Joint Program in Nuclear Medicine
Ictal PET Imaging in Status Epilepticus
David A. Israel, MD PhD
Alan J. Fischman, MD PhD
September 28, 1999
Presentation
A previously well 9 year old girl presented with onset of seizures, continuing
in chronic epilepsia continuans for 2 months. She was febrile, and the
ESR was elevated. Despite exhaustive workup, the etiology remained unknown;
a brain biopsy was non-diagnostic, showing only "gliosis and astrocytosis".
She was maintained in a pentobarbital coma to control her continuing seizure
activity.
Imaging Technique
Positron Emission Tomography
8.6 milliCuries of 18-FluoroDeoxyGlucose were administered intravenously
with the patient in a pentobarbital-induced coma. 45 minutes after injection,
tomographic images of the head were obtained. PET imaging was repeated
after a 2-week interval (with better pharmacologic control of the seizure
activity) to assess for change (10.5 mCi FDG).
Magnetic Resonance Imaging
T1-weighted, T2-weighted, and FLAIR images were obtained with the patient
in a pentobarbital-induced coma.
Imaging Findings
Magnetic Resonance Imaging
Selected axial T2-weighted and FLAIR images
show diffuse signal abnormalities in a large portion of the right cerebral
hemisphere, consistent with diffuse cerebral edema. No focal abnormality
is demonstrated.
18-FDG Positron Emission Tomography
The first FDG PET study show increased metabolic
activity throughout much of the right cerebral hemisphere, similar in distribution
to the abnormalities on MRI one day prior. There is an extensive area of
markedly increased tracer accumulation in the right cerebral hemisphere,
encompassing the right insula, inferior frontal lobe, middle frontal gyrus
and the entire superior portion of the right frontal and anterior right
parietal lobes. There is also markedly increased uptake in the right lentiform
nucleus and thalamus. There is more subtle but clearly abnormal increased
uptake in the lentiform nucleus on the left. There is increased uptake
in the left cerebellum. The findings are consistent with persistent seizures
during FDG imaging.
The repeat study performed 2 weeks later
shows a more focal site of FDG uptake in the cortex in the precentral gyrus
and the superior frontal gyrus regions. This represents a small subset
of the total area of uptake on the previous study. The thalamic activation
seen on the prior study is no longer appreciable, and the cerebellar uptake
is symmetric. There continues to be mildly increased bilaterally symmetric
uptake in the basal ganglia.
PET - MRI Fusion Images
Ictal FDG images reflecting metabolic rate of glucose were registered with
T1-weighted MR images (registered axial images,
coronally-sliced
3D reconstruction).
Discussion
Epilepsy is not a disease per se, but rather a collection of conditions
characterized by recurrent spontaneous seizures. CNS abnormalities due
to a wide variety of causes, including congenital (both inherited and developmental),
infectious, inflammatory, metabolic, vascular, neoplastic, and traumatic,
may result in epilepsy. A number of different pathophysiologic mechanisms
have been identified, at the level of individual neurons, at the level
of populations of interconnected neurons, and at the tissue level (involving
vascular and glial components), reflecting the variety of etiologies. While
over 10% of the population will have at least one seizure in their lifetime,
only between 1-2% of the population will develop epilepsy.
The term status epilepticus applies to a variety of "epileptic seizures
that are sufficiently prolonged or repeated at sufficiently brief intervals
so as to produce an unvarying and enduring epileptic condition" (Gastaut,
1973). The incidence of status epilepticus in the general population has
been estimated to be between 440 to 650 cases per million population per
annum. Among all adult patients presenting with seizures, approximately
4% will have one or more episodes of status epilepticus, whereas in children
with seizures, 16% will have a presentation of status epilepticus. Seizures
in status epilepticus may be either non-convulsive or convulsive ("tonic-clonic").
Convulsive status epilepticus is a medical emergency because it may lead
to permanent brain damage or death. Physiologic alterations during prolonged
tonic-clonic seizures include hyperpyrexia, systemic hypotension with resultant
systemic and cerebral hypoperfusion and hypoxia, and acidosis. Sequelae
include circulatory collapse, pulmonary edema, renal failure, aspiration,
electrolyte disturbances and myoglobinuria. Focal sclerotic changes have
been identified within the brain histologically.
The primary therapy of epilepsy is pharmacologic, and the majority of
patients with primary generalized seizures are well-controlled medically.
The primary anti-epileptic drugs are phenobarbital, phenytoin, carbamazepine,
ethosuximide, valproate, and the benzodiazepines; newer and experimental
agents also exist. However, some patients cannot be controlled pharmacologically
or suffer intractable side-effects such as marrow suppression. Medical
management is less successful in complex partial epilepsies, failing in
up to 45% of these cases. Intractable epilepsy which has failed medical
management can be treated by surgical resection of the seizure focus with
a 65% to 85% success rate. The majority of these partial epilepsies (85%)
arise from the temporal lobe, hence the most common surgical procedure
is resection of the anterior temporal lobe. Resectional surgery requires
accurate identification of the seizure focus. A combination of methods
may be used for this purpose, including recording of EEG by scalp electrodes
and sometimes by surgically placed depth electrodes, MRI, SPECT scanning
with cerebral blood flow agents, and PET scanning with 18-FDG and other
tracers. Only the use of FDG PET is considered here (for a detailed discussion
of all imaging methods, please see reference 1).
18-FDG Positron Emission Tomography in the Pre-surgical Evaluation of Epilepsy
Tomographic PET images are typically acquired 30 to 45 minutes following
the IV administration of FDG. In most cases, injection and imaging are
performed in the inter-ictal state. In the typical case of a patient with
complex partial seizures, the abnormal finding is unilateral inter-ictal
hypometabolism, or decrease in cerebral metabolic rate of glucose, located
in the temporal lobe. Such a finding is closely correlated with the presence
of a lesion histologically in surgically resected cases, and can be present
even in cases where no lesion is detectable on MRI scanning. When visible
on both modalities, the apparent size of the lesion is greater on PET than
on MRI, probably due to a combination of physiologic and technical factors.
Many centers combine the PET and MRI images into fusion images for better
anatomic localization.
Ictal FDG-PET studies of epilepsy are not usually practical because
the high cost and short half-life of 18-FDG (109 minutes) prohibit waiting
for the chance occurrence of a seizure for tracer injection (as is routinely
done with SPECT cerebral perfusion tracers, for example). When ictal PET
studies are performed (as in the case presented here), the typical finding
is an increased metabolic rate of glucose in the region of the seizure
focus, which shows a decreased rate inter-ictally. Because of the spread
of seizure activity by stimulation of surrounding areas, which then also
exhibit increased metabolic rate and tracer uptake, the localization provided
by an ictal scan may not be as accurate as than seen on an inter-ictal
study (as seen in the first set of PET images in the case presented here).
Conclusion
The typical role of PET scanning in the management of intractable epilepsy
is in the identification of a region of inter-ictal hypometabolism, most
often in the temporal lobe. The atypical case presented here demonstrates
the use of PET in the localization of the hypermetabolic epicenter of seizure
activity in the ictal state.
References
1. Cascino, G., Jack, C. Eds. Neuroimaging in Epilepsy: Principles and
Practice; Butterworth-Heinemann, Boston 1996.
2. Shorvon, S. Status Epilepticus; Cambridge University Press, Cambridge
1994.
3. Froscher, W. Treatment of Status Epilepticus; University Park Press,
Baltimore 1979.
4. Henry, T.R. Functional Neuroimaging with Positron Emission Tomography,
Epilepsia 37(12):1141-1154 1996.
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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu
