Three sentences: 1) The study aimed to determine if early electroencephalographic (EEG) abnormalities could predict neurodevelopmental outcomes at 24 months for term infants with hypoxic-ischemic encephalopathy (HIE). 2) Fifty infants with HIE underwent continuous video-EEG monitoring within 6 hours of birth, and EEG findings at 6, 12, 24, and 48 hours were correlated with outcomes assessed at 24 months. 3) The results showed that normal or mildly abnormal EEG findings within the first 24 hours highly accurately predicted normal outcomes, while more severe abnormalities were strongly associated with abnormal neurodevelopment.

1. Journal club
Yassin M. Al-saleh
Dr.Sumahya Al-hajjaj

2. ‫بسم ا الرحمن الرحيم‬
‫)انما يخشى‬
‫ا من عباده‬
‫العلماء(‬

4. INTRODUCTION
• Hypoxic-ischemic encephalopathy (HIE)
occurs in 3 to 5 cases per 100 deliveries.
• remains an important cause of neonatal
death and long-term neurologic disability.

5. INTRODUCTION
• Interventions, including induced
hypothermia, may limit secondary cerebral
damage.
• To offer effective hypothermia, clinicians
need to establish the infant’s prognosis
within 6 hours after birth.

6. INTRODUCTION
• Electroencephalographic (EEG)
abnormalities can be used to aid outcome
prediction for infants with HIE.

7. Objectives
• Our aim was to collect detailed, early,
continuous, video-EEG data for a well
defined group of infants with HIE.
• We wished to determine which of the early
EEG features would best predict neurologic
outcomes at 24 months of age.

9. METHODOLOGY
• Study Design:
• The prospective study was conducted in a
large maternity service with 6000 deliveries
per year.
• Between May 2003 and May 2005

10. METHODOLOGY
• term infants (37weeks of gestation) with
HIE were recruited if they fulfilled 2 of the
following criteria:
• initial capillary or arterial pH of 7.1.
• Apgar score at 5 minutes of 5.
• initial capillary or arterial lactate level of 7
mmol/L.
• abnormal neurologic features/clinical
seizures.

11. METHODOLOGY
• After recruitment, EEG electrodes were
applied to the scalp.
• Recordings were commenced as soon as
possible after birth, generally within 6
hours.

12. METHODOLOGY
• Developmental follow-up assessments were
performed at 6, 12, and 24 months using the
Revised Griffiths Scales of Mental
Development.
• Abnormal outcome was defined as death,
cerebral palsy, or a Griffiths quotient (GQ)
of 87.

13. METHODOLOGY
EEG Analyses:
• The evolution of EEG findings was examined
including:
• background.Amplitude.
• presence of discontinuity,
• length of EEG activity burst . Interburst interval.
• return of sleep-wake cycling (SWC).
• presence or absence of seizures.
• EEG segments that were 1 hour in length and free
of visual artifacts were chosen at 6, 12, 24, and 48
hours of age for each infant

14. METHODOLOGY
• All patient identifiers were removed.
• The segments were stored as separate files
and then were visually analyzed separately
by a neurophysiologist .

15. METHODOLOGY
• Clinicians were blinded to all EEG data,
and antiepileptic medications were
administered if seizures were suspected
clinically.

16. METHODOLOGY
Statistical Analyses
• Means and SDs were calculated for
demographic factors.
• The predictive ability of EEG grades was
by using:
• positive predictive value (PPV).
• Negative predictive value (NPV).
• Statistical significance was taken as P .05.

18. RESULTS
Study Group
• In total, 54 infants with clinical HIE were
recruited soon after delivery.
• Of those, 50 had early, continuous, videoEEG recording performed during the first 3
days of life.
• Forty-four infants completed
neurodevelopmental followup.
• Of those, 20 (45%) had abnormal outcomes.

19. 54
RESULTS
50
38/12
2
48
4
44
24
20

20. RESULTS
EEG Grades
• At 24hours, the number of infants assigned to each
grade was as follows: normal,6; mild, 11;
moderate, 9; severe, 9; isoelectric,3.

21. EEG Grades and Prediction of
Outcomes
• The EEG grades assigned were highly
predictive of outcomes at all times.
• EEG grades correlated significantly with
both outcomes and GQ scores at 24 months.
• The timing of EEG recording did affect the
predictive value of the EEG results

22. RESULTS
• Normal or mildly abnormal EEG results at
6, 12, or 24 hours had a 100% PPV for a
normal outcome and a NPV of 67% to 76%.
• the NPV of normal EEG results being
greater at 48 hours (93%), with a concurrent
PPV of 71%.

23. RESULTS
Evolution of EEG Results
• EEG abnormalities improved with time,
with the worst EEG grade seen on the
earliest recording in all cases.
• Normal or mildly abnormal EEG results at
6 hours remained normal/mild and were
associated with normal outcomes in 100%
of cases.

24. RESULTS
Individual EEG Features
• EEG features that were associated with
abnormal outcomes were background
amplitude of 30V, interburst interval of 30
seconds, electrographic seizures, and
absence of sleep-wake cycling at 48 hours.

25. RESULTS
• Clinical Sarnat grades at 24 hours were
correlated significantly with outcomes (R
0.703; P .001).
• No correlation was found between
socioeconomic group and
neurodevelopment.

27. Critical
apprasial

28. PICO
• Population: term infants (37 weeks of
gestation) with HIE.
• Intervention: EEG recording.
• Control: clinical assesment.
• Out come:prediction of outcome in
HIE

29. Relevance
• 1. Does the study address a common
problem in your practice?
•
YES
• 2. Does the study address an
important outcome to you or to your
patient? (DOE vs. POEM).
•
YES

30. Relevance
3. Assuming that the study conclusion is
true would it lead to a change in your
practice?
yes

31. Are the Results of the Study
Valid?
• Was the assignment concealed?
Yes
• Was follow-up complete& long enough?
YES
• Sensitivity analysis (WCS)
NO

32. Are the Results of the Study
Valid?
Were all clinically important outcomes
considered?
yes

33. Are the Results of the Study
Valid?
• Is reference standard used acceptable?
• No.
• Was there an independent, blind comparison
with a reference standard?
• YES.
• Were both reference standard and test applied
to all patients?
• YES

34. Are the Results of the Study
Valid?
• Did the patient sample include an
appropriate spectrum of patients to
whom the diagnostic test will be applied
in clinical practice?
• yes

35. Are the Results of the Study
Valid?
• Did the results of the test being evaluated
influence the decision to perform the
reference standard?
• NO

36. Are the Results of the Study
Valid?
• Were the methods for performing the
test described in sufficient detail to
permit replication?
• YES

37. What Were the Results?
• Are likelihood ratios for the test results
presented or data necessary for their
calculation provided?
• YES

40. calculation
At 6h
standered
refernace
abnormal
9
4
13
0
13
13
9
EE abnormal
G
not
not
17
26
+
• Sensitivity: 9/9+0=1
• Specificity:13/13+4 = 0.76
• Positive Predictive Value
(PPV)= 9/9+4=0.69
• Negative Predictive Value
(NPV)=13/0+13=1
Test
result
-
+
a
b
-
c
d
PPV
NPV

41. calculation
At 6h
standered
refernace
abnormal
abnormal
9
2
11
not
0
15
15
9
EEG
not
17
26
+
Likelihood Ratio for Positive Test
(LR+) 4.16
Test
resul
t
-
+
a
b
-
c
d

43. Will the results Help Me in Caring
for My Patients?
• Will the reproducibility of the test result
and its interpretation be satisfactory in
my setting?
• NO.

44. Will the results Help Me in Caring
for My Patients?
• Are the results applicable to my
patient?
• Similar distribution of disease severity?
(spectrum)
• YES.

45. Will the results Help Me in Caring
for My Patients?
• Will the results change my
management?
• Test and treatment thresholds? (is it
between)
• YES.
• High or low LR's?

46. Will the results Help Me in Caring
for My Patients?
• Will patients be better off as a result
of the test?
• Is target disorder dangerous if left
undiagnosed?
• YES.
• Is test risk acceptable?
• YES

47. Will the results Help Me in Caring
for My Patients?
• Does effective treatment exist?
• YES.
• Information from test will lead to change of
Management beneficial to patient?
• YES.

49. Glossary
• Cohort study: Follow-up of exposed and
non-exposed defined groups, with a
comparison of disease rates during the time
covered. ( Harm, Prognosis)

50. Glossary
• Blind(ed) study (Syn: masked study): A study in which
observer(s) and/or subjects are kept ignorant of the group
to which the subjects are assigned, as in an experimental
study, or of the population from which the subjects come,
as in a nonexperimental or observational study. Where
both observer and subjects are kept ignorant, the study is
termed a double-blind study. If the statistical analysis is
also done in ignorance of the group to which subjects
belong, the study is sometimes described as triple blind.
The purpose of "blinding" is to eliminate sources of bias.
(Diagnosis, Harm, Therapy)

51. Glossary
• Exclusion Criteria: Conditions which
preclude entrance of candidates into an
investigation even if they meet the inclusion
criteria.
• Reproducibility (Repeatability,
Reliability): the results of a test or measure
are identical or closely similar each time it
is conducted.

52. Glossary
• Gold Standard: Accepted reference
standard or diagnostic test for a
particular illness.
• Sensitivity: The probability of the test
finding disease among those who have
the disease or the proportion of people
with disease who have a positive test
result.
• Sensitivity = true positives / (true
positives + false negatives)

53. Glossary
• Specificity: The probability of the test
finding NO disease among those who
do NOT have the disease or the
proportion of people free of a disease
who have a negative test.
• Specificity = true negatives / (true
negatives + false positives)

54. Glossary
• Positive Predictive Value (PPV): The percentage
of people with a positive test result who actually
have the disease.
• Positive predictive value = true positives / (true
positives + false positives)
• Negative Predictive Value (NPV): The percentage
of people with a negative test who do NOT have
the disease.
• Negative predictive value = true negatives / (true
negatives + false negatives)

55. Glossary
• Likelihood Ratio: The likelihood that a
given test result would be expected in a
patient with a disease compared to the
likelihood that the same result would be
expected in a patient without that disease.

56. Glossary
• Likelihood Ratio Positive (LR+): The odds that a
positive test result would be found in a patient
with, versus without, a disease.
• Likelihood Ratio Positive (LR+) = Sensitivity / (1
- Specificity).
• The probability of a test result being positive in a
person with the disease divided by the probability
of a test result being positive in a person without
the disease.
• LR(+) = [TP / (TP + FN)] / [FP / (FP + TN)]

57. Glossary
• Likelihood Ratio Negative (LR-): The odds that a
negative test result would be found in a patient
without, versus with, a disease.
• Likelihood Ratio Negative (LR-) = (1- Sensitivity)
/ Specificity.
• The probability of a test result being negative in a
person who has the disease, divided by the
probability of a negative test result in a person
who doesn't have the disease.

58. Glossary
• Griffiths Mental Development Scales :
• During the 1960s the Griffiths scales, which were
originally designed to measure children from birth
to two years, were extended to cover birth to eight
years and a sixth scale (Practical Reasoning) was
added to the five scales comprising the measure
for the early years. The first edition was published
in 1970 and revised in 1984. The third and most
current edition was published in 2006.

59. Glossary
• The six sub-scales are:
• Sub-scale A: Locomotor: Gross motor skills
including the ability to balance and to co-ordinate
and control movements.
• Sub-scale B: Personal-Social: Proficiency in the
activities of daily living, level of independence and
interaction with other children.
• Sub-scale C: Language: Receptive and expressive
language.

60. Glossary
• Sub-scale D: Eye and Hand Co-ordination:
Fine motor skills, manual dexterity and visual
monitoring skills.
• Sub-scale E: Performance: Visuospatial skills
including speed of working and precision.
• Sub-scale F: Practical Reasoning: ability to
solve practical problems, understanding of basic
mathematical concepts and understanding of moral
issues.

61. CONGRATULATION
To Dr.Sameer , his
team and our
department.

62. THANK
YOU FOR
YOUR
ATTENTIO