Karnataka Paediatric Journal Vol. 28, No. 1 ; Jan - March 2013

Karnataka Paediatric Journal Vol. 28, No. 1 Jan - March 2013

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Karnataka Paediatric Journal Vol. 28, No. 1 ; Jan - March 2013

Journal of the IAPKarnataka State Branch

CONTENTS

1. President�s Message 3

2. A study on cord blood troponin in perinatal birth asphyxia 4

Dr.Anas Mohamed*, Dr.Chandrashekar*, Dr.Santhosh Soans*,Dr.Divakar Rao

Dr. Pavan Hegde#, Dr.Saleeqath V*

3. �Clinical Profile And Outcome Underlying Neonatal Transport From Periphery 10

To A Tertiary Care Center In South India�

Dr. Gaurav Porwal * ,Dr. Ramanath Mahale** Dr. Kanchan Mahale

*Dr. Chetan G* Dr. Rajiv Aggarwal*

4. Effect Of Haart On The Hematological Profile Of Pediatric Hiv Patients 16

Dr.Kamalakshi Bhat, Shwetha Seetharam

5. Tips To Aid The Diagnosis Of Childhood Tuberculosis 21

Dr.Basavaraja G.V., Dr.K.R.Bharath Kumar Reddy

6. Sickle Cell Disease- An Atypical Presentation With Fever And Polyarthralgia 28

Dr Shreeshail V Benakanal, Dr Manjunathaswamy , Dr R B Patil

7. Land Mark Judgement In Neonatology- It Is Time Now To Wake Up 31

Dr. Venkatesh. H.A, Consultant Neonatologist ,Manipal Hospital,Bangalore

8. Transient Abnormal Myelopoiesis - A Case Report 35

Dr Anil Kumar Kh, Drbopanna, Drniranjan.H.S, Dr Naveen Benakappa, Dr.Premalatha.R

9. Tuberous Sclerosis With Rhabdomyoma 38

Dr.Ajay V ,Dr.Vikram Singhal*,Dr.Vardhelli Venkateshwarlu,Dr.Rajesh S M

10. Congenital Myasthenic Syndrome � A Rarity In The Field 41

Dr.Nirupama S, Dr.Koujalgi M B Dr.C R Banapurmath

11. .Multiple Intracranial Mycotic Aneurysms With Rupture: 45

A Rare Neurological Complication In Cyanotic Heart Disease.

Dr. Mysore Satyanarayanaravindra*. Dr. Vijay Keshavraokulkarni

Dr. Gautam Mohan Kabbin , Dr. Poornimakulkarni. Dr. Kavitakonded

EDITORIAL BOARD

Editor in Chief : Editor

Dr. B. Sanjeev Rai Dr. Sudharshan SE-mail : [email protected] E mail: [email protected]. : 94481-33494 Mob: 9880008471

EDITORIAL OFFICEMedicare Centre, Karangalpady, Mangalore - 575 003

MEMBERS : Dr. Santhosh Soans Dr.Sridhar Avabratha Dr. Kamalakshi Bhat

Dr. Vijay Kulkarnia, Dr. Basavaraj Dr.Mahendrappa Dr. G K Gupta Dr.A N Tobbi,

Dr. Veerashanker, Dr. Amarnath K

PAGE No.


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INDAN ACADEMY OF PAEDIATRCSKarnataka State BranchSociety Reg No: EKM � S460-2006-2007

President Secretary Treasurer President Elect – 2013Dr.N.S.MAHANTH SHETTY Dr.BABANNA K HUKKERI Dr.P.SUBBA RAO Dr. NARAYANAPPA

Belgaum :9448157237 Belgaum :9448188212 Mangalore. M: 98458-72653 Mysore M: 9845112560

Historian Joint Secretary Editor K.P.J.Dr. SANTOSH SOANS Dr. PAVAN HEGDE Dr. B.SANJEEV RAI

Mangalore. M: 93435-65558 Mangalore. M: 98450-88116 Mangalore. M: 94481-33494

Executive Board Members

Bagalkot Dr. Ramesh Pattar

Bangalore Urban Dr. Ravishanker M

Bangalore Rural

Belgaum Dr. Tanmaya Metgud

Bellary Dr. B K Srikanth

Bidar Dr.Sanjeev Biradar

Bijapur Dr Sadashiv Ukkali

Chamrajnagar

Chikkamagalur Dr.Ramesh.M.B.

Chikkaballapur

Chitradurga Dr. Basanth P

Dakshina Kannada Dr.Kiran Baliga

Davangere Dr. Madhu Pujar

Dharwad Dr. Vijay Kulkarni

Gadag Dr.Shivkumar I Manvi

Gulburga Dr.Prashanth kulkarni

Hassan Dr. Prasanna Kumar

Haveri Dr.Anand Ingalgavi

Kodagu Dr. Krishnananda,

Kolar Dr.Arun

Kollegal Dr.Sridhar M

Koppal Dr. Anand Kumar.

Address for Correspondence:

DR. B K HUKKERI803,Rana Pratap Road, "C" Scheme, Tilakwadi, Belgaum 59006

Email : [email protected] , iapkarnataka [email protected]

Mandya Dr.G K Gupta

Mysore Dr. Bhaktavastala

Raichur Dr.Basavanagouda Patil

Ramanagar

Shimoga Dr. Yateesh

Tumkur Dr Manjesh

Udupi Dr. Dinesh Nayak

Uttar Kannada Dr Enrita D'Souza.

Yadir

Ex . Officio.

Dr.Suresh Babu , Dr. N.K. Kalappanavar

Central Council Executive Board Members

Dr. . N.K. Kalappanavar Dr. Preeti Galagali

Dr. Subramanya NK.

Mobil: 94498-64828 Mobil: 98452-63322

Mobil: 98451-39149

Zonal Coordinators

Bangalore : Dr. Prahladkumar Dharwad :

Dr. P K Warii

Gulbarga : Dr.R N Vanaki Davangere :

Dr. Dinesh Hegdd Mysore Dr.Mahendrappa


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Indian Academy of Pediatrics is

striving hard for child survival. Despite the

efforts the struggle for child survival needs

to be strengthened. The child survival

strategies and interventions are in line with

MDG No 4 which focused on reducing

child mortality of under five children by 2/

3rd before the year 2015. Every year nearly

10 million children under age five die,

mostly from preventable and treatable

diseases. Nearly 30,000 children die every

day as a result of diseases like pneumonia,

diarrhea and complications during

childbirth. Malnutrition is an underlying

contributor in over half of these deaths.

Similarly, 4 million newborns die in the first

4 weeks of life (40 percent of under -5

deaths). 98 percent of under-5 deaths occur

across only 42 developing countries. India

may have advanced in technology and

known to be one of the largest countries for

Human Resource, but on the darker side it

is contributing to one fifth of the child

mortality in the world, the diseases all

being preventable - Pneumonia, Diarrhea,

Malaria, Measles, Tuberculosis, HIV andNeonatal Deaths. Rightly IAP has actionplans, guidelines has conducted Workshops,CMEs etc. to address all these diseases. Agreat achievement is involvement of healthcare policy makers and in establishingPublic Private Partnerships (PPP). To reduceneonatal mortality we have the NSSK andNRPFGM Program - a perfect example ofPublic Private Partnership. We also have thePALS & NALS Program. In Karnataka weare fortunate to have the Bal SanjeevaniScheme to take care of these problems. Thisyear's action plan of IAP is to help GoI in aPPP model to take on important majorkillers like pneumonia, diarrhea, measles,TB, malnutrition, lack of immunization, andother infectious diseases in a 'bundled'

program with a staggered approach

PRESIDENT�S MESSAGE

throughout the country, and quite aptly

described as 'Mission Uday'.

Our job as pediatricians, is to help

the IAP and the Government to implement

these programs and give every child what

he / she deserves.

We also need to look at the other

silent killers like Developmental Problems,

Behavioral Problems, Scholastic backwardness,

Child Abuse, Adolescent Issues, which if we

don't address to-day , we may have reduced

mortality, but not healthy children. I think

what children need to-day is a holistic

development which in the long run is a

good investment for a healthy society.

Pediatricians alone cannot do this. We need

to educate our parents, teachers and society

at large.

Friends I seek your advice and

assistance to help me carry on the mission

of IAP. Let's keep the team spirit of IAP. For

this we need numbers. When I look at the

history of IAP an organization which was

established in 1962 with just 12 members to

have grown to-day to more than 20,000

members in just 50 years, it tells me the

strong heritage and hard work that the

pioneers have put in to make this one of the

strongest heath care association in India.

IAP Karnataka Chapter contributes to less

than 2000 members of this giant organization.

Hence I appeal to all the District Branches

to strengthen their membership.

To conclude, Quotes:

Coming together is a beginning.

Keeping together is progress.

Working together is success.

Jai IAP, Jai Karnataka

Dr. (Mrs) N S Mahantashetti

President IAP Karnataka


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ABSTRACT

Background: Perinatal asphyxia is one

of the most important causes of morbidity

and mortality in neonates. Hypoxia causes

release troponin from cardiac muscles.

Elevated levels of troponin T in cord blood

may be associated with intrauterine

hypoxia.

Objective: To study the relation

between cord blood Troponin T levels in

birth asphyxiated and normal new born and

its correlation between birth weight, mode

of delivery, gestation and sex.

Methods: Cord blood samples were

collected from 45 neonates (15 with birth

asphyxia and 30 normal newborns) and

analysed for pH and cTnT.

Results: A total of 45 cord blood

cTnT samples were analysed (15birth

asphyxia and 30 normalnewborn). Among

the normal new born 60% were males and

40% were females and among the

asphyxiated group 67% were males and

33% were females. The median (interquartile)

gestational age among the normal new born

were 38.5 (37.75-39) weeks and among the

asphyxiated group were 38 (37-39) weeks.

The birth weight of perinatal asphyxia

group was 2826±586.6gm and in the

normal new born were 2689±713.5gm (P

value 0.53). Mean rank score among elective

LSCS was found to be higher than normal

delivery(p=0.2). There was no significant

relation between cTnT levels with birth

weight, mode of delivery, gestation and sex.

The median value for cord blood pH among

asphyxiated group was 6.98 compared to

7.38 among normal new born (p<0.001).

Foetuses with distress had significantly

higher cord troponin T levels than normal

new born 0.13ng/ml versus 0.03ng/ml

(p<0.001).

Conclusions: Cord blood cTnT are

unaffected by sex, weight, gestation & mode

of delivery. New born with foetal distress

had significantly higher cord cardiac

troponin T levels, suggesting that troponin

T may be a useful marker for early detection

of hypoxia in neonates.

Keywords: Cord blood; Troponin T;

Birth asphyxia Birth asphyxia is defined as

a severe disturbance of oxygen supply to

the fetus, which develops during the

first or second stage of labor.1Perinatal

asphyxia will cause hypoxic brain damage.

It is associated with cardiac dysfunction.

This may be secondary to myocardial

ischemia.2Cardiac troponins are very

sensitive markers for the detection of

myocardial damage.1,3 They are also

powerful prognostic indicators of future

adverse cardiac events.1 Cardiac troponin T

is the ideal marker for myocardial necrosis.

1,2 Elevated levels in cord blood may

A STUDY ON CORD BLOOD TROPONIN T IN PERINATALBIRTH ASPHYXIADr.Anas Mohamed*, Dr.Chandrashekar*, Dr.Santhosh Soans*,Dr.Divakar Rao*,

Dr. Pavan Hegde#, Dr.Saleeqath V*

*Dept Of Pediatrics, A J Institute Of Medical Sciences, Mangalore,# Father Muller's Medical College, Mangalore,


5

be associated with intrauterine hypoxia

and increased perinatal morbidity2. Cardiac

troponin T levels in the cord blood are

unaffected by gestation, birth weight, sex,

or mode of delivery.1,2

Maternal cardiac Troponin cannot

cross the placenta because of heavy

molecular weight.4This study is to find

out the level of cord blood cardiac troponin

T in normal neonates and perinatal asphyxiated

neonates. With this study it can be

found whether cardiac troponin T is a

useful marker for myocardial damage or

not.

MATERIALS AND METHODS

Source of Data:

The present study was carried out in

the department of Pediatrics, A.J. Institute of

Medical Sciences, Mangalore from October

2010 to September 2012. This was a hospital

based prospective study in which forty five

cases (15 birth asphyxia and 30 normal

newborn) were included.

Inclusion Criteria:

All newborn babies delivered at A.J.

Institute of Medical Sciences, Mangalore

with perinatal birth asphyxia and Apgar

score (≤ 6 in 5 min) between the period

October 2010 to September 2012 were

included in the study. Cord bloods of

consecutive thirty normal new born babies

were also taken for Troponin T.

During labor fetal cardiac monitoring

was done. Criteria for fetal distress include

fetal heart rate less than 110, fetal heart rate

more than 160, late deceleration, variable

deceleration and amniotic fluid with thick

meconium.

Evidence of asphyxia indicated by the

following feature: (i) Apgar ≤6 at 5 minutes.

(ii) Changes in fetal heart rate (iii)

Meconium stained amniotic fluid.

Exclusion Criteria:

1. Major congenital Cardiac anomalies in

newborn

2. Evidence of prenatal maternal infections

3. Thyroid supplements in mother

4. Glucocorticoid treatment in mother

5. Chromosomal anomaly

Method of Collection of the Data:

All deliveries were attended by post

graduates trained in neonatal resuscitation.

After birth, umbilical cord was double-

clamped and approximately 1 ml of arterial

blood was obtained for pH, and second

sample of umbilical cord blood (2 ml) was

collected in heparinisedvacutainer and send

to the A.J.Hospital laboratory for troponin

measurement. The troponin-T level was

detected by "The Roche Cardiac T

Quantitative test".

Along with that cardiotocography

(CTG) were correlated with cord blood pH

and troponin T. Data on gestation , birth

weight, sex, Apgar score, Ballard score

and mode of delivery were recorded

Statistical analysis: Data was

analysed using Mann Whitney U test, t test,

Fishers exact test, chi square test. Statistical

software SPSS17 & MS Excel was used to

analyses the data. p<0.05 were considered to

be statistically significant.


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RESULT:

Table No. 1: Population characteristics

Variable Healthy New born with perinatal asphyxia

Total number of New born 30 15

Sex Males 18(60%) 10 (67%)

Females 12(40%) 5 (33%)

Maternal age in years 27.5 (24-32.5)* 25 (23-29)*

28.23(5.34)** 25.73(3.73)**

Gestation in weeks 38.5 ( 37.75-39)* 38 (37-39)*

38.23(1.85)** 37.87(1.89)**

Apgar at 5 min 10 (8.75- 10)* 5 (5-6)*

NST Normal 24 (80%) 0(0%)

Dip in heart rate 6 (20%) 15(100%)

Mode of

delivery

Normal vaginal delivery 17 (56.7%) 1 (6.7%)

Assisted normal vaginal delivery

0(0%) 4 (26.7%)

Elective LSCS 10 (33.3%) 1 (6.7%)

Emergency LSCS 3 (10%) 9 (60%)

Meconium stained

Present 1 (3.3%) 15(100%)

Absent 29(96.7%) 0(0%)

Cord

around the neck

Present 0 2 (13.3%)

Absent 30(100%) 13(86.7%)

A total of 45 cord blood cardiactroponin T samples were analyzed; 15 ofthem were collected from infants who werecategorized as having perinatal birthasphyxia. And 30 were included as normalnew born.

Among the normal new born 18(60%)were males and 12(40%) were females andamong the asphyxiated group 10(67%) weremales and 5(33%) were females.

The mean age of the mothers ofnormal new born were 28.23±5.34 years andthe mean age in perinatal asphyxia group

25.73 ± 3.73 years.

Apgar Score in 5

min

Perinatal

asphyxia

Normal new

born

Median 5 10

Q1 5 9

Q3 6 10

IQR 1 1

* Median and interquartile range. ** Mean and standard deviation.

The median (interquartile) gestationalage among the normal new born were 38.5(37.75-39) weeks and among theasphyxiated group were 38 (37-39) weeks.

Table No. 2: Showing the Apgar score

in 5 min in the two study groups


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P value <0.001; p value analysed by Mann

Whitney U test

Q1- 25th percentile;Q3-75th percentile; IQR -

Interquartile range.

Figure No. 1: Box and whisker plots

for cord blood cardiac troponin T

concentration in the normal new born and

those with perinatal asphyxia. (Whiskers

give 5th [in grey] to 95th percentiles, the box

is the interquartile range, and the line

within the box is the median.)

In this study median value for cord

blood cardiac troponin T concentration

among asphyxiated group was 0.13

compared to 0.03 among normal new born

and this difference was found to be highly

statistically significant.

Table No.4: Association between Gender

and cardiac Troponin T concentration

p value 0.73 ; p value analysed by Mann

Whitney U test.

Mean rank score among males was

found to be higher than females, but this

association was found to be statistically

insignificant.

Table No.5: Association between gestational

period and cardiac troponin T concentration

p value 0.75; p value analysed by Mann

Whitney U test.

There is no statistical significant

association for cardiac troponin T concentration

between gestational period less than 37

weeks and more than or equal to 37 weeks.

Table No.6: Association between mode of

delivery and cardiac troponin T concentration

(n=29)

p value = 0.2 ; p value analysed by Mann

Whitney U test.

Mean rank score among elective LSCS

was found to be higher than normal

delivery, but this association was found to

be statistically insignificant.

Table No. 7: The association for cord blood

pH concentration in the normal new born

and those with perinatal asphyxia.Gender Number Mean rank

Male 28 23.36

Female 17 22.41

Gestational age in weeks

Number Mean rank

Less than 37 weeks

7 22

37 and more weeks

38 23.18

Perinatal asphyxia

Normal new born

Median 0.13 0.03

Q1 0.03 0.03

Q3 0.19 0.03

IQR 0.16 0

Mode of delivery Number Mean rank

Normal delivery 18 14.50

Elective LSCS 11 15.82

p value <0.001; p value analysed by Mann

Whitney U test


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Q1- 25th percentile;Q3- 75th percentile; IQR

- Interquartile range.

In this study median value for cord

blood pHamong asphyxiated group was

6.98 compared to 07.38 among normal new

born and this difference was found to be

highly statistically significant.

Table No. 8: Outcome between perinatal

asphyxia and normal newborn.

P value=.0032, analysed by Fishers exact

test.

In this study, 6.7% of the study

subjects expired. Eighty percentage of

outcome were alive in perinatal asphyxia

and in normal newborn 100% were alive.

This differs significantly.

DISCUSSION:

A total of 45 cord blood cardiac

troponin T samples were analysed; fifteen

were from new born having perinatal birth

asphyxia and 30 were from normal new

born. Among the normal new born 18(60%)

were males and 12(40%) were females and

among the asphyxiated group 10(67%) were

males and 5(33%) were females.The median

(interquartile) gestational age among the

normal new born were 38.5 (37.75-39) weeks

and among the asphyxiated group were 38

(37-39) weeks.The birth weight of perinatal

asphyxia group was 2826±586.6gm and in

the normal new born were 2689±713.5gm (P

=0.53).Mean rank score among elective LSCS

was found to be higher than normal

delivery(p=0.2). There was no significant

relation between Cord blood Cardiac

TroponinT levelswith birth weight, mode of

delivery, gestation and sex. This result was

similar withRafati SH et al, Morisson,

Trevisanuto and Turker's studies.5,6,7

Cardiac deceleration in the normal

new born in our study was 20% while in

the perinatal asphyxia group was 100%

which was statistical significant (p <0.001).

However, Clark SJ and co-worker8found

only 25 % of normal new born and 37% of

new born in birth asphyxia had cardiac

deceleration.All newborn with perinatal

asphyxia had meconium staining while in

normal new born only 3.3% had meconium

staining which was statistically significant (

p value <0.001).

In the present study, cord blood for

Troponin-T level was 0.13ng/ml in perinatal

asphyxia group and 0.03ng/mlin normal

new born group which was statistically

significant(p<0.001). Adamcová et al in their

study of the cTnT in the cord blood of

newborn suggested that its increase would

indicate foetal distress and myocardial

compromise. They evaluated cord blood

cTnT in 15 healthy term newborn and

found plasma concentrations of

0.05±0.04ng/mL in 10 of the 15 infants

studied. Among these, five new born

showed higher concentrations of cTnT (0.1

9 ± 0.07ng/mL).9

In the present study, the median

value for cord blood pH among

Group Outcome Total (%)

Alive(%) Expired (%)

Perinatal asphyxia

12(80) 3(20) 15(100)

Normal 30(100) 0(0) 30(100)

Total 42(93.3) 3(6.7) 45( 100)


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asphyxiated group was 6.98 compared to

7.38 among normal new born and this

difference was found to be highly

statistically significant (p<0.001). Rafati SH

and co researcher noticed, infants with

foetal distress had lower pH levels that was

significantly different from those of without

foetal distress (p value = 0.002). This was

consistent with Morrison's study, which

showed neonates who had lower pH had

higher troponin level.10

CONCLUSION

There was no relation between cord

blood troponin T levels with mode of

delivery, sex, age and gestation.Infants with

fetal distress had lower pH levels that were

significantly different from those of without

fetal distress.. New born with foetal distress

had significantly higher cord cardiac

troponin T levels, suggesting that troponin

T may be a useful marker for early detection

of hypoxia in neonates.

BIBLIOGRAPHY

1. Correale M, Nunno L, Ieva R, Rinaldi

M, Maffei G, Magaldi R. Troponin in

Newborns and Pediatric Patients.

CardiovascHematolAgents MedChem

2009;7:270-78.

2. Clark S, Newland P, Yoxall C,

Subhedar N. Cardiac troponin T in

cord blood. Arch Dis Child Fetal

Neonatal Ed 2001;84: F34-F37.

3. Lefèvre G. Troponins: biological and

clinical aspects. Ann BiolClin 2000;58:

39-48.

4. Lipshultz SE, Simbre VC, Hart S, Rifai

N, Lipsitz SR, Reubens L. Frequency of

elevations in markers of cardiomyocyte

damage in otherwise healthy

newborns. Am J Cardiol 2008;102:761-

66.

5. TrevisanutoD,Zaninotto M, Altinier S,

PlebaniM, ZanardoV. Cardiac troponin

I, cardiac troponin T and creatine

kinase MB concentrations in umbilical

cord blood of healthy term neonates.

ActaPaediatr 2003;92:1463-67.

6. Morrison J, Grimes H, Fleming S,

Mears K, McAuliffe.Fetal cardiac

troponin I in relation to intrapartum

events and umbilical artery pH.Am J

Perinatol 2004; 21:147-52.

7. Türker G, Babao?lu K, Duman C,

Gökalp A, Zengin E, Arisoy AE. The

effect of blood gas and Apgar score

on cord blood cardiac troponin I. J

Matern Fetal Neonatal Med 2004;16:315-

19.

8. Clark S, Newland P, Yoxall C,

Subhedar N. Concentrations of cardiac

troponin T in neonates with and

without respiratory distress. Arch Dis

Child Fetal Neonatal Ed 2004;

89:F348-52.

9. Adamcová M,Kokstein Z, Palieka V,

PodholováM, KostálM. Troponin T

levels in the cord blood of healthy

term neonates. Physiol Res 1995;44:99-

104.

10. Rafati SH, Rabi M, AKhavirad MB,

Sharifzade F. Relations Between

Umbilical Troponin T Levels And

Fetal Distress. SEMJ2012;13:53-92.


10

ABSTRACT:

Objective: To identify the clinical

profile and outcome underlying the

transport of sick neonates from peripheral

hospitals to a tertiary care center.

Study Design: Neonates referred from

local hospitals and nursing homes in

Bangalore were prospectively enrolled for

18months (May 2007 to November 2008).

They were evaluated for various risk factors

and treated accordingly in a level III

Neonatal Intensive Care unit.

Results. Out of 125 neonates enrolled

during the study period, 55% were males

and 45% were females. Only 36% of the

babies were preterm and the rest were term

babies. Only 18.4% were brought in an

ambulance to the hospital. The rest used

public transport or private vehicles.

Hypoglycemia (42.2%) and Hypothermia

(42.2%) were the most common risk factors

encountered in preterm newborns, whereas

Hypoxia (33.3%) was most common in term

neonates. Multivariate logistic regression

done for the risk factors to predict outcome

found Hypoxia to be a significant predictor

of mortality.

Conclusions: Transport of sick

newborns to a referral centre is far from

satisfactory in our region and there is a

pressing need to create awareness and

change current practices in developing

countries like India.

Keywords: Neonates, Neonatal

transport, Prematurity

Introduction:

Neonatal intensive care, a branch of

Pediatrics is an emerging specialty in India.

It is still a paradox that in spite of so much

interest in neonatal care among Pediatricians,

the National Neonatal Mortality rate (NMR)

continues to remain alarmingly high. The

current neonatal mortality rate of 44 per

1000 live births accounts for two thirds of

the infant mortality in India and translates

into at least two newborn deaths every

minute somewhere in this vast country.1

Majority of the causes of neonatal morbidity

are preventable. Most of the out born

babies that require referral are not stabilized

sufficiently and sent to the next higher

centre in a poor condition thus increasing

the morbidity and mortality. The high

mortality is attributed to delay at three

levels 2, 3 ; delay in recognition of severity

of illness, delay in transport of the neonate

and delay in delivery of appropriate health

care. The present system of referral and

transport of mother or neonate is far from

satisfactory. Transport of high risk mother's

to a tertiary care centre is not encouraged

and newborns are referred to a higher centre

only after they are born. The data on the

current status of neonatal transport in India

shows the virtual absence of medical

personnel, emergency care facilities and

**Dept of Pediatrics Srinivas Institute of Medical Sciences, Srinivasnagar, Surathkal, Mangalore,E-mail:[email protected]

*Dept of Pediatrics Narayana Hrudayalaya Institute of Medical Sciences,Bangalore,

CLINICAL PROFILE AND OUTCOME UNDERLYING NEONATAL

TRANSPORT FROM PERIPHERY TO A TERTIARY CARE CENTER

IN SOUTH INDIADr. Gaurav Porwal * ,Dr. Ramanath Mahale** Dr. Kanchan Mahale * Dr. Chetan G* Dr. Rajiv Aggarwal*


11

monitoring 4. We undertook a study to

determine the clinical profile and risk

factors underlying neonatal transport that

were referred to a tertiary care hospital.

Material & Methods:

This prospective cross-sectional study

was conducted at our level III neonatal unit

from May 2007 to November 2008. The

Neonatal Intensive care unit at Narayana

Hrudayalaya Institute of Medical Sciences

serves as a tertiary care center of referral

from various surrounding districts of

Karnataka and many bordering districts of

Tamilnadu and Andhra Pradesh. It is an 8

bedded neonatal intensive care unit which

is well equipped with facilities for

mechanical ventilation and advanced

hemodynamic monitoring and support. All

out born neonates admitted to NICU at

Narayana Hrudayalaya during the

designated study period were included. All

in born neonates, babies referred with lethal

congenital malformations, referred for

surgical problems, with structural cardiac

disorders, neonates who were brought dead

and moribund neonates with an explicit

physician decision not to provide life

support made at the time of NICU

admission were excluded. A detail history

was elicited from the caretakers of the

admitted baby and a thorough examination

was done to evaluate the condition of the

baby and recorded in a standard format.

Gestational age estimation was done using

New Ballard scoring system. Usual

measurement of saturation, blood pressure

and random blood sugar measurement

(GRBS) was done at the time of admission

for all neonates. All the data collected over

the 18 months of study period was entered

in a Microsoft Excel sheet. Descriptive

statistical analysis was done. Results on

continuous measurements were presented

on Mean SD (Min-Max) and results on

categorical measurements were presented in

Number (%). Significance was assessed at 5

% level of significance. Chi-square 2x2,

2x4,2x3 Fisher Exact test was used to find

the significance of study parameters on

categorical scale between two groups.

Computer generated software was used to

analyze the data.

1. Observations:

In this prospective cross sectional

descriptive clinical study, 125 newborns

were enrolled over a period of 18 months.

The demographic and clinical profile, of the

newborns studied were as mentioned in

Table 1 & 2.

Table 1: Demographic profile of the Newborns.

BASIC CHARACTERISTICS

NUMBER (n=125)

PERCENTAGE

<24hrs 65 52

24 � 7 days 40 32

Age at presentation

>7days 20 16

Male 69 55.2 Gender

Female 56 44.8

<1kg 3 2.4

1 � 1.49kg 10 8

1.5 � 2.5kg 37 29.6

Birthweight

>2.5kg 75 60

Preterm 45 36

Term 77 61.6

Gestational age

Postdated 3 2.4

Total 125 100


12

Table 2: Clinical profile of the Newborns. babies were brought in an ambulance.

Among the others 21 used public transport

and 81 used some form of private transport.

Most of them (68.8%) had to travel about

10 - 50 kms distance. Only 20% of the babies

were brought from far place (>100kms).

Most of the babies were LBW ( Low

Birth Weight) (40%). Prematurity (36%)

was the most common reason for referral. A

major chunk was found to be Septic (34.4%).

Other common neonatal problems like MAS

(Meconium Aspiration Syndrome) (25.6%),

birth asphyxia (19.2%), Jaundice (19.2%),

Metabolic (18.4%), IUGR (Intra Uterine

Growth Retardation) (16%), RDS

(Respiratory Distress Syndrome) (13.6%) and

seizures (8.8%) were also noted. Among the

risk factors studied at admission hypothermia

(37.6%) was the most common, followed by

hypoperfusion (28.8%), hypoglycemia (28%)

and hypoxia (25.6%). In the management of

these newborns 68(54.4%) babies required

level III NICU care whereas the rest could

be managed at level II care. There were no

deaths in the babies managed in level II

care but among the babies managed in

level III care 16(23.5%) died (p<0.001). The

mean duration of hospital stay among the

survived was 10.06±11.94. Among the

babies who died the mean duration of

hospital stay was 5.68±4.93 (p=0.151).

Multivariate logistic regression done for the

risk factors to predict outcome found

Hypoxia as significantly predicting the

mortality, while hypoglycemia and

hypothermia were positively associated with

mortality but were not statistically

significant

CLINICAL CHARACTERISTICS

STANDARD PARAMETERS

NUMBER (n=125)

PERCENTAGE (%)

>35.6 78 62.4 Temperature( ? C)

<35.6 47 37.6

<120 14 11.2

120 � 160 92 73.6

Heartrate

(per minute)

>160 19 15.2

<30 8 6.4

30 � 60 87 69.6

Respiratory rate

(per minute)

>60 30 24.0

? 30 105 84.0

20 - 29 18 14.4

MBP (mmHg)

<20 2 1.6

<3 89 71.2 CFT (Secs)

>3 36 28.8

<88 32 25.6 SPO2

>88 93 74.4

<45 35 28.0 GRBS

? 45 90 72.0

Felt 94 75.2

Feeble 24 19.2

Peripheral Pulse

Absent 7 5.6

Pink 71 56.8

Pale 31 24.8

Acrocyanosis 17 13.6

Colour

Central Cyanosis 6 4.8

Almost all the babies were delivered

in hospitals. There was no baby who was

delivered at home. Sixty four babies were

delivered by cesarean sections. Most of the

babies (75%) did not require any form of

resuscitation as per the records. Only 23


13

Table 3: Association of Risk factor with

mortality

2. Discussion:

Each year 20% of the world's infants

(26 million) are born in this vast & diverse

country5. Of these 1.2 million die before

completing the first four weeks of life, a

figure amounting to 30% of the 3.9 million

neonatal deaths worldwide 6. ICMR (Indian

council of Medical Research) Young Infant

Study Group8 in their cross sectional study

of age profile of neonatal death collected

retrospectively for one year reference period

on 30,473 births found 1521 neonatal

deaths and 2218 infant deaths from five

rural sites in India. Of all the neonatal

deaths, 39.3% occurred on first day of life

and 56.8% during the first three days. This

study highlights the importance of first

three days as the most risky phase in life. It

has been universally accepted that the

treatment of sick newborns in specialized

neonatal intensive care units leads to

decrease in mortality and morbidity 7. The

report from the National Neonatal-Perinatal

Database (NNPD) 1 for the year 2002-03

shows a mortality rate of 16.9% among

extramural neonates . These data provide

chilling evidence that there is a 6.7 fold

higher risk for infant death among neonates

referred to a tertiary institute, as compared

to those who are in-born. Most of these

causes of neonatal mortality are preventable.

The demographic profile of the

newborns studied was similar to the data

from other published studies in literature

9,10,11,12,13. The data on the current

status of neonatal transport in India shows

the virtual absence of medical personnel,

emergency care facilities and monitoring.

Many of the babies transported in this way

are cold, blue and hypoglycaemic and 75 %

of babies transferred in this way have

serious clinical complications6.

The observations and conclusions of

the various studies related to neonatal

transport is given in the chart below:

RISK FACTORS STUDIED WITH MORTALITY

NUMBER OF PATIENTS

NUMBER OF PATIENTS DIED

% OF MORTALITY

P VALUE

Hypoglycemia 35 7 20.0

Normoglycemia 90 9 10

0.145

Hypothermia 47 10 21.3

Normothermia 78 6 7.7

0.028*

Hypoxia 32 9 28.1

Non hypoxic 93 7 7.6

0.005**

Hypoperfusion 36 9 25

Normal perfusion 89 7 7.9

0.016*

SL No: STUDY OBSERVATIONS CONCLUSIONS

1. Kumaret al 4 Biochemicaland Temperature disturbances are

more common in babies transported on their

own.Survival was 89% compared to 96.2% in

babies transported by specialised neonatal

transport service.

2. Singh H et al10 Common indications for referral:

hyperbilirubinemia (35.4%), prematurity

(27.3%),birth asphyxia(17.3%) and sepsis(15.5%)

Mortality was higher in hypothermic

babies(p<0.001)

The outcome of babies referred after 72hrs of

age was unfavourable.

Specialized neonatal

transport service could

improve the survival of

sick babies at birth.

Referral of newborns to

tertiary care centers is far

from satisfactory and

needs improvement.

Standard of high risk


14

Although these studies haveevaluated the common cause of referral to ahospital, data regarding the commonmorbidities due to transport have not beenevaluated. Additionally mode of transportused would be required to plan neonatalreferral services at the community level.Thus transport forms the weakest link in thechain of optimal critical care leading to pooroutcome 3.

The high incidence of risk factors inour study could be explained by poor pre-transport stabilization, lack of awarenessamong the caretakers about maintaining the

temperature. Overall poor transport facilities

could be the most important reason for the

risk factors.

None of these risk factors were found

to be statistically significant. This could

probably be attributed to the varied mode of

transport used and distance travelled to

transfer these newborns. The small sample

size could also have affected the results. A

larger study with controlled transport and

distance travelled could assess the causal

relationship between birth weight and the

above mentioned risk factors in a more

reliable manner

Hence from our study we found

that transport of sick newborns to a referralcentre is far from satisfactory in our regionand there is a pressing need to createawareness and change current practices.Stabilization of newborns prior to transportis grossly inadequate. Appropriatecoordination and communication with thehigher centers is deficient. Lastly an

3. Fok et al11 Clinical condition of neonates on arrival to

tertiary care center showed: Hypothermia

(26.3%), academia (24%), hypercapnia (23.4%),

hypoxaemia (23.4%), central cyanosis (18.7%)

and circulatory failure (15.8%)

4. Shah et al12 Outborn infants admitted to freestanding

pediatric hospitals were at higher risk of

death, nosocomial infection and oxygen

dependency at 28days of age when compared

to outborn infants admitted to perinatal centers.

5. Modi N et al14 Among the reasons for admission: suspected

sepsis (24%), preterm care (14%),

phototherapy(13%), observation of LBW babies

(8%)Among the neonatal deaths: 4% were

inborn and 18% were outborn admissions

Among the causes of deaths: RDS (49%),

lethal Congenital malformations(22%),

Asphyxia (20%) and sepsis(5%)

6. Orimadegun Problems in outborns: Hypothermia (53.6%),

et al 15 Perinatal asphyxia(48.5%), Hemorrhage(26.5%),

Cephalhematoma (12.9%), Prematurity (9.9%)

and neonatal tetanus(4.2%)Outcome of

newborns: Mortality rate of outborns was

12.6% compared to 6.3% in inborn (p= 0.019)

infant transport in the

community is appallingly

unsatisfactory which

result in unwarranted

mortality and morbidity.

Outborn infants had

better outcomes if they

were admitted to

perinatal centers.

Although the pattern of

admissions and deaths

still reflects the substantial

problems of suspected

sepsis, asphyxia, and

congenital malformations,

problems of immaturity

may be on the increase.

Outborn babies who

were referred had greater

risk of morbidity than

inborn

SL No: STUDY OBSERVATIONS CONCLUSIONS


15

alarming number of the ambulances/transport vehicles in use, lack incubators,oxygen supply, neonatal ventilators, facilityfor intravenous fluid administration andmost importantly skilled medical staff. Thisinvariably results in temperatureinstabilities, hypoxia, hypoglycaemia andhypoperfusion during transport. Multiplefactors are responsible for this situation like,lack of awareness among caretakers,financial constraints, improper transportconditions and lack of skilled manpower.

There is a need to organize awarenessprogrammes among the caretakers and otherpersonnel involved in the neonatal care.Feedback to the referring doctors incorporatingsuggestions for future referrals can help indecreasing the incidence of the more easilypreventable adverse factors. The importanceof early �at risk� identification, in uterotransport, pre-transport stabilization and roleof skilled manpower during transport needsto be stressed upon during educationalprogrammes.

There is also a certain need to developa neonatal transport program to meet thecommunity�s needs, and assist the primaryhealth care institutions and neonatal healthcare providers. A streamlined geographicallystructured and practical, high qualityprogram should be developed which isrelevant to the health care providercommunity and the society-at-large to assurea risk appropriate care for all mothers andinfants with a goal of improving perinatal

outcomes and reducing neonatal mortality.

REFERENCES:

1. Indian Council of Medical Research.

National Neonatal-Perinatal Database

(NNPD), Report 2002-2003.

2. Siddharth Ramji. Transport in community.

Journal of Neonatology. 2005; 19(4): 328-331.

3. Rachna Sehgal, Harish Chellani.

Pretransport Stabilization. Journal of

Neonatology.2005;19 (4): 342-346.

4. Kumar P, Kumar D, Venkatlakshmi A.

Long distance neonatal transport � need of

the hour. Indian paediatrics, 2008; 45: 920-922.

5. Registrar General of India: Census of India

2011, Advance release calendar. Available

from: www.censusindia.net. Accessed on

march 18 ,2012.

6. Black RE, Morris SS, Bryce J. Where and

why are 10 million children dying every

year?Lancet. 2003; 361:2226-34.

7. Kumar PP, Kumar CD, Shaik FA, Ghanta

SB, Venkatalakshmi A. Prolonged neonatal

interhospital transport on road: Relevance

for developing countries. Indian J Pediatr.

2010; 77(2): 151-154.

8. ICMR YOUNG INFANT STUDY GROUP.

Age Profile of Neonatal Deaths. Indian

Pediatr. 2008; 45: 991-994.

9. Pankaj Garg, Rajeev Krishak, D.K. Shukla.

NICU in a community level hospital.

Indian J Pediatr.2005; 72: 27-30.

10. Singh H, Singh D, Jain B K . Transport

of referred sick neonates: How far from

ideal? Indian Pediatr. 1996;33: 851-853.

11. T F Fok, S P Lau. High risk infant

transport in Hong Kong. The bulletin-

journal of the Hong Kong medical

association. 1984; 36: 39-45.

12. Shah P, Shah V, Qiu Z. Improved

outcomes of outborn preterm infants if

admitted to perinatal centers versus

freestanding pediatric hospital. The

Journal of Pediatrics. 2005; 146 : 626-31.

13. Samuel N Obi, Benson N Onyire. Pattern

of neonatal admission and outcome at a

Nigerian Tertiary health Institution. OJM.

2004: 16 (3 & 4): 31-37

14. Modi N, Kirubakaran C. Reasons for

admission, causes of death and costs of

admission to a tertiary referral neonatal

unit in India. J Trop Pediatr. 1995;

41(2):99-102

15. Orimadegun AE, Akinbami FO, Tongo OO.

Comparison of Neonates born outside and

inside hospitals in a Children Emergency

Unit, Southwest of Nigeria. Pediatric

Emergency Care. 2008; 24(6):354-358


16

Abstract

Objective: To study the effect of

HAART on the haematological profile in

pediatric HIV patients. Study Design:

Prospective hospital based cross sectional

study. Patients: 40 children between 2-15

yrs of age with HIV who are eligible for

HAART based on WHO recommendations

with baseline blood counts and transaminases

within the normal range were studied for a

period of 6 months. Results: Out of 40

children, with a mean age of 8.63 years,

who were a part of this study, one child

expired after completing 3 months of

HAART and 2 children who were on

zidovudine , had to have drug substitutions

due to severe anemia. A significant rise in

the mean hemoglobin levels was noted. One

case developed thrombocytopenia (51,000/

cumm) after 3 months of HAART. A

significant fall in the mean hemoglobin

from 10.3mg/dl to 9.6mg/dl was seen in

those children who were on zidovudine as

compared to a rise in the hemoglobin level

seen in those who were not on the drug.

Conclusion: HAART improves the

hematological parameters especially

haemoglobin and CD4 counts. Inclusion of

zidovudine in the HAART has a higher

incidence of drug induced anemia.

Neutropenia (ANC<500/cumm) was not

seen in any of the cases.

Key Words: HAART,

Haematological, HIV, Paediatric

The introduction of highly active anti

retroviral therapy (HAART) has led to

substantial reduction in morbidity and

mortality and many regimens result in near-

complete suppression of HIV-1 replication.

HAART prolongs the life of the patient but

associated adverse effects influences

compliance to treatment and quality of life

of the patient. Frequent and early monitoring

for these toxicities is warranted in

developing countries where HAART is

increasingly available.

METHODS

The study was carried out at

Government Wenlock Hospital and Kasturba

Medical College Hospital, Attavar. Forty

children aged between 2-15 years who are

diagnosed cases of HIV and are eligible for

HAART based on WHO recommendations

with baseline blood counts and transaminases

within the normal range. Children with pre

existing abnormal complete blood count i.e

Hb less than 7.5g/dl, ANC less than 500/

cumm, platelet count less than 100,000 were

excluded from the study. Informed consent

was obtained from the families and

approval was obtained from the Time Bound

Research Ethics Committee.

The history and physical examination

findings were recorded in a proforma. 2ml

EDTA venous blood samples was collected

following informed written consent. Baseline

complete blood counts and CD4 counts was

done for each of the included cases.

Children were then started on HAART

according to WHO recommendations.

EFFECT OF HAART ON THE HEMATOLOGICAL

PROFILE OF PEDIATRIC HIV PATIENTS*Dr.Kamalakshi Bhat,Dr. Shwetha Seetharam

*Department of Pediatrics, KMC, Mangalore, Manipal University


17

Cases were evaluated after 3 months

and 6months of therapy . Evaluations

included clinical assessment, laboratory tests

and physical examination. Blood analysis at

each visit included complete blood count

(hemoglobin, total count, platelet count) and

peripheral smear. Hemoglobin =7.5g/dl,

platelet count =100,000cells/cumm and

ANC = 500/cumm1 is considered to be

significant.

Statistical analysis

The data was analyzed with the

Statistical Package for Social Sciences

program (version 11.5) (SPSS, Chicago, IL,

USA). Paired T test was used to compare

the baseline hemoglobin, total count and

platelet levels to the levels after starting

HAART. P value of less than 0.05 is

considered to be significant.

RESULTS

40 children, [22(55%) males, 18(45%)

females] with a mean age of 8.63 years were

a part of this study. Of these 10(25%),

24(60%) and 6(15%) were placed in stage 2,

3 and 4 of the WHO clinical classification1,

respectively. One child expired after

completing 3 months of HAART. 3 children

had to have drug substitutions; two due to

severe anemia, both of whom were on

zidovudine (after 3 months in one case and

after 5 months in the other), and one due to

nevirapine induced Steven Johnson�s

syndrome. Compliance to HAART was

>95% in all cases, according to data

collected from the ART center in

Government Wenlock Hospital. Children

were given fixed drug combinations (FDC)

as per WHO and NACO recommendations2

(Table I).

Table I Differentiation of Cases

according to Fixed Drug Combinations

The most commonly used regimen

was a combination of stavudine, lamivudine

and nevirapine.

The effect of ART on various

hematological parameters is shown in Table

II.

Table II Differences in Various Parameters

after 6 Months of ART

One case developed thrombocytopenia

(51,000/cumm) after 3 months of HAART.

However, the sample was taken when the

child was admitted with sepsis and the

child expired shortly afterwards.

As two children, who were on

zidovudine, required drug substitution,

further analysis of those on zidovudine was

done (Table III).

Fixed Drug Combinations (FDC)

(n=40) No.of Cases

%

Zidovudine, Lamivudine, Nevirapine 4 10

Zidovudine, Lamivudine, Efavirenz 2 5

Lamivudine, Stavudine, Nevirapine 30 75

Lamivudine, Stavudine, Efavirenz 4 10

Parameter

Before starting HAART

After 6 months of HAART

P Value

Mean weight (kg) 19.26 21.08 <0.001 Mean Hemoglobin(mg/dl) 9.8 10.82 <0.001

Mean ANC/cumm 3269 2560 0.014

Mean CD4 count/cumm 428 836

<0.001

Mean platelet count/cumm 2.18 lakh 2.14 lakh

0.667


18

Table III Analysis of Various Parameters in

Cases on Zidovudine vs Stavudine

*n=6

+N=34

This analysis revealed a fall in the

mean hemoglobin from 10.3mg/dl to 9.6mg/

dl as compared to a rise in the hemoglobin

level as seen in those children who were

not on zidovudine. This fall in the

hemoglobin level was significant (P value

0.006). However there was no significant

neutropenia noted in this group.

DISCUSSION

In a meticulously conducted review

on the global prevalence of HIV-associated

anemia, Calis et al reported that anemia

was a common complication occurring in

50�90% of children living with HIV in both

resource-limited and resource-rich settings

and that anemia prevalence was over three

times higher among these children when

compared with those without HIV infection.3

Recent studies show that anemia is an

independent predictor of mortality among

children with HIV infection4.

The numerous etiologies of anemia

among children with HIV have been well

summarized3,5. Common causes include

nutrient deficiencies, HIV-mediated

suppression of erythropoiesis, drug effects,

other opportunistic infections and HIV-

associated malignancies. In developing

countries, nutritional deficiencies are mainly

seen, especially iron, folic acid, zinc and

vitamin A deficiencies6.

The beneficial effect of ART on

anemia and growth parameters has been

demonstrated previously7. A large analysis

from South India that included a cohort of

295 children (mean age, 7.6 years; median

baseline CD4 percentage, 14%) who were

newly initiated on ART reported that

baseline prevalence of anemia (Hb < 11gm/

dL) was 66%. Within just 6 months of ART

initiation, a significant increase in hemoglobin

and weight gain (1.6 gm/dL and 2 kg,

respectively) was noted8. In the present

study we have recorded baseline anemia

prevalence of 77% with an increase in

hemoglobin and weight gain of 1gm/dl and

1.8kg respectively after 6 months of HAART.

The significant increase in CD4

count observed in this study replicates the

findings of some Indian studies9,10 which

show a rise in CD4 count paralleled by a

similar rise in ALC. Studies have

demonstrated that a reliable relationship

exists between ALC and CD4 counts11 as

well as the suitability of the use of ALC in

the absence of CD4 counts12.

Infectious complications of

neutropenia generally occur when

neutropenia is severe (ANC <250 cells/

mm3) and prolonged. Neutropenia as a

complication of ARV therapy is most often

attributed to the use of ZDV. In other cases,

neutropenia may be attributable to bone

marrow suppression secondary to non-ARV

drug toxicity, as can be seen with

trimethoprim-sulfamethoxazole, ganciclovir,

rifabutin, or hydroxyurea. Our data analysis

yielded a fall in the ANC which was

significant but not in the range of

neutropenia. Analysis of the children on

Parameter On Zidovudine

Mean Std Deviation

P value

YesÖ 10.3 1.7 .405 Baseline Hemoglobin

NoÈ 9.7 1.4 .475

Yes 9.6 1.2 .006 Hemoglobin after 6 months

No 11.0 1.0 .039

Yes 6495 4392 .402 Baseline ANC

No 5264 3075 .535

Yes 5445 3253 .489 ANC after 6 months

No 4645 2455 .587


19

zidovudine also did not yield any

significance with respect to ANC. This fall

in the ANC may be attributed to underlying

infections at the time of enrollment into the

study which resolved with improved

immunity following 6 months of HAART

treatment.

Thrombocytopenia (platelet count

<100,000 cells/mm3), like anemia and

neutropenia, is relatively common in

children with HIV infection13.

Thrombocytopenia is most likely a

complication of HIV infection, and not a

complication of ARV therapy. Children with

undiagnosed and untreated HIV infection

may present with thrombocytopenia as the

first manifestation of disease. This appears

to be much more common than the

development of thrombocytopenia secondary

to ARV therapy14. Thrombocytopenia may

resolve once ARV therapy is initiated.

Thrombocytopenia was only noted in one

critically ill case in this study.

In conclusion, HAART has been

seen to improve the hematological

parameters especially haemoglobin and CD4

counts. However, the inclusion of

zidovudine in the HAART has a higher

incidence of drug induced anemia, leading

to requirement of drug substitution later on

in the course of therapy. Neutropenia

(ANC<500/cumm) was not seen in any of

the cases. Platelet counts were not

significantly altered during HAART.

REFERENCES

1. WHO. HIV/AIDS programme:

Antiretroviral therapy for HIV infection

in infants and children:Towards

universal access: Recommendations for

a public health approach Geneva ,

Switzerland 2006: 31-32

2. Manual for management of HIV/AIDS

in children. WHO, UNICEF, IAP,

NACO. 2004-2005. Available from:

URL: http://www.whoindia.org/EN/

Section3/ Section123/ Section375/

Section377_983.htm. Accessed

September 12, 2009.

3. Calis JC, van Hensbroek MB, de Haan

RJ, Moons P, Brabin BJ, Bates I. HIV-

associated anemia in children: a

systematic review from a global

perspective.AIDS 2008,22(10):1099-1112.

4. Markers for predicting mortality in

untreated HIV-infected children in

resource-limited settings: a meta-

analysis. AIDS 2008, 22(1):97-105.

5. Pol R, Shepur TA and Ratageri VH.

Clinico-Laboratory Profile of Pediatric

HIV in Karnataka. Indian J Pediatr

2007; 74 (12) : 1071-1075

6. Eley BS, Sive AA, Abelse L, Kossew G,

Cooper M, Hussey GD: Growth and

micronutrient disturbances in stable,

HIV infected children in CapeTown.

AnnTrop Paediatr 2002,22(1):19-23.

7. Nachman SA, Lindsey JC, Moye J,

Stanley KE, Johnson GM, Krogstad PA,

Wiznia AA: Growth of human

immunodeficiency virus infected

children receiving highly active

antiretroviral therapy. Pediatr Infect Dis

J 2005, 24(4):352-357.

8. Rajasekaran S, Jeyaseelan L,

Ravichandran N, Gomathi C, Thara F,

Chandrasekar C: Efficacy of

Antiretroviral Therapy Program in

Children in India: Prognostic Factors

and Survival Analysis. J Trop Pediatr.

2009;55(4):225-32.

9. Lodha R, Upadhyay A, Kabra SK.

Antiretroviral Therapy in HIV-1

Infected Children. Indian Pediatr 2005;

42: 789-796.

10. Natu S.A, Daga S.R: Antiretroviral


20

Therapy in Children: Indian Experience.

Indian Pediatr 2007; 44: 339-343

11. Shapiro NI, Karras DJ, Leech SH,

Heilpern KL. Absolute lymphocyte

count as a predictor of CD4 count.

Ann Emerg Med 1998; 32: 323-328.

12. Beck EJ, Kupek EJ, Gompels MM,

Pinching AJ. Correlation between total

and CD4 lymphocyte counts in HIV

infection: not making the good an

enemy of the not so perfect. Int J STD

FORM IV

1. Place of Publication : Mangalore

2. Periodicity of its Publication : Quartterly

3. Printer�s Name : Dr. B. Sanjeev Rai

Nationality : Indian

Address : Medicare Centre, Mangalore � 575 003

4. Publisher�s Name : As above

Nationality

Address

5. Editor�s Name : As above

Nationality

Address

6. Name and address of individuals who : The journal is owned by own the

Newspaper, partners and/ or Karnataka. The Indian Academy of Pediatrics State

Share holders, holding more than branch, Medicare Center, Mangalore

one percent of the total capital 575003

I, Dr. B. Sanjeev Rai, hereby declare that the particulars given above are true

to the best of my knowledge and belief.

Mangalore

(Sd/-Dr. B. Sanjeev Rai)

Signature of the Publisher

AIDS. 1996; 7: 422-428.

13. Adewuyi J, Chitsike I. Haematologic

features of the human

immunodeficiency virus (HIV) infection

in Black children in Harare. Cent Afr J

Med, 1994. 40(12):333-6

14. Najean Y, Rain JD. The mechanism of

thrombocytopenia in patients with HIV

infection. J Lab Clin Med, 1994.

123(3):415-20.


21

Introduction

Tuberculosis as a disease has almost

been stagnant in its prevalence since times

gone by. With new challenges each day, this

�master of all diseases� has remained an

enigma to many a clinician. Nearly 4.8

million cases of tuberculosis have been

reported worldwide in a prevalence study

in the early 21st century1 . Of these many

cases, nearly 1.6 million cases belong to the

South East Asian region. Majority of cases

are in the most populous countries of Asia

like Bangladesh, China, India, Indonesia

and Pakistan which account for half (48%)

of the new cases that arise every year.

Diagnosing tuberculosis in children

has always been a challenge for pediatricians.

The confirmation of active tuberculosis and

the difficult question of whether to treat or

not to treat with antitubercular drugs have

troubled pediatricians in every day clinical

practice across the country. Thus, inspite of

advances in the field, establishing a

definitive diagnosis of childhood TB

remains a challenge for various reasons

even in today. Firstly, sputum is rarely

available in children to aid the diagnosis. It

is a tedious procedure for clinicians to obtain

a sputum sample or a gastric aspirate2 .

Secondly, once a sample is obtained, only

20 % of smears of sputum or gastric aspirate

test positive for Acid Fast Bacilli (AFB),

unless 3 consecutive samples are taken

when it increases to 30 -50% 3 . Thirdly,

X-ray abnormalities, which are easily

reported in adult patients, may not be seen

classically in children. Radiological changes

are also not accompanied by symptoms

even if present adding to the confusion in

diagnosis4 . Fourthly, the distinction between

infection and disease not clear, thus, the

distinction between active disease or not

remains at many times a blur. Lastly, the

misplaced faith in that we have in the BCG

vaccine has further added to the problem of

misdiagnosis of tuberculosis5 .

Thus, the diagnosis of tuberculosis

should be based on not any single

parameter but should include a combination

of symptom based diagnosis, a clinical

diagnosis, radiological diagnosis, immunological

diagnosis and microbiological diagnosis.

Each of these holds importance in

establishing a diagnosis in children and

should be considered together to aid

management decisions.

Tip 1 � The diagnosis of Tuberculosis

is a combination of different

parameters

Symptom based diagnosis is

considered by many clinicians due to the

varying false positive and negative rates of

laboratory parameters. A symptom based

diagnosis can be considered in children

presenting with principal history of (1)

Fever � of recent onset lasting for more than

3 weeks. Fever can be of any type in children,

and is non specific. (2) Cough � of recent

inset along with fever is considered a

significant finding. (3) Unexplained weight

loss or loss of appetite in the recent past (4)

History of contact with an adult who is

diagnosed and taking anti-tubercular

medication in the past 2 years and (5) Risk

factors � such an age less than 1 year,

failure to thrive, recent history of measles or

TIPS TO AID THE DIAGNOSIS OF CHILDHOOD TUBERCULOSISDr.Basavaraja G.V., Dr.K.R.Bharath Kumar Reddy

Dept of Pediatric Intensive Care, Indira Gandhi Institute of Child Health, Bangalore


22

pertusis, immunocompromised state and on

treatment with steroids. Table 1 shows the

frequency of various symptoms and signs

with age of the child. In infancy, fever,

cough and hurried breathing are the main

complaints with associated rales. Symptoms

seen in adults such as hemoptysis,

productive cough and night sweats are

relatively rare in children of all ages. Studies

have shown that the most helpful symptoms

in children as per evidence6 include (1)

persistent, non-remittent coughing or

wheezing, (2) documented failure to thrive

despite food supplementation (3) fatigue or

reduced playfulness (4) children with a

persistent (longer than 4 weeks) cervical

mass of 2 cm or more, without a visible

local cause or response to first-line

antibiotics, showed excellent diagnostic

accuracy

A diagnosis of childhood tuberculosis,

however, should not be done in isolation but

requires a combination of symptoms,

radiology, laboratory and microbiological

diagnosis to aid clinical decisions. Thus the

role of various scoring systems established

come to the picture. In low-burden a

country, a triad is often used with includes:

(1) known contact with an infectious source

case, (2) a positive TST, and (3) a suggestive

CXR can be frequently used to establish a

diagnosis of childhood TB. This however is

difficult to apply in endemic areas and

developing countries like India7 . Table 2

shows the various scoring systems used in

the past to aid the diagnosis of childhood

tuberculosis. The principal parameters

considered included presence/absence of

acid fast bacilli, biopsy findings, Mantoux

test, X ray findings, history of contact and

other compatible physical signs.

Table 2 � Various scoring systems considered

for diagnosis of childhood tuberculosis

Osborne et al1 , consider using a

classification of possible, suspected and

definite to aid the diagnosis in children as

shown in Table 3. Definite diagnosis is

always established by demonstration of the

organism.

Table 3 � Classification for the

diagnoses of childhood tuberculosis

Parameters Stengen et ali

Nair et al ii

Seth et aliii

Acid Fast bacilli +3 +5 +5

Tubercle in biopsy +3 +5 +5

Tuberculin test >10mm +3 +3 +3

Suggestive radiology +2 +3 +3

Compatible physical signs +1 +3 +2

Contact with TB +2 +2 +3

Scores: 1- 2 TB unlikely ; 3-4: TB possible; 5-6: TB probable

>7 � TB unequivocal

Suspected Tuberculosis

Any child with history of contact with aconfirmed case of pulmonary TB

Is not gaining normal health after measles,pertusis

Has a loss of weight, cough or wheeze notresponding to antibiotic therapy

Has painless swelling in superficial group oflymph nodes

Possible Tuberculosis � Suspectedtuberculosis with any of the following:

Positive Mantoux test (induration > 10mm)

Suggestive radiological finding

Suggestive histological appearance on biopsy

Favorable response to ATT

Confirmed Tuberculosis

Detection of tubercle bacilli by microscopy orculture

Identification of tubercle bacilli asmycobacterium by culture charcateristics


23

Tip 2 � Family Screening is a

must in all cases of suspected

Tuberculosis

History of contact with pulmonary TB

may not be available always, hence

screening of family plays an important role

in establishing the diagnosis. All family

members who come in contact with the

child, living within the same household or

without, have to be screened with Chest X

ray and sputum examination. Many cases

have been reported where the child may not

fulfill the criteria for the diagnosis of

tuberculosis but family screening have been

shown to be positive and hence aids the

further management. Current guidelines also

concentrate on the treatment of children

who may be asymptomatic but come in

contact with an open case of tuberculosis,

thus necessitating prophylactic treatment of

the child. Figure 1 shows a flow diagram

demonstrating the protocol for the

management of a child exposed to a TB

contact.

Figure 1 � Management of a

child with history of contact with TB

Tip 3 � Remember that atypical

presentations are not that uncommon

Look for the other peripheral markers

of tuberculosis; they can give you a clue to

the diagnosis. It is always known that

extrapulmonary tuberculosis is more

common in children, and hence other forms

of tuberculosis beyond pulmonary

manifestations should be looked for in a

suspected case of tuberculosis. Look for

markers of TB such as a phlycten or

episcleritis in the eye. Look for Tuberculous

osteomyelitis in an adolescent manifesting

as a lytic lesion with an associated

periosteal reaction and minimal sclerosis.

Tuberculosis verrucosa cutis is a lesion with

a warty appearance of the skin which is an

important marker. Tubercular lymphadenitis

is a timeless clue. Scrofuloderma, with

tuberculosis disease of the skin overlying a

caseous lymph node is often described. A

sinus tract can be looked for with

preauricular adenopathy is also present.

Tip 4 � Radiological Diagnosis: Don�t

miss the subtle signs

Despite its many limitations, the

chest X ray remains the most practical and

helpful test in everyday practice. The chest X

ray has been time proven to aid the

diagnosis if only the subtle signs are not

missed. High-resolution computed tomography

is the most sensitive tool currently available

to detect markers such as hilar adenopathy

and/or early cavitation1 . Figure 2 shows

the chest X ray of a 14 year old child with

suspected tuberculosis. Subtle signs which

can be seen in the X ray which would aid

the diagnosis of TB include a (1) Splaying

of the subcarinal angle (2) Mediastinal

widening and (3) Miliary shadows. These

are important radiological markers which

can be missed.

Figure 3 shows the various radiological

findings that need to be looked for in a

child with suspected tuberculosis.


24

Tuberculous pericarditis is diagnosed with

the presence of cardiomegaly, which when

associated with the splaying of the

mainstem bronchi due to adenopathy of

subcarinal lymph nodes, and low lung

volumes, can suggest tuberculous etiology.

Ghon complex can be visible on a simple

Chest X ray as seen in the figure as a right-

sided calcified lymph node with associated

right hilar adenopathy. The third component

of the Ghon complex, regional lymphatic

vessels is generally not visible on radiography.

Consolidation with air bronchogram can

also be a manifestation of TB. Early

cavitation and round pneumonias are

always described. Unilateral hyperinflation

of the lung with flattening of the diaphragm

and herniation of the left lung across the

midline is a described feature. This is

attributed to tuberculous lymph gland

obstruction of the left main bronchus

causing a ball-valve� effect. Miliary shadows

seen in the form of millet sized shadows is

diagnostic of TB in children. However,

remember that these signs are sometimes

usually transient and not indicative of

disease in the absence of symptoms.

Therefore, it is important to evaluate the

presence of other clinical signs and

symptoms, and not to base a diagnosis of

TB solely on the radiographic findings

Figure 2 � Chest X ray of a 14 year child

with suspected Tuberculosis

Figure 3 � Various Chest X ray findings in

children with suspected tuberculosis

A.Tubercular pericarditis. B.Ghon complex

C.Round pneumonia (consolidation)

D. Right upper lobe consolidation

E.Unilateral hyperinflation F.Miliary

s h a d o w s .

Tip 5 � Interpret the Tuberculin skin

test (TST) with caution

The tuberculin skin test (TST) is the

basis for an immune based diagnosis in

children. Conventional diagnosis is based

on the TST or Mantoux test done with 1TU

PPD with RT23 Tween 80 using a

tuberculin syringe. The PPD is injected

intradermally on the volar surface and the

reaction is read between 48 to 72 hrs. An

induration of 10mm or more in an

immunocompetant child or 5mm or more in

immuno compromised host is considered

positive. These values are derived from the

current consensus guidelines for the

diagnosis of tuberculosis1 . The BCG test is

found to be of no value and is not

recommended.

Ensure that the technique of performing

TST is accurate as is the interpretation of

the same to avoid an false readings. False

positive reactions can occur due to non

tuberculous mycobacteria, anergy and BCG

vaccination. False negative reactions can

occur due to recent TB infection, age of less


25

than 6 months, overwhelming infection, an

immunocompromised state and associated

live virus vaccination2 .

Tip 6 � Do not rely on TB

serology or IFN-gamma assay alone to

make a diagnosis

Evidence currently shows that no

serological assay is currently accurate

enough to replace microscopy and culture.

A recent systematic review showed that

currently available serological, antibody-

based tests have highly variable sensitivity

and specificity3 . Table 4 demonstrates the

varied sensitivity and specificity of ELISA,

ELISA IgG complex and ELISA and Western

Blotting. Current guidelines state that

commercial antibody assays have no role in

the care of pediatric patients.

Like the TST, current versions of

these interferon-gamma release assays fail to

differentiate M. tuberculosis infection from

active disease. Most studies have not proven

the benefit of Quantiferon Gold test in

establishing the diagnosis of TB4 . Hence,

IFN-gamma assay is not yet an answer to

establish diagnosis of TB in children.

Research in on way to for another

innovative approach which measures the

immune response (a delayed-type

hypersensitivity response similar to the TST)

to the transdermal application of the MPB-64

antigen. In initial pilot studies, the MPB-64

skin patch test successfully distinguished

active TB from LTBI (88�98% sensitivity,

100% specificity)5 . Table 5 shows a

comparison between the various diagnostic

tests used currently for childhood

tuberculosis. TST is shown to have a high

rate of false positives and negatives, and a

lower cost, and a booster effect in

comparison to the other diagnostic tests.

Although the Quantiferon Gold test and

ELISPOT appear to be attractive alternatives,

current evidence available does not support

the use of either for the diagnosis of TB in

children.

Table 4 � Sensitivity and Specificity ofserological tests in tuberculosis

Table 5 – Comparison between various diagnostictests for childhood tuberculosis

Tip 7 � Microbiological Diagnosis is

the gold standard

Demonstration of tubercle bacilli

establishes an unequivocal diagnosis even

in children. Culture of MTB is still the Gold

Standard for the diagnosis of tuberculosis.

All children with suspected TB should be

subjected to microbiological tests to aid

diagnosis. Unfortunately, this is often missed

by most clinicians. Microscopic examination

of sputum or gastric Lavage specimens have

been studied world over. 3 samples of

sputum / gastric lavage smears are optimal

with a cumulative positivity of nearly 100%

and thus the most reliable method. The

AFB Staining using Zeihl Neelsen technique

has a sensitivity of 66% and a specificity of

99%1 . Other methods of staining such as

Flourochrome staining (FCS) using auramine

rhodamine is found to be more sensitive

and faster with a decrease in reading time

to 1.5 minutes in comparison to 15 minutes

Antibody Assay Sensitivity specificity

ELISA 72 92

ELISA(immunoglobulin G complexes)

64 91

ELISA & Western blotting 93 96

Performance Characteristics

TST Quantiferon Gold Test

ELISPOT

Technique In vivo skin test

ELISA ELISPOT

Results given in Mm of skin induration

IFNg units Spot forming units

Antigen used PPD ESAT6 CFP10 ESAT6 CFP10

Time for results(d) 2 1 1

Influenced by prior BCG

Yes No No

Influenced by atypical mycobacteria

Yes No No

Booster effect if repeated

Yes No No

Cost pre test Low High High

Sensitivity 85-90% 58-80% 62-90%

Specificity 60-90% 95% 90%


26

with AFB staining. The Positivity rate is

however variable from 35-86%2 . Culture for

mycobateria include Lowenstein Jenson (LJ)

medium (egg based) which takes around 7

to 10 weeks. Most commonly however is

Middle brook (agar based/liquid based)

which is found to be less inhibitory to

mycobacterial growth and allows early

detection of growth after 10-12 days by

observing microcolonies. MGIT (mycobacterial

growth inhibitor tubes) which report

withing 10 to 12 days are based on an

oxygen sensitive fluorescent sensor.

BACTEC as a technique is known to take 9

to 14 with the aid of C14 labeled palmitic

acid medium3 .

PCR (Polymerase Chain Reaction) is

used to identify tubercular antigen by

nucleic acid amplication. Specific replication

of target DNA and insertion sequences IS

6110 is the method used. It is found to be

the fastest technique with the shortest

diagnostic time of 24 hrs with good

specificity. The Montenegro study demonstrated

a sensitivity of 71%, specificity of 95%,

positive predictive value of 92% and

negative predictive value of 79%4 . It can be

used to determine and differentiate

M.tuberculosis and atypical mycobacterium.

Another use of PCR also includes the

identification of resistance to anti TB drugs.

INH resistance strains carry the KatG gene

and Rifampicin resistance strains rpoB

mutation. The number of bacilli required for

diagnosis by AFB staining is more than

10,000 organisms per ml of sample, by

culture (LJ medium) 10 to 100 organisms/

ml of sample and by PCR even a single

bacteria can be identified. However, the

routine use of PCR in the diagnosis of

tuberculosis is not recommended. It is

suggested to use two probes if at all used.

PCR in Pulmonary TB and gastric aspirate

has a sensitivity of 20 %. PCR in CSF &

Pleural fluid have a high specificity and

sensitivity and hence may be useful in

neurotuberculosis5 .

Conclusion

The diagnosis of tuberculosis in

children always remains a challenge to

practicing pediatricians. The dilemma of

deciding when to start anti tubercular

medication is a problem in daily practice.

Tips to aid the diagnosis have been based

on symptomatic diagnosis, radiological

diagnosis, immunological diagnosis and

microbiological diagnosis. Clinicians can

consider the mentioned suggestions to assist

the further management.

References

1. Dye C. Global epidemiology of

tuberculosis. Lancet 2006; 367: 938�

940

2. Starke JR. Pediatric tuberculosis: time

for a new approach.Tuberculosis

2003;83:208�12

3. Vallejo J, Ong L, Strake J. clinical

features, diagnosis and treatment of

tuberculosis in infants. Pediatrics 1994;

94:1-7

4. Schulger NW, Harkin TJ. In: Sahn SA

Heffner JE (Eds): Tuberculosis pearls.

PhiladelphiaL Mosby 1955; 17 -85

5. Eamranond P, Jaramillo E. Tuberculosis

in children: reassessing the need for

improved diagnosis in global control

strategies. Int J Tuberc Lung Dis 2001;

5: 594�603.

6. Marais BJ, Gie RP, Schaaf HS et al. A

refined symptom-based approach to

diagnose pulmonary tuberculosis in

children. Pediatrics 2006; 118: 1350�


27

1359

7. Marais BJ, Gie RP, Schaaf HS,

Hesseling AC, Enarson DA, Beyers N.

The spectrum of childhood

tuberculosis in a highly endemic area.

Int J Tuberc Lung Dis 2006; 10: 732�

738.

8. Stengen G, Kenneth J, Kaplas P.

Criteria for guidance in the diagnosis

of tuberculosis. Pediatrics; 1969;43: 260

-3

9. Nair PM, Philip T. A scoring system

for the diagnosis of tuberculosis in

children. Indian Pediatrics 1981; 18:

299 - 303

10. Seth Vimlesh, Singhal PK, Semwal OP

et al. Childhood tuberculosis in a

referral center: clinical profile and risk

factors. Indian Pediatrics 1993;30: 479

- 85

11. Osborne CM. The challenge of

diagnosing childhood tuberculosis in

a developing country. Arch Dis Child

1995;72: 369 - 74

12. Marais BJ, Gie RP, Schaaf HS, Donald

PR, Beyers N, Starke J. Childhood

pulmonary tuberculosis � old wisdom

and new challenges. Am J Resp Crit

Care Med 2006; 173: 1078�1090

13. Consensus Statement of IAP working

Group Indian Pediartic 2004 41; 148-

155

14. Nayak S, Acharjya B. Mantoux test

and its interpretation. Indian Dermatol

Online J 2012;3:2-6

15. Steingart KR, Henry M, Laal S, et al. A

systematic review of commercial

serological antibody detection tests for

the diagnosis of extrapulmonary

tuberculosis. Thorax 2007.

16. Bartu V, Havelkova M, Kopecka E;

QuantiFERON-TB Gold in the

diagnosis of active tuberculosis; J Int

Med Res. 2008 May-Jun;36(3):434-7

17. Nakamura RM, Velmonte MA,

Kawajiri K, Ang CF, Frias RA,

Mendoza MT, Montoya JC, Honda I,

Haga S, Toida I; MPB64 mycobacterial

antigen: a new skin-test reagent

through patch method for rapid

diagnosis of active tuberculosis; Int J

Tuberc Lung Dis.1998 Jul;2(7):541-6

18.Hajime Fukunaga, Tomoyuki Murakami,

Toshikazu Gondo, Kazuo Sugi, and

Tokuhiro Ishihara; Sensitivity of Acid-

Fast Staining for Mycobacterium

tuberculosis in Formalin-fixed Tissue;

Am J Respir Crit Care Med (2002) Vol

166. pp 994�997

19. Paul W. Wright, Richard J. Wallace, Jr.,

Nathan W. Wright,Barbara A. Brown,

and David E. Griffith; Sensitivity of

Fluorochrome Microscopy for

Detection of Mycobacterium

tuberculosisversus Nontuberculous

Mycobacteria; J Clin Microbiol.1998

April;36(4): 1046�1049

20. Abe C; Standardization of laboratory

tests for tuberculosis and their

proficiency testing; Kekkaku.2003

Aug;78(8):541-51

21. Montenegro et al: Clin Infect Dis 2003;

36 : 16-23

22. Consensus statement of IAP working

group Indian Pediatr 2004;41:146-155


28

Abstract :- The diagnosis of sickle

cell anaemia (SCA) is usually made in

childhood, often before the age of 2 years.

In early childhood, the mortality is high,

many children dying in the first 7 years of

life. However, it has been appreciated that

a significant number of adults with SCA are

able to lead a relatively normal life, punctuated

by only occasional episodes of illness. Here

we wish to present such a case in an

adolescent with mild clinical symptoms

Here is a case of a 14 year old boy of sickle

cell anemia presented with intermittent

history of fever and polyarthralgia for 3

years without any other significant history

suggestive of sickle cell anemia..

Key words:- SCD- Sickle cell disease,

Introduction

The diagnosis of sickle cell anaemia

(SCA) is usually made in childhood, often

before the age of 2 years. In early childhood,

the mortality is high, many children dying

in the first 7 years of life. However, it has

been appreciated that a significant number

of adults with SCA are able to lead a

relatively normal life, punctuated by only

occasional episodes of illness.[1] Here we

wish to present such a case in an adolescent

with mild clinical symptoms Here is a case

of a 14 year old boy of sickle cell anemia

presented with intermittent history of fever

and polyarthralgia for 3 years without any

other significant history suggestive of sickle

cell anemia..

Case report:- 14 year old Anand, S/O

Krishnappa a coolie worker from raichur,

born to nonconsaguinous marriage came to

pediatric OPD with complaints of recurrent

joint pains since 2 to 3 years, intermittent

fever since 2 to 3 years. Joint pains since 2

to 3 years predominantly larger joints in

lower limbs (ankle, knee joint and hip joints)

and upper limb (elbow shoulder and wrist

joint) usually involvement of more than 4

joints each time. Asymmetrical involvement

of joints, associated with mild restriction of

movements, Not associated with swelling,

redness . Joint pains associated with fever

mild to moderate degree without chills and

rigors subsides after taking fever

medications; child was also having pain all

over the chest but not associated with

significant breathing difficulty or cyanosis.

No rash, or muscle weakness, No h/o

trauma f/b infection, no history contact

with pt of Koch�s, GI infection, Rash ,

Photosensitivity, chronic diarrhea, Bleeding

gums, Bone pain or morning stiffness, No

history of blurring of vision and blood

transfusion.

The patient has been admitted for

above complaints 3 times before coming to

SIMS and he was improved with fever

medications antibiotics and intravenous

fluids. Family history was nothing

contributory. Patient�s weight was 36 kg (No

malnutrion) and blood pressure is 120/70.

Systemic examination was normal except

Dept of Pediatrics,Shimoga Institute of Medical Sciences , Shimog Email:- [email protected],

SICKLE CELL DISEASE- AN ATYPICAL PRESENTATION

WITH FEVER AND POLYARTHRALGIADr Shreeshail V Benakanal, Dr Manjunathaswamy, Dr R B Patil


29

mild swelling of knee joints and ankle

joints, No redness. Initial reports Hb

9.1gms/dl ,TC 6400cells/cmm ,DC N80, L

19,ESR 10,Platelets 1.58,RA factor Negative

,ASLO negative ,CRP positive, Urine routine

Normal, P smear:- Microcytic hyopochromic

anemia. LFT proteins � 7.8, Alb 4.21,

Globulin- 3.66,A:G ratio 1.15, Bilirubin

Total of 1.14, Direct of 0.63mg/dl, SGOT -

36,SGPT � 11, ALP- 96, 2 D ECHO was

showing changes of rheumatic activity over

mitral valve- suggestive of RHD,X ray of

knee joints was normal. Hence diagnosis of

RHD was made and child was sent on

Benzathine penicillin prophylaxis. After 10

days child was again admitted with similar

complaints. On examination child was

having mild splenomegaly, Hb was 8 gms/

dl (reduced). Bilirubin Total was 2.14

(increased), Direct bilirubin -0.93, Reticulocyte

count was 4 and Peripheral smear was

showing ,Anisopoikilcytosis, Microcytic

hypochromasia ,Target cells fragmented

cells, occasional tear drop cells,WBC and

platelets adequate. Sickling test was

performed at this stage which was positive

and later Sickle cell disease was confirmed

with Hemoglobin electrophoresis which was

showing HbF of 28% and HbS of 62%.

Child was given antipyretics, intravenous

fluids and sent home with proper advise

and sick day guidelines.

