RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE

BANGALURU, KARNATAKA

SYNOPSIS FOR REGISTERATION OF SUBJECT FOR

DISSERTATION

A STUDY OF EITIOLOGY, ONSET AND CLINICAL

MANIFESTATIONS OF NEONATAL SEIZURES

- PROSPECTIVE

STUDY

Dr. JAFAR MOIDEEN KUTTY

PG IN PAEDIATRICS

AL-AMEEN MEDICAL COLLEGE

BIJAPUR

1

1. Name of the candidate DR JAFAR MOIDEEN KUTTY

2. Name of the institution Al Ameen Medical College

3. Course of the study M.D Paediatrics

4. Date of admission to course May 2013

5. Title of the topic A STUDY OF ETIOLOGY,

ONSET AND CLINICAL

MANIFESTATION OF

NEONATAL SEIZURES.

6. Brief resume of the intended work:

6.1 need of the study

6.2 review of literature

6.3 objective of the study

ANNEXURE I

ANNEXURE II

ANNEXURE III

7. Material and methods:

7.1 Source of data

7.2 Sample size

7.3 Settings

7.4 Inclusion criteria

7.5 Exclusion criteria

7.6 Method of collection of data

ANNEXURE IV

ANNEXURE IV

ANNEXURE IV

ANNEXURE IV

ANNEXURE IV

ANNEXURE IV

8. Does the study require any

investigation and intervention to be

conducted on patients, human or

animals? If so please describe briefly.

ANNEXURE V

9. List of references ANNEXURE VI

2

10. Has ethical clearance been obtained

from your institution in case of 8.

ANNEXURE VII

11. Signature of candidate

12. Remarks of the guide This study wil help to know

the prevalence , type and

etiology of seizures in our

department.

13. 13.1 Name and designation of the

guide

13.2 Signature

13.3 Co-guide

13.4 Signature

13.5 Head of the Department

Dr. A.B.TALIKOTI

M.D(PAED)

PROFESSOR

AL-AMEEN MEDICAL

COLLEGE

BIJAPUR

Dr. NAUSHAD ALI N.MALAGI

D.N.B(PAED)

ASSOCIATE PROFESSOR

AL-AMEEN MEDICAL

COLLEGE,

BIJAPUR

Dr. A.N THOBBI

M.D.(PAED)

PROFESSOR & HEAD OF THE

DEPARTMENT OF

PAEDIATRICS

AL-AMEEN MEDICAL

COLLEGE,

3

13.6 signature BIJAPUR

14. 14.1 Remarks of the Chairman and

Principal

14.2 signature

4

Annexure -I

Brief resume of intended work

6.1 Need for the study:

Neonatal seizures are common and may be the first manifestations of

neurological dysfunction after a variety of insults. Neonatal seizures are clinically

significant because very few are idiopathic.

Neonatal seizures present with varying manifestaions like generalized tonic,

clonic and subtle activity. Seizures represent the most distinctive signal of

neurological disease in the newborn period. The convulsive phenomenon are the most

frequent of the overt manifestation of neonatal neurological disorders.

Therefore it is important to recognize the seizures and treat it, as delay in

recognition and treatment may lead to brain damage.

The time of onset of seizures has relationship with the etiology and

prognosis. For example, birth asphyxia usually present in the first three days of life

whereas meningitis presents after first week. If baby convulse within hours of

delivery, it signifies poor prognosis and brain damage.

5

Annexure-II

Review of literature:

Epilepsy was known to ancient Babylonians and was described by Hippocrates

who considered it as disease of brain. Its history related by Temprin, spans that of

medicine itself.

Hughlings Jackson described seizures as “excessive discharge of nerve tissue

on muscle”. Jackson went on to say that this discharge occurs in all degrees, it occurs

with all sorts of conditions of ill health, at all ages and under innumerable

circumstances. these observations by Jackson remain as true today as they did 130

years ago.(1)

Von rosentein in 1776 stated that “lastly we may observe, to the great comfort

and satisfaction of the parents of those young children subject to convulsion or

epilepsia infantilis, that they need not be apprensive for its changing into the true

epilepsy, for it generally disappear by degree, as they grow older and acquire more

strength”.(2)

