Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments

Abstract

Summary:Purpose: To determine gender differences of hypometabolism and their implications for cognitive impairment in patients with medically refractory mesial temporal lobe epilepsy (mTLE).Methods: Regional cerebral glucose metabolism (rCMRGlu) was studied in 42 patients (21 male, 21 female) with either leftor right-sided mTLE (22 left, 20 right) and in 12 gender-and age-matched healthy controls during resting wakefulness and in 12 sex-and age-matched healthy controls. Clinical characteristics were balanced across the patient subgroups. All patients were subjected to neuropsychological assessment: 41 patients had histologic changes of definite or probable hippocampal sclerosis.Results: Data analysis based on pixel-by-pixel comparisons and on a laterality index of regions of interest (ROIs) showed significant depressions of the mean rCMRGlu extending beyond the mesiotemporal region and temporolateral cortex to extratemporal regions including the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal and frontal regions was related to performance in the Trail-Making Test and WAIS-R subitems.Conclusions: Our data showed a gender-specific predominance of extramesiotemporal hypometabolism in male patients with mTLE related to abnormalities of temporal and frontal lobe functions. Key Words: FDG-PET-mTLEGender differences-Hypometabolism-Neuropsychology.Mesial temporal lobe epilepsy (mTLE) is the most common and best-defined syndrome of symptomatic localization-related epilepsy (1). Positron emission tomography (PET) using 18-fluoro-deoxyglucose (FDG-PET) was the first functional neuroimaging method allowing location of regions generating epileptiform EEG changes noninvasively (2) and has been established as a sensitive and reliable method for presurgical evaluation of TLE patients (3-5). FDG-PET has been used for lateralization of the seizure-onset zone, especially in those cases in which surface EEG and magnetic resonance imaging (MRI) provided discordant findings. However, FDG-PET revealed not only hypometabolism in the epileptogenic zone in mTLE, but also extratemporal metabolic disturbances (6-8).Accepted July 2, 2003. Address correspondence and reprint requests to Dr. R.J. Seitz at University-Hospital Düsseldorf, Department of Neurology, Moorenstrasse 5, D-40225 Düsseldorf, Germany. E-mail: seitz@neurologie.uniduesseldorf.de These "remote depressions" can affect the ipsi-and contralateral neocortical part of the temporal lobe, the frontoorbital cortex, and the thalamus. These areas are supposed to be affected secondarily by ongoing subclinical seizure activity, inhibition, and deafferentation rather than by morphologic tissue damage (8,9). The degree of hypometabolism in these regions was shown to correlate well with neuropsychological impairments such as verbal memory function or cognitive abilities (6,7).Apart from its use in the assessment of neuropsychiatric abnormalities, FDG-PET also has the capacity to provide phy...

Structural and functional correlates of epileptogenesis — Does gender matter?

“…This gender difference reflected a difference in the spread pattern of seizures. In a different study of a similar population, it was observed that women with MTLE had temporal hypometabolism contralateral to the zone of ictal onset, while ipsilateral frontal hypometabolism was seen in men (Nickel et al, 2003). Together, these findings might explain the observation that hippocampal seizures are more prone to generalize in men compared to women (Janszky et al, 2004).…”

Sex differences in the neurobiology of epilepsy: A preclinical perspective

“…Voxel based morphometry shows abnormalities in men with TLE that are frontal whereas they are more often temporal in females with TLE (Santana et al, 2014). Extratemporal hypometabolism has been reported to be more common in men than women with TLE using neuroimaging (Savic and Engel, 1998; Nickel et al, 2003). Despite these findings, there still are many aspects of epilepsy where sex differences are understudied and as yet unclear.…”

Thyroid hormones: Possible roles in epilepsy pathology

“…On the other hand, males may be more vulnerable to brain damage induced seizure [132], and development of generalized tonic-clonic seizures [133]. They are also more susceptible to develop symptomatic localization-related epilepsy which can be attributed to higher risk of physical damage to the brain and the consequent seizures [128,134].…”