Discussion

A number of factors influence the rate

and degree of HbS aggregation required to

produce sickling of red cells. Hb-C, Hb-D

and Hb-O greatly potentiate sickling by

interacting with Hb-S and promoting gel

formation. Hb-F interacts poorly or not at all

with Hb-S. Hb-F is postulated to act as inert

diluent of Hb-S solutions.[2] Singtr and

Singer[3] noted that Hb-F interfered with

Hb-S aggregation in proportion to its relative

concentration. Bertles and Milner[4] have

also been able to demonstrate that cells with

a high Hb-F concentration survive longer in

circulation and do not readily form

irreversibly sickled cells (ISCs). High levels

of Hb-F are always associated with low ISC

counts and hence this relationship is

reflected in the significant inverse

correlationship between Hb-F and ISCs in

patients with sickle cell disease.[2] The most

striking evidence for the ameliorating effect

of high levels of Hb-F was apparent in the

Saudi Arabian population with sickle cell

disease.[5] This group of patients manifested

with mean Hb-F levels of approximately

20% and were characterised by an

extremely benign clinical course, high Hb

levels, less rapid haemolysis and a virtual

absence of painful crises. This finding

suggests that this group has a genetically

determined ability to synthesize large

amounts of Hb-F, possible reasons being

that the population may be carrying an

extra gamma loci; alternatively, many of

these patients, in addition to being

homozycous for Hb-S, carry one or more B-

thalassemiagene.[2] High Hb-F levels in

sickle cell disease are associated with more

normal red cell survival, more normal O2

affinity and more normal red cell

characteristics whereas clinically they have

more benign course.

Conditions which can reduce the

severity of SCD are maintaining the high

concentration of Fetal Hemoglobin, as HbF

>10% offers protection against stroke and

Avascular necrosis, HbF>20% offers


30

protection against painfull crisis and

pulmonary crisis and also Co inheritance of

alpha thallassemia reduces the severity of

hemolysis

Treatment of SCD includes appropriate

antibiotics during infection, Prophylaxis

with oral penicillin starting from 4 month

of age- 62mg/125mg/250mg for ages up to

1 year, 1to 3 year and 3 to 6 years

respectively. 24 valent Pneumococcal

vaccine for children more than 2 years and

conjugate pneumococcal vaccine below 2

years and a revaccination after the age of 4

years improves the levels of protective

antibodies. Family education during fever (

temperature greater than 38.5 degree

Celsius) with a consultation from

pediatrician. Prompt treatment of painfull

crisis with good hydration, analgesics,

partial exchange transfusion . Other

treatment modalities include Antisickling

therapy which stimulate the HbF

production are 5 azacytidine, hydroxyurea,

and Recombinant human erythropoietin.

and stem cell transplantation whenever

possible. Hydroxy urea is one of the

commonest drugs used to raise the level of

HbF at a dose of 15mg/kg/day helps in

reducing the number of vasoocclusive crisis,

acute chest syndrome and reduces the

transfusion needs. Adverse effects mainly

include myelosupression, hair loss, skin

pigment changes, teratogenicity and increase

in creatinine.

References:

1. Steinberg, M. H., Dreiling, B. J.,

Morrison, F. S. and Necheles, T. F.:

Mild sickle cell disease. Clinical and

laboratory studies, J. Amer. Med.

Assoc. 224: 317-321, 1973

2. Serjeant, G. R.: Fetal haemoglobin in

homozygous sickle cell disease, Clinics

in Haematology, 4: 109-122, 1975

3. Singer, K. and Singer, L.: Studies on

abnormal haemoglobins VIII. The

gelling phenomenon of sickle cell

haemoglobin, its biologic and

diagnostic significance, Blood, 8: 1008-

1023, 1953.

4. Bertles, J. F. and Milner, P. F. A.:

Irreversible sickled erythrocytes: A

consequence of the heterogenous

distribution of haemoglobin types in

sickle cell anaemia, J. Clin. Invest. 47:

1731-1741, 1968.

5. Brown, M. J., Wetherall, D. J., Clegg, J .

B. and Perrine, R. P.: Benign sickle cell

anaemia. Brit. J. Hematol., 22: 635,

1972.


31

Abstract:

The Neonatology as a speciality has

grown up from tender budding seed to a

huge tree with lot of branches.As the

speciality is being sophisticated,thereare a

lot of changes we see from the point of

view of understanding the subject,

evidenced based management and

progressive change in the relationship

between doctors and patients.For the

overallbetterment of the medical practice the

proper communication(intra and inter) and

valid documentation Are the major

foundation without which the whole effort

done for the benefit of baby goes in vain.

The nature of communication and

documentationis very much lacking in our

education systemand needs to be critically

looked into.

Key points: medical practice; ethics;

judgement

At the end of reading, the readers

will understand the following objectives.

1. Changing trend in medical practice

2. Changing relationship between

doctors and patients

3. Medical practice and legal issues

4. Land mark judgement

5. Prevention

Changing trend in medical practice:

Medical practice is dated back to

Vedas, the Athrvaveda, a sacred Veda of

Hinduism, is the first Indian text dealing

with medicine. Post Vedic India has given

the traditional medicine system called

Ayurveda, thanks to Charka and Sushruta

for their unbeaten contributions for the

welfare of human kind. Medical system was

only the doctor and his or her client. The

system started to have a lot of sub branches

as the customer becomes more intelligent

and more able financially demanding more

specialised service.A Lot of advances in the

development of technology like internets,

advertisements, medical equipment have

made the generation to bend towards

technology rather than depend upon clinical

acumen. The customer is becoming more

knowledgeable superficially interfering with

the management. Growing preponderance of

chronic illness, newer medical technologies

including equipment and internet, shifting

medical reimbursement practices, changing

social norms, increasing cost and

government regulations has led to sweeping

changes in the medical field

Changing relationship between

doctors and patients

There is a constant moulding

amongst the physician and the patient. The

physician used to be advocates for their

patients in addition to just taking care.The

physician used to be called as �next to

God�. Now the treating doctor and the

patient have become partners in the medical

care. The way doctor was considered in

yester years and the changing trend

between patients and doctor is well depicted

in the picture 1.

LAND MARK JUDGEMENT IN NEONATOLOGY- IT IS TIME

NOW TO WAKE UP

Dr. Venkatesh. H.A

Consultant neonatologist ,Manipal hospital,Bangalore


32

individualto society.

Medical practice and legal

issues: legal issue has so much

intertwined in the medical practice that it

has become two faces of a coin. Some of the

terms commonly used like Informed consent,

practices of withholding and withdrawing,

euthanasia are briefly discussed.

Informed consent:this is more than

simply getting a patient to sign a written

consent4.A component of an informed

consent is shown in table 1.

Table 1.components of informed consent

1. The patient, diagnoses if known

2. The nature and purpose of a

proposed treatment or procedure

3. The risks and benefits of a proposed

treatment or procedure

4. Alternatives( regardless of their cost

or the extent the treatment options are

covered by health insurance)

5. The risks and benefits of the

alternative treatment or procedure

6. The risks and benefits of not

receiving or undergoing a treatment

or procedure

This was first used in Martin salgo

case in the year 1957. The nature of the

procedure, the risks involved in the

procedure, the consequences of the

procedure and any alternatives available are

discussed in detail. It isa matter of

judgement enabling for the patient. This has

2 components. 1.Cliniciancentred, the

clinician should tell the patient about the

nature of procedure and the risks involved

Picture 1. Trust and doctor

AdvocacyX partnership

Unfortunately the uniform trust by

patients towards doctors is fading away.

The health care is divided into 3 categories

1. The age of paternalism- age of

doctor (500BC-1945), was the era of patient

dependency and physician control. Doctor�s

word was God�s word. It was just a

symptomatic care and not targeting the cure.

Satisfied basic human needs for most of the

patients

2. The age of Autonomy(1945-1990).

This is the era where in the power is shifted

from physician to patient.Patients� rights

were acknowledged and informed consent

was considered. Emphasis was on treatment

rather than prevention and on cure rather

than care

3. The age of beauracracy: (the age of

payor)in this era the cost containment and

the cost efficiency are based on social risk

benefit analysis. The need is shifted from


33

2. Patient centred,enabling the patient to

make an informed choice

Withholding and withdrawing:

Irrespective of religion, race, gender each

patient�s welfare is taken into consideration.

Infants where aggressive treatment might not

be desirable like in patients with no hope

situation and no purpose situation

considering withdrawing of the care are

encouraged.The essentialaction is to provide

good comfort care and good nursing care

even when aggressive intensive therapy is

contraindicated after discussion with patient

care taker. After the infamous �baby Doe� in

1963, there is now a strong consensus in

the medical, legal and ethical literature that

it is the best interest of the infant-not the

desire of the parents, or the determination

of the physician-that must prevail in the

care of new borns1

Euthanasia:

It is a practice of ending life

intentionally in relieving pain and

suffering5. 2 known types are active

euthanasia and passive euthanasia. In active

euthanasia, the person who is terminally ill

is killed by using lethal substances like

high dose morphine

In passive euthanasia, the medical

treatment for continuing life is withheld like

taking the baby off ventilator to end the

suffering

Euthanasia is different from Physician

aid in dyingn (PAD), where in Physician

prescribes drugs to competent terminally ill

patients upon the patients request,with the

understanding that the patient intends to

use them to end his or her own life. This is

being practiced in OregonState in USA,

claiming �death in dignity�.

What is the state in our country?Well

most of the hospitalsdo have ethics

committee to get legal suggestions

periodically as the issue arises.Alot of

confusion exists among the treating

physicians in the care of neonates.

Ultimately most of us manage the issue with

mereunderstanding with the parents. But

just this understanding is not enough and

we should all have uniform legal decision

while handling these terminally ill babies.

Rules are extrapolated from adults to

neonates. Do we have any land mark

judgements focussed to neonatology? I could

not search any such judgement pertaining

to neonatal care. What is evident is,case

related to Aruna shanbaug �nurse at KEM

hospital where in Supreme Court of

India,rejects the plea for mercy killing for

Aruna.This was a land mark judgement.

The decision of which included were

,passive euthanasia is legal in our country

subjected to parliament passing law, it is

subjected to the approval of high court and

the committee of 3 doctors reporting to the

high court.

Land mark judgement: A legal case

acquires land mark status because of its

historical or precedential value to the

field.The particularcase with its facts is the

first time that the particular court has

confronted with in the court�s jurisdiction.

Historical judgement reflects the judicial

reasoning.3The best known example is the

right to self-determination as in schloendorff

casewhich led to the development of

informed consent


34

Can we prevent litigations?

Yes of course.As itwas mentioned,

the medical practice and legal issue are the

2 sides of a coin.To make sure, focus on the

issues required to strengthen our medical

practice. Prevention is better than cure and

hence practicing evidence based medicine,

mutual respect, honest communication and

documentation will help in the long run

and prevent us in getting involved into the

litigations. According to Ancient wise

saying �if it is not written down,it did not

happen!� soeffective documentation is

imperative to avoid errors.

Communication is a vehicle navigating

the stressful circumstances that accompany

acute medical illness;and a frame work for

maintainopens discussion and appositive

relationship even when there is uncertainty

about the medical outcome. Very important

is to document whateveris communicated to

the parents. Communication without

documentation is equated to not

communicate.

References

1. KoplemannLM, IronsTG,:Koplemann

AE:neonatologists judge the �baby

doe� regulations. N Engl J Med

318:677-683, 1988

2. Supreme court of India. Judgement in

the case of Aruna Ramachandra

Shanbaug V. Union of India and

others.2011 Mar7.Writ petition

(criminal) No.115 of 2009

3. SchloendorffV.Society of New York

Hospital. 211 N.Y.125,N.E.92 (1914)

4. Faden R.R. & Beauchamp TL. A history

and Theory of informed consent. New

York. Oxford university press

5. Harris NM. (Oct 2001). �The

Euthanasia debate� JR Army med

corps 147(3):367-70.PMID 11766225


35

Abstract

Transient myeloproliferative disorder

(TMD), a rare clonal myeloproliferation1,2

characterized by peripheral leukocytosis

indistinguishable at presentation from acute

megakaryocytic leukemia, FAB M7, or acute

myeloid leukemia. Its predilection for Down

Syndrome neonates and typical spontaneous

regression within 3-7 months of life

distinguishes it from leukemias.

Case report

Day 1 male baby born to non-

consanguineous parentage, with no ante-

natal complaints (fever, rash,lymphadenopathy

during any trimesters),delivered vaginally at

term with weight of 2.5 kg and good

Apgars. PresentedwithMaculopapular skin

lesions predominantly over trunk and face

with no erythematous base, Hepatosplenomegaly,

Liver span of 7 cm, firm in consistency,

smooth surface, rounded border, non-

tenderness and Spleen palpable 3 cm below

left costal margin, firm in consistency,

smooth surface, non-tender, no

dysmorphisms observed. Investigation

revealed very high leucocyte counts in blood

with 95% blast cells. Bone marrow study

showed lesser number of blasts than in

peripheral blood smear study. Cytogenetics

revealed Trisomy-21 genotype from

leucocytes. Flow cytometry was suggestive of

Megakaryoblastosis. TORCH screen was

negative. Childs general condition remained

stable, with adequate weight gain over 3

months of followup. Periodic follow up over

3 months showed declining total leucocyte

count and blast percentage with preserved

other cell lines. Based on these findings case

was Diagnosed as TransientMyelo-

proliferative disorder with Trisomy-21

genotype of haematological cell

Fig 1.Profile view of baby showing macula-

papular rashes predominantly

Fig 2. Peripheral smear image showing

myeloblast cells with Table 1 : Showing

decline in total

TRANSIENT ABNORMAL MYELOPOIESIS - A CASE

REPORTDr Anil Kumar KH, DrBopanna, DrNiranjan.H.S, Dr Naveen Benakappa, Dr.Premalatha.R

Dept of Pediatric Intensive Care, Indira Gandhi Institute of Child Health, Bangalore


36

Table 1 : Showing decline in total cell counts and blast percentage over 2 months.

Discussion:

Transient myeloproliferative disorder

(TMD), a rare clonalmyeloproliferation1,2

characterized by peripheralleukocytosis

indistinguishable at presentation from acute

megakaryocytic leukemia, FAB M7, or acute

myeloid leukemia (AML) with minimal

differentiation, FAB M0. Itspredilection for

Down Syndrome neonates coupledwith its

unique characteristics of a relative paucity

of leukemicblasts within the marrow,

variable pancytopenia, a propensity formild

to life-threatening hepatic infiltration, and

typically a spontaneousregression without

any intervention help to clinically

distinguishthis entity.3 Between 4% and 10%

of newborn infants with Down Syndrome

are thoughtto develop TMD.4-6in addition to

its typical spontaneous regression within3-7

months of life7 without intervention,8 it

appeared to have ahighly fatal form, and

among those who survived there was up to

a20%-30% risk of subsequent

leukemia.9,10Overall mortality was 21.5%.

Zipursky et al first in a literature review

and later in a survey,identified that 26%-

30% went on to develop leukemia in the

first3years of life. More recently, identified

19%-23% who later developed acute

leukemia, primarilymyeloid.9,11Blast cells in

TMD carry unique mutations in the

hematopoietic transcription factor GATA-

1and that the identicalmutation can be

found in AMKL(Acute megakaryoblasticleukemia)

blasts, thus indicating that AMKL evolves

from TMD99TMD and AMKL originate from

a hematopoietic progenitor cell of

embryonic/fetalhematopoiesis rather than

from mature hematopoiesis in bone marrow,

a finding that explains the onset in early

childhood and the transient nature of

TMD.12

References:

1. Gamis AS, Hilden JM. Transient

myeloproliferativedisorder, a disorder

with too few data andmany

unanswered questions: does it contain

animportant piece of the puzzle to

understandinghematopoiesis and acute

myelogenousleukemia?J PediatrHematol

Oncol. 2002;24(1):2-5.