The great Swedish proto paediatrician V on rosentein in his rather optimistic

prognosis for early convulsions, showed remarkable insight not only in concerns of

the parents, but also into the tendencies towards spontaneous improvement. He clearly

recognised the distinction made between those young children, who are subjected to

seizures for a limited period and those who showed tendency to recurrent attacks

some what late, justifying the use of the word epilepsy.(3)

Epilepsy is the expression of occasional sudden excessive rapid local

discharge in the gray matter is of little practical use to paediatrician involved in the

problem of seizures. The discharge may result in an almost instantaneous loss of

6

consciousness, alteration of perception or impairment of psychic function, convulsive

movements, disturbance of sensation or some combination thereof.

A terminologic difficulty arises from the diversity of clinical manifestations.

The term convulsion, refering as it does to an intensive paroxysm of involuntary

repetitive muscular contractions, is inappropriate for a disorder that is known as an

alteration of sensation or consciousness. Seizure is preferable as a generic term, since

it enhances the diversity of paroxysmal events and also for the reason that it tends

itself to qualification.(4)

Seizures in the newborn are identified by direct clinical observation. However,

the findings of a series of studies performed largely on the past several years EEG

monitoring with simultaneous direct clinical observation, raise two important

possibilities about clinically identified neonatal seizures. First, some clinically

identified motor and behavioural phenomenon characterized as seizures do not have a

simultaneous EEG seizure correlate i.e, the number of certain seizures may have been

over estimated in the past. Second, many EEG seizures are not accompanied by

clinically observable alterations in neonatal motor or behavioural function, i.e, the

total number of neonatal seizures may have been underestimated in the past. The

revised classification of neonatal seizures by JJ Volpe were based on above findings.

A seizure may arise from varying foci at different times. Not all clinical

seizures are correlated with EEG changes and not all seizures shown on EEG

recordings are clinically apparent.(5)

7

The incidence varies from 1.5–3.7/ 1000 live births in term babies and 6-12% in

babies weighing less than 1500 grams.(6)

Types of seizures:

Four essential seizure types can be recognized in neonates according to the JJ

Volpe(7) i.e, (1) subtle, (2) clonic, (3) tonic, (4) myoclonic. Multifocal refers to

clinical activity that involves more than side, is asynchronous and usually is

migratory, where as generalized refers to clinical activity i.e, diffuse bilateral,

synchronous and non migratory.

8

Classification of neonatal seizures:

electrographic seizure

Clinical seizure -----------------------------------

Common uncommon

Subtle +

Clonic

Focal +

Multifocal +

Tonic

Focal +

Generalized +

Myoclonic

Focal, multifocal +

Generalized +

Common causes of neonatal seizures:

9

1) hypoxic ischemic encephalopathy (HIE)

2) Intracranial haemorrhage (ICH)

Intraventricular haemorrhage (IVH)

Subdural haemorrhage (SDH)

Subarachnoid haemorrhage (SAH)

Parenchymal haemorrhage

3) Central nervous system infections:

Intrauterine

Postnatal

4) Congenital malfomations:

induction anomalies

migration anomalies

5) Cerebrovascular syndrome

cerebral infarction

vascular infarction

6) Metabolic:

Electrolyte and chemical abnormalities

Neurometabolic disorders

10

7) Drug withdrawal and toxins

8) Benign neonatal seizures.

Most important etiologies and their usual time of onset:(8)

First day: HIE, hypocalcemia, pyridoxine dependency, accidental injection of

local anaesthetics.

Between 1-3 days: ICH, hypoglycaemia, inborn errors of metabolism.

4- 7 days: meningitis, TORCH infections, developmental malformations.

>7 days: late onset meningitis, late onset hypocalcemia.

11

Hypoxic Ischemic Encephalopathy (HIE)

HIE is the most common cause of neonatal seizures. Perinatal asphyxia

usually refers to an insult accompanied by decreased oxygen delivery to the

fetal/neonatal brain. When asphyxia is followed by abnormal neonatal behaviour, a

syndrome has been described as HIE. The hypoxic ischemic insult may result from

impaired placental exchange or blood flow from umbilical cord compression or may

occur postnatally as a result of neonatal respiratory or cardiac compromise.

