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Frontal lobe glucose abnormalities may indicate increased SUDEP risk


Certain patterns of frontal lobe glucose hypometabolism may be associated with higher risk for sudden unexpected death in epilepsy (SUDEP) among patients with refractory focal epilepsy, new research suggests.

“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.

If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.

The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.


Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.

“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.

In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.

The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.

The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.

The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.

The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).

The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.

The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.

“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”

Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.

A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.

MRI findings were normal for 40 patients.

Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”

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