2. Kurahashi H, Hara J, Yumura-Yagi K, et

al. Monoclonalnature of transient

abnormal myelopoiesisin Down�s

syndrome. Blood. 1991;77(6):1161-1163.

3. Zipursky A, Brown EJ, Christensen H,

Doyle J.Transient myeloproliferative


37

disorder (transientleukemia) and

hematologic manifestations ofDown

syndrome. Clin Lab Med. 1999;

19(1):157-67, vii.

4. Pine S, Guo Q, Yin C, Jayabose S,

Druschel C,Sandoval C. Incidence and

clinical implications ofGATA1

mutations in newborns with Down

syndrome.Blood. 2007;110:2128-2131.

5. Zipursky A, Brown E, Christensen

H,Sutherland R, Doyle J. Leukemia

and/or myeloproliferativesyndrome in

neonates with Downsyndrome.

SeminPerinatol. 1997;21(1):97-101.

6. Bajwa RPS, Skinner R, Windebank KP,

Reid MM.Demographic study of

leukaemia presentingwithin the first 3

months of life in the NorthernHealth

Region of England. J ClinPathol.

2004;57(2):186-188.

7. Hayashi Y, Eguchi M, Sugita K, et al.

Cytogeneticfindings and clinical

features in acute leukemiaand transient

myeloproliferative disorder inDown�s

syndrome. Blood. 1988;72(1):15-23.

8. Weinstein HJ. Congenital leukaemia and

the neonatalmyeloproliferative disorders

associated withDown�s syndrome.

ClinHaematol. 1978;7(1):147-154.

9. Massey GV, Zipursky A, Chang MN, et

al. A prospectivestudy of the natural

history of transientleukemia (TL) in

neonates with Down syndrome(DS):

Children�s Oncology Group (COG)

studyPOG-9481. Blood. 2006;107(12):

4606-4613.

10. Homans AC, Verissimo AM, Vlacha V.

Transientabnormal myelopoiesis of

infancy associated withtrisomy 21. Am

J PediatrHematolOncol. 1993;15(4):392-

399.

11. Zipursky A, Rose T, Skidmore M,

Thorner P,Doyle J. Hydropsfetalis and

neonatal leukemia inDown syndrome.

PediatrHematolOncol,. 1996;13(1):81-87.

12. Li Z, Godinho FJ, Klusmann JH, et al.

Developmentalstage�selective effect of

somatically mutated leukemogeni

ctranscription factor GATA1. Nat

Genet. 2005;37:613-619.


38

Abstract:

Tuberous Sclerosis is a neurocutaneous

syndrome characterized by abnormalities of

both the integument and central nervous

system. We present a case of Tuberous

Sclerosis with rhabdomyoma in heart. This

was a one and half year old female child

with infantile spasms and rhabdomyoma in

heart with mother having neurocutaneous

markers of Tuberous Sclerosis. MRI brain

and EEG findings were consistent with

diagnosis.

Key Words: Neurocutaneous;

Infantile spasms; Rhabdomyoma.

Introduction

Tuberous Sclerosis Complex (TSC) is

an autosomal dominant neurocutaneous

syndrome with a high incidence of sporadic

cases and variable clinical expression .1,2,3 It

has an estimated frequency of 1/6000 .1,4

Major manifestations of TSC include skin

lesions in more than 95%, autism & seizures

in 85% ,kidney disease in 60%, mental

retardation in 50% and cardiac rhabdomyoma

in 50 % .3 Mental retardation and autism

are more in TSC patients who presents

with generalized seizures including infantile

spasms in the first 2 years of life .1,2,3 We

present a one and half year old female

child with features suggestive of TSC .

Case report

A one and half year old female child

born out of a non-consanguineous marriage

to a primi mother at 34 weeks of gestation ,

presented with abnormal jerky movements

of both upper and lower limb for past 2

months .The development was normal for

age, except for speech and language delay .

Clinical and CNS examination was normal .

During hospital stay child was found to

have infantile spasms . EEG done showed

hypsarrhythmic pattern . MRI brain was

suggestive of multiple sub ependymal

nodules and cortical tubers (Figure Ia and

Ib) . USG abdomen was normal . Antenatal

scan had revealed a mass in fetal heart in

left ventricle . ECHO done at this admission

was suggestive of rhabdomyoma in left

ventricular cavity 21 x 15 mm size (Figure

II) .Ophthalmological examination was

normal .On clinical examination of parents ,

mother had adenoma sebaceum on face and

shagreen patch in right lumbosacral region .

Based on the criterias a diagnosis of TSC

was made and child was started on

topiramate. There was no further episode of

infantile spasms. Now on follow up child is

seizure free.

Figure Ia - Multiple minimally enhancing

Sub Ependymal nodules along the

lateral wall of body of lateral ventricles

TUBEROUS SCLEROSIS WITH RHABDOMYOMA

Dr.Ajay V ,Dr.Vikram Singhal*,Dr.Vardhelli Venkateshwarlu,Dr.Rajesh S M

Department of Pediatrics, Kasturba Medical College, Mangalore, Manipal University.


39

Figure Ib �Hyperintense areas in subcortical

location in B/L cerebral hemispheres: Tubers

Fig II -ECHO Cardiography showing

Rhabdomyoma in Left Ventricular Cavity

21×15 mm size

DISCUSSION

The first complete description of

Tuberous Sclerosis Complex ( TSC ) was

given by Bourneville in 1880 4. TSC is a

disorder of cellular differentiation and

proliferation that can affect the brain , skin ,

kidneys ,heart and other organs. Abnormal

neuronal migration plays a major additional

role in neurological dysfunction 1.Two genes

responsible for TSC are TSC1 at

chromosome 9q34 (hamartin) and TSC2 on

16p13.3 (tuberin)1,4,5.Diagnostic criteria

include-

Major features �

1) Facial angiofibroma or forehead

plaques.

2) Non traumatic ungual or periungual

fibroma.

3) Shagreen patch (connective tissue

nevis).

4) Multiple retinal nodular hamartomas .

5) Cortical tuber .

6) Subependymal nodule.

7) Subependymal giant cell astrocytoma.

8) Cardiac rhabdomyoma ,single or

multiple.

9) Angiomyolipoma.

Minor features-

1) Multiple randomly distributed pits in

dental enamel.

2) Hamartomatous polyps .

3) Bone cysts .

4) Cerebral white matter radial migration

lines .

5) Gingival fibromas .

6) Nonrenal hamartoma .

7) Retinal achromic patch.

8) �Confetti � skin lesions .

9) Multiple renal cysts.

Diagnosis of TSC is established when

two major features or one major plus two

minor features can be demonstrated. 1,2,4,5

This child had 3 of the major features

; subependymal nodules , cortical tubers and

rhabdomyoma . Recent 2-D ECHO studies

have reported that 50% of patients with TSC

have cardiac rhabdomyomas. Incidence of

Tuberous Sclerosis is as high as 59-80 % in

patients with confirmed fetal rhabdomyomas.6

Cardiac rhabdomyomas are hamartomas;

they tend to be multiple and evidence exists

that they involute with time .These lesions


40

sometimes are evident on prenatal ultrasound

testing and most of the patients with

cardiac dysfunction present soon after birth

with heart failure.6 But our child has no

features suggestive of cardiac involvement

except antenatal scan showing a cardiac

mass . A few children later develop cardiac

arrhythmias or cerebral thromboembolism

from the Rhabdomyomas. Some patients

stabilize after medical treatment with

digoxin and diuretics and eventually

improve while others require surgery.6 For

existing Rhabdomyomas surveillance studies

should be done every 6 to 12 months until

stabilization or involution occurs.1 In TSC

vigabatrin is an effective treatment option

for infantile spasms .Other drugs which

may be useful are topiramate and ACTH.

Occassionally children can discontinue their

antiepileptic medication .1,2,4 Oral rapamycin

has been shown to cause regression of

astrocytomas associated with TSC and may

eventually be an alternative to operative

therapy .2,5 In general in TSC the disease

advances so slowly that years must elapse

before one can be sure of progression . Of

the severe cases approximately 30% die

before fifth year and 50-75% before attaining

adult age . The child with infantile spasm

is at great risk of later intellectual deficit .2,7

Conclusion-

Any child with fetal rhabdomyoma

should be evaluated for TSC . Diagnosed

cases should be followed up regularly with

neurodevelopment testing at school entrance,

MRI brain and renal ultrasound every 1-3

years during childhood and adolescence

should be done .Other tests like EEG ,

Ophthalmological examination & 2-D ECHO

are repeated only if clinical findings are

present .

References:

1. Monica P Islam ,E Steve Roach;

Neurocutaneous Syndromes �(eds)

Walter G Bradley, Robert B Daroff ,

Gerald M Fenichel , Joseph Jankovic;

Neurology in Clinical Practice 5th

edition 2010 ;69:1822-1827.

2. Arnold P Gold ,Marc C Patterson ;

Tuberous Sclerosis Complex �(eds)

Lewis P Rowland , Timothy A Pedley ;

Merritt�s Neurology 12th edition 2010

;109:698-704.

3. Raymond S Kandt ;Tuberous Sclerosis

Complex and Neurofibromatosis type 1:

the two most common neurocutaneous

diseases �Neurologic Clinics of North

America 20 (2002) 941-964.

4. Bernard L Maria ,John H Menkes,Harry

B Sarnat ; Neurocutaneous Syndromes �

Child Neurology 7th edition

2000;12:810-815.

5. Mustafa Sahin ; Neurocutaneous

Syndromes � (eds) Kliegman , Stanton ,

St Geme, Schor, Behrman ;Nelson

Textbook of paediatrics 19th edition

2011 ;589.2:2049-2051.

6. Gerald R Marx ; Cardiac tumours �

Hugh D Allen , David J Driscoll ,

Robert E Shaddy , Timothy F Felter ;

Moss and Adams Heart Disease in

Infants , Children and Adolescents

including the Fetus and Young Adult

5th edition 1995;104:1774-1776.

7. Developmental Disease of the Nervous

System � (eds) Allan H Ropper , Martin

A Samuel ;Adams and Victor�sPrinciples

of Neurology 9th edition 2009 ;38:977-

979.


41

ABSTRACT

Congenital myasthenic syndromes (CMSs)

form a heterogeneous group of genetic

diseases characterized by dysfunction of

neuromuscular transmission, causing

fatiguable weakness of skeletal muscles

(ocular, bulbar, limb muscle) with onset at

or shortly after birth or in early childhood,

usually with positive family history and

absence of acetyl choline receptor antibodies

.[1]

Myasthenia gravis in infancy and

childhood fall into two major groups i.e.

acquired autoimmune and congenital. The

congenital group comprises a number of

phenotypically and genetically heterogeneous

disorders.

In this article we discuss an approach

to a case of CMS , and the limitations faced

in the diagnostic strategy in our setup.

Key words � congenital myasthenic

syndrome, diagnostic approach, limitations.

INTRODUCTION

Congenital myasthenic syndromes

(CMSs) form a heterogeneous group of

genetic diseases characterized by a dysfunction

of neuromuscular transmission. This

dysfunction causes muscle weakness, which

is increased by exertion and usually starts

during childhood.

Ever since the knowledge of CMS has

increased in the past 25 years, its incidence

remains a mere countable. The prevalence

was estimated at 1 in 5,00,000 in Europe

[1], with a recent study showing 1-5/1

million/ year affected in the age group of

1-19 year[2].

A study from a single tertiary referral

center in India, showed 5 CMS cases in a

total of 841 myasthenia gravis cases

collected over a period of 43 years[3], apart

from which 4 cases else have been reported[4].

The exact incidence not estimated.

Classification , three clinical varieties

distinguished in childhood

1. juvenile myasthenia gravis in late

infancy and childhood

2.Transient neonatal myasthenia

3.Congenital myasthenic syndrome [6]

The current classification of CMS is

based on pathophysiology,i.e. on the precise

identification of the neuromuscular

transmission anomaly. The location of the

dysfunction of neuromuscular transmission

(Fig. 1)[5], which is specific to the different

CMSs, is either presynaptic (generally

caused by an anomaly of ChAT), synaptic

(corresponding to an anomaly of the

CONGENITAL MYASTHENIC SYNDROME � A

RARITY IN THE FIELDDr. Nirupama S, Dr.Koujalgi M B Dr.C R Banapurmath

Departement of Pediatrics, JJMMC,Davangere.


42

acetylcholinesterase collagen tail), or

postsynaptic (secondary to an anomaly of

acetylcholine receptor or rapsyn).

CASE REPORT

Baby J now 4 year 11months, first

born of a consanguineous marriage , vaginal

delivery, with h/o drooping eyelids,

difficulty in swallowing, and weakness in

limbs from 1 year of age, worsening as the

day progresses. Negative family history

.Milestones attained appropriate for

age.Presented with history of recurrent

lower respiratory tract infection, one episode

requiring admission.(no ventilator

requirements).

On examination had B/L ptosis ,

with sluggish extraocular movements ,

normal pupillary light response .Tensilon

test done to test for ptosis and ophthalmoplegia

showed improvement in the distance

between upper and lower eyelid and eye

movements, with ptosis reappearing after 2

minutes. Acetylcholine receptor autoantibodies

- <0.15 tested was negative and hence

classified as CMS. Contributory Investigations

like CT scan thorax showed prominent

thymus with no obvious focal lesion,

Antinuclear antibodies were negative

,Thyroid panel was within normal limits.

Further Electromyography/ repetitive nerve

conduction showed maximum decrement of

18% seen in orbicularis oris muscle,findings

consistent with mild neuro muscular fatigue.

Muscle biopsy and molecular genetic

analysis were not done.

DISCUSSION

Congenital myasthenic syndromes

(designated as CMS throughout this entry)

are characterized by fatigable weakness of

skeletal muscle (e.g., ocular, bulbar, limb

muscles) with onset at or shortly after birth

or in early childhood; rarely, symptoms may

not manifest until later in childhood.

Cardiac and smooth muscle are not

involved. Severity and course of disease are

highly variable, ranging from minor

symptoms to progressive disabling weakness.

In some subtypes of CMS, myasthenic

symptoms may be mild, but sudden severe

exacerbations of weakness or even sudden

episodes of respiratory insufficiency may be

precipitated by fever, infections, or

excitement. Clinical signs suggesting an

anomaly of neuromuscular transmission

include ophthalmoplegia and ptosis,

dysphonia and swallowing disturbance,

facial paresis, and muscle fatigability. The

occurrence of bouts and worsening by

exertion are characteristics of the disease

The diagnostic strategy includes

roughly two successive steps: (1) the

association of a clinicalelectrophysiological

picture of a myasthenic syndrome, and data

in favour of a congenital origin; and (2) the

recognition of the pathophysiological type,

which is based on clinical data, the type of

hereditary transmission, the response to

cholinesterase inhibitors, the results of

electromyography, and finally the muscle

biopsy and molecular genetics.

However, in most of the centers

where such advanced investigations are not

possible, only the broad heading of CMS is

applied.

A positive family history is a essential


43

argument in favor of the genetic origin of

myasthenic syndrome.Most CMSs are of

autosomal recessive inheritance.Slow

channel syndrome is the only autosomal

dominant.

Titration of anti-acetylcholine receptor

antibodies in the Serum, the absence of

antibodies against acetylcholine receptor and

muscle-specific receptor tyrosine kinase (MuSK)

is a prerequisite for the diagnosis of CMS.

Electromyography is determinant for

the diagnosis where a search for

neuromuscular block, repetitive motor

responses and increments has to be

made.Certain characteristics like in ChAT

deficiency- the decrement may appear only

after an initial 5-min 10 Hz stimulation and

repetitive CMAPs(compound muscle action

potential) are pathagnomonic of two

varieties of CMS: slow channel syndrome

and acetylcholinesterase deficiency.