Significant intra partum asphyxia usually results in birth of an infant with depressed

cardio-respiratory function evidenced by low apgar scores, which further

compramises the hypoxic ischemic insult. Following delivery, these infants display

alterations in consciousness, muscle tone and primitive reflexes, producing a

recognizable syndrome.(9)

12

Sarnat classified HIE into 3 stages depending on examination of

baby(10):

HIE 1 HIE 2 HIE 3

1. Level of consciousness Alert Lethargic Comatose

2. Muscle tone Normal Hypotonia Flaccid

3. Deep tendon reflexes Increased Increased Depressed

4. Myoclous + + -

5. Moro’s response exaggerated Incomplete Absent

6. Grasping Normal exaggerated Absent

7. Dolls eye Normal Overeactive Absent

8. Pupils Dilated Constricted Variable

9. Heart rate Normal/

tachycardia

Bradycardia Bradycardia

10. Seizures None Common Decerebrate

11. EEG Normal low voltage Isoelectric

13

Intracranial haemorrhage (ICH):

This is one of the important causes of neonatal seizures. The incidence

varies from 2 - >30% in newborns depending upon the gestational age at birth and the

type of ICH. Bleeding within the skull can occur:

External to the brain into epidural, subdural or subarachnoid spaces.

Into the parenchyma of cerebellum or cerebrum.

Into venticles from the sub ependymal germinal matrix or choroid plexus.

Subdural heamorrage (SDH) and epidural heamorrage:

The pathogenesis of SDH relates to rupture of the draining veins and sinuses

of brain that occupy the sub dural space. Vertical moulding, fronto occipital

elongation and torsional forces acting on the head during delivery may provoke

laceration of dural leaflets of either of falx cerebri or tentorium cerebelli. This results

in rupture of veins of galen, inferior sagital sinus and a posterior fossa SDH. Breech

presentation also predisposes to dipressed fracture of the occipital bone which may

lead to rupture of occipital sinus. SDH in the supratentorial space usually results from

rupture of bridging superficial veins over the cerebral convexity. Other risk factors for

SDH include large head size, rigid pelvis, prolonged labour, breech, face presentation,

difficult instrumental delivery, thrombocytopenia, vitamin C deficiency, haemophilia,

infection or disseminated intravascular coagulation.(11)

14

Subarachnoid haemorrhageSAH):

SAH is a common form of ICH among newborns. Primary SAH is probably

quiet frequent but clinically insignificant. Heamorrhagic/ xanthocromatic CSF may be

the only indication of such a haemorrhage. The source of bleeding is usually ruptured

bridging veins of the SA space of the ruptured small lepto meningial vessels. SAH

should be distinguished from the sub arachnoid extension of blood from germinal

matrix haemorrhage/ IVH, which occur most commonly in preterm infants.

Intraparanchymal haemorrhage(IPH):

Primary intracerebral IPH is uncommon in all newborns, while intra cerebellar

IPH is found in 5-10% of autopsy specimen in the premature infant. Commonly,

cerebral IPH occurs as a secondary event such as haemorrhage into a region of

hypoxic-ischemic brain injury. Iph may also occur as a result of venous infarction.

Intracerebellar haemorrhage:

occurs more commonly in the preterm newborns and may be missed by

routine cranial ultrasound. Intracerebellar IPH may be a primary haemorrhage or

result from venous haemorrhagic infarction or from extension of GMH/IVH.(12)

Hypocalcemia:

Neonatal hypocalcemia is defined as total serum calcium level <7.5 mg/dl in

preterm and <8 mg/dl in term infants. The exact level of hypocalcemia at which

seizure occur is debatable. An ionized fraction of 0.6 or less may have a more

predictable association with the occurance of seizures. Hypocalcemic is divided into

early onset and late onset types.(13)

15

Early onset hypocalcemia:

Hypocalcemia occurring during first three days of life is termed early neonatal

hypocalcemia. It is characteristically seen in any of the four circumstances.(14)

1. prematurity

2. severe stress

3. maternal diabetes

4. IUGR.

Late neonatal hypocalcemia:

Hypocalcemia develops after 3-5 days of life, occurs more frequently in term

newborns and is not correlated with meternal diabetes, birth trauma or asphyxia. It is

associated with cows milk and formula feeding.

