Role of Imaging in pediatric epilepsy
Summary: An epileptic seizure is a clinical manifestation of abnormal, excessive neuronal activity arising in the gray matter of the cerebral cortex. Epilepsy in the pediatric population is fairly a common problem in day today practice. Recent advances in the imaging sciences has revolutionized the diagnosis and management of all types of epilepsies, especially with the advent of epilepsy surgery, detailed imaging has become mandatory. Yet the crucial aspect of assessment is not the radiological, but the clinical history and examination. Imaging is not required in all cases of childhood epilepsy, a proper clinical history is thus essential to identify the epileptic seizure. This group includes idiopathic generalized epilepsy (benign myoclonic epilepsy of infancy, childhood absence epilepsy, juvenile absence epilepsy juvenile myoclonic epilepsy) or benign epilepsy of childhood with Centro temporal spike where imaging is usually not necessary. CT and MRI are routinely used for imaging purpose ,though in an ideal situation MR should be the choice of imaging modality except in those cases calcification is to be ruled out, CT plays a major role. Out of common causes of epilepsy where imaging is necessary include hypoxic ischaemic encephalopathy, congenital abnormalities, mesial temporal sclerosis, infections, tumors and vascular malformation.
Diagnosis of epilepsy involves four stages.
· Recognition of epileptic seizure
· Classification of seizure types
· Identification of epilepsy syndrome
· Identification of the underlying etiology
These can be achieved by clinical including family history, examination findings, EEG including video imaging, blood tests, metabolic screening and lastly neuroimaging.
Indications for imaging
MRI is particularly indicated in patients with one or more of the following (Ideal practice)
International league against epilepsy.
· Onset of seizures at any age with evidence of a partial onset on clinical or EEG findings
· Onset of unclassified seizures or apparently generalized seizures in first year of life or in adulthood.
· Evidence of focal fixed deficit in clinical or EEG findings
· Failure to control the fits with first line of drugs
· Failure to control fits or change in the seizure pattern.
Neuroimaging is not done with a definite EEG evidence of idiopathic generalized epilepsy like benign myoclonic epilepsy of infancy, childhood absence epilepsy, Juvenile absence epilepsy ,JME and benign epilepsy of childhood with Centro temporal spikes.
Aim of neuroimaging
· To identify underlying pathology
· To aid the formulation of syndromic and etiological diagnosis.
· CT scanning
· Nuclear medicine SPECT and PET
· Plain X-ray
· Routine study,
· Dedicated seizure sequences,
· Functional MRI (fMRI)
Routine MR study
Conventional sequences aims to find out any overt structural lesion in the brain. Axial, coronal and sagittal sequences with T1 and T2 weighted images are obtained. Additional FLAIR sequence is helpful to detect minor signal alteration.
Dedicated seizure protocol
This is necessary when no gross pathology is found in the routine sequences. This is done specially in the temporal lobe epilepsy to demonstrate any lesion in the structures of the medial temporal lobe.
· Heavily T2 weighted sequence in coronal plane
· T1 inversion recovery sequence in oblique coronal (the
right angles to the hippocampus).
· Hippocampal volumetric study to study the size and asymmetry
· T2 relaxometry ( T2 mapping) for Hippocampus and amygdala
This is necessary when question of epilepsy surgery is considered. The technique used is called BOLD.(Blood Oxygen Level Dependant ).Patient is asked to perform some activity. The activated areas of the cerebral cortex will have increased blood flow without increase in the oxygen consumption suggesting anaerobic metabolism. This leads to increase in the oxyhaemoglobin level in the activated area. Deoxyhaemoglobin is paramagnetic and affects the T2 signal. The signal intensity in the activated area becomes different from the rest of the brain where the deoxyhaemoglobin predominates. In the activated area the T2 signal is preserved. This is the basis of BOLD. This difference in signal can be depicted in map. Increased BOLD signal can be obtained in the seizure focus in the interictal states in sites of EEG discharge. The main application of this in seizure is localization of motor strip.
By MR spectroscopy brain metabolites are analysed. Usually proton magnetic spectroscopy is performed. N-acetyl aspartate, choline and creatine. With neuronal loss the NAA level is reduced and in gliosis and astrocytosis the Creatine and Choline are increased. These can be analysed quantitavely or in graphical manner.
CT can be used as an initial screening procedure for overt tumours, infection etc, however MRI is preferred due to lack of radiation, increased spatial resolution and multiplanar capability. CT is specifically indicated to find out calcific foci.
Nuclear medicine: SPECT- ictal, post ictal and interictal SPECT
PET- glucose metabolism
Plain radiography- Limited role.
Imaging can be discussed according specific seizures
· Temporal lobe epilepsy
· Other Focal seizures
Temporal lobe epilepsy
This is complex partial seizure where the focus is generally in the temporal lobes. Causes can be divided into following category.
Mesial temporal sclerosis – Hippocampal sclerosis
– Hippocampal sclerosis and other temporal lobe abnormality
– Hippocampal sclerosis and extratemporal abnormalities
– Amygdalar sclerosis
Structural lesions Tumours
Congenital and developmental lesions
Mesial temporal sclerosis
In this condition there is gliosis and neuronal loss involving the structures of mesial temporal lobe. Mesial temporal structures include hippocampus, parahippocampal gyrus, amygdala, entohinal cortex and subiculum.
This is condition in which there is focal sclerosis in the hippocampus. It is the most common cause of intractable epilepsy. Hippocampal sclerosis is important in epilepsy because
· It is the commonest lesion found in intractable epilepsy
· It is epileptogenic
· Identification of epileptic surgery
· Altered signal in the hippocampus
· Ipsilateral temporal horn dilatation
· Reduced hippocampal volume
· T2 relaxometry-increased signal
· Loss of grey white demarcation
Hippocampal sclerosis and extratemporal structural abnormality.
Other Focal seizures:
In most of the cases CT and routine MR sequences are enough to give an etiological diagnosis. The common causes of paediatric importance can be broadly classified as followed-:
· Congenital and developmental abnormality.
· Hypoxic ischaemic lesions
· White matter diseases
· Infections and infestation
Congenital and developmental abnormalities
Neuronal migration disorders:
This is one of the common conditions causing seizures in the paediatric population and most of the time this is under diagnosed. This is a condition were there is incomplete or abnormal migration of neurons from the germinal matrix to the cerebral cortex. During 7th weeks of gestation proliferation of neurons occur in the subependymal layer in the wall of lateral ventricles. This is area is called germinal matrix. From this region neurons start migrating to its final destination from 8th weeks of gestation and continues upto 20th week of gestation.
Lissencephaly means smooth brain. There is paucity of sulcal development. If there is arrest of migration then it produces classical lissencephaly and when there is over migration the it produces cobblestone lissencephaly.
Classical lissencephaly the patient present with DDM and seizure. There is hypotonia at birth and spasticity at later life. There may be infantile spasm and medically refractory epilepsy at early age. Systemic abnormalities in heart, ear, eyes and kidneys may be present. On imaging there is smooth brain, shallow vertically oriented sylvian fissures giving rise to figure of 8 appearance. There is a zone of white matter separating the thin superficial cortical gray matter from thick layer of gray matter. There is reduced white matter density.
Collection of nerve cells in abnormal location due to arrest of migration. Patients invariably presents with seizure. Some of them presents with medically refractory epilepsy. Three types of heterotopia.
In subependymal heterotopia presents with normal development, normal motor function and seizure disorder. In focal subcortical Type there is medically refractory seizure and delayed motor development. In band heterotopia there is delayed developmental mile stones and seizure.
These are gray matter lined clefts extending from the pial surface to the subependymal layer. These may be closed lip when the lips are closed and open lip when the lips are open. This may be unilateral or bilateral, symmetrical or asymmetrical. Symptoms are more sever in the bilateral type. Varible motor dysfunction and seizures are common features.
Abnormal too many gyri separated by shallow sulci. Histologically there is laminar cortical necrosis in the cortical layer V .The cortical layer II, III, IV are normal. 90% patients present with seizures.
Focal cortical dysplasia
Focal abnormality in the cerebral cortex which may be trivial to be diagnosed in the MR scans. In mild cases there is mild blurring in the grey white junction. In others there may be flat smooth gyri( pachygyria) . Histologically they are not associated with abnormal balloon cells extending from cortex to the lateral ventricular wall.
Focal transmantle cortical dysplasia.
Here there is abnormal cells extending from the walls of the ventricles to the cortex. Histologically abnormal cells are seen in the cortex and in the underlying white matter. Abnormal cells include large atypical neurons, atypical glial cells, and balloon cells mixed with normal neurons. On imaging the involved portion is large, abnormal cortical pattern, broad gyri, irregular sulci.There is change in the signal intensity also .A Hyperintense linear line is seen extending from the abnormal cortex to the lateral ventricular wall. The gray white matter junction is blurred.
Neuro-cutaneous syndrome :
Four types of these, out of which the tuberous sclerosis usually presents with Seizure.
These patients presents with classical triad.- seizure, adenoma sebaceum and delayed developmental milestones. The pathogenesis of this entity is uncertain, however this it thought to be due to disordered migration of dysgenetic neurons. There are four types of CNS lesions may be present.
· Cortical Tubers
· White matter abnormality
· Subependymal nodules
· Subependymal giant cell Astrocytoma.
Hypoxic ischaemic lesions
Localized infarction: –
These patients have variable presentation. Neonates typically present with seizures, hypotonia and lethargy whereas infants present with hand preference. In older children representation is like adults.
All most in 50 % of local brain infarction the cause is not known. In patients where cause is identified commonly related to cyanotic heart disease, sickle cell disease and moya moya disease. There are other metabolic causes of stroke in children. Imaging appearance are similar to that of older children and adult.
Diffuse ischaemic brain insult: –
Antenatal, postnatal and perinatal vascular events ,either hypoxic , ischaemic or hemorrhagic
May lead to wide range of abnormalities . Most of these insults will produce seizures at a later life .
Three factors are responsible for different pattern of brain injury.
Severity of hypotension.
Maturity of brain at the time of insult.
Duration of insult.
Severity of hypotension :-
In mild to moderate hypotension blood flow is shunted from anterior to posterior circulation. To maintain perfusion in brainstem, cerebellum and basal ganglia. Watershed zones of cerebral hemispheres are effected. In profound hypotension shunting is not possible so deeper structures like thalamus, basal ganglia and brain stem are affected.
Maturity of brain at the time of insult :-
Knowledge of blood circulation to the brain is necessary to understand the hypoxic damage to the neonatal brain. There are two sets of vessels. One cortical vessels the penetrate and they anastomose with the ventricular vessels in the periventricular region. In premature brain the cortical branches anastomose with the ventricular vessels in immediate periventricular region whereas in mature infant the anastomosing zone shifted to the peripherally. If ischaemic injury occurs in premature infant the infarctions are located in the immediate periventricular regions. But in mature infant or older children the infarctions are watershed zone and the subcortical periventricular white matter. The periventricular region contains the corticospinal tracts. These tracts are arranged in such a way that the immediate periventricular region contains fibres for the legs so bilateral involvement produces spastic diplegia at a later date. Again the geniculocalcarine fibres also travel in the peritrigonal region so most of these child suffers from visual abnormality.
· Both meningitis and encephalitis can produce seizures.
· Parenchymal infections like tuberculomas and cysticercosis frequently produces seizures. Cerebral abscesses rarely produce seizures.
· Congenital infections –
D/D of ring lesion.
· Micro abscess
· Vascular lesion
· Demyelinating lesions
Cysticercosis Vs Tuberculoma
· Eccentric nodule
MRI in ring lesions
MRI is superior to CT scan in differentiating the different ring lesions. It is much more efficient diagnosing cysticercus cyst. A classical granuloma is identified by T2 hypointense Signal. A vascular lesion like aneurysm and AVM is seen as flow void if it associated with high flow.
Congenital infections include Cytomegalovirus, Toxoplasmosis, Rubella, Herpes simplex, HIV and Syphilis etc.
Cytomegalovirus infection: There are parenchymal calcifications predilection for the periventricular region. There is ventriculomegaly, atrophic changes, delayed Myelination and neuronal migration disorder.
There are parenchymal calcifications not specific for periventricular region hydrocephalus and atrophy. No migrational disorder is noted.
Four types vascular malformation is seen
· Arteriovenous malformation
· Cavernous angioma
· Capillary telangectasis
· Venous angioma.
Though most of the tumors present with raised ICP some of the tumors grow very slowly like temporal lobe glioma, DNET, gangliglioma and oligodendroglioma etc.