3. Introduction
• A seizure is a transient occurrence of signs and/or symptoms resulting
from abnormal excessive or synchronous neuronal activity in the
brain.
• Incidence - 57.5 per 1000 in infants with birth weights <1500 g
2.8 per 1000 for infants with birth weight 2500 to 3999 g.
• Recognition and evaluation of seizure is necessary
-Related to significant illness
-Interfere with important supportive measures
- Brain injury.
5. Neuroanatomical Features
1. Lamination of cortical neurons- Attainment of proper
- orientation
- alignment
- layering
2. Myelination
-Neurite outgrowth- Elaboration of axonal and dendritic ramifications
-Synaptogenesis - Establishment of synaptic connections.
Deficient myelination in new born and relatively advanced cortical
development in limbic structures and the connections of these structures to
diencephalon and brain stem causes– Predominant oral-buccal-lingual
movements
6. Neurophysiological features
• In limbic and neocortical regions, development of excitatory
mechanisms before inhibitory mechanisms that enhances excitation
- NMDA receptors overexpressed & exhibit multiple properties
- AMPA receptors overexpressed & have deficient GluR2 subunit
- GABAA receptors excitatory rather than inhibitory
• Deficient development of substantia nigra system for inhibition of
seizures
• Impaired propagation of electrical seizures, and resulting lack of
correlation of synchronous discharges recorded from surface
electroencephalogram with behavioural seizure phenomena
7. Critical Development Relationships of Neuronal Chloride
Levels and Chloride Transport in Excitation of GABA
• GABA is excitatory rather inhibitory in perinatal neurons because of elevated
neuronal Cl .
• GABAA receptor activation therefore causes Cl efflux and depolarization
(excitation) rather than influx and hyperpolarization (inhibition).
• Elevated neuronal Cl levels result in the perinatal period because of exuberant
development of NKCC1, which mediates Cl influx, in the presence of
developmentally low levels of KCC2, which mediates Cl! efflux.
• With development, NKCC1 declines, KCC2 increases, and thus neuronal Cl levels
decrease; GABAA receptor activation then results in Cl! influx and
hyperpolarization (inhibition).
• These developmental changes may explain the imperfect response of neonatal
seizures to GABA-agonist anticonvulsant drugs
17. Clinical aspects
• A seizure is defined clinically as a paroxysmal alteration in neurological
function (i.e., behavioural, motor, or autonomic function) associated
temporally with (surface-recorded) EEG seizure activity.
Classification
• Subtle
• Clonic
Focal
Multifocal
• Tonic
Focal
Generalized
• Myoclonic
Focal, multifocal
Generalized
18. Subtle seizures
• Ocular phenomena
Tonic horizontal deviation of eyes with or without jerking of eyes
Sustained eye opening with ocular fixation
• Peculiar extremity movements (e.g., resembling ‘‘boxing’’ or cycling
‘‘hooking’’ peddling movements),
• Oral-buccal-lingual movements like Chewing, lip smacking
• Apnoea – term newborn than in preterm
The most common manifestations of subtle seizure- ocular phenomena.
In premature infants- sustained eye opening with ocular fixation
In term infants- horizontal deviation of the eyes
19.
20. Clonic seizures
• Associated most consistently with time-synchronized EEG seizure
activity.
• Rhythmic and usually rather slow approximately one to three jerks
per second at the onset with the rate progressively declining with the
seizure
• Types
1. Focal clonic seizures
Involve the face, upper or lower extremities on one side of the
body, or axial structures (neck or trunk) on one side of the body
. Associated with metabolic encephalopathies
21. Clonic seizures
2. Multifocal clonic seizures
involve several body parts often in a migrating fashion, although
the migration most often ‘‘marches’’ in a nonjacksonian manner
3. Generalized clonic seizures
Diffusely bilateral, generally symmetrical, and synchronous
movements are rarely observed in the newborn.
22. Tonic seizures
• Tonic seizures are not commonly associated with time-synchronized
EEG discharges
• Types
• 1. Focal tonic seizures- most common, consist of sustained
posturing of a limb or asymmetrical posturing of trunk or neck
Consistently associated with EEG seizure discharges
2. Generalized tonic seizures- Characterized most commonly by
tonic extension of both upper and lower extremities (mimicking
‘‘decerebrate’’ posturing) but also by tonic flexion of upper extremities
with extension of lower extremities (mimicking ‘‘decorticate’’
posturing)
23. Myoclonic seizures
• Myoclonic seizures are most commonly unassociated with time-
synchronized EEG discharges
• Distinguished from clonic movements because of the faster speed of
the myoclonic jerk and the particular predilection for flexor muscle
groups
• Types
1. Focal
2. Multifocal
3. Generalized
24. Types of myoclonic seizures
• 1. Focal myoclonic seizures typically involve flexor muscles of an
upper extremity
• 2. Multifocal myoclonic seizures are characterized by asynchronous
twitching of several parts of the body
• 3. Generalized myoclonic seizures are characterized by bilateral jerks
of flexion of upper and occasionally of lower limbs. These seizures
may appear identical to the infantile spasms observed in older
infants. Generalized myoclonic seizures are more likely to be
associated with EEG seizure discharges than are focal or multifocal
myoclonic
25.
26.
27.
28. Neonatal Clinical Seizures Not Accompanied
by Electroencephalographic Seizure Activity
Pathophysiology
• Such seizures include certain subtle seizures, most generalized tonic
seizures, and the focal and multifocal examples of myoclonic seizures
• myoclonic jerks may originate as isolated events from several levels of
the nervous system (i.e., brain stem and spinal cord, as well as
cerebral cortex) many of these seizures do not have an EEG correlate
• ‘‘tonic posturing and motor automatisms may be primitive brain stem
and spinal motor patterns released from the tonic inhibition normally
exerted by forebrain structures,’’ that is, ‘‘brain stem release
phenomena- motor automatism in subtle seizures and most
generalized tonic seizures.
29. • Epileptic phenomena can occur in the absence of surface-recorded
EEG discharges, and such phenomena can be generated at subcortical
(i.e., deep limbic, diencephalic, brain stem) levels.
• Brain stem structure, the inferior colliculus, can generate an electrical
seizure that is accompanied by clinical activity highly reminiscent of
the subtle seizure of the human newborn.
• Neurons of the inferior colliculus of the newborn are particularly
sensitive to injury by hypoxic-ischemic insults.
31. Etiology
1. Hypoxic-Ischemic Encephalopathy
- single most common cause of neonatal seizures in both full-term
and premature infants
- seizure occur in the first 24 hours
- In 60% seizures secondary to this type of encephalopathy onset of
spells within 12 hours of birth
- Subtle seizures, multifocal clonic or focal clonic seizures are also
particularly common.
- Focal cerebral ischemic injury associated with focal clonic seizures.
32. 2. Intracranial haemorrhage
- more common in preterm
- 15% of term infants have intracranial haemorrhage as the
primary cause of their spells.
3. primary subarachnoid haemorrhage
- although very common, not of major clinical significance
- onset on the second postnatal day
33. • 4. Germinal Matrix-Intraventricular Haemorrhage
- Emanating from small blood vessels in the subependymal
germinal matrix
- Principally a lesion of the premature infant
- occurring in the first 3 days of life.
- develop periventricular haemorrhagic infarction in association
with severe IVH most often develop the parenchymal lesion and the
seizures in the latter part of the first week of life
34. 5. Subdural haemorrhage
- often associated with a traumatic event & cerebral contusion
-most common variety is the convexity type
-seizures are often focal
- 50% of seizure in the first 48 hours of life
6. Intracranial Infections
- 5% to 10% cases
- sepsis early as well late onset
-TORCH infections
35. 6. Developmental Defects
- 5 to 10 %
- cerebral cortical dysgenesis, related most commonly to a disturbance
of neuronal migration
- lissencephaly, pachygyria, and polymicrogyria
7. Metabolic Disturbances
- disturbances in the levels of glucose, calcium, magnesium,
electrolytes
- amino acids, organic acids, blood ammonia and other metabolites
certain intoxications especially with local anaesthetics
- mitochondrial or peroxisomal disturbance; pyridoxine and folinic acid
responsive seizures and glucose transporter deficiency
38. Pyridoxine dependency
• Defect in pyridoxine metabolism may produce severe seizures,
recalcitrant to all therapy.
• The usual time of onset is the first hours of life, but intrauterine
seizures as well as onset after the neonatal period have been
observed.
• Seizures are usually multifocal clonic and recalcitrant to all
therapeutic modalities
40. Ten minutes after vitamin B6 injection. The discharges have subsided
and the patient shows normal sleep background with early sleep
spindles appearing in the tracing
• From Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT: Pyridoxine-dependent epilepsy:
EEG investigations and long-term follow-up, Electroencephalogr Clin Neurophysiol 78:215-221, 1991.
41. Folinic acid–responsive seizures
- Onset as early as the first hours of life
- Responsiveness to oral administration of folinic acid
- Presence on CSF analysis for monoamine neurotransmitters
- Discontinuous EEG pattern with multifocal sharp waves
- Progressive cerebral cortical and white matter atrophy
- Doses ranging from 2 to 20 mg twice daily
42. Glucose transporter disorder(DeVivo’s syndrome)
• A disorder of glucose transport from blood to brain
• Important to recognize because prompt treatment can lead to
cessation of seizures and improved neurological development.
• Low glucose concentrations in CSF with normal blood glucose
concentration.
• Mean ratio of CSF to blood glucose has been 37%.
• Defect of the glucose transporter (Glut1) responsible for the
facilitative diffusion of glucose across the blood-brain endothelial
barrier and across the neuronal plasma membrane
• Treatment with a ketogenic diet, which supplies metabolic fuel for
brain energy metabolism not transported by the glucose transporter
43.
44. Benign Familial Neonatal Seizures
• Onset of seizures is usually on the second or third postnatal day
• in the interictally period the infants appear well.
• Seizures occur with a frequency of 10 to 20 per day or even higher.
• The episodes most often are focal clonic or focal tonic
• Initial brief period of EEG flattening followed by a bilateral discharge of spikes and
slow waves
• 10 to 15% of infants exhibit subsequent nonfebrile seizures and may require long-
term anticonvulsant therapy.
• Neurological development is normal.
• autosomal dominant inheritance with incomplete penetrance.
• Two separate chromosomal loci have been identified (i.e., chromosome 20q13.3
and chromosome 8q24).
• Both genes encode voltage-gated K+ channels (KCNQ2 on chromosome 20 and
KCNQ3 on chromosome 8)