Hyperphosphatemia is a prominent feature of late neonatal hypocalcemia.

Serum calcium level frequently increase when these infants are placed on a low

phosphate formula and calcium supplement. Maternal vitamin D deficiency can cause

late neonatal hypocalcemia.

Causes of neonatal hypocalcemia:

1. early onset

2. late onset

3. neonatal hypoparathroid syndromes.

4. abnormal vitamin D production.

5. hyperphosphatemia

6. hypomagnesemia (15)

16

ANNEXURE III

OBJECTIVES OF THE STUDY

1. To study the etiology of neonatal seizures.

2. To study the time of onset of neonatal seizures and its relationship with the

etiology.

3. To study the various types of presentation of seizures in neonates.

17

Annexure IV

Material and methods

7.1 source of data:

The study is conducted in neonates admitted in NICU of AL AMEEN

MEDICAL COLLEGE, BIJAPUR from july 2013 to june 2015.

7.2 sample size:

100-150 neonates (28 days of life).

7.3 setting:

The study is approved by ethical committee of AL AMEEN MEDICAL COLLEGE

BIJAPUR.

7.4 inclusion criteria:

Neonates (first 28 days of life) presenting with at least one of the following clinical

types of seizures:

generalized tonic seizures

multifocal clonic seizures

focal clonic seizures

myoclonic seizures

with or without accompaniment of subtle motor movements,

autonomic changes or the sole combination of subtle motor and

autonomic manifestation are included.

18

7.5 exclusion criteria:

1. neonates with isolated subtle phenomenon, apnea or paroxymal autonomic

changes, i.e, only subtle motor moments or apnea without tachycardia or

hypertension were excluded from the study.

2. jitteriness in neonates.

3. tetanic spasms in neonates.

Detailed antenatal, natal and post natal history were taken as per the performa

enclosed.

7.6 methods of collection of data:

In all the cases detailed history and presenting symptoms and signs with

clinical criteria is taken up for the study.

19

Annexure -V

8. Does the study require any investigation and intervention to be

conducted on patients, human or animals? If so please describe

briefly.

following investigations are to be done for this study:

complete blood count(haemoglobin, total count, differential count)

sepsis screening: peripheral smear, CRP an blood culture if necessary.

Blood glucose.

Serum electrolytes

Serum calcium

Serum magnesium

Serum pyridoxine

Drug levels:

- Phenobarbitone

- phenytoin

CSF analysis: in cases where meningitis is suspected.

20

Radiologic investigations:

Cranium USG.

CT scan of head.

21

ANNEXURE VI

LIST OF REFERENCES:

1. Holmes gregory L, khazipov roustem, Beni-ari yehezkiel. New concepts in

neonatal seizures,

2. Rosenstein von diseases of children and their remedies. British edition,

1776.

3. Brett EM. Epilepsy & convulsions, In: textbook of paediatric neuorology,

Churchill livingstone, new york.275-276:1983.

4. Victor Maurice, ropper AH. Epilepsy and other seizure disorders, in: adam

& victors principles of neurology,7th edition, McGraw Hill, USA(new york),

331-332:2001

5. Evans david, levene malcom. Neonatal seizures. Archives of disease in

childhood, jan 1998; vol.78(1):70F-75F.

6. Rennie jannet, boylan Geraldine. Neonatal seizures and their treatment.

Current opinion on neurology, april 2003; vol. 16(2): 177-181.

7. Volpe jj. Neonatal seizures. Current concepts and revised classification.

Paediatrics, sept 1989;84(3): 422-428.

8. Bernes Saunders M, kalpan Allen M. evolution of neonatal seizures.

Paediatric clinics of north America, oct. 1994;41(5):1072-1073.

9. Finer NN et al. hypoxic ischemic encephalopathy in term neonates; Perinatal

factors and outcome. The journal of paediatrics, jan 1981;98(1): 112-117.

10. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: A

clinical and EEG study. Arch neurol. 1976; 33:696-705.

22

11. Haase Ronald et al. Acute subdural hematoma after caesarean section. A

case report. Paediatric critical care medicine, April 2003; 4(2): 246-248.

12. Soul Janet S. Intracranial haemorrhage. In: Manual of neonatal care.

Lippincott Williams & Wilkins Philadelphia, 5th Edition; 523-527:2004

13. Keen JH, Lee L. sequelae of neonatal convulsions. Archives of disease in

childhood, 1973; 48: 541-542.

14. Sheth Dipak. Hypocalcemic seizures in neonates. The American journal of

emergency medicine, 1997; 15(7): 638-641.

15. Lynch Brayn J and Rust Robert S. Natural history and out come of neonatal

hypocalcemic and hypomagnesemic seizures. Paediatric Neurology, july

1994; 11(1): 23-27.

23

PERFORMA

Name: sl no.:

Age: DOB:

Sex: DOA:

Address: DOD:

I.P No.:

Informant:

CHIEF COMPLAINTS:

History of seizure since:

Started on ________ day of birth

Duration of seizures

Type of seizures a) subtle b) generalized tonic

c) myoclonic d) multifocal clonic

e) myoclonic f) mixed

How often

Consciousness during attack and in between seizures

History of fever

History of refusal to feeds

History of excessive cry

History of vomiting

24

FAMILY HISTORY:

History of consanguinity:

History of birth order of child:

History of similar complaints in siblings:

History of neurological disorder in other siblings:

ANTENATAL HISTORY:

Age of mother:

Parity of mother:

HISTORY OF

Regular antenatal checkup:

Fibrile illness during pregnancy:

Maternal toxaemia & PIH:

Diabetes:

Intake or administration of any drugs:

Prenatal steroid given:

PV leak & PV bleeding:

Oligohydromnios/ poluhydromnios:

Injection of TT:

Duration of labour: 1st stage 2nd stage 3rd stage

25

BIRTH HISTORY:

Place of delivery

Gestation: term/ preterm/ post term

Foetal growth: AFD/ SFD/ LFD

LBW:

Type of delivery: normal/ caesarean/ forceps/ assisted

Apgar score: 1”minute 5”minute

Cried immediately after birth/ any resuscitation done

Meconium stained/ foul smelling liquor/ PROM

Umbilical catheterization/ bleeding

h/o birth injury

h/o local anaesthesia injection

POST NATAL HISTORY:

Activity of the baby:

Breast feeding started after:

History of difficulty in feeding:

History of jaundice – onset/ duration/ treatment received:

26

GENERAL PHYSICAL EXAMINATION:

General appearance and posture of baby

Any external congenital anomalies:

Head - size and shape

- hair distribution

- anterior fontanelle

- caput/ cephal haematoma

Eyes

Cyanosis

Icterus

Dehydration

Skin

Umbilicus

Anthropometry

Head circumference

Chest circumference

Length ratio US LS

Birth Weight gms. Present weight

27

Vital signs:

Heart rate

Respiratory rate

Blood pressure

Temperature

Gestational age ________ weeks.

SYSTEMIC EXAMINATION

Central nervous system:

1. Higher mental functions

2. Cranial nerves

3. Motor examination: tone

power

involuntary movements

Reflexes: superficial: abdominal

Cremastric

Deep: Biceps

Triceps

Knee

28

Ankle

4. Neonatal reflexes: Moro’s

Sucking/ rooting

Palmar grasp

Tonic neck reflex

4. skull/ spine: modified sarnat staging of HIE.

Abdominal examination:

Respiratory system:

Cardiovascular system:

INVESTIGATIONS:

1. Complete blood count, CRP, Blood culture

2. Serum electrolytes

- RBS,

- Serum calcium,

- Serum magnesium

- Serum pyridoxine

- Serum phospahate

3. Cranial CT

4. IEM study

5. CSF analysis

6. Drug level

FINAL DIGNOSIS:

29

TREATMENT GIVEN:

REMARKS:

ANNEXURE VII

ETHICAL COMMITTEE

AL-AMEEN MEDICAL COLLEGE BIJAPUR

The following study entitled “A STUDY OF ETIOLOGY, ONSET

AND CLINICAL MANIFESTATIONS OF NEONATAL SEIZURES” by

Dr. JAFAR MOIDEEN KUTTY P.G. student in department of paediatrics

belonging to 2013-2014 batch has been cleared from ethical committee of this

institution for the purpose of dissertation work.

Chairman

Ethical committee

Al- Ameen medical

college, Bijapur.

30