilepsia. 2022 Jun;63(6):1349-1397.

35. Treatment
Epilepsia, 56(8):1185–1197, 2015

36. Treatment

37. ACTH? Oral corticosteroids?
Front Neurol. 2022 Feb 10;13:772333

38. ACTH vs. Oral Corticosteroids
•Meta-analysis revealed that the effectiveness
of ACTH and corticosteroids on electro-clinical
response was comparable, regardless of the
dosage of corticosteroids
Front Neurol. 2022 Feb 10;13:772333

39. Corticosteroid Dosage
•High:4 mg/kg/day; usual: 2mg/kg/day
prednisolone
–On day 14 after the initiation of treatment, 12 (38.7%)
and 7(21.9%) of participants achieved electro-clinical
response in highandusual-dose groups, respectively
(p = 0.15)
•Methylprednisolone pulse
–By day 14, no difference was found in the proportion
of patients achieving spasm cessation and electro-
clinical response between MEP and oral prednisolone
groups
Front Neurol. 2022 Feb 10;13:772333

40. Hormonal Therapy vs. VGB
•ACTH had a more favorable effect than VGB
on cessation of spasms (RR = 1.31, 95% CI
1.05–1.64)
Front Neurol. 2022 Feb 10;13:772333

41. Monotherapy vs. Multitherapy
•Spasm cessation on days 13 and 14 was achieved in
166 (89%) of 186 patients treated with combination
therapy compared to 132 (69%) of 191 patients on
hormonal therapy (95% CI 11.8–28.6; p < 0.001)
•Electro-clinical remission was achieved in 123 (66%)
patients on combination therapy compared to 104
(55%) who were allocated to hormonal therapy (95% CI
1.4–21.6; p = 0.023)
•Time taken to reach spasm-free was shorter on
combination therapy than hormonal therapy [median 2
days (interquartile range (IQR) 2–4) vs. median 4 days
(IQR 3–6); z = 6.04; p < 0.001].
Front Neurol. 2022 Feb 10;13:772333

43. Introduction
•STXBP1 (more commonly known as MUNC18-
1) is encoded by the STXBP1genes
(NM_003165.3), consisting of 20 exons and
located on chromosome 9q34.11
•The STXBP1 is a member of the SEC1 family of
membrane trafficking proteins predominantly
expressed in the brain, which modulate the
presynaptic vesicular fusion reaction by
docking and fusing with the synaptic vesicle

47. •Thanks for your attention!