Muscle Biopsy is done firstly to

eliminate the diagnosis of myopathy

(congenital myopathy or mitochondrial

cytopathy). Though non-specific the

predominance of type I fibers and the

marked atrophy of type II fibers are seen in

CMS. The neuromuscular junctions are

visualized for (acetyl)cholinesterase by the

histochemical technique of Koelle, fasciculin

or specific antibodies - absence - establishes

the diagnosis of acetylcholinesterase deficiency.

Acetylcholine receptor are identified by

fluorescent á-bungarotoxin, which binds to

it, and significant reduction in number

proves primary anomaly of acetylcholine

receptor or rapsyn

Molecular Genetics , 8 genes whose

mutations are so far known to cause CMS

mainly are as follows.

1. 4 genes encoding-various AChR subunits

(CHRNE,CHRNA1,CHRNB1, CHRND)

2. The genes encoding rapsyn (43-kd

receptor-associated protein of the

synapse- RAPSN)

3. The collagen tail of acetylcholinesterase

(COLQ)

4. Choline Acetyltransferase (CHAT)

5. Sodium channel protein type 4 subunit

alpha (SCN4A)

Polymerase Chain Reaction amplification

of each fragment on genomic DNA is

required. Many others are known to cause

CMS but not described in detail.

Treatment of non-specific measures

are essential: immediate treatment of

respiratory distress, the prevention of

infections and of malnutrition as a result of

swallowing disorders, and orthopaedic

surveillance of spinal complications and

retractions.Drug contraindications to

be followed like in any other case of

myasthenia gravis.In the case of CMS,there

is no reason to apply the immunosuppressive

therapy used for myasthenia gravis.

Cholinesterase inhibitors are efficient in all

CMSs, with the exception of slow channel

syndrome and acetylcholinesterase deficiency,

which they can even worsen. They exert a

preventative effect on the respiratory

decompensations of CMS caused by ChAT

mutations . 3,4-Diaminopyridine,whose

mode of action is presynaptic, is sometimes


44

effective in pre- or postsynaptic CMSs

.Patients suffering from slow channel

syndrome benefit from the regulatory action

of acetylcholine receptor blockers: quinidine

is effective by correcting the prolonged

opening of the acetylcholine receptor ,but is

formally contraindicated in all the other

forms of CMS. A favourable effect of

fluoxetine was recently demonstrated in

some patients, and is of interest despite the

large amount needed . At present, there is

no specific treatment for acetylcholinesterase

deficiency.[1]

LIMITATIONS

l The Diagnosis of seronegative autoimmune

myasthenia may be difficult to

eliminate.

l Muscle-specific receptor tyrosine

kinase (MuSK) antibodies have been

detected in more than half of the

patients presenting with seronegative(no

acetylcholine receptor antibodies) auto-

immune myasthenia � not done in our

case.

Referrences

1. Daniel H, Pascale R. Congenital

myasthenic syndromes.Curr Opin Neurol

2004 ;17:539�551. Lippincott Williams &

Wilkins.

2. Anita M, Samantha S, Corinne

S.The Incidence of Myasthenia Gravis: A

Systematic Literature Review

.Neuroepidemiology 2010;34:171-183

3. Singhal BS, Bhatia NS, Umesh

T, Menon S. Myasthenia gravis: a study

from India.Neurol India. 2008;56(3):352-5

4. Khwaja GA, Chowdhury D, Gupta

M. Congenital myasthenic syndrome : report

of four cases and brief review of literature.

Neurol India 2000;48:266

5. Engel AG. Congenital myasthenic

syndromes. In: 73rd European

Neuromuscular Center (ENMC) International

Workshop. Naarden, the Netherlands,22�23

October 1999. Neuromusc Disord 2001;

11:315�321.

6. Robert M, Kliegman M D .Nelson

textbook of Pediatrics.19th edition;2011;2554-

2557


45

INTRODUCTION:

In children growing up with congenital

heart disease, infective endocarditis is a serious

complication. Neurologic complications of

infective endocarditis (IE) most commonly

occur as a result of embolization from

endocardialvegetations, with resultant

occlusion of cerebral arteries. Cerebral

hemorrhage is the most dramatic, though

fortunately rare, neurologic complication of IE.

It can be caused by a rupture of a mycotic

aneurysm. Clinicians should be aware of the

wide variety of cerebral presentations in

patients with IE, since these complications may

constitute the first symptoms of the disease,

thus provoking the suspicion of endocarditis.

Neurologic manifestations are generally

accepted as major determinants of poor

prognosis in patients with endocarditis. [1, 2]

CASE REPORT:

A nine year old boy was hospitalized

with h/o fever for 2 � 3 weeks and sudden onset

headache, vomiting, convulsions and altered

sensorium for one day. During infancy the child

was diagnosed to have inoperable, complex,

cyanotic congenital heart disease. He had

central cyanosis since infancy, and history of

repeated admissions to hospital for recurrent

fever for the past one to two years. On the day

of admission, the child was in altered

sensorium, with irregular breathing. His vital

signs were: temperature 102°F, blood pressure

130/100mmHg, heart rate 110/min, and

respiratory rate 48/min, SpO2- 66% in room

air. Physical examination revealed central

cyanosis and marked clubbing [grade 2] of all

the digits. In CVS examination: precordial

bulge was present, apex beat palpable over fifth

intercostal space (ICS) just lateral to mid

clavicular line, systolic thrill palpable over left

2nd, 3rd and 4th ICS just lateral to sternal

border. On auscultation, ejection systolic

murmur of grade four was heard over left 2nd,

3rd and 4th ICS. CNS examination: the child

was having irregular breathing, intermittent

posturing and restlessness with hypertension

suggesting raised intra cranial pressure. Pupils

were bilaterally equal and reactive to light with

horizontal nystagmus. Fundus examination

norml. Motor system examination showed

generalized floppiness and hypotonia with

areflexia and extensor plantar response both

sides. No signs of meningeal irritation. In Per

abdomen examination hepatomegaly and

splenomegaly was present. No signs of

petechiae or purpuric rash noted. Respiratory

system examination was normal.

Laboratory studies were as follows:

haemoglobin (Hb) 18.9 gm/dl, packed cell

volume (PCV) 65.9, white blood cells (WBC)

23,960 cells/mm3 with 73% neutrophils and

22% lymphocytes; erythrocyte sedimentation

rate (ESR) was 05 mm at the end of first hour.

Platelet counts 1.11 lakhs /mm3. Peripheral

smear showed microcytosis with neutrophilic

leukocytosis and thrombocytopenia. Serum

electrolytes, blood glucose, urea and creatinine

were normal. Multiple blood culture samples

were drawn on the day of admission.

MULTIPLE INTRACRANIAL MYCOTIC ANEURYSMS WITH

RUPTURE: A RARE NEUROLOGICAL COMPLICATION IN

CYANOTIC HEART DISEASE.

Dr. Mysore SatyanarayanaRavindra*. Dr. Vijay KeshavraoKulkarni .Dr. Gautam Mohan Kabbin ,

Dr. PoornimaKulkarni. Dr. KavitaKonded

Dept of Pediatrics, SDM College of Medical Sciences Dharwar Karnataka 580009 INDIA

Email: [email protected]


46

Computed Tomography (CT) scan brain

showed large acute intra-parenchymal bleed

in left parafalcine frontal region with extension

into frontal horn of left lateral ventricle it

measured 60×45×40mm with significant mass

effect and cerebral edema � possibility of

aneurismal rupture in ACA (anterior cerebral

artery) territory was considered. Patient was

treated with anti convulsants, anti cerebral

edema measures, IV broad spectrum antibiotics

and monitoring in PICU. The initial

hypertension noted was considered as part of

Cushing � Kochre response secondary to

raised ICP due to intracranial bleed and

watchfully monitored. Cerebrospinal fluid

(CSF) was: turbid in appearance, opening

pressure normal with CSF cell count of 25 cells/

cmm (90% neutrophils and 10% lymphocytes)

and numerous crenated red blood cells (5360

cells/cmm). CSF proteins 39 mg/dl and CSF

sugar 50 mg/dl, CSF Gram stain smears were

negative. CSF culture was negative. At this

time, the first blood culture sample was

reported has showing Staphylococcus aureus

growth, sensitive to penicillin group of drugs.

Trans thoracic 2D ECHO was done to look for

evidence of intra cardiac vegetations and there

was no vegetations noted. However,

transesophageal ECHO could not be done. The

child improved with antibiotics and other

supportive measures. He was shifted out of

PICU on fifth day of admission and no focal

neurologic deficits were observed.

CT cerebral angiogram showed:

multiple irregular ectasia of intracranial

bilateral internal carotid arteries, anterior

cerebral arteries (ACA), and middle cerebral

arteries (MCA). Multiple small saccular

aneurysms were noted at multiple sites of the

above blood vessels. There was no evidence of

arteriovenous malformation. It was reported as

intracranial multiple mycotic aneurysms and

rupture of one of them in the ACA territory had

caused the intra cranial bleed.

The child was managed with appropriate

parenteral antibiotics for six weeks and was

advised a follow up CT cerebral angiogram.

However, repeat CT angiogram was not

possible due to financial constraints and at four

months of follow up he was normal with no

fever, no headache and no focal neurologic

deficits and oral antibiotics were continued.

DISCUSSION:

Inoperable or unrepaired complex

cyanotic heart disease is a high risk group for

infective endocarditis. Central cyanosis

causing chronic hypoxemia is a known

pathogenic factor in the development of IE. Lack

of information and noncompliance with

antibiotic prophylaxis for ongoing infections

and unrecognised source of infections in a

cyanotic heart disease predisposes the patient

to IE [3, 4]. Diagnosis of IE is not straight

forward. As in our case, Trans thoracic 2D


47

ECHO did not show any vegetation except for

the cardiac malformation and blood culture

grew the typical microorganism staphylococcus

aureus in only one culture sample signifying

bacteraemia rather than endocarditis. The

occurrence of metastatic septic foci of mycotic

cerebral aneurysms complicated with rupture

and intra cranial hemorrhage lead to the

diagnosis of possible infective endocarditis

and was treated accordingly [5, 6].

Two to 10% of patients with IE have

mycotic aneurysms and half of these involve

cerebral vessels. These develop in IE when

friable cardiac vegetations give rise to septic

emboli that lodge in intracranial vessels at

distal branching points. Aneurysms arise

either from occlusion of vessels by septic emboli

with secondary arteritis and vessel wall

destruction or from injury caused by

bacteraemia seeding the vessel wall through

the vasa vasorum and causing inflammation

and necrosis of adventitia. Staphylococcus

aureusbacteraemia is implicated in the former

mechanism and viridians streptococci in the

latter [7]. Mycotic aneurysms associated with

IE occur most frequently on middle cerebral

artery at its distal branches. The mortality rate

in patients with intact aneurysms is about 30%

and it increases to 90% if the aneurysm

ruptures. Aneurysms that leak rather than

rupture are associated with a sterile meningeal

syndrome, with elevations of CSF protein and

of red cell and white cell counts. Mycotic

aneurysms should be excluded in all cases of

IE complicated by severe headaches, stroke like

events, or cranial nerve abnormalities [8].

Given the relative rarity of this clinical

entity, the medical intervention that is

uniformly recommended is early initiation of

intravenous antibiotic therapy and continued

for at least 6 weeks. Up to 50% of patients

experience full clinical recovery of their

neurologic deficits with complete resolution of

mycotic aneurysms associated with IE after

completing the full course of appropriate

antimicrobial therapy. Indications for

neurosurgical interventions such as surgical

excision, clip application and endovascular

procedures are controversial [8]. It is observed

that unruptured MAs could undergo

spontaneous thrombosis, suggesting that MAs

could resolve completely with antibiotic

therapy alone. The outcome of MAs associated

with IE is better although the risk of rebleed in

these is unpredictable [9].

Acknowledgements Dr S. N. Joshi

Professor and HOD, Paediatrics SDMCMSH

REFERENCES:

1. Heiro M, Nikoskelainen J, Engblom E et

al. Neurologic manifestations of Infective

Endocarditis. Arch intern Med. 2000; 160:

2781-2787.

2. Johnson MD, Johnson CD. Neurologic

presentations of Infective Endocarditis.

NeurolClin. 2010; 28: 311�321.

3. Filippo SD, Delahaye F, Semiond B, et al.

Current patterns of infective endocarditis

in congenital heart disease. Heart.2006;

92: 1490-1495.

4. Knirsch W, Haas NA, Uhlemann F, Dietz

K, Lange PE. Clinical course and

complications of infective endocarditis in

patients growing up with congenital

heart disease.International journal of

Cardiology.2005; 101: 285-291.

5. Saiman L. Endocarditis. In: Gershon AA,

Hotez PJ, Katz SL eds. Krugman�s

Infectious Diseases of Children. 11th

edition. Elsevier: Philadelphia; 2004. pp

97-115.

6. Haldar SM, O�gara PT. Infective

Endocarditis. In: Fuster V, O�rourke RA,


48

Walsh RA et al eds. Hurst�s the Heart. 12th

edition.Volume 2. China: McGraw Hill;

2008. pp 1975-2004.

7. Karchmer AW. Infective endocarditis. In:

Bonow RO, Mann DL, Zipes DP, Libby P,

eds. Braunwald�s Heart disease. A text

book of Cardiovascular Medicine.9th

edition. Elsevier: Saunders; 2012. pp 1540-

1560.

8. Limeperopoulos C, du plesis AJ.

Neurologic disorders in Children with

Heart disease. In: Swaiman KF, Ashwal

S, Ferriero DM, SchorNF.eds. Swaiman�s

The Karnataka Pediatric Journal, the

official publication of the Indian Academy

of Pediatrics, Karnataka State branch is

published four times a year. The Journal

solicits articles from the members of the

Academy and also persons interested in

furthering Pediatric

Knowledge. The Journal will publish

articles on different facets of Pediatrics.

Original articles, review articles, brief

reports, case reports and also work done

by the graduates are welcome.

The Journal will also cover

proceedings of seminars, CME programs,

workshops and conferences on Pediatrics

in Karnataka State.

Preparation of Manuscript: The entire

manuscript should not exceed 4-5 type

written pages. Brief reports and case

reports should not exceed 2 type written

pages. We request all the contribution to

follow the style of Indian Pediatrics while

submitting their articles for publication.

Each part of the manuscript should

be on a new page in the following manner.

Title page,

Abstract,

Text,

Acknowledgement,

References.

Table should be typed separately

must have title. Diagrams should also be

titled. 2

photographs (glossy print, 5. x 7.) is

printed free of charge, additional

photographs are charged Rs. 200/- each.

The editorial board will have the right to

edit the article and make suitable changes,

if accepted for publication.

All articles should be sent both Soft

copy and hard copy to The Editor,

Karnataka Pediatric Journal, Medicare

Center Karangalpady, Mangalore.575 003.

Email: [email protected]

INSTRUCTIONS TO CONTRIBUTORS

Pediatric Neurology. Principles and

Practice.5th edition.Volume 2. 2012.

Elsevier: Saunders; pp1777-1778.

9. Kannoth S, Iyer R, Thomas SV et al.

Intracranial Infectious aneurysm:

Presentation, management and outcome.

Journal of the Neurological Sciences.2007;

256: 3-9.

10. Kovoor JME, Jayakumar PN, Srikanth SG,

Sampath S. Intracranial Infective

Aneurysms: Angiographic evaluation

with Treatment. Neurol India 2001; 49:

262-266.

Karnataka Paediatric Journal Vol. 28, No. 1 ; Jan - March 2013

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