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 series of PET images 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