Journal club222 EEG as predictive tool for development

Journal clubYassin M. Al-saleh

Dr.Sumahya Al-hajjaj

)انما يخشى الله من عباده

العلماء(

بسم الله الرحمن الرحيم

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.

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.

INTRODUCTION• Electroencephalographic (EEG)

abnormalities can be used to aid outcome prediction for infants with HIE.

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.

METHODOLOGY• Study Design:

• The prospective study was conducted in a large maternity service with 6000 deliveries per year.

• Between May 2003 and May 2005

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.

METHODOLOGY• After recruitment, EEG electrodes were

applied to the scalp.

• Recordings were commenced as soon as possible after birth, generally within 6 hours.

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.

METHODOLOGYEEG 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

METHODOLOGY• All patient identifiers were removed.

• The segments were stored as separate files and then were visually analyzed separately by a neurophysiologist .

METHODOLOGY• Clinicians were blinded to all EEG data,

and antiepileptic medications were administered if seizures were suspected clinically.

METHODOLOGYStatistical 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.

RESULTS Study Group

• In total, 54 infants with clinical HIE were recruited soon after delivery.

• Of those, 50 had early, continuous, video-EEG recording performed during the first 3 days of life.

• Forty-four infants completed neurodevelopmental followup.

• Of those, 20 (45%) had abnormal outcomes.

54

50

38/12

48

44

2

4

24 20

RESULTS

RESULTSEEG Grades

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

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

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%.

RESULTSEvolution 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.

RESULTSIndividual 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.

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.

Critical apprasial

PICO• Population: term infants (37 weeks of

gestation) with HIE.

• Intervention: EEG recording.

• Control: clinical assesment.

• Out come:prediction of outcome in HIE

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

Relevance

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

yes

Are the Results of the Study Valid?

• Was the assignment concealed?

Yes

• Was follow-up complete& long enough?

YES

• Sensitivity analysis (WCS)

NO


Were all clinically important outcomes considered?

yes


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


• Did the patient sample include an appropriate spectrum of patients to whom the diagnostic test will be applied in clinical practice?

• yes


• Did the results of the test being evaluated influence the decision to perform the reference standard?

• NO


• Were the methods for performing the test described in sufficient detail to permit replication?

• YES

What Were the Results?

• Are likelihood ratios for the test results presented or data necessary for their calculation provided?

• YES

calculation

• 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

At 6h standered

abnormal not

EEG

abnormal 9 4 13

not 0 13 13

9 17 26

refernace

+ -

Test result

+ a b

- c d

PPV

NPV

calculation

At 6h standered

abnormal not

EEG abnormal 9 2 11

not 0 15 15

9 17 26

refernace

+ -

Test resul

t

+ a b

- c d

Likelihood Ratio for Positive Test (LR+) 4.16

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.


• Are the results applicable to my patient?

• Similar distribution of disease severity? (spectrum)

• YES.


• Will the results change my management?

• Test and treatment thresholds? (is it between)

• YES.

• High or low LR's?


• Will patients be better off as a result of the test?

• Is target disorder dangerous if left undiagnosed?

• YES.

• Is test risk acceptable?

• YES


• Does effective treatment exist?

• YES.

• Information from test will lead to change of Management beneficial to patient?

• YES.

Glossary • Cohort study: Follow-up of exposed and

non-exposed defined groups, with a comparison of disease rates during the time covered. ( Harm, Prognosis)

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)

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.

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)

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)

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)

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.

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)]

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.

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.

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.

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.

To Dr.Sameer , his team and our department.

CONGRATULATION

THANK YOU FOR YOUR ATTENTION

Health & Medicine

Journal club222 EEG as predictive